Menopause - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

ENOPAUSE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J AMES N. P...

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ENOPAUSE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2003 by ICON Group International, Inc. Copyright Ó2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Menopause: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83629-9 1. Menopause-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on menopause. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON MENOPAUSE ............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Menopause .................................................................................. 21 E-Journals: PubMed Central ..................................................................................................... 144 The National Library of Medicine: PubMed .............................................................................. 146 CHAPTER 2. NUTRITION AND MENOPAUSE ................................................................................. 257 Overview.................................................................................................................................... 257 Finding Nutrition Studies on Menopause ................................................................................. 257 Federal Resources on Nutrition ................................................................................................. 265 Additional Web Resources ......................................................................................................... 266 CHAPTER 3. ALTERNATIVE MEDICINE AND MENOPAUSE ........................................................... 271 Overview.................................................................................................................................... 271 The Combined Health Information Database............................................................................. 271 National Center for Complementary and Alternative Medicine................................................ 272 Additional Web Resources ......................................................................................................... 282 General References ..................................................................................................................... 297 CHAPTER 4. DISSERTATIONS ON MENOPAUSE ............................................................................. 299 Overview.................................................................................................................................... 299 Dissertations on Menopause...................................................................................................... 299 Keeping Current ........................................................................................................................ 305 CHAPTER 5. CLINICAL TRIALS AND MENOPAUSE ........................................................................ 307 Overview.................................................................................................................................... 307 Recent Trials on Menopause...................................................................................................... 307 Keeping Current on Clinical Trials ........................................................................................... 327 CHAPTER 6. PATENTS ON MENOPAUSE ........................................................................................ 329 Overview.................................................................................................................................... 329 Patents on Menopause ............................................................................................................... 329 Patent Applications on Menopause ........................................................................................... 342 Keeping Current ........................................................................................................................ 347 CHAPTER 7. BOOKS ON MENOPAUSE ........................................................................................... 349 Overview.................................................................................................................................... 349 Book Summaries: Federal Agencies............................................................................................ 349 Book Summaries: Online Booksellers......................................................................................... 350 The National Library of Medicine Book Index ........................................................................... 376 Chapters on Menopause ............................................................................................................. 377 Directories.................................................................................................................................. 378 CHAPTER 8. MULTIMEDIA ON MENOPAUSE ................................................................................. 381 Overview.................................................................................................................................... 381 Video Recordings ....................................................................................................................... 381 Audio Recordings....................................................................................................................... 382 Bibliography: Multimedia on Menopause.................................................................................. 382 CHAPTER 9. PERIODICALS AND NEWS ON MENOPAUSE .............................................................. 385 Overview.................................................................................................................................... 385 News Services and Press Releases.............................................................................................. 385 Newsletter Articles .................................................................................................................... 389 Academic Periodicals covering Menopause ............................................................................... 389 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 393 Overview.................................................................................................................................... 393 NIH Guidelines.......................................................................................................................... 393

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NIH Databases........................................................................................................................... 395 Other Commercial Databases..................................................................................................... 398 The Genome Project and Menopause ......................................................................................... 398 APPENDIX B. PATIENT RESOURCES ............................................................................................... 403 Overview.................................................................................................................................... 403 Patient Guideline Sources.......................................................................................................... 403 Associations and Menopause ..................................................................................................... 413 Finding Associations.................................................................................................................. 413 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 415 Overview.................................................................................................................................... 415 Preparation................................................................................................................................. 415 Finding a Local Medical Library................................................................................................ 415 Medical Libraries in the U.S. and Canada ................................................................................. 415 ONLINE GLOSSARIES ................................................................................................................ 421 Online Dictionary Directories ................................................................................................... 425 MENOPAUSE DICTIONARY..................................................................................................... 427 INDEX .............................................................................................................................................. 517

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with menopause is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about menopause, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to menopause, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on menopause. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to menopause, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on menopause. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON MENOPAUSE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on menopause.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and menopause, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “menopause” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: ·

Hormonal Decline Indicator in Women (Age at Menopause) Modifies Age of Onset in Alzheimer's Disease Source: Alzheimers Reports. 2(1): 27-99. January 1999. Summary: This journal article describes a retrospective study that looked for a correlation between age at onset of menopausal symptoms and age at onset of Alzheimer's disease (AD). Participants were 45 females diagnosed with late-onset AD. Researchers ascertained age at menopause retrospectively from the family or caregivers. Data analysis indicated that the mean age of menopause was 51.1 years. In 23 percent of the cases, age at menopause alone could adequately explain the age at onset of AD symptoms. The results indicate a positive correlation between age of symptomatic onset of AD and age at menopause. These findings support the role of estrogens in AD development and the potential benefit of estrogens in delaying the development of AD

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symptoms. Additionally, since age at menopause is genetically influenced, new ADlinked. Genes can be supposed to exist. 1 figure, 11 references. ·

Cognitive Function in Nondemented Older Women Who Took Estrogen After Menopause Source: Neurology. 50: 368-373. February 1998. Summary: This journal article describes a study of the effects of estrogen replacement therapy on cognitive function in older women without dementia. Data were obtained from women participating in a large, community-based epidemiologic study of aging and dementia in Manhattan, New York. The sample selected for this analysis consisted of 727 women, mean age of 74.2 years, who were free of dementia and had no signs of Parkinson's disease or stroke. The group was 27.5 percent white, 27.5 percent black, and 43.7 percent Hispanic. Cognitive function was assessed at baseline and at 2.5-year followup, using measures of verbal recall memory (immediate and delayed), verbal abstract reasoning and concept formation, and word-finding ability. Eighty-one women (11 percent) reported using estrogen after menopause, with the average duration of use being 4.55 years; only 12 women (2 percent) were still using estrogen at study entry. Women who had used estrogen scored significantly higher than nonusers on the baseline and followup cognitive tests, and their performance on verbal memory improved slightly over time. The effect of estrogen on cognition was independent of age, education, ethnicity, and apolipoprotein E genotype. The authors conclude that estrogen may help maintain cognitive function in postmenopausal women without dementia. 2 tables, 24 references. (AA-M).

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Effect of Oestrogen During Menopause on Risk and Age at Onset of Alzheimer's Disease Source: Lancet. 348: 429-432. August 17, 1996. Summary: This journal article reports the effects of estrogen during menopause on the risk of Alzheimer's disease and age at onset. The study involved 1,124 older women who were initially free of Alzheimer's disease (AD), Parkinson's disease, or stroke; and who were taking part in a longitudinal study of aging and health in a New York City community. Overall, 156 (12.5 percent) of the women reported taking estrogen after the onset of menopause. The age at onset of AD was significantly later in women who had taken estrogen than in those who did not, and the relative risk of AD was significantly reduced (5.8 percent of estrogen users versus 16.3 percent of nonusers) even after adjustment for differences in education, ethnic origin, and apolipoprotein E gene status. Women who used estrogen for longer than 1 year had a greater reduction in risk. None of the women who were using estrogen at the start of the study has developed AD. The authors interpret these findings to suggest that estrogen use in postmenopausal women may delay the onset and decrease the risk of AD. 1 figure, 2 tables, 28 references.

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Informed Choices: Your Most Valuable Role in Menopause Care is Education Source: Advance for Nurse Practitioners. 10(1): 65-68. January 2002. Summary: This article provides information for nurse practitioners on menopause and how to treat its symptoms. It lists recommendations from the North American Menopause Society about how to help women achieve optimum health through the menopause transition, and discusses the pharmacologic treatment of menopause and post menopause. Alternative treatments for women who are reluctant or unable to take hormone replacement therapy are also covered. The article includes tables of the most

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common menopausal symptoms and the most commonly used hormone replacement therapies. 11 references. ·

Menopause: The Latest on Hormone Replacement Therapy Source: Diabetes Self-Management. 19(4): 90, 92, 95-97. July-August 2002. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Website: www.diabetes-self-mgmt.com. Summary: Hormone replacement therapy (HRT) is a medical therapy option that can alleviate and treat both the short-term symptoms and some of the long-term consequences of menopause. HRT can also increase the risk for certain health problems, so a menopausal woman and her physician need to consider her individual risk factors before starting HRT. This article discusses the benefits, risks, and alternatives to HRT for women with diabetes. Other topics include common symptoms of perimenopause and menopause, the long-term consequences of menopause, the effects of menopause on diabetes, the different types of HRT, the effects of HRT on diabetes, and alternative treatments.

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Menopause: Transition with Balance Source: Diabetes Forecast. 54(3): 37-39. March 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article discusses the challenges facing women who have diabetes during their transition to menopause. For most women, menopause occurs around the age of 51, and this natural transition is often accompanied by symptoms such as hot flashes, vaginal dryness, sleeplessness, and irritability. The years prior to menopause are referred to as the perimenopausal years. During this time, the menstrual cycle becomes more irregular and symptoms associated with menopause begin. For women who have diabetes, this is also the time when blood glucose levels fluctuate widely. Diabetes control may suffer because, as estrogen production decreases, the body may become more resistant to insulin. As the levels of estrogen and progesterone drop off permanently, the body once again becomes more sensitive to insulin. At this stage, hypoglycemia can occur more often. Menopause is also the time when a woman's risk for heart disease, osteoporosis, and other chronic health problems increases. Women who have diabetes already have an increased risk of heart disease and a slightly increased risk of osteoporosis. Symptoms associated with menopause, including hot flashes, moodiness, short term memory loss, sweating, and flushing, can be confused with the symptoms of both low and high blood glucose. Women who have diabetes need to check their blood glucose levels more often to determine whether they are experiencing a low or menopausal symptoms. Vaginal dryness and frequent vaginal and urinary tract infections can also occur during menopause. These problems can be made worse by persistent high blood glucose levels. Women can adjust their diabetes regimen to reduce the frequency of high and low blood glucose levels.

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Menopause in Type 1 Diabetic Women: Is It Premature? Source: Diabetes. 50(8): 1857-1862. August 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org.

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Summary: This review article describes a study that explored the menopause transition in a unique and representative cohort of adult Caucasian women with type 1 diabetes, their sisters, and unrelated control subjects without diabetes. The Familial Autoimmune and Diabetes (FAD) Study, which is the basis of the current study, recruited a cohort of 656 people who were retrospectively defined in 1981 for a study of type 1 diabetes mortality. People were eligible if they were on insulin therapy at diagnosis between 1950 and 1964, less than 17 years old at disease onset, and seen at the Children's Hospital of Pittsburgh within 1 year of type 1 diabetes onset. During 1990, registered patients were recontacted to update the data collected in 1981. Information was obtained for 561 patients. Beginning in 1993, living patients who completed the 1990 survey were recruited for the FAD Study. All participants received a clinical evaluation. Menstrual and menopausal events were self reported. The study found that the mean age of menarche was statistically significantly older for women with type 1 diabetes compared with women who did not have diabetes. In addition, women with type 1 diabetes were had more menstrual irregularities and a younger age at menopause than women without diabetes. This resulted in a 6 year reduction in the number of reproductive years for women with type 1 diabetes. Risk factors univariately associated with earlier menopause included type 1 diabetes, menstrual irregularities before 30 years of age, nulliparity, and unilateral oophorectomy. Multivariate analysis confirmed that type 1 diabetes, menstrual irregularities by 30 years of age, and unilateral oophorectomy were independent determinants of earlier menopause in the cohort. The article hypothesizes that an earlier menopause, which resulted in a 17 percent decrease in reproductive years, is a major unstudied complication of type 1 diabetes. 1 figure. 2 tables. 62 references. (AA-M). ·

Managed Menopause Source: Diabetes Forecast. 54(5): 69-70. May 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reviews evidence on the use of hormone replacement therapy (HRT) for older women with diabetes. Although some evidence suggests that HRT may be useful for women with diabetes, other research shows that HRT has mixed effects on blood lipids. However, the overall consensus that is emerging is that postmenopausal women with diabetes should be considered for HRT, as long as the risks and benefits are carefully weighed. Contraindications include a personal or family history of breast, endometrial, or uterine cancer. However, HRT may be beneficial for women with a personal or family history of heart disease or osteoporosis. HRT can take the form of pills or patches. When menopause begins, HRT can cause unexplained hypoglycemia that can be managed with adjustment to insulin doses. Once menopause is established, HRT can help maintain hormone levels in a stable range. The decision to start HRT is an intensely personal one, and women should talk with their health care providers to help them make this decision.

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Sexuality and Menopause. Part 1: Physical Outlook Source: Diabetes Self-Management. 12(5): 6-8, 10, 12. September-October 1995. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: This article is the first in a two-part series that explores the emotional and physical issues that influence sexuality throughout menopause. The author offers

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suggestions for enhancing and maintaining sexuality during the second half of life. This segment focuses on physical issues. The author emphasizes that menopause should not be regarded as a roadblock to sexuality, but rather a detour on a lifelong journey. Topics include a definition of menopause; research on female sexuality; the biological aspects of female sexuality; the physical changes of menopause; the problem of urinary incontinence; sexuality and chronic disease; the impact of complications that come from increasing age and duration of diabetes on one's sexuality; the role of drugs and alcohol; and the importance of communication in solving any problems of sexual relations. ·

Sexuality and Menopause. Part 2: The Emotional Issues Source: Diabetes Self-Management. 12(6): 6-8, 10, 11. November-December 1995. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: This article is the second in a two-part series that explores the emotional and physical issues that influence sexuality throughout menopause. The author offers suggestions for enhancing and maintaining sexuality during the second half of life. This segment focuses on the emotional issues. The author offers information to help readers navigate their way through some of the emotional problems that can occur at this time of life. Topics include the public perception of the aging female; personal expectations about aging; the physiology of sexual desire; sociological factors that can impact on a woman's experience of menopause, including parenting at an older age and/or caring for her own parents; the impact of diabetes on a woman's sexuality; body image; grief; dealing with anger and depression; the role of a support group and friendship in dealing with menopause; the importance of obtaining adequate information about menopause; and enhancing and maintaining sexuality throughout one's lifetime. The article concludes with a brief list of suggested readings.

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Managing Menopause Without Estrogen Source: Diabetes Self-Management. 11(1): 38-42. January-February 1994. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: This article provides readers with an overview of hormone replacement therapy and a guide to nonhormonal therapy for managing menopause and preventing postmenopausal cardiovascular disease. The authors review the patients for whom nonhormonal therapy might be appropriate, cautioning that most of the nonhormonal treatment options have not yet been subjected to controlled scientific evaluations. The authors discuss symptoms and the recommended treatment options for each. Topics include hot flashes; sexual problems; urinary tract problems; and other menopausal symptoms, including irritability, mood swings, sleep disorders, and fluid retention. The article concludes with a discussion of cardiovascular disease and ways to minimize the potential for heart problems.

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Does the Menopause Influence the Risk of Bacteriuria? Source: International Urogynecology Journal. 12(5): 332-336. June 2001. Contact: Available from Springer-Verlag New York Inc. 175 Fifth Avenue, New York, NY 10010. (212) 460-1500. Fax (212) 473-6272.

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Summary: This article reports on a study undertaken to test the hypothesis that the risk of bacteriuria (bacteria in the urine) is increased as a result of estrogen deprivation following the menopause (end of menstruation). All midstream urine samples (MUS) sent to the King's College Hospital department of microbiology by general practitioners in 1997 were assessed. Logistic regression analysis was performed to investigate the effects of age and sex on the likelihood of having a positive result. Nonlinear effects of age were investigated, with interest focusing in particular on the time around the menopause. There were 15,392 MSU samples analyzed: 11,811 (77 percent) were from women and 3,581 (23 percent) from men. In both sexes the proportion of positive results increased with increasing age. The specimens taken from women were significantly more likely to be positive than those taken from a man of the same age. In women there was no evidence of any nonlinear relationship between age and the log odds of a positive result. A plot of the proportion of positive results versus age did not suggest any departure from a linear relationship at or following the menopause. The authors conclude that the increased risk of bacteriuria which occurs as women get older appears to happen gradually as a result of the aging process, rather than as the result of pathophysiological changes in the urogenital tract that take place at or following the menopause. 3 figures. 1 table. 22 references. ·

Physiology, Medical Management and Oral Implications of Menopause Source: JADA. Journal of the American Dental Association. 133(1): 73-81. January 2002. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: Approximately 36 million women in the United States are in the postmenopausal phase of life. The physiological changes associated with spontaneous or surgical menopause (after surgical removal of both ovaries) cause some women to experience uncomfortable symptoms such as hot flashes, night sweats, and vaginal dryness. In addition, estrogen deprivation arising from menopause in association with age-related factors disproportionately increases the risk of developing cardiovascular disease, osteoporosis, Alzheimer disease, and oral disease. Hormone replacement therapy (HRT, featuring estrogen or estrogen and progestin) often is prescribed on a short term basis to alleviate the uncomfortable symptoms associated with estrogen deficiency and on a long term basis to prevent some of the chronic illnesses common to postmenopausal women. This article reviews the physiology, medical management, and oral implications of menopause. Dentists who treat women entering menopause need to consider the stressful phase of life their patients are experiencing. Clinical findings of postmenopausal problems on dental examination may include a lack of saliva, increased dental caries (cavities), dysesthesia (reduced or altered sense of feeling), taste alterations, atrophic gingivitis (inflammation of the gums), periodontitis, and osteoporotic jaws unsuitable for conventional prosthetic devices or dental implants. Panoramic dental radiographs may reveal calcified carotid artery atheromas. The author stresses that dentists have an opportunity to refer women who are not under the care of a gynecologist for an evaluation to determine the appropriateness of HRT for its systemic and oral health benefits. 1 figure. 111 references.

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Dental Hygienists' Knowledge of Menopause and Its Potential Oral Manifestations Source: Journal of Dental Hygiene. 73(1): 22-28. Winter 1999. Contact: Available from American Dental Hygienists' Association. Subscription Department, 444 North Michigan Avenue, Suite 3400, Chicago, IL 60611. (312) 440-8900.

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Summary: Oral symptoms or discomforts reported in the literature associated with menopause include burning mouth syndrome, dry mouth or xerostomia, menopausal gingivostomatitis, alveolar bone loss in the osteoporosis population, and abnormal taste sensations. This article reports on a study undertaken to assess dental hygienists' general knowledge of menopause and its possible oral manifestations. Demographic descriptors, including education level, course work, and menopausal status, were examined to determine their influence on knowledge levels. A 27 item, self administered survey was mailed to a random sample of Connecticut dental hygienists. Fifty four percent of respondents scored 75 percent or higher in general knowledge about menopause. Seven percent scored the same about its oral effects. Educational level and dental hygiene college curricula influenced the oral effect scores. The findings suggest that dental hygienists need more education about menopause and its related oral conditions. Those with additional knowledge might be more able to provide comprehensive care to menopausal and postmenopausal dental patients. 3 tables. 41 references. (AA-M). ·

Menopause-Related Oral Alveolar Bone Resorption: A Review of Relatively Unexplored Consequences of Estrogen Deficiency Source: Menopause: The Journal of the American Menopause Society. 6(2): 129-133. Summer 1999. Summary: The alveolar processes of the maxilla (upper jaw) and mandible (lower jaw) provide the bony framework for tooth support. Osteoporotic changes of these bones may directly affect tooth stability and retention. This article reviews studies that have evaluated the relationship between systemic osteoporosis and oral alveolar bone mass as well as the effect of estrogen use on oral alveolar bone and tooth retention. The literature review covered the years 1989 to 1998. Studies reviewed demonstrate a positive correlation between systemic bone mass and systemic osteoporosis to oral bone resorption. Estrogen replacement therapy affects oral bone in a manner similar to the way it affects other sites. The authors conclude that postmenopausal estrogen users may retain more teeth after menopause. Sustained oral health and better tooth retention are potentially additional benefits for hormone replacement therapy users after menopause. 25 references.

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Oral Manifestations of Menopause Source: Compendium of Continuing Education in Dentistry. 14(12): 1584-1592. December 1993. Summary: This article discusses the oral manifestations of menopause: oral discomfort, including pain, a burning sensation, dryness, and altered taste perception; and alveolar bone loss as a result of osteoporosis. The article's topics include the basic physiology of menopause; the relationship between menopause and oral discomfort; the effects of menopause on oral cytology, salivary gland function, and alveolar bone mass; and the effects of estrogen on bone development. The article concludes with a post-test for receiving continuing education credits. 1 figure. 42 references. (AA-M).

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Exercise and Menopause: A Time for Positive Changes Source: The Physician and Sportsmedicine. 26(12):45-50,52. December 1998. Contact: The Physician and Sportsmedicine, 4530 W. 77th St., Minneapolis, MN 55435. (612) 835- 3222. FAX (612) 835-3460.

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Summary: Shangold and Sherman discuss how regular exercise can lessen or prevent many of the undesirable effects of menopause. These include depression, weight gain, loss of muscle mass and bone density, and heart disease. They recommend 20 to 60 minutes of aerobic exercise three to five days per week. Shangold and Sherman then offer guidelines on tailoring exercise to the patient, taking into consideration age, physical condition, weight, experience, and preferences. ·

Postmenopausal Estrogen Replacement Therapy and the Risk of Alzheimer Disease Source: Archives of Neurology. 58(3): 435-440. March 2001. Summary: This article examines the effect of postmenopausal estrogen replacement therapy (ERT) on the risk of Alzheimer's disease (AD). Data were obtained from the United Kingdom's General Practice Research Database. The sample consisted of 112,481 women who had received at least one prescription for ERT (n=112,481) and 108,925 women who had never used ERT. All participants were born on or before January 1, 1950. A total of 59 newly diagnosed cases of AD and 221 matched controls were identified from the 2 cohorts. Fifteen of the newly diagnosed AD cases (25 percent) and 53 controls (24 percent) were current estrogen users. The adjusted odds ratio for all current estrogen users compared with nonusers was 1.18. The odds ratio for users who took estrogen for 5 years or longer compared with nonusers was 1.05. Odds ratios were similar for women who used estrogen alone and those who used combined estrogenprogestin treatment. In this study, the use of ERT by postmenopausal women was not associated with a reduced risk of developing AD. 4 tables, 28 references.

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Reproductive Period and Risk of Dementia in Postmenopausal Women Source: JAMA: Journal of the American Medical Association. 285(11): 1475-1481. March 21, 2001. Summary: This article explores whether a longer reproductive period, as an indicator of longer exposure to endogenous estrogen, is associated with a lower risk of dementia and Alzheimer's disease (AD) in women who have natural menopause. Data were obtained from the Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands. This analysis included 3,601 women aged 55 years or older who did not have dementia at baseline (1990-1993) and who reported age at menarche, age at menopause, and type of menopause. Participants were re-examined in 1993-1994 and 1997-1999. During 21,046 person-years of follow-up, 199 women developed dementia (including 159 with AD). After adjusting for multiple covariates, risk of dementia was consistently higher in women with natural menopause and more reproductive years. Risk of dementia was 1.78 times higher in women with more than 39 reproductive years than in women with less than 34 reproductive years. For AD, there was a similar but not significant pattern of higher risk with longer reproductive period. The findings do not support the hypothesis that a longer reproductive period reduces the risk of dementia in women who have natural menopause. 1 figure, 4 tables, 49 references. (AA- M).

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Endogenous Estrogen Levels and Alzheimer's Disease Among Postmenopausal Women Source: Neurology. 54: 833-837. February 2000. Summary: This journal article examines the relationship between endogenous estrogen levels and Alzheimer's disease (AD) among postmenopausal women. The study participants were an ethnically diverse sample of postmenopausal women, age 65 years or older, with or without AD, who were not currently taking estrogen replacement

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therapy. The patients with AD had lower estradiol levels than did the controls. AD patients also had lower levels of estrone, but the difference was not significant. The results suggest an association between endogenous estradiol levels and AD in postmenopausal women, but the directionality of the association could not be determined. 3 tables, 41 references. ·

Postmenopausal Estrogen Replacement Therapy and Risk of AD: A Population-Based Study Source: Neurology. 52: 965-970. March 1999. Summary: This journal article describes a study of the association between Alzheimer's disease (AD) and estrogen replacement therapy (ERT) in postmenopausal women. Researchers used a case-control design and assessed estrogen exposure (any form of estrogen used for at least 6 months after menopause onset and before the onset of AD) in subjects matched by age and length of enrollment in the records-linkage system. Data showed that AD patients and control subjects had identical ages at menarche and menopause. The frequency of estrogen use was higher among control subjects than among AD patients. Researchers found a significant trend of decreasing odds ratios with increasing duration of use. The inverse association between ERT and AD remained significant after adjustment for education and age at menopause. The authors conclude that their results suggest that ERT is associated with a reduced risk of AD in postmenopausal women. 3 tables, 32 references. (AA-M).

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Effect of Estrogen on Brain Activation Patterns in Postmenopausal Women During Working Memory Tasks Source: JAMA. The Journal of the American Medical Association. 281(13): 1197-1202. April 7, 1999. Summary: This journal article describes the effects of estrogen on brain activation patterns in post-menopausal women during verbal and nonverbal working memory tasks. Forty-six postmenopausal women, aged 33 to 61 years, were enrolled in a randomized, double-blind, placebo-controlled trial. Women were randomly assigned to 21 days of treatment with conjugated equine estrogens (1.25 mg/d) or placebo, followed by a washout period of 14 days before crossover to the other treatment. Brain activation patterns were measured with functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material, whereas it decreased activation during storage of nonverbal material. Estrogen also produced a sharpening of the hemisphere encoding/retrieval asymmetry effect; it increased activation in the right superior frontal gyrus during retrieval tasks, with greater left hemisphere activation during encoding. Estrogen did not affect actual performance on the verbal and nonverbal memory tasks. The results suggest that it may be possible to affect functional brain organization in older women. 4 figures, 34 references. (AA-M).

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Postmenopausal Estrogen Use and Parkinson's Disease With and Without Dementia Source: Neurology. 50: 1141-1143. April 1998. Summary: This journal article describes a study of the effects of estrogen replacement therapy (ERT) on the risk of dementia in women with Parkinson's disease (PD). The participants were 87 women with PD without dementia (PDND), 80 women with PD with dementia (PDD), and 989 healthy women from the Washington Heights-Inwood community of New York, New York. The researchers collected information about age,

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education, ethnicity, and current and past ERT use. Apolipoprotein E (apoE) gene status was determined for a subset of patients and all controls. In a comparison of the two groups of women with PD, adjusting for age, education, and ethnicity, ERT use was associated with a lower risk of dementia. In a second analysis comparing PDD patients and controls, ERT use was again associated with a lower risk of PDD, and this finding was not affected by apoE gene status. In a third analysis comparing PDND patients and controls, ERT use was not associated with PD. The authors conclude that ERT use in postmenopausal women does not appear to affect the risk of PD, but it may be protective for the development of dementia in women with PD. Results of this study suggest that a randomized clinical trial of ERT may be warranted. 2 tables, 10 references. ·

Postmenopausal Estrogen Replacement Therapy and the Risk of Alzheimer's Disease: A Population-Base Case-Control Study Source: American Journal of Epidemiology. 140(3): 262-267. 1994. Summary: Researchers compare the exposure of estrogen replacement therapy of 107 female Alzheimer's disease cases with 120 age- and sex-matched control subjects by using computerized pharmacy data. The study examines whether postmenopausal estrogen replacement therapy reduces the risk of AD in women. AD cases were obtained from the Alzheimer's Disease Patient Registry of the University of Washington, Seattle, Washington, which is based on the enumerated health plan population from 1987 to 1992. Enrolled in the Registry are newly recognized cases of probable AD. These cases are ascertained and evaluated according to standardized diagnostic criteria. The control subjects were selected from the same defined population by stratified random sampling. The authors find use of estrogens did not show an association with AD. Oral and vaginal estrogens yielded similar results. The researchers conclude there is no evidence that estrogen replacement therapy has an impact on the risk of AD in women. 5 tables, 24 references. (AA-M).

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Hormone Replacement Therapy, Insulin Sensitivity, and Abdominal Obesity in Postmenopausal Women Source: Diabetes Care. 25(1): 127-133. January 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study undertaken to determine whether insulin sensitivity differs between postmenopausal women taking estradiol, women on estrogen plus progesterone hormone replacement therapy (HRT), and women not on HRT and whether differences are explained by the differences in total or abdominal adiposity and fat deposition in the muscle. The authors studied 28 obese, sedentary postmenopausal Caucasian women. Women taking oral estrogen (n = 6) were matched for age, weight, and body mass index (BMI) with women not on HRT (n = 6). Eight women taking oral estrogen plus progesterone were matched with eight different women not on HRT for age, weight, and BMI. Maximal aerobic capacity, percentage of fat, total body fat mass, and fat-free mass (FFM) were similar between groups. Visceral fat, subcutaneous abdominal fat, sagittal diameter, and mid thigh low density lean tissue (intramuscular fat) did not differ by hormone status. Basal carbohydrate and fat utilization was not different among groups. Fasting plasma glucose and insulin did not differ by hormone use. Glucose utilization (M) was measured; postmenopausal women taking oral estrogen had a 31 percent lower M than women not on HRT. M was 26 percent lower in women taking estrogen plus progesterone than women not on HRT. M per I, the

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amount of glucose metabolized per unit of plasma insulin (I), an index of insulin sensitivity, was 36 percent lower in women taking estrogen compared with matched women not on HRT and 28 percent lower in women taking estrogen plus progesterone compared with matched women not on HRT. The authors conclude that postmenopausal women taking oral estrogen or those taking a combination of estrogen and HRT are more insulin-resistant than women not on HRT, even when women are of comparable total and abdominal adiposity. 1 figure. 3 tables. 49 references. ·

Effect of Estrogen Use on Levels of Glucose and Insulin and the Risk of Type 2 Diabetes in American Indian Postmenopausal Women: The Strong Heart Study Source: Diabetes Care. 25(3): 500-504. March 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study undertaken to examine the associations between estrogen use and levels of insulin and glucose, as well as the effect of estrogen use on the risk of type 2 diabetes. The report is based on 857 American Indian women who were both nondiabetic and postmenopausal at the baseline examination (1989 to 1992) and who completed a second examination (1993 to 1995) an average of 4 years later. The participants were divided into three groups: never, past, and current users based on their baseline estrogen use status. Postmenopausal estrogen use was associated with lower fasting glucose but higher 2 hour glucose levels compared with never users. Postmenopausal estrogen use was not significantly associated with the risk of type 2 diabetes compared with past and never users, based on the American Diabetes Association or World Health Organization definitions of diabetes. However, the risk of type 2 diabetes increased with increasing duration of estrogen use among current users. The authors conclude that these data suggest that estrogen use in American Indian postmenopausal women may relate to deterioration of glucose tolerance. Longer duration of estrogen use among current users may relate to an increased risk of type 2 diabetes. 3 tables. 26 references.

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Effects of Moderate Alcohol Intake on Fasting Insulin and Glucose Concentrations and Insulin Sensitivity in Postmenopausal Women: A Randomized Control Trial Source: JAMA. Journal of the American Medical Association. 287(19): 2559-2562. May 15, 2002. Summary: Epidemiological data demonstrate that moderate alcohol intake is associated with improved insulin sensitivity in nondiabetic individuals. No controlled-diet studies have addressed the effects of daily moderate alcohol consumption on fasting insulin and glucose concentrations and insulin sensitivity. This article reports on a study undertaken to determine whether daily consumption of low to moderate amounts of alcohol influences fasting insulin and glucose concentrations and insulin sensitivity in nondiabetic postmenopausal women. The randomized controlled crossover trial included 63 healthy postmenopausal women. Results showed that consumption of 30 grams per day of alcohol compared with 0 grams per day reduced fasting insulin concentration by 19.2 percent and triglyceride concentration by 10.3 percent, and increased insulin sensitivity by 7.2 percent. Normal weight, overweight, and obese individuals responded in similar ways. Fasting glucose concentrations were not different across treatments. The authors conclude that consumption of 30 grams of alcohol (2 drinks per day) has beneficial effects on insulin and triglyceride

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concentrations and insulin sensitivity in nondiabetic postmenopausal women. 1 figure. 2 tables. 35 references. ·

Diabetes and the Risk of Acute Urinary Tract Infection Among Postmenopausal Women Source: Diabetes Care. 25(10): 1778-1783. October 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study that examined whether the presence of diabetes alters the risk of acute urinary tract infection (UTI) in postmenopausal women. The authors conducted a case-control study of the Group Health Cooperative of Puget Sound (GHC), a staff-model nonprofit health maintenance organization in Washington State. Subjects were women aged 55 to 75 years who had been members of GHC for at least 1 year and who had had an acute symptomatic UTI within the preceding month. Of the 901 case and 913 control subjects, diabetes was reported in 13.1 and 6.8 percent, respectively. The health plan diabetes registry confirmed the diagnosis in 92 percent of women who self-reported the condition. The age-adjusted odds ratio for UTI in relation to self-reported clinician-diagnosed diabetes was 2.2. Adjustment for frequency of sexual intercourse and history of UTI had little effect on this estimate. Compared with nondiabetic women, higher UTI odds were seen in subjects who used oral hypoglycemic agents and insulin, but not in subjects with untreated diabetes or diabetes treated by lifestyle changes. The authors conclude that diabetes under pharmacologic treatment is associated with increased risk of clinically apparent UTI in postmenopausal women. 3 tables. 28 references.

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Beneficial Effects of Soy Phytoestrogen Intake in Postmenopausal Women with Type 2 Diabetes Source: Diabetes Care. 25(10): 1709-1714. October 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease. Type 2 diabetes confers an adverse cardiovascular risk profile, particularly in women after menopause. This article reports on a study undertaken to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance, glycemic control, and cardiovascular risk markers in postmenopausal women with type 2 diabetes. A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a randomized, double-blind, crossover trial of dietary supplementation with phytoestrogens versus placebo for 12 weeks, separated by a 2 week washout period. Compliance with the dietary supplementation was more than 90 percent for both treatment phases. Phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin, insulin resistance, total cholesterol, LDL cholesterol, cholesterol to HDL cholesterol ratio, and free thyroxine. No significant change occurred in HDL cholesterol, triglycerides, weight, blood pressure, creatinine, dehydroepiandrosterone sulfate, androstenedione, and the hypothalamic-pituitaryovarian axis hormones. The authors conclude that these results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes, thereby improving their cardiovascular risk profile. 1 figure. 2 tables. 32 references.

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Hormone Replacement Therapy and Its Relationship to Lipid and Glucose Metabolism in Diabetic and Nondiabetic Postmenopausal Women Source: Diabetes Care. 25(10): 1675-1680. October 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Among postmenopausal women, those with diabetes experience more cardiovascular diseases than those without diabetes. In this study, the authors examined the relationship of hormone replacement therapy (HRT) with indicators of lipid and glucose metabolism using a national sample of postmenopausal women with and without diabetes. The authors used data from the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1994. A total of 2,786 postmenopausal women aged 40 to 74 years participated in an oral glucose tolerance test (OGTT), had blood drawn for lipid (fats) assessment, and responded to HRT questions. The results showed that postmenopausal women with diabetes had increased dyslipidemia compared with nondiabetic women. Among diabetic women, current users of HRT had significant different lipid and glucose control levels than never users of HRT for the following variables: total cholesterol, non-HDL, apoA, fibrinogen, glucose, insulin, and glycosylated hemoglobin. The authors conclude that women with diabetes and nondiabetic postmenopausal women currently taking HRT had better lipoprotein profile than never or previous users of HRT. Women with diabetes currently taking HRT had better glycemic control than never or previous users of HRT. 3 tables. 29 references.

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Type 1 and Type 2 Diabetes and Incident Hip Fractures in Postmenopausal Women Source: Diabetes Care. 24(7): 1192-1197. July 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes a study that examined whether postmenopausal women with diabetes experienced a higher incidence of hip fracture than women without diabetes. The study sample consisted of 32,089 postmenopausal women residing in Iowa who were surveyed by mail in 1986 and followed for 11 years. Diabetes status and other potential risk factors were assessed by questionnaire at baseline. Incidence of hip fracture was ascertained by follow up questionnaires. Over 306,900 person years of follow up, 490 hip fractures were identified, for an incidence rate of 1.6 per 1,000 person years. After adjustment for age, smoking status, estrogen use, body mass index, and waist to hip ratio, women with type 1 diabetes were 12.25 times more likely to report an incident hip fracture than women without diabetes. Women with type 2 diabetes had a 1.70 fold higher risk of incident hip fracture than women without diabetes. Longer duration of type 2 diabetes was associated with higher incidence, as was use of insulin or oral diabetes medications in women with type 2 diabetes. Furthermore, women who were initially free of diabetes but in whom diabetes developed had a relative risk of hip fracture of 1.60 compared with women who never had diabetes. The article concludes that postmenopausal women who have diabetes or in whom diabetes develops are at higher risk for hip fracture than postmenopausal women without diabetes. Strategies to prevent osteoporosis or falling may be especially warranted in women with diabetes. 2 tables. 31 references. (AA-M).

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Physical Activity and Incident Diabetes Mellitus in Postmenopausal Women Source: American Journal of Public Health. 90(1): 134-138. January 2000. Summary: This article describes a study that determined whether the incidence of diabetes is reduced among physically active older women. In January 1986, a questionnaire about diet and lifestyle was mailed to 99,826 women aged 55 to 69 years old who had a valid Iowa driver's license. A total of 41,836 women completed and returned the questionnaire, and 34,257 women had complete data on all covariates. The cohort was followed via mailed questionnaires in 1987, 1989, 1992, and 1997. The study found that, compared with women in the low physical activity category, women in the medium and high physical activity categories were less likely to be overweight, to have a high waist to hip ratio, and to be smokers; however, they were more likely to drink alcohol, to be educated beyond high school, and to take replacement estrogen. The two higher physical activity groups also had a higher mean intake of energy and whole grains than the low activity group. Diabetes incidence was associated positively with age, pack years of smoking, energy intake, Keys' score, body mass index (BMI), waist to hip ratio, and family history of diabetes, but it was negatively associated with education level, alcohol intake, estrogen use, and whole grain intake. Compared with those reporting no regular physical activity, those regularly engaging in physical activity had a relative risk of diabetes of 0.69 after adjustment for major confounding variables. As expected, adjustment for BMI and waist to hip ratio attenuated this relative risk to 0.86. Frequency of both moderate physical activity and vigorous physical activity showed strong monotonic negative associations with diabetes incidence, so the most frequently active women had half the risk of diabetes as the least frequently active. In a supplemental analysis of 26,124 women who reported no vigorous activity, moderate activity was still associated negatively with diabetes. The physical activity index, which combined moderate and vigorous activity frequencies, was also associated negatively and strongly with diabetes incidence. The article concludes that the findings suggest that physical activity is important for type 2 diabetes prevention among older women. 3 tables. 34 references. (AA-M).

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Effects of Postmenopausal Hormone Replacement Therapy on Central Abdominal Fat, Glycemic Control, Lipid Metabolism, and Vascular Factors in Type 2 Diabetes: A Prospective Study Source: Diabetes Care. 22(9): 1401-1407. September 1999. Contact: Available from American Diabetes Association, Inc. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 806-7801. Website: www.diabetes.org. Summary: This article describes a 12-month prospective study that examined the early and longer term effects of hormone replacement therapy (HRT) on lipid metabolism, glycemic control, total body and central abdominal fat, blood pressure, and arterial pulse wave velocity (APWV) in overweight postmenopausal females who had type 2 diabetes. Participants were 14 women who were randomized to 6 months of observation or open label HRT before crossover. HRT consisted of 2 months of conjugated equine estrogen (CEE) 0.625 milligrams daily, followed by 4 months CEE and medroxyprogesterone 5 milligrams daily. The study found that 6 months of HRT induced significant reductions in waist circumference, waist to hip ratio, glycosylated hemoglobin (HbA1c), total and low density lipoprotein cholesterol, and central abdominal fat. HRT also improved physical functioning. There was a minor increase in resting energy expenditure. Total fat mass, fasting glucose, insulin, triglyceride, apolipoprotein B, nonesterified fatty acids, resting blood pressure, APWV, and physical

Studies 17

activity were unchanged. The article concludes that postmenopausal HRT in these overweight women who had type 2 diabetes was associated with a reduction in central adiposity and improvement in lipid metabolism and glycemic control without deterioration in weight status or cardiovascular parameters measured. Further study is needed to determine whether HRT induced improvements in these cardiovascular risk factors result in lower long term cardiovascular morbidity and mortality, as observed in nondiabetic women. 3 tables. 50 references. (AA-M). ·

Hormone Replacement Therapy or Prophylaxis in Postmenopausal Women with Recurrent Urinary Tract Infection Source: Journal of Infectious Diseases. 183(Supplement 1): S74-S76. March 1, 2001. Contact: Available from Journal of Infectious Diseases. University of Chicago Press, Journals Division, P.O. Box 37005, Chicago, IL 60637. (773) 753-3347. Fax (773) 753-0811. E-mail: [email protected]. Website: www.journals.uchicago.edu. Summary: Urinary tract infection (UTI) is the most common bacterial infection in women, and it occurs with much greater frequency among elderly than among younger women and with increasing frequency among postmenopausal women. This article explores the role of hormone replacement therapy (HRT) as prophylaxis (preventive therapy) in postmenopausal women with recurrent UTI. The author reviews the related literature and concludes that estrogen replacement is effective not only in the treatment of urogynecological symptoms related to menopause but also in the prevention of recurrent UTIs. Younger postmenopausal women can benefit from oral hormonal therapy, which improves clinical symptoms related to menopause and helps avoid osteoporosis and ischemic heart disease; the use of vaginal estrogen should be limited to women older than 60 years for the treatment of atrophic vaginitis, recurrent UTIs, and urge incontinence. The use of HRT, including vaginal therapy, is contraindicated in women with active venous thromboembolism, severe active liver disease, and endometrial and breast carcinoma (cancer) but can be administered to women with diabetes, gallstones, and other relative contraindications. The author calls for additional studies evaluating the safety and comparative efficacy of oral and vaginal estriol. 1 figure. 10 references.

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Role of Vaginal Estrogen in the Treatment of Urogenital Dysfunction in Postmenopausal Women Source: Urologic Nursing. 17(3): 92-95. September 1997. Contact: Available from Urologic Nursing. Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-3318. (314) 453-4351. Summary: This article explores the role of vaginal estrogen in the treatment of urogenital dysfunction in postmenopausal women. The authors note that decreased estrogen levels result in significantly lower urogenital tract changes and adversely influence quality of life. Consequences include atrophic vaginitis, atrophic urethritis, urinary incontinence, and pelvic organ prolapse. The authors note that estrogen replacement therapy (ERT) prevents, delays, and in many cases ameliorates these pathologic conditions. Potential side effects of ERT are dependent on dosage and route of administration; however, it appears that low-dose vaginal estrogen preparations do not have systemic side effects and are sufficient to treat postmenopausal genital atrophy. The authors review the evaluation of lower genital tract estrogen status. Nurses performing urodynamics and pelvic floor therapy have an ideal opportunity to assess

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urogenital health. A thorough history and careful visual examination should be an integral part of the assessment. 23 references. (AA-M). ·

Relationships Between Clinical Attachment Level and Spine and Hip Bone Mineral Density: Data from Health Postmenopausal Women Source: Journal of Periodontology. 73(3): 298-301. March 2002. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: There are physiological reasons to expect an association between bone mineral density of the spine and hip and attachment loss. To this point, however, most studies have found no correlation. The 135 patients reported on in this article were part of a randomized, controlled trial of estrogen replacement. All patients were in good oral health at entry and received annual oral prophylaxis as part of the study. Standard probing measurements were made with a pressure sensitive probe at 6 sites on each tooth. Bone mineral density was measured at the lumbar spine and proximal femur (thigh bone). These procedures were performed at baseline and at annual intervals for 3 years. Correlations between cross sectional measurements of clinical attachment level and bone mineral density were very weak and did not approach statistical significance. A few somewhat stronger correlations were found between longitudinal changes in bone mineral density and attachment. Although the correlations in the longitudinal changes were weak, they were consistently in the direction of greater bone mineral density being associated with less attachment loss. The authors conclude that there is no clear association between clinical attachment level and bone mineral density of the lumbar spine and proximal femur, whether examined on a cross sectional or longitudinal basis. 1 figure. 1 table. 7 references.

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Pattern of Alveolar Crest Height Change in Healthy Postmenopausal Women After Three Years of Hormone-Estrogen Replacement Therapy Source: Journal of Periodontology. 73(11): 1279-1284. November 2002. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: The loss of ovarian function at menopause is associated with loss of postcranial and oral bone. Hormone or estrogen replacement therapy (HRT) has a positive effect on both postcranial and oral bone. The objective of this study was to determine if the positive effect of HRT on alveolar crest height (ACH) is generalized or site specific. The sample consisted of 49 women who completed a 3-year, HRT prospective study. Mean ACH changes had an average correlation of minus 0.24 with femoral and lumbar spine bone mineral densities (BMDs). Overall, the correlations for site-specific changes were substantially smaller than those for generalized change. The authors conclude that studies of the effect of HRT on ACH should employ multiple measurements to minimize measurement errors associated with site-specific measurements. 1 table. 29 references.

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Carotid Artery Atheromas in Post-Menopausal Women: Their Prevalence on Panoramic Radiographs and Their Relationship to Atherogenic Risk Factors Source: JADA. Journal of the American Dental Association. 132(8): 1130-1136. August 2001.

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Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: More than 60 percent of the deaths in the United States attributed to stroke occur in postmenopausal women. As estrogen levels decline, atherosclerotic lesions (atheromas) develop in the region of the carotid bifurcation (where the carotid artery splits in the neck) and have been implicated as the precipitating cause in the majority of these strokes. Atheromas often are calcified and have been detected on the panoramic radiographs of neurologically asymptomatic male veterans; however, similar studies have not been conducted among female veterans. This article reports on a study in which the authors assessed panoramic radiographs and medical records of 52 neurologically asymptomatic female veterans (mean age, 70.4 years), with a history of amenorrhea (cessation of menstruation) of more than 12 months' duration, for atheromas and risk factors associated with atherosclerosis. The radiographs (x rays) of 16 subjects (31 percent) exhibited atheromas located in the neck about 2.0 centimenters inferior and posterior to the angle of the mandible (lower jaw). These findings were confirmed in all instances by the presence of atheromas on anteroposteriod cervical sping radiographs. The medical histories of these subjects were heavily laden with atherogenic risk factors (hypertension, 94 percent; overweight, 25 percent; obesity, 25 percent; smoking more than 15 pack years, 38 percent; hyperlipidemia, 69 percent; type 2 diabetes mellitus, 21 percent). Hypertension (high blood pressure) was significantly associated with the presence of atheromas. The authors conclude that some neurologically asymptomatic women at high risk of developing stroke can be identified in the dental office via panoramic radiography. Dentists should refer patients with such calcifications to an appropriate physician for further evaluation and treatment. 2 figures. 1 table. 33 references. ·

Postmenopausal Bone Loss and Osteoporosis as Possible Risk Factors in Periodontal Disease: An Update Source: Ontario Dentist. 78(1): 31-36. January-February 2001. Contact: Available from 4 New Street, Toronto, ON M5R 1P6. (800) 387-1393. Fax (416) 922-9005. Website: www.oda.on.ca/. E-mail: [email protected]. Summary: This article considers the role of postmenopausal bone loss and osteoporosis as possible risk factors in periodontal disease. The author reviews current research and conclusions in the areas of peak bone mass and bone loss, osteoporosis and osteopenia, the relationship between systemic and mandibular (lower jaw) bone density, common risk factors for both osteoporosis and periodontal disease, and common strategies for the treatment of osteoporosis and periodontal disease. The author concludes that while a relationship between osteoporosis and oral bone loss has long been postulated, the existing studies have been preliminary in nature. The author calls for longitudinal studies that could make it possible to determine if the progression of periodontal disease is more rapid in patients with osteopenia than in patients with normal bone density. This, in turn, may lead to better diagnostic measures and treatment outcomes for both periodontal disease and osteoporosis. 4 tables. 22 references.

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Relationship Between Bone Mineral Density and Periodontitis in Postmenopausal Women Source: Journal of Periodontology. 71(9): 1492-1498. September 2000. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225.

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Summary: Systemic bone loss has been proposed as a risk factor for periodontal disease; however, the relationship between these two diseases is still not clear. This article reports on a study undertaken to assess the relationship between systemic bone density and periodontal disease (controlling for known cofounders). The study population included 70 postmenopausal Caucasian women aged 51 to 78 years (mean 62.10 years plus or minus 7.1 years). Skeletal bone mineral density (BMD) was assessed and periodontal disease severity was represented by clinical attachment loss (CAL) and interproximal alveolar bone loss (ABL). Other measures of periodontal status included probing depth (PD), supragingival plaque, gingival (gum) bleeding on probing, and calculus. Results showed that the mean alveolar bone loss was significantly correlated with BMD of the trochanter (the trunk end of the femur), Ward's triangle, and total regions of the femur (thigh bone). Mean CAL appeared to be related to BMD consistently at all regions of the skeleton, although the association did not reach statistical significance. The authors conclude that skeletal BMD is related to interproximal alveolar bone loss and, to a lesser extent, to clinical attachment loss, implicating postmenopausal osteopenia (subnormally mineralized bone) as a risk indicator for periodontal disease in postmenopausal Caucasian women. 1 figure. 4 tables. 45 references. ·

Post-Menopausal Bone Loss and Its Relationship to Oral Bone Loss Source: Periodontology 2000. 23(1): 94-102. June 2000. Contact: Available from Munksgaard International Publishers Ltd. Commerce Place, 350 Main Street, Malden, MA 02148-5018. (781) 388-8273. Fax (781) 388-8274. Summary: Osteoporosis and osteopenia are characterized by reductions in bone mass and both may lead to skeletal fragility and fracture. This article reviews postmenopausal bone loss and its relationship to oral bone loss. Women are at greater risk for osteoporosis after menopause. The authors review this risk factor and others, discuss methods used to measure of bone mass and density, consider the relationship between systemic and mandibular (lower jaw) bone density, report preliminary data from the Women's Health Initiative Oral Ancillary Study, and outline common strategies for treatment of osteoporosis and periodontal disease. The authors conclude that while a possible relationship between osteoporosis and oral bone loss has long been postulated, the existing studies have been preliminary in nature. Longitudinal studies will make it possible to determine if the progression of periodontal disease is more rapid in patients with osteopenia than in patients with normal bone density. 6 figures. 3 tables. 52 references.

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Tooth Loss and Skeletal Bone Density in Healthy Postmenopausal Women Source: Osteoporosis International. 4(2): 104-109. March 1994. Summary: This article reports on a study in which associations between dental status and skeletal bone density were investigated in a group of 329 healthy postmenopausal women with normal bone density. Bone mineral density (BMD) of the lumbar spine, femoral neck and distal radius were measured by dual-or single-photon absorptiometry. Number of teeth remaining were counted and presence of complete dentures noted by a nurse practitioner. Forty-eight women (15 percent) wore a complete maxillary and/or mandibular denture. Among women without complete dentures, significant positive linear relationships were observed between number of teeth and BMD at the spine and radius, controlling for years since menopause, pack-years of smoking, education, and body mass index. BMD did not differ between the groups with and without dentures.

Studies 21

However, women who acquired dentures after the age of 40 years had significantly lower mean spinal and radial BMD than women who acquired dentures at age 40 years or earlier. The authors conclude that these associations between dental status and BMD support the hypothesis that systemic bone loss may contribute to tooth loss. 3 figures. 3 tables. (AA-M). ·

Body Weight Changes in Perimenopausal Women Source: Healthy Weight Journal. 16(3):42-44. May/June 2002. Summary: Perimenopause is defined as the transitional period into menopause. It begins a few years before and 1 year after the permanent cessation of menses. This article reviews perimenopause and age- related changes in body weight. As women age, body fat percentage increases. Following menopause, women experience changes in fat distribution with more fat becoming centrally located. Additionally, energy intake requirements decrease with age due to declining muscle mass and level of physical activity. These changes may result in weight gain if energy intake and expenditure remain constant. Perimenopausal overweight occurs in approximately 60 percent of American women. Studies have not clearly shown whether it is the process of perimenopause, age-related changes in body weight, or lifestyle choices that most significantly affect weight gain during perimenopause. The American College of Obstetricians and Gynecologists (ACOG) emphasizes the importance of lifestyle counseling for perimenopausal women. Starting and maintaining positive health habits can reduce the future incidence of chronic health problems. Behavioral change, such as eating a healthy diet and exercising, exerts influence in determining whether a woman gains weight perimenopausally.

Federally Funded Research on Menopause The U.S. Government supports a variety of research studies relating to menopause. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to menopause. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore menopause. The following is typical of the type of information found when searching the CRISP database for menopause:

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

22 Menopause

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Project Title: A LONGITUDINAL STUDY OF THE MENOPAUSE AND FAT PATTERNING Principal Investigator & Institution: Powell, Lynda H. Professor; Rush-Presbyterian-St Lukes Medical Ctr Chicago, IL 60612 Timing: Fiscal Year 2002; Project Start 10-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): It was once believed that menopause-related coronary risk was associated with a gain in total body fat, but recent research has suggested that it is not total fat per se, but the location of that fat, that is a key risk factor. Indices of central adiposity, particularly intra-abdominal fat (IAF), have: (1) predicted coronary events better than indices of total fat; (2) been associated with altered glucose and lipid metabolism and elevated blood pressure; and (3) been associated with changes in menopausal status. This gives rise to the hypothesis that menopause-related changes in sex hormones accelerate the accumulation of IAF, which in turn is associated with adverse cardiovascular risk. Existing studies of this hypothesis share major limitations in that they are small, cross-sectional and primarily Caucasian, focus only on comparisons of pre-and post-menopausal status, and have minimal controls for the important covariates of age and total fat. This is a study of the natural history of the accumulation of IAF as women transverse the menopause. It will be conducted on an intact biracial cohort of 868 women (419 African Americans; 449 Caucasians) who are participating in a larger study of women undergoing the menopausal transition. This is a population-based cohort that was randomly selected from an existing census with a 72 percent participation rate, approximately equal distribution of socioeconomic status within the African American and Caucasian subgroups, and a dropout rate of only 1 percent/year. As part of the larger study, this cohort undergoes annual exams in which a variety of cardiovascular, hormonal, and lifestyle factors are tracked. For this study, 2 clinical tests will be added to the battery at the 4th or 5th annual exam for the 536 women who are expected to be eligible by virtue of not having had a hysterectomy or begun taking hormone therapy. The 2 tests will be a CT scan for the assessment of IAF, and a DEXA scan for the assessment of total body fat. These tests will be repeated on an annual basis for the next 3 years. By the end of the study, it is projected that 462 transitions in menopausal status will have taken place. Random effects models will be used to estimate longitudinal changes in level and rate of IAF as one moves from one menopausal status to another. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: A NON-HUMAN PRIMATE MODEL OF NATURAL MENOPAUSE Principal Investigator & Institution: Honore, Erika K.; Southwest Foundation for Biomedical Res San Antonio, TX 782450549 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 14-MAR-2006 Summary: (Adapted from the applicant's abstract): The proposed training and research will be conducted at the SRPRC and the University of Texas Health Science Center at San Antonio. Dr. Erika Honore is seeking SERCA support to advance her development as an independent investigator in comparative medicine, with emphasis on models for women's health. Dr. Honore has completed a postdoctoral fellowship at Wake Forest University studying estrogens and atherosclerosis in macaques. As part of the current proposal, she will receive further training and guidance from investigators in genetics, cardiology and reproductive endocrinology. Studies will utilize a well characterized, pedigreed colony of more than 250 female baboons to establish a NHP model of naturally occurring perimenopause and menopause. Postmenopausal women are at

Studies 23

increased risk for cardiovascular disease and osteoporosis, as well as other conditions. Hormone replacement therapy (HRT) effectively reduces the risk, but only a fraction of U.S. women receive HRT. Research into menopause and HRT has relied on surgically ovariectomized NHPs as models of menopause. This does not adequately reflect the condition in women, where ovarian function declines gradually over several years and the postmenopausal ovary continues to produce androgens. Pilot data from the SRPRC indicate that aging female baboons undergo a natural transition into menopause with hormonal and physiological changes similar to those seen in women. The specific aims of this proposal are: 1) to characterize the perimenopausal period; 2) to determine the hormonal profiles of pre-, peri- and postmenopausal females; 3) to longitudinally assess relevant physiological variables in these three cohorts. These aims will be achieved through menstrual cycle analysis, assays of annual blood samples for hormones and lipoproteins, ultrasound measurements of peripheral vascular reactivity, and radiographic measurements of bone density. Interventional studies of novel HRT regimens are proposed for years 4 and 5 with the goal of increasing national compliance with HRT by developing an acceptable alternative. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: AGE AND GENDER EFFECTS ON CEREBRAL BLOOD FLOW Principal Investigator & Institution: Beske, Stacy D.; Hebrew Rehabilitation Center for Aged 1200 Centre St, Roslindale Boston, MA 02131 Timing: Fiscal Year 2001; Project Start 01-AUG-2001 Summary: Cerebrovascular disease incidence, specifically stroke, increases with advancing age; each passing decade after age 55 doubles the risk for stroke. Moreover, the risk is greater for men than women. An important physiologic risk factor for stroke is the capacity of cerebral vasculature to control and maintain brain blood flow. Two factors determine brain blood flow: cerebrovascular reactivity and cerebral blood flow autoregulation. The latter of these two may most profoundly affect risk for stroke; impairments in cerebral blood flow autoregulation reduce the ability of the cerebral circulation to buffer against rapid and large pressure changes. Age-related impairments in cerebral autoregulation have been described in animals, however there are no comparable data in humans. One factor which may reduce cerebral autoregulation with age is elevated sympathetic outflow. Increased sympathetic activity occurs with aging in humans and also decreases autoregulatory capacity. Therefore, increased stroke risk with age may derive from a shift in cerebral autoregulation due to increased sympathetic activity. Furthermore, in women, this shift may not occur until after menopause. This study will examine gender- and age- related differences in cerebral autoregulation in young, middle-aged, and older healthy men and women. I hypothesize that aging men demonstrate progressively reduced cerebral autoregulation related to increased sympathetic activity and that premenopausal women demonstrate preserved autoregulation with age related to lesser increases in sympathetic activity compared to postmenopausal women. Beat-by-beat relations between pressure and cerebral flow during lower body suction oscillating at 0.03, 0.05, and 0.10 Hz will provide an autoregulation index from differences in spectral gain from higher to lower frequencies. Since both aging and menopause are risk factors for stroke, this data may provide insight into the possible role of impaired cerebral autoregulation as the underlying commonality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

24 Menopause

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Project Title: AGE, CELL CYCLE MARKERS AND BREAST CANCER OUTCOMES Principal Investigator & Institution: Demichele, Angela; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-AUG-2004 Summary: My academic career goal is to develop a multidisciplinary, patient-oriented research program to study the complex biologic, genetic and clinical factors that determine prognosis in patients with breast cancer, to improve the ability to predict an individual's response to standard treatment approaches, and to translate this knowledge to the development of new therapeutic and cancer control strategies. The Mentored Patient-Oriented Research Career Development Award will provide me with the means to take two important steps in implementing this goal. First, I will obtain additional education in cancer pathobiology and practical experience in molecular genetics that will augment previous training in clinical oncology, epidemiology and biostatistics. Second, I will undertake a research program that utilizes a multidisciplinary, patientoriented approach to better understand breast cancer prognostic and predictive markers, and translate this knowledge to the clinical setting. The unifying hypothesis underlying the proposed research is that biological mechanisms of tumor development, growth and proliferation are influenced by clinical patient characteristics and that these mechanisms, in turn, result in distinct tumor behaviors that impact response to therapy and clinical patient outcomes. Earlier studies have demonstrated the prognostic and predictive significance associated with estrogen receptor expression and c-erb B2 (Her 2/neu) overexpression in breast tumors, suggesting links between a patient's clinical characteristics, the occurrence of a specific cancer phenotype and the reduced efficacy of adjuvant therapy. Two studies are proposed here to test this hypothesis in the context of another potentially important biological mechanism in breast cancer biology: dysregulation of cell cycle control. Biomarkers of cell cycle control ("cell cycle markers"), including proteins p53, p21, p27, cyclin D1 and cyclin E will be measured in a population of patients with early breast cancer. Biomarker expression will be measured by immunohistochemical staining of primary tumor tissue. In the first study, a crosssectional design will be utilized to determine a) whether alterations in the expression of cell cycle markers are associated with age or menopausal status at diagnosis, and b) whether alterations in the expression of cell cycle makers are associated with the presence of other molecular prognostic markers. The results of the cross-sectional study will contribute information about the role of this mechanism in further explaining the differences in breast cancer biology by age. In the second study, a prospective observational cohort design will be utilized to determine whether the presence of alterations in cell cycle markers are associated with a) an increased overall risk of breast cancer recurrence or b) an earlier time to recurrence than that seen in women without this phenotype. The results of the cohort study will contribute to understanding whether cell cycle markers can identify a group of breast cancer patients at high risk of recurrence with standard treatment approaches, in whom new therapeutic strategies should be targeted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AGED FOREBRAIN CHOLINERGIC NEURONS--ESTROGEN AND NGF Principal Investigator & Institution: Granholm, Ann-Charlotte E. Associate Professor; Physiology and Neuroscience; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 08-APR-1994; Project End 31-AUG-2005

Studies 25

Summary: (Adapted from the Investigator's Abstract) Aging and age-related degenerative disease has received increased attention due to its socioeconomic impact in the western world. Even though there are significant gender differences in age-related diseases such as AD, we still do not know which internal or external factors regulate this process. AD is signified by a marked loss of forebrain cholinergic neurons, and this disease occurs more often in women than men. Incorrect processing of amyloid precursor protein (APP) may play a significant role in AD, and the high incidence of AD in elderly women could depend on menopause and a lack of estrogen in the brain. Recent evidence from tissue culture experiments suggests a multifactorial process, and a relationship between APP, steroid hormones and NGF. However, no in vivo models have been designed to explore this relationship. Ts65Dn mice with segmental trisomy of Chr 16 (including the APP gene) have an overexpression of APP, loss of cholinergic forebrain neurons, and cognitive impairment that occurs around 6 months of age. A shorter Chr 16 trisomy, Ts1Cje (excluding the APP gene) lacks cognitive impairment and cholinergic loss. The Ts65Dn mouse can thus be used as a model for accelerated aging and neurodegeneration, to test the hypothesis that APP, estrogen and NGF interact to maintain the cholinergic system. Using a problem-based approach to study degeneration, the lab has used an aged rat model over the past five years to study a new, noninvasive delivery system for NGF. This delivery system will now be used to study memory loss and cholinergic degeneration in Ts65Dn mice. The specific aims are: 1) is there an alteration in APP processing and/or alterations in NGF levels in forebrain or hippocampus during the time of cholinergic cell loss in Ts65Dn mice? 2) Do ovariectomy and estrogen replacement therapy alter cognitive impairment, cholinergic degeneration and/or NGF/APP levels? 3) Do transplants of wildtype cholinergic neurons succumb to the same phenotype loss when grafted into a TS65DN host? And 4) Can treatment with NGF and/or estrogen alleviate cognitive alterations and cholinergic phenotype loss in the Ts65Dn mouse? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: AGE-RELATED DYSFUNCTION

LOSS

OF

CYCLICITY--LHRH

NEURONAL

Principal Investigator & Institution: Rubin, Beverly S. Anatomy and Cellular Biology; Tufts University Boston Boston, MA 02111 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: Reproductive cycles cease relatively early in the life-span of female mammals. Whereas alterations at all levels of the hypothalamic- pituitary-ovarian axis occur with age, considerable evidence confirms the importance of altered hypothalamic function to reproductive decline in female rodents. In contrast menopause is correlated with the loss of follicular reserves in the ovary and not routinely associated with hypothalamic dysfunction: however, recent studies reveal altered gonadotropin levels prior to the perimenopausal period and accelerated follicular loss in the 10 years prior to menopause. The potential contribution of altered patterns of gonadotropin secretion to follicular loss remains to be determined. Because luteinizing hormone releasing hormone (LHRH) is the primary signal regulating pituitary gonadotropin secretion, understanding the cause of age-related alterations in LHRH neuronal function are pivotal to unraveling the mechanisms of reproductive aging. Our studies have consistently revealed deficits in LHRH neuronal activity in aging female rats in conjunction with the spontaneous or steroid-induced LH surge, times of increased demand for LHRH secretion and biosynthesis. Alterations in excitatory and inhibitory influences on LHRH secretion have been identified with age and may be sufficient to

26 Menopause

explain the deficits observed in LHRH neuronal function. However, whether LHRH neurons in aging animals remain capable of responding to the relevant signals with significantly increased levels of gene transcription, biosynthesis and secretion remains to be determined. The studies in the present proposal test the following hypotheses: 1) LHRH gene transcription is markedly reduced in middle-aged females on the day of an LH surge; 2) reduced LHRH gene expression contributes to attenuation of the LH surge, and 3) diminished excitatory influences and / or increased inhibitory influences contribute to the marked decline in LHRH neuronal function with age. The studies proposed will determine if modulation of excitatory and inhibitory neurotransmission can enhance the normally diminished levels of LHRH neuronal activity in middle-aged females. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: AGING OF THE NORMAL HUMAN OVARY FROM BIRTH TO MENOPAUSE Principal Investigator & Institution: Klein, Nancy A. Obstetrics and Gynecology; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 18-SEP-1998; Project End 30-NOV-2003 Summary: Due to recent demographic and socioeconomic trends, a large number of women are delaying childbearing until their late 30s and early 40s when their fertility is significantly compromised. Whereas there is a clear age-related decline in female fertility, many questions remain regarding its etiology. This grant proposes to address several of the questions, which remain regarding the physiology of reproductive aging in women. Human females are endowed with a finite number of ovarian follicles, the majority of which expire secondary to atresia. Ultimate depletion coincides with the onset of menopause therefore, the rate of ovarian follicle depletion is the final determinant of the duration of the reproductive life span. The scant data, that are available (based on data generated from only 103 subjects from newborn to menopause), suggest that there is a steady decline in primordial follicle number and that there may be a threshold number below which the rate of atresia escalates, signaling a significant decline in reproductive capacity. These data are based on old morphometric techniques with inherent inaccuracies due both to sampling errors and to assumptions that are made to estimate follicle number. In addition, these older studies did not attempt to correlate primordial follicle number or rate of atresia with any endocrine parameters. We propose to employ modern morphometric techniques to count primordial follicle number in 300 pairs of human ovaries from females ages 0 to 55. In addition, we will obtain serum samples in a subgroup of these subjects for determination of gonadotropins, estradiol and inhibins. Specific aims of this proposal are: 1) to determine whether the duration of the reproductive lifespan is more dependent on initial follicle endowment or rate of loss; 2) to more accurately determine the normal decay curve for follicle loss from fetus to menopause; 3) to determine whether there is a critical threshold(s) of non-growing and early antral follicle number below which there are changes in hormone secretion (specifically inhibin B and FSH) and/or menstrual cyclicity; 4) to determine whether circulating levels of these hormones predict (or reflect) the number of follicles remaining; 5) to begin to determine the minimum size of an ovarian sample (biopsy) that is sufficient to accurately approximate the total number of follicles present. These studies will increase our understanding of the natural history of follicle atresia and provide insight into the factors, which determine the duration of the reproductive lifespan. Such an understanding is vital to our ultimate goal to be able to predict, recognize and treat age-related infertility.

Studies 27

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: AGING, HYPERTENSION AND ESTROGEN NEUROPROTECTION Principal Investigator & Institution: Carlson, Scott H. Biology; Luther College Decorah, IA 52101 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 29-SEP-2002 Summary: Following menopause many women experience progressive cognitive impairment and have a significantly higher risk of dementia. While the mechanisms which contribute to these progressive cognitive deficits are unknown, the loss of estrogen appears to be a major underlying factor. The loss of estrogen at menopause is also associated with an increased risk of hypertension which contributes to cognitive impairment. Previous work from our laboratory has shown that male spontaneously hypertensive rats (SHR) display age-related learning and memory impairments that are associated with neuronal remodeling in the retrosplenial cortex, an area that is important for spatial learning in rats and humans. While these deficits normally become apparent in aged (2 year-old) male Sprague-Dawley rats, they are first identifiable in male SHR at a significantly younger age (1 year-old). Chronic anti-hypertensive therapy (captopril) significantly delays both cognitive impairment and neuronal remodeling in SHR, suggesting that hypertension contributes to these changes. Few studies have examined the effects of hypertension and estrogen loss on cognitive function. We have established for the first time that elimination of both endogenous estrogen (ovariectomy) and exogenous estrogens (plant phytoestrogens in the diet) has a dramatic effect on arterial pressure control in female SHR, i.e., female SHR normally do not show an increase in arterial pressure when fed a high NaCl diet, but following elimination of both endogenous and exogenous estrogen, they respond to a high NaCl diet with a very large increase in arterial pressure (> 60 mm Hg). This provides a provocative model with which to test the hypothesis that both the loss of estrogen and hypertension can accelerate the age-related decline in cognitive ability and neuronal stability in female SHR. The proposed studies test the hypotheses that: Specific Aim 1. Estrogen depletion accelerates cognitive impairment and neuronal remodeling in the retrosplenial cortex, and that estrogen replacement protects against these changes. Specific Aim 2. Estrogendepletion reduces cerebral blood flow in female SHR and estrogen replacement reverses these decreases. Specific Aim 3. Estrogen-depletion impairs vascular reactivity and causes arteriolar hypertrophy in female SHR, and that estrogen replacement reverses these effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALCOHOL INTERACTIONS

AND

ESTROGEN

REPLACEMENT

THERAPY

Principal Investigator & Institution: Gavaler, Judith S. Chief, Women's Health Research; Pharmaceutical Sciences; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 29-SEP-1996; Project End 30-APR-2003 Summary: APPLICANT'S ABSTRACT: By 1991 census data, there are 33 million women age 50 and older, the median age at which natural menopause occurs. With the addition of surgical menopause women, there are over 40 million postmenopausal women. Estimates of the prevalence of Estrogen Replacement Therapy (ERT) use range from 12 to 33 to 45%. Estimated current moderate alcoholic beverage consumption among women age 50-60 is 59%, and 37% among women over 60. Thus 5 to 18 million women

28 Menopause

are being treated with ERT, while as many as 20 million postmenopausal (PMP) women drink moderately. The number of postmenopausal who both drink and use ERT is unknown. Both ERT therapy and moderate alcohol consumption increase PMP estrogen levels; both ERT and moderate alcohol consumption, significantly reduce coronary heart disease risk, the major cause of death in PMP women. There are 3 goals, of the proposed research: 1) To determine the patterns of alcohol consumption, of health behaviors such as smoking, dietary habits/nutrient intake and physical activity, and of estrogen replacement therapy (ERT) use among 1250 normal PMP volunteers of different ethnic/racial backgrounds participating in a study determinants of PMP estrogen levels. 2) To determine in normal PMP women not treated with ERT whether smoking, physical activity, nutrient intake and ethnic/racial origin influence PMP estrogen levels in addition to already identified estrogen determinants which include moderate alcoholic beverage consumption, body fat mass, and ovariectomy. 3) To determine in normal PMP women treated with ERT to what degree circulating levels of estrogen achieved with estrogen replacement therapy are modulated by factors which influence the production and metabolism of estrogen and other hormones in PMP women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ALTERNATIVE THERAPIES FOR MENOPAUSE: A RANDOMIZED TRIAL Principal Investigator & Institution: Newton, Katherine M. Associate Investigator; Center for Health Studies 1730 Minor Ave, Ste 1600 Seattle, WA 98101 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-NOV-2004 Summary: (Adapted from Investigator's Abstract) Hormone replacement therapy (HRT: estrogen and progestin) remains the treatment of choice for women with vasomotor symptoms, and long-term HRT has been recommended for prevention purposes. The demand for alternatives to HRT, and the availability and use of over-the-counter products including dietary phytoestrogen supplements and naturopathic medicines, has grown dramatically. Few of these products have faced the rigors of randomized trials and none have been tested to evaluate their effects on long-term outcomes. The purpose of this four-year randomized controlled trial is to evaluate the efficacy and safety of three alternative approaches utilizing phytoestrogens to treat vasomotor symptoms in peri- and postmenopausal women. The treatments were chosen because of the scientific evidence supporting a possible benefit, the availability of products with adequate quality control their frequency of use in naturopathic medicine, and our ability to blind participants to the intervention. The five proposed treatment arms are as follow: 1) esterified estrogen and micronized progesterone: 9) a single herbal product, black cohosh; 3) a multibotanical preparation; 4) a combination regimen that includes the same multibotanical preparation plus soy diet counseling; and 5) placebo. The primary aim is to compare the effects of three alternative treatments, HRT, and placebo on the frequency and intensity of vasomotor symptoms measured by The Wiklund Menopause Symptom Checklist and a daily Vasomotor Symptom Diary. The secondary aims are to compare the effects of three alternative treatments, HRT, and placebo on the following: 1) vaginal cytology (vaginal maturation index); 2) serum lipids (total cholesterol, HDL and LDL cholesterol, triglycerides); 3) bone mineral density (hip and spine dual energy x-ray absorptiometry scan); 4) glucose metabolism (insulin, fasting blood glucose); and 5) coagulation factors (fibrinogen, PAI-1). The hypotheses are that compared to placebo the three alternative treatments tested in this study will have the following effects: reduce frequency of hot flashes and night sweats, improve vaginal maturation and decrease vagina atrophy as measured by maturation index, lower total cholesterol and

Studies 29

LDL with no effect on HDL, reduce the rate of decline in bone mineral density (BMD), and have no effect on glucose metabolism or clotting factors. To accomplish the specific aims the investigators propose to do the following: 1) recruit and randomize 400 periand post-menopausal women to one of five treatment arms for one year; 2) collect measurements of primary and secondary outcomes at baseline, three, six, and 12 months; and 3) compare changes in outcomes in the groups taking alternative treatments to those in the HRT and placebo groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ANTIOXIDANTS AND FEMALE HORMONES IN THE ETIOLOGY OF RA Principal Investigator & Institution: Karlson, Elizabeth W. Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: The candidate is an Instructor in Medicine in the Department of Medicine, Division of Rheumatology, Immunology and Allergy at the Brigham and Women's Hospital and Harvard Medical School. Her research area is the epidemiology of rheumatic diseases, and the social and biological determinants of outcome in rheumatic diseases. Dr. Matthew Liang, Director, Multipurpose Arthritis and Musculoskeletal Diseases Center (MAMDC), Professor of Medicine at Harvard Medical School and Professor of Health Policy and Management at Harvard School of Public Health, will be her sponsor and co-mentor along with Drs. Frank Speizer, Charles Hennekens, Walter Willett and Meir Stampfer from the Channing Laboratory and Division of Preventive Medicine. The research training program consists of the two studies described below, Research Seminars in the MAMDC, Channing Laboratory and Division of Preventive Medicine, courses at the Harvard School of Public Health, and close review by an Advisory Committee. The goal of the proposed studies is to define the role of dietary and hormonal risk factors in the development of rheumatoid arthritis (RA) in women. Specifically, it will test the potential protective role of antioxidants and N-3 fatty acids on the risk of RA, whether postmenopausal estrogen reduces risk and whether menopause increases risk of RA. The study utilizes information from two separate, complementary cohorts, the Nurses' Health Study, a prospective cohort of 121,700 women aged 30-55 years at baseline, followed since 1976, and the Women's Health Study, a randomized, double-blind, placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health professionals, aged 45 years and older. RA will be confirmed by a screening questionnaire regarding rheumatic symptoms and review of medical records. The study will identify potentially modifiable risk factors for primary prevention of RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GORILLAS

ASSESSING

REPRODUCTIVE

SENESCENCE

IN

CAPTIVE

Principal Investigator & Institution: Margulis, Susan W.; Chicago Zoological Society 3300 Golf Rd Brookfield, IL 60513 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: The proposed research addresses research topic #22: Animal Models of Aging. In an effort to determine whether gorillas may serve as a suitable model for the physiological processes associated with menopause, we propose a pilot study to investigate reproductive senescence in western lowland gorillas. More specifically, we

30 Menopause

will evaluate the following questions: (1) Do gorillas undergo physiological cessation of ovulation at advanced age? We will assess levels of estrogen and progesterone from fecal and urine samples in order to determine if hormonal patterns are consistent with normal ovulatory function, or are indicative of irregular or inadequate ovarian function. (2) Are behavioral patterns associated with reproduction linked to hormonal changes? We will use standard observational sampling methods (Altmann, 1974) to collect simultaneous behavioral and hormonal data on geriatric and non-geriatric gorillas to determine whether pronounced episodes of proceptive behavior parallel, or are independent of, hormonal patterns. (3) Do aging gorilla females exhibit health-related problems similar to those experienced by menopausal human females? Aging gorillas are known to experience osteoarthritis, cardiovascular disease, and neurological degeneration. We will evaluate whether occurrence of these disorders is associated with declines in estrogen consistent with menopausal symptoms. We will review pathology reports for deaths of sexually mature female gorillas to evaluate the extent to which typical age-related, and hormonal-related, disease associations are prevalent in this population. (4) Given their close evolutionary ties to Homo sapiens, do gorillas represent a new model for longitudinal studies on the consequences of aging and reproductive senescence? Depending on the findings of (1) through (3), above, we will evaluate the efficacy of utilizing retrospective and prospective data from the captive gorilla population as a model for the physiological processes associated with the human menopause. We will collect concurrent behavioral and hormonal data on a minimum of 16 geriatric females and 6-11 prime-age control females to determine the extent to which these aging females differ from prime-age females in proceptive behavior and ovulatory patterns, and to evaluate whether the patterns are consistent with menopause. Given the current state of the captive gorilla population (roughly 30% of females are considered to be geriatric), this research is timely. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: BALTIMORE LONGITUDINAL STUDY OF AGING (BLSA)-PERIMENOPAUSAL INITIATIVE Principal Investigator & Institution: Bellantoni, Michele F.; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOBEHAVIORAL MECHANISMS OF BLOOD PRESSURE DIPPING Principal Investigator & Institution: Sherwood, Psychiatry; Duke University Durham, NC 27706

Andrew;

Associate

Professor;

Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): The primary objective of the proposed research is to further our understanding of the causes and consequences of individual differences in blood pressure (BP) dipping during nighttime sleep. Growing evidence indicates that elevated nighttime BP is superior to either clinic BP or daytime ambulatory BP as a prognostic indicator of cardiovascular morbidity and mortality. Blunted BP dipping favors the development of concentric left ventricular hypertrophy (LVH), a geometric restructuring of the heart that is often evident early in hypertension. LVH is the strongest known predictor of cardiovascular morbidity and mortality, other than advancing age. Despite compelling evidence for the pathophysiological consequences of

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blunted BP dipping, its biobehavioral determinants remain to be defined. The proposed study will evaluate several likely mechanisms of blunted BP dipping, including: (i) Sleep Quality; (ii) Psychosocial Stress; (iii) Sympathetic nervous system (SNS) activity, as well as: (iv) Vascular disease, in 200 men and women with high normal BP or Stage 1 hypertension. In addition, this study will characterize BP dipping in terms of the underlying hemodynamic mechanisms by supplementing 24-hour ambulatory BP monitoring with concurrent monitoring of cardiac output (CO) and systemic vascular resistance (SVR).The study will include a focus on African American ethnicity, and on menopause in women, because they are established risk factors for LVH. These factors are also related to blunted BP dipping, and to the biobehavioral mechanisms of BP dipping that we propose to assess. By defining the factors responsible for individual differences in BP dipping, the proposed research will yield information that should facilitate the development of effective biobehavioral interventions (e.g., pharmacological therapy, sleep therapy, stress management training) aimed at optimizing nighttime BP, and reducing cardiovascular disease risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: BIODEMOGRAPHIC MODELS OF REPRODUCTIVE AGING Principal Investigator & Institution: Wood, James W. None; Pennsylvania State University-Univ Park 201 Old Main University Park, PA 16802 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAY-2003 Summary: The research outlined in this application is designed to (1) characterize the transition to menopause in a well-defined cohort of U.S. women, (2) analyze patterns of individual-level variation in reproductive aging, (3) relate these patterns of variation to previous history including information on reproduction, menstrual patterns, and health, and (4) link the hormonal changes of menopause to the underlying etiologic process of follicular depletion. The study population includes women enrolled in the Tremin Trust project: these women have been providing detailed prospective reports of menstrual and reproductive histories and other information for up to 30 years. For around 150 of these women, urine specimens will be collected during a six-month window for up to five years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIODEMOGRAPHIC MODELS OF REPRODUCTIVE AGING Principal Investigator & Institution: Weinstein, Maxine A. Distinguished Professor; Demography; Georgetown University Washington, DC 20057 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2004 Summary: The transition to menopause encompasses a wide ranging set of changes for women. The work we propose offers a unique opportunity to explore the transition and link it with the prior history of a large, well-defined cohort of women. We will study a cohort of women enrolled in the Tremin Trust. They have been providing detailed prospective reports of menstrual and reproductive histories, and information on lifecycle events and health status for up to 30 years. For 150 women, we will collect daily first-morning urine specimens during a 6-month window during each of the five project years. The specimens will be assayed for the principal steroids and gonadotropins involved in regulating ovarian cycles and in signalling reproductive aging. Statistical models will link the women's menstrual, reproductive, and health related histories to the experience of the transition, model the effects of hormonal patterns on menstrual bleeding during the perimenopause, and relate features of the transition to the

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underlying process of follicular depletion. The proposed work differs from other studies of the menopause in several important respects. First we have access to decades worth of prospectively- reported data. Second, unlike most other studies of the endocrinology of the menopause, we will work with a population- based cohort of women who were all recruited well before the transition. Thus, they are not selected for any aspect of their experience of the transition. Third, we propose to develop and apply new mathematical models that will allow us to link characteristics of the menopausal transition to prior history and underlying biological mechanisms. The work complements, but does not reproduce, the current NIA initiative. The project will give new insight into the patterns and causes of variation in women's experience of the menopausal transition, will yield a better understanding of how individual-level experience gives rise to population-level patterns of reproductive aging, will enrich clinical practice by providing information on how past menstrual patterns are linked to experience throughout the menopausal transition, and will provide a foundation for future epidemiological studies of the health consequences of patterns of reproductive aging. The data set produced in conjunction with this research will provide a rich resource for future investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: BIOTRANSFORMATION OF ESTROGENS TO CARCINOGENIC QUINOIDS Principal Investigator & Institution: Bolton, Judy L. Professor; Medicinal Chem & Pharmacognosy; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2006 Summary: There is a clear association between excessive exposure to estrogens and the development of cancer in several tissues including breast and endometrium. The risk factors for women developing these cancers are all associated with longer estrogen exposure; early menses, late menopause, and long term estrogen replacement therapy. The mechanism(s) of estrogen carcinogenesis is not known. The central hypothesis is that the formation of quinoids is an important mechanism of estrogen carcinogenesis. oQuinones are known metabolites of estrogens. These redox-active compounds have been shown to cause oxidative damage to cellular DNA. Furthermore, these o-quinones can alkylate DNA that may lead to genotoxicity. Our data also suggests that DNA damage may be potentiated by the presence of an estrogen receptor (ER). The specific aims are: 1. What is the predominant mechanism of catechol estrogen-induced DNA damage? Oxidation versus alkylation. Using synthetic oligonucleotides with defined sequences, we will explore the effect of time, concentration, sequence, and redox status on formation of each DNA lesion. Of special interest is the role of the estrogen responsive element since our hypothesis predicts that extensive damage should occur at estrogen sensitive genes. 2. Correlation between DNA damage and estrogen receptor status in cell lines. We will further investigate the role of ERa and/or ERb in mediating catechol estrogen-induced DNA damage and toxicity. The cell lines to be examined include tumorigenic and nontransformed human breast cell lines with no estrogen receptor or ERa or ERb. The comet assay will be employed to examine DNA single strand cleavage and oxidation and alkylation of DNA bases will be studied using LCMS-MS. 3. Evaluation of the binding affinity of catechol estrogens for ERa and ERb and the functional consequences of ER activation. We propose to evaluate the estrogenic potency of catechol estrogens and correlate these effects with the extent of DNA damage observed in Aims 1 and 2. The relative binding affinity of these compounds to ERa and ERb proteins will be measured using a competitive binding assay. These results will be

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compared to studies evaluating the ability of the catechol estrogens to transcriptionally activated ER WERE luciferase and ERb /ERE luciferase assays. Finally, we will study the modulation of certain estrogen responsive genes by catechol estrogens in the cell lines described in Aim 2. 4. Role of quinoids in the carcinogenic effects of estrogens. We plan to further explore the relative ability of the catechol estrogens to induce cellular transformation in the non-transformed human breast epithelial cell lines discussed above. The transformed colonies will be implanted into athymic nude mice to establish their ability to induce tumor formation. Finally, to determine whether the parent estrogens are carcinogenic in vivo, ACT rats will be treated with estrogens and the mammary tissue will be analyzed for tumor formation. These data will determine the role of quinoids in the carcinogenic effects of estrogens and provide a basis for the development of estrogen replacement drugs devoid of carcinogenic activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: BONE SPARING EFFECTS OF SOY PHYTOESTROGENS IN MENOPAUSE Principal Investigator & Institution: Levis, Silvina; Medicine; University of Miami Box 016159 Miami, FL 33101 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant) Women will live a third of their lives in menopause. The complications of prolonged estrogen deficiency during the menopausal years are well established. Although hormone replacement therapy (HRT) can spare women some of these complications, the Women's Health Initiative findings indicate significant potential health risks, risks that prompt more and more women to turn from prescribed HRT to over-the-counter products in the hope that soy phytoestrogens and other "estrogens" from natural sources can replace prescription estrogens in terms of benefits while sparing critical side effects. In spite of the fairly widespread and now rapidly growing use o f phyto estrogens, maj or gap s remain in our knowledge o f their longterm efficacy and safety. We propose to conduct a "Soy Phytoestrogens As Replacement Estrogen (SPARE)" study in young menopausal women to evaluate the effectiveness of a 2-year treatment with purified soy isoflavones in preventing bone loss. Our study will also explore the effectiveness of oral isoflavones in preventing menopausal symptoms and other changes associated with estrogen deficiency. The study will characterize the actions of a defined preparation of soy isoflavones in humans and will correlate these actions with the circulating serum levels of the principal isoflavone metabolites, providing new insights on their long term biological actions. This 5-year study will provide a foundation of knowledge from which menopausal women can begin to make more informed decisions regarding HRT and menopausal signs and symptoms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BOTANICAL DIETARY SUPPLEMENTS FOR WOMEN'S HEALTH Principal Investigator & Institution: Farnsworth, Norman R. Research Professor; Prog/Collab Res/Pharmactl Scis; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: (verbatim from the applicant's abstract) The Center for Dietary Supplements Research on botanicals will consist of a multidisciplinary team of investigators who will focus their initial efforts on the study of the clinical safety and efficacy of botanicals used to treat women's health with particular emphasis on therapies for menopause.

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Additional studies will address mechanisms of action, identification of active compounds, and characterization of metabolism, bioavailability and pharmacokinetics of active species contained in these botanicals. The research component will consist of four projects, which will be supported by three cores as follows: Project 1. This pharmacognosy project will carry out standardization of botanical dietary supplements and structure elucidation of active compounds using bioassay-guided fractionation in collaboration with Project 2. Project 2 will use bioassay-guided fractionation to isolate active compounds for structure elucidation, and then will carry out biochemical studies to determine the mechanism(s) of botanicals used for women's health. Project 3. Novel in vitro methods for the study of metabolism, absorption and toxicity of active compounds in botanicals will be developed and applied during this project. Immunotoxicity of botanical preparations will be evaluated. Project 4. This Clinical Project will carry out Phase I and Phase II clinical trials of black cohosh (Cimicifugae racemosa) and red clover (Trifolium pratense). Phase I studies will focus on human toxicity, absorption, distribution, metabolism and elimination of active compounds, and in Phase II, efficacy for the relief of menopausal symptoms will be evaluated. Core A. This Administrative Core will facilitate the exchange of data between investigators, coordinate data archiving, will provide administrative assistance and statistical support, and will coordinate meetings with the Advisory Committee. Core B. The Education and Information Core will be responsible for pharmacognosy curriculum development and the implementation of graduate and post-doctoral training programs, for the implementation of interactive on-line learning and continuing education programs, phone-in services for the public, and botanical information database searches. Core C. The LC-MS-MS Core will provide analytical support including: identification/dereplication and quantitative analysis of active compounds; bioavailability and pharmacokinetic profiles, and identification of urinary metabolites. With these research facilities in place, the Center will be positioned to expand its efforts in the future to include studies on other botanicals used for a wider range of human health issues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: BREAST CANCER PREVENTION IN HODGKINS DISEASE Principal Investigator & Institution: Garber, Judy E. Assistant Professor of Medicine; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 29-JUN-2001; Project End 31-MAY-2003 Summary: (Applicant's Description) Hodgkin's Disease carries an excellent prognosis, with the majority of patients cured of their primary tumor. However, late complications of therapy in these patients are of increasing concern, especially new primary cancers of particular importance in this group is the increased risk of breast cancer among female Hodgkin's disease survivors who received mantle or chest radiation (RR approximate 20 by 15 yrs after treatment). Tamoxifen has been shown to reduce the risk of breast cancer by nearly 50percents in women at increased risk on the basis factors considered in the Gail model, DCIS or prior breast cancer II. It has not yet been evaluated in radiogenic breast cancer. HD survivors may also experience early menopause if their HD treatment included chemotherapy 12, and early atherosclerotic heart disease l3,14 and other second cancer risk from radiation or combined modalities I. These concerns may affect the risk/benefit considerations of tamoxifen in this high risk population whose risk becomes manifest at young ages. Because of these issues, it seems important to prove, rather than assume, that tamoxifen ireduces breast cancer risk in this population. However, since there are a limited number of women available for a study of sufficient

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size to address the question with sufficient power, demonstration of feasibility seems critical. In the proposed study, we will address aspects of feasibility , including recruitment/acceptance, adherence, toxicities and quality of life, and reproductive hormone status. We propose to recruit 50 female Hodgkin's Disease survivors whose treatment included radiation therapy (mantle or other chest), diagnosed before age 30, current age greater than 30 years, greater than 8 years from radiation to participate in a pilot study in which they will receive tamoxifen for 2 years on study, and 5 years in total. We will estimate recruitment rates, evaluate adherence, and assess quality of life and toxicities using measures employed in the BCPT, as well as questions developed for this population. Our advisory board will consider the one year data and assist us in deciding whether or not to proceed to attempt the larger study. A definitive randomized trial would be feasible with available HD survivors if adherence were 90 percents, based upon an estimated absolute risk of 8 percents over a 5 year period in women without tamoxifen. This is a risk much greater than the average risk in the BCPT cohort, permitting the smaller sample size. We will also evaluate mammographic density as a potential intermediate endpoint that might permit more rapid completion of a randomized study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: BREAST CANCER RISK--RESIDENTIAL ENVIRONMENT AND GENETICS Principal Investigator & Institution: Freudenheim, Jo L. Professor and Interim Chair; Social and Preventive Medicine; State University of New York at Buffalo 402 Crofts Hall Buffalo, NY 14260 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: (Applicant's Description) Breast Cancer Risk: Residential Environment and Genetics There is evidence that environmental factors related to industrialization may be important in breast cancer etiology. There has been little study of proximity to potentially toxic industrial sites as breast cancer risk factors. We propose to conduct a case-control study to examine location of residence during adult life in relation to breast cancer risk. The aims of the study are: 1) To investigate distance from steel mills, chemical factories, and other industrial sites of the residence as risk factors. The time periods to be examined will be (1 ) the primary residence during the period between menarche and first pregnancy (if any, otherwise menopause) and (2) residence (s) 10 and 20 years ago; 2) To examine estimated exposure to benzene and to PAHs based on residential exposure during these time periods as risk factors. Secondary objectives are: 3) To examine genetic variability in metabolism by NQ01, GST M1-1 , GST P1-1 and CYP 1A1 in relation to these exposures and breast cancer risk; 4) To evaluate all adult residences in relation to distance from potentially important exposures (steel mills, chemical factories, etc.) and risk; 5) To examine estimated exposure to benzene and to PAHs during the entire adult life and risk. We will use data from an ongoing casecontrol study of breast cancer in Erie and Niagara Counties including approximately 1000 cases of incident, primary, histologically-confirmed breast cancer and more than 2000 controls, age 35-79, frequency-matched to cases. About 75 percents of participants in the original study lived in these counties at the time of their menarche. Addresses for the women at the time of their birth and at menarche will be geocoded using a Geographic Information System (GIS). Historical data will be collected regarding location of potentially important industrial sites. We will calculate odds ratios and 95 percents confidence intervals for distance from each category of potential exposure and for an index of probable level of exposure to PAHs and to benzene and we will examine

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risk within categories stratified on genotype. This is a unique and cost effective opportunity to examine a hypothesis of potentially great public health importance in a relatively residentially stable population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: BREAST CANCER SURVIVORS: EXERCISE AND RALOXIFENE Principal Investigator & Institution: Schwartz, Anna L. Associate Professor; Primary Care Nursing; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 29-FEB-2004 Summary: It is estimated that 178,799 women will be diagnosed with breast cancer in 1998. While breast cancer has become more treatable, the long-term treatment-related side effects have a significant negative effect on morbidity and non-cancer related risk of mortality. The increasingly common use of adjuvant chemotherapy for breast cancer has led to a rise in long-term treatment- related side effects including osteoporosis, early menopause, increased risk for cardiovascular disease, and declines in quality of life. Osteoporosis is a major public health problem and a common finding in breast cancer survivors. Nationally, 20 million women are estimated to be at risk for osteoporosis, with 1.3 million sustaining osteoporotic fractures. Four factors place breast cancer survivors at high risk for muscle, bone and cardiovascular complications: inactivity, menopause (especially premature menopause), chemotherapy and catabolic steroids. This innovative study will use a randomized placebo-controlled design to test the effects of (a) exercise and (b) raloxifene in postmenopausal breast cancer survivors (N=240) between 3 months and one year after completing chemotherapy on: one resorption, formation and density (serum osteocalcin and bone specific AST, urine n-telopeptide, DEXA scan); multidimensional quality of life (SF-36, 12-minute walk, muscle strength, fatigue, menopausal vasomotor symptoms positive and negative affect, and Trail Making); and lipid profile (serum lipid levels). Subjects in the exercise intervention will follow a supervised home-based exercise program and asked to exercise 5 days/week. Exercise dose and adherence will be monitored with Caltrac accelerometers, exercise logs, regularly scheduled follow-up phone calls and supervised exercise sessions, and results on 12-minute walks and 1-repetition maximum tests. Subjects in the ralosifene and placebo control groups will be asked to take the medication (60mg/day) or placebo as prescribed. Subjects in the exercise+raloxifene group will be asked to take the medication and follow the exercise program. All subjects will be instructed to take a daily calcium supplement (1000mg/day). Subjects will be followed for 2 years. All measures will be re-evaluated at 3- month intervals except the DEXA scans, which will be obtained at 12-month intervals. Results of this study may reduce the morbidity, mortality and health care costs of these common, long- term complications that confront breast cancer survivors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CAFFEINE INFLUENCES ON EXERCISE AND PSYCHOLOGICAL STRESS Principal Investigator & Institution: Lovallo, William R. Professor; Psychiatry and Behavioral Scis; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, OK 73126 Timing: Fiscal Year 2001; Project Start 01-DEC-1984; Project End 30-JUN-2005 Summary: Description (adapted from the investigator's abstract): Understanding caffeine's effects in persons as they age is critical to our understanding of how caffeine

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affects health. This project will examine caffeine effects in 210 men and women in early (35-49 years) vs. late (50-64 years) middle age, with a secondary emphasis on variations in response as women enter menopause, a time of increased risk of heart disease and hypertension. Caffeine is widely used in significant quantities. Caffeine affects the central nervous system, cardiovascular activity, and endocrine function, and intake may increase during times of stress. Caffeine increases cardiovascular disease risk factors such as serum cholesterol and lipids. Accordingly, in a randomized crossover trial, men and women will be placed on each of two levels of caffeine intake (0 mg/day vs. 240 mg/day) for 6 days each, ending with 24-hr ambulatory monitoring of blood pressure and cortisol. Laboratory testing on day 7 will establish the effect of acute doses (200 mg x 2) on responses to mental and exercise stress. The project has 3 hypotheses: First, caffeine elevates blood pressure and cortisol secretion even with daily consumption. Second, these effects are enhanced during mental and exercise stress. Third, the effects increase from early to late middle age. It is anticipated that caffeine effects will be prominent in postmenopausal women not on estrogen replacement. Cardiovascular variables are blood pressure and hemodynamic and cardiodynamic measures taken using impedance cardiography and echocardiography. The target neuroendocrine variable will be cortisol because it is the central component of the response to stress and is responsive to caffeine. Modest elevations over long periods are thought to alter immune system function and to affect the aging process. A recent study shows that caffeine increases cortisol in the evening hours, disturbing its normal diurnal cycle. This new information should aid in evaluating caffeine's effects over the span of midlife, a time at which the cardiovascular health of women changes markedly relative to men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CALCIUM ABSORPTION IN CACO-2 CELLS: MOLECULAR MECHANISM Principal Investigator & Institution: Fleet, James C. Associate Professor; Foods and Nutrition; Purdue University West Lafayette West Lafayette, IN 479072040 Timing: Fiscal Year 2003; Project Start 15-SEP-1997; Project End 29-SEP-2004 Summary: (provided by applicant): 1,25 dihydroxyvitamin D (1,25(OH)2 D)-mediated intestinal calcium absorption is an important adaptive mechanism utilized by the body when calcium status is low. Low calcium absorption efficiency is a risk factor for osteoporosis and intestinal resistance to 1,25(OH)2 D action develops with aging and after menopause. Our long-term objective is to clarify the mechanisms used by 1,25(OH)2 D to promote calcium absorption and to determine how dysfunction in the regulatory control of intestinal calcium absorption during aging or due to menopause leads to reduced absorption efficiency and, ultimately, low bone density. Recent research demonstrates that 1,25(OH)2 D rapidly activates scr kinase, protein kinase C (PKC), and MAP kinases and that inhibition of these kinases blunts 1,25(OH)2 Dmediated activation of the CYP24 gene. The goal of the proposed research is to determine how the adaptive increase in intestinal calcium absorption due to 1,25(OH)2 D-dependent; vitamin D receptor (nVDR)-mediated gene activation is influenced by the basal or induced activity of these kinases. The specific aims of this project are to: (1) Identify the nVDR-mediated genomic pathways controlling intestinal calcium absorption that are modulated by 1,25(OH)2-induced activation of src kinase, PKC, and MAPK, (2) Establish the mechanisms by which 1,25(OH)2 D-induced kinase activation promotes 1,25(OH)2 D-mediated gene expression and intestinal calcium absorption, and (3) Identify new, 1,25(OH)2 D-regulated transcripts in differentiated enterocytes and determine whether their regulation is modulated by activation of protein kinases. We

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will accomplish these aims by studying the effect of 1,25(OH)2 D in a well-characterized cell culture model (Caco-2 cells) and in the small intestine of mice. Biological actions of 1,25(OH)2 D will be studied in the presence of activators and inhibitors of protein kinases (pharmacologic inhibitors, dominant negative kinases) and the rapid actions of vitamin D (vitamin D analogs), nVDR action and function will be studied with cellular imaging, RT-PCR, DNA microarrays, Western blotting and chromatin immunoprecipitation (CHIP) assays. Elucidating the mechanism for how signal transduction pathways influence the genomic actions of 1,25(OH)2 D will permit us to design prevention and pharmacologic intervention strategies to enhance intestinal calcium absorption, especially when vitamin D resistance associated with aging or estrogen deficiency is present. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CHICAGO CONSORTIUM WOMEN'S INTERAGENCY HIV STUDY LLL Principal Investigator & Institution: Cohen, Mardge H.; Hektoen Institute for Medical Research 2100 W Harrison Chicago, IL 60612 Timing: Fiscal Year 2003; Project Start 01-JAN-1994; Project End 30-NOV-2007 Summary: (provided by applicant) As a multicenter, prospective cohort study The Women's Interagency HIV Study (WIHS) is designed to directly address key hypotheses related to the natural history and clinical manifestation of HIV among women. During WIHS-III (12/02-11/07), WIHS scientific Aims are to 1) develop, refine, and evaluate composite measures of antiretroviral therapy (ART) exposure and relate these measures to markers of HIV disease progression, 2) define the treated history of HIV-1 infection and the individual determinants, including host and viral genetic factors, of clinical, virologic and immunologic response to highly-active antiretroviral therapy (HAART), 3) evaluate adverse events associated with ART, 4) investigate the long term effects of HIV, and use of HMRT, on the incidence/natural history of viral co-infections that cause disease in women with or at risk for HIV, focusing on human papillomavirus infection and cervical neoplasia, and hepatitis C virus infection and liver disease, 5) evaluate the effects of age, ovulatory function, menopause and its treatment on the course of HIV infection and response to ART, 6) describe the epidemiology of HIV- associated cancers in women, and further define the natural history of malignancies in women on HAART , and 7) evaluate the oral manifestations of HIV disease. Chicago WIHS will use its nine years of successful retention strategies to engage and retain 390 participants (295 HIV+, 95 HIV-) at four clinical sites including150 participants at the oral site through six month visit cycles. These will include interviews, exams, blood, gynecologic and oral specimens, medical record abstractions, registry matches, and local and centralized laboratory analysis. Chicago WIHS will contribute the highest quality data, lead and participate in epidemiologic analyses, and disseminate the results and scientific information learned from this research initiative. As our site-specific scientific initiative, we will investigate immune recovery in HIV infected women on HMRT with particular interest in the effects of age, drug use, exogenous hormones and menopause on immune recovery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHROMOSOME PAIRING AND NONDISJUNCTION IN HUMAN MEIOSIS Principal Investigator & Institution: Cheng, Edith Y. Obstetrics and Gynecology; University of Washington Seattle, WA 98195

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Timing: Fiscal Year 2000; Project Start 01-MAR-1996; Project End 28-FEB-2004 Summary: The goals of this project are to determine by fluorescent in situ hybridization (FISH) the pairing behavior and the level of gametic aneuploidy of specific chromosomes in human female germ cells from fetal life to the menopausal period. This data, collected over the entire germ cell developmental period, will be used to establish normative data for chromosomal anomalies in oocytes throughout reproductive life and has the potential to distinguish among the various hypotheses that have been proposed to explain the high incidence of aneuploidy in female gametes and the related maternal age effect. The operation of reduced recombination in disomic 21 gametes should be reflected in unpaired chromosome 21 homologues in post pachytene gametes. If maternal age is involved in the recombination effect, the level of unpaired chromosome 21's should increase with oocyte age. The level of aneuploidy at different ages could distinguish among the models of selection that have been proposed to explain maternal age dependent trisomy. If oogonial nondisjunction followed by selection of euploid gametes in early reproduction plays a significant role in trisomy 21, then a detectable level of gametic aneuploidy should be seen in oocytes from older women. Multicolor FISH analysis will permit the detection of heterologous associations in early meiosis which could be indicative of the hypothesized "searching" or "trial and error" process preceding pairing. It will allow determination of possible heterologous associations between acrocentrics which are known to form Robertsonian translocations. Identification of individual chromosomes in mammalian oogonial meiosis is normally not possible. This proposal represents the first time in which molecular technique will permit the general identification of chromosome and their possible interaction in mammalian oogenesis. Aneuploidy and pairing anomalies on fetal and adult oocytes will be identified using FISH with whole chromosome probes (chromosome painting). Fetal specimens will be obtained from second trimester terminations and from all stillborns undergoing autopsy. Adult oocytes will be extracted from surgical ovarian specimens from women of all ages who are undergoing indicated gynecologic surgery. Dual color FISH will be used to evaluate for heterologous associations between acrocentrics to analyze pairing relationships and their possible role in the formation of Robertsonian translocations. Multicolor FISH will be used to evaluate for heterologous associations in early meiosis to determine their significance in the formation of structural rearrangements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CIMICIFUGA RACEMOSA AS A SEROTONIN MODULATOR Principal Investigator & Institution: Burdette, Joanna E. Pharmacognosy; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 20-JUL-2001 Summary: (Provided by applicant): Despite the known correlation between estrogens and carcinogenesis, estrogen replacement therapy remains the number one treatment for menopausal symptoms. Cimicifuga racemosa is a rhizome that has been proven effective in reducing hot flashes in several clinical trials. The exact mechanism of action of the herb remains unknown. Studies may reveal that the plant works by modulating serotonin levels and thereby reduces hot flashes. If the plant ameliorates hot flashes without increasing estradiol levels, the botanical will provide a safe and effective solution for women with a history of breast cancer. The focus of this proposal is to train the applicant how to research botanicals by investigating the mechanism of Cimicifuga racemosa. The specific aims are (I.) to identify the active componant(s) of the plant using competitive serotonin receptor binding assays. (II.) Cellular in vitro studies will be

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conducted to determine the herbs agonistic or antagonistic properties, to establish and quantify serotonin subtype binding specificity, to characterize up- or down-regulation of receptor, and to monitor the serotonin dependent excretion of gonadotropic releasing hormones. (III.) Finally, an ovariectomized rat model will be used to evaluate the serotonergic effects of extracts and compounds in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CIRCULATING NITRIC OXIDE CONCENTRATION IN AGING RHESUS MACAQUES Principal Investigator & Institution: Khorram, Omid A. Associate Visiting Professor; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001 Summary: OBJECTIVE To explore the possible role of NO in aging in a rhesus macaque model. RESULTS A trend for somewhat lower NO concentrations was found in older, postmenopausal monkeys, while circulating levels of NO did not seem to be influenced by age or long-term dietary restriction in male rhesus monkeys. DISCUSSION Nitric oxide (NO) has been proposed to play a role in the aging process and to be relatively low during menopause. Dietary restriction (DR) retards aging and increases lifespan in rodents, and it has recently been shown to have beneficial effects on health in rhesus and cynomolgus macaques. In order to explore the possible role of NO in aging in this nonhuman primate model, we measured circulating levels of NO in group of premenopausal (n=9; aged 12.610.3 years [mean1SEM]) and postmenopausal (n=10; aged 26.810.4 years) female rhesus monkeys, young adult (n=9; aged 11.910.5 years) and old (n=10; aged 26.711.0 years) male rhesus monkeys, and in male rhesus monkeys (1622 years old) that had undergone 30% DR for 8 years (n=12) and their matched control group fed ad libitum (n=12). Premenopausal monkeys had marginally higher serum NO concentration than postmenopausal monkeys 37.8912.79 5M vs. 31.2312.66 5M, respectively, p=0.099. In contrast, young adult male macaques did not differ from older males in serum NO concentration 37.8414.39 5M vs. 37.1714.84 5M, respectively. Also, plasma NO values did not differ between control and restricted male monkeys 34.0814.17 5M vs. 33.6512.88 5M, respectively. The trend for somewhat lower NO concentrations in the older, postmenopausal monkeys merits further investigation. On the other hand, circulating levels of NO do not seem to be influenced by age or by longterm DR in male rhesus monkeys. These results do not preclude an important role for localized, i.e., tissue specific, NO influences on the myriad physiological changes that occur during the menopausal transition and as a consequence of DR. FUTURE DIRECTIONS We plan to further investigate the relationship and significance of circulating NO in relation to the menopausal transition and dietary restriction. KEY WORDS Dietary restriction, aging, menopause FUNDING NIH PO1 AG11915 Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL EVALUATION OF BOTANICAL DIETARY SUPPLEMENT Principal Investigator & Institution: Derman, Richard J.; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COGNITION AND ESTROGEN IN MENOPAUSE:A MONKEY MODEL Principal Investigator & Institution: Voytko, Mary L. Associate Professor; Pathology; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 31-AUG-2007 Summary: (Provided by applicant): Ovarian hormone deficiency of menopause brings on changes that can have far reaching consequences on the future health and well being of women. Nondemented postmenopausal women frequently note alterations in cognitive functions, particularly memory and attention. Determining the relationship between ovarian hormones and cognitive function in menopause can be difficult to study in women because of a variety of confounding factors. We have developed a monkey model of menopause that allows us to more rigorously control many of these factors and additionally, that has allowed us to begin to identify cholinergic mechanisms of ovarian hormone action in the primate brain. Our initial behavioral and neurobiological studies were performed in young ovariectomized monkeys so that we could determine the effects of estrogen therapy (ERT) without the influence of other confounding factors, including advanced age. However, there are many important questions that remain unanswered, including the effects of estrogen plus progesterone therapy (HRT) and the effects of ovarian hormones in monkeys of an age that more closely models that of the middle-aged postmenopausal woman. These issues will be addressed in middle-aged monkeys in the present project. Behavioral experiments in Specific Aim 1 will determine the cognitive effects of ovarian hormone replacement therapy (ERT and HRT) using a series of behavioral tasks that measure several different cognitive functions that rely on the cholinergic system. In Specific Aim 2. functional imaging studies of the cholinergic system will be performed in the monkeys of Specific Aim 1 in parallel with their behavioral assessments to determine if measures of presynaptic cholinergic activity correlate with measures of cognitive function in monkeys treated with ovarian hormones. In Specific Aim 3. pharmacological studies will be performed in the monkeys following their initial behavioral and imaging studies to determine the effects of cholinergic, muscarinic and nicotinic receptor blockade on cognitive function in monkeys treated with ovarian hormones. Thus, the overall objectives of the experiments proposed in this application are to extend and broaden our initial investigations in young monkeys by determining the effects of ovarian hormone replacement therapy on cognitive function and in vivo cholinergic system function in middle-aged surgically menopausal rhesus monkeys. The findings from these novel experiments in middle-aged monkeys will significantly advance our understanding of the effects of ovarian hormone therapy on cognitive and neurobiological profiles of primates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COGNITIVE EFFECTS OF CANCER CHEMOTHERAPY Principal Investigator & Institution: Ahles, Tim A. Professor; Psychiatry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: APPLICANT'S Cognitive deficits associated with cancer treatment can have a dramatic effect on patients' quality of life and have been recognized as a problem by the President's Cancer Panel (1999) and the National Coalition for Cancer Survivorship as a challenge facing people with cancer. The present application is an extension of work completed by researchers at Dartmouth with a supplement from the Office of Cancer

42 Menopause

Survivors to the Norris Cotton Cancer Center Core grant (Grant No. P30CA23 108, supplement) entitled "Cognitive Impact of Systemic Chemotherapy in Long-Term Survivors of Breast Cancer and Lymphoma." Survivors who were greater than 5 years post-diagnosis and disease free were administered a battery of standardized neuropsychological and psychological tests. The results demonstrated that survivors who had been treated with systemic chemotherapy scored significantly lower in overall neuropsychological functioning as compared to survivors who had been treated with local therapy only. In this next phase of research, we propose to prospectively study the cognitive deficits experienced by breast cancer and lymphoma patients treated with their first course of systemic chemotherapy versus local surgery or non-CNS radiation. Patients will be assessed at pre-treatment and 6, 12 and 24 months post-diagnosis with a standardized battery of neuropsychological and psychological tests. The primary hypothesis is that patients treated with systemic chemotherapy will demonstrate greater decrements in performance from pre- to post-treatment on standardized measures of neuropsychological functioning as compared to patients treated with local therapy only after controlling for important confounding variables such as age, education, and psychological state. Secondarily, we will evaluate the associations between cognitive functioning and other factors that may effect cognition in cancer patients including genetic markers (APOE status), metabolic factors, menopausal status (pre- vs. postmenopausal at diagnosis), and use of tamoxifen (breast cancer only). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: COOPERATIVE MULTICENTER REPRODUCTIVE MEDICINE NETWORK Principal Investigator & Institution: Carr, Bruce R. Dir, Div of Reproductive Endocrinology; Obstetrics and Gynecology; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 30-JUN-2000; Project End 31-MAR-2005 Summary: This research proposal describes the qualifications and experience of the Division of Reproductive Endocrinology faculty and research team at the University of Texas Southwestern Medical Center at Dallas, the facilities, and patient population available to them for carrying out clinical protocols to be designed by the NICHD Reproductive Medicine Unit (RMU) Network. The UT Southwestern Division of Reproductive Endocrinology includes 6 clinicians, 4 of whom are board certified in Reproductive Endocrinology. Within the division is the Women's Research Center which includes 3 research nurses led by a research nurse coordinator with 20 years experience in protocol development and implementation are available for participation in RMU network protocols. This research team has successfully completed an extensive number of randomized trials, some of which were supported by NIH grant support as well as multi-center randomized trials supported by pharmaceutical companies. These investigations included infertility, andrology, endometriosis, uterine leiomyomata, androgen excess, contraception, and menopause. In order to develop an interdisciplinary approach to the study of reproductive disorders we have brought to the RMU network support of UT Southwestern's NIH General Clinical Research Center, Department of Urology, Psychiatry, Radiology, and Internal Medicine. A concept protocol is included which proposes to investigate pain relief in women suffering from endometriosis. This trial compares the effect of the medical treatment standard with gonadotropin releasing-hormone agonist versus continuous low-dose combined oral contraceptive pills. It is proposed that if continuous oral contraceptive pills are close in efficacy of relieving pain in women with endometriosis as are gonadotropin releasing

Studies 43

hormone agonists, this mode of treatment would benefit a significant number of women wishing to save their reproductive organs for later reproduction. In summary, the reproductive endocrinology research team is experienced in multi- center clinical trials and is committed to collaborative participation consistent with the goals of the RMU network. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CORE--COHORT FOLLOW UP AND DATA BASE MAINTENANCE Principal Investigator & Institution: Colditz, Graham A. Professor of Medicine and Epidemiology; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001 Summary: The goals of the cohort follow-up and database maintenance core (Core A) are to: 1. develop and mail follow-up questionnaires, to process returned questionnaires, verify responses and compile the database of exposure data; 2. to trace lost subjects and maintain their name and address file for the Nurses' Health Study (NHS) cohort. 3. to maintain cohort participation through newsletter, certificate of appreciation and correspondence and reply to queries from participants. Core A, under the direction of Graham A. Colditz, M.D., Dr. P.H., develops and designs the questionnaire for biennial follow-up of study participants. This questionnaire design incorporates input from other investigators on the Program Project through the bi-weekly meetings. New questions are pilot tested and follow-up methods are refined to address the needs of the aging cohort members. Returned questionnaires are checked for completeness., optically scanned, and verified for scanning errors. The questionnaires are finally stored on CDrom. Core A uses a range of methods to trace participants and to maintain high level of participation. A the completion of the 1996 follow-up cycle, 90 percent of participants responded. The 1998 follow-up cycle is continuing. Core A is responsible for derivation of variables from the questionnaire responses. This included maintaining a nutrient database to derive nutrient values after the completion of food frequency questionnaires (FFQs), the updating of menopause and duration and type of hormones used after menopause, and the general documentation of the Nurses' Health Study (NHS) database. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DECISION MAKING REGARDING HORMONE REPLACEMENT THERAPY Principal Investigator & Institution: Padonu, Georgia; None; Michigan State University 301 Administration Bldg East Lansing, MI 48824 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: The career goal of this applicant is to develop the research skills to become an independent, externally funded biomedical researcher in the field of health decision making and achieve a record of research and publication productivity. The research focus is the development and testing of decision support interventions and their adaptability in the study of decision making regarding HRT among low income menopausal African American women. To accomplish the research career goals, the following objectives are developed for the proposed award period: 1. To expand knowledge of selected concepts, measurement and analytical strategies predominately used in decision support research development and testing. 2. To build on and expand skills in developing culturally sensitive research materials, instruments and interventions. 3. To increase knowledge of select conceptual frameworks used in

44 Menopause

decision making research to including both initial and continuance decision making, and with adaptability to low income African American women. 4. To increase theoretical knowledge of risk communication in the context of decision making research, issues of communication style, format preferences, with focus on application to low income, low literacy and diversity in study populations. 5. To maintain currency in clinical competency related to menopause and HRT with special interest in health risk assessment and quality of life as health status outcome. 6. To utilize knowledge and skills gained from career development activities to conduct pilot research of decision support for community-based low-income African American women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: DECISION SUPPORT FOR PREVENTIVE HORMONE THERAPY Principal Investigator & Institution: Taylor, Thomas R. Family Medicine; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 30-APR-2003 Summary: Specific Aims: This study will: 1)develop a computer-based decision support system, accessible through the World Wide Web, for women making decisions about the use of preventive hormone therapy (PHT) and related issues, and 2)test the efficacy of this decision support system on women's decisions in randomized controlled trials comparing usual care to usual care plus the computer-based decision support. Background and Significance: As the number of women living to advanced old age increases, interest in PHT to reduce the risk of heart disease and osteoporosis has escalated. Our research has indicated that, for many women, the decision to start PHT is an iterative process involving trading off perceptions of biological benefits and risks with values about the menopause and issues such as "putting foreign substances into one's body." We will develop and evaluate an interactive decision support that will help women to obtain and understand information to make this and related decisions. It will fit the iterative model of decision-making we have found many women use. It will be easily accessible through the World Wide Web and be inexpensive to update as new information appears. Research Design and Methods: The study will take place in 2 phases, a development phase and an efficacy trial phase. In the developmental phase, software for the Comprehensive Health Enhancement Support System (CHESS) will be adapted by the CHESS development team in Madison, WI to run on a webserver and be accessible via the World Wide Web. Seattle investigators will gather scientific information, women's stories, and other resources for women making decisions related to PHT and work with the CHESS team in Madison to incorporate this information into CHESS. Pilot-testing will occur in both sites, with approximately 100 women recruited at each site to help with this process. When the development phase is completed, an efficacy trial will be started in Milwaukee, WI, recruiting 210 women to be randomized to receive either a printed brochure or the brochure and CHESS. 3 months later, a similar efficacy trial will be started in Seattle. At both sites, women will complete an initial survey and follow-up surveys at 3 and 6 months. Analyses will compare the decisions made by women randomized to receive CHESS with those of the control women. Primary outcomes will be measures of decisional quality, including decisional satisfaction and conflict. Adherence to decisions will be measured by survey data at both sites and, in Seattle, pharmacy data on filling of prescriptions for PHT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies 45

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Project Title: DETERMINATION OF RATE UNDERGOING CASTRATION FOR CANCER

OF

BONE

LOSS

IN

MEN

Principal Investigator & Institution: Bruder, Jan; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001 Summary: Hypogonadism results in a high turnover bone loss; the rate of bone loss in women after menopause has been studied, but the rate of bone loss in men with hypogonadism due to surgical or chemical castration is unknown. This study is designed to assess the rate of bone loss in men immediately following surgical or medical castration because of prostate cancer. Men who are scheduled to undergo surgical orchietomy or medical castration and normal age-matched controls will be studied. Bone mineral density measurements will be determined at baseline, 6 and 12 months. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: DIETARY SOY SUPPLEMENT IN MENOPAUSAL WOMEN Principal Investigator & Institution: Burke, Gregory L. Professor and Vice Chair; Wake Forest University 2240 Reynolda Rd Winston-Salem, NC 27106 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECT OF ADVANCING AGE ON BONE MINERAL CONTENT OF FEMALE RHESUS MONKEY Principal Investigator & Institution: Binkley, Neil C.; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001 Summary: OBJECTIVE To assess the effect of advancing age upon bone mass as measured by dual energy x ray absorptiometry. RESULTS While age-related bone loss in humans is well established, the effect of advancing age and menopausal status upon bone density in non-human primates is not. We have previously been unable to demonstrate "age-related" loss cross sectionally. It is possible that this is the result of the standard laboratory chow diet which is very high in calcium and vitamin D by human standards. FUTURE DIRECTIONS We will assess age related skeletal changes in bone mass and markers of bone turnover in this cohort of older female monkeys to document the presence or absence of "age related" bone loss. KEY WORDS Osteoporosis, bone density, bone strength FUNDING Geriatrics section discretionary funds PUBLICATIONS Todd, H., Bruner, J., Haffa A., Krueger, D., & Binkley, N. Bone Loss with Natural Menopause and Advancing Age in Female Rhesus Monkeys. 1998 Bone, 23(5 suppl) S508. [A] Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECT OF SELF-REGULATORY EDUCATION ON WOMEN WITH ASTHMA Principal Investigator & Institution: Clark, Noreen M. Dean; Health Behavior and Hlth Educ; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274

46 Menopause

Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: More than half of the adults with asthma in the US are female. Prevalence of asthma in women appears to be increasing, and morbidity and mortality rates for this group are significantly higher than rates for men. Recent studies point to unique features in women's management of asthma potentially attributable to gender. These include, for example, factors associated with hormonal cycles, (e.g. menses, pregnancy, menopause) and social roles (e.g. household tasks exposing one to environmental triggers, caregiving to children and relatives interfering with asthma management etc.) To date, no rigorously evaluated intervention expressly designed for women with asthma has been reported in the literature. The proposed study will evaluate an asthma education program in a study of 512 women with asthma modeled on a successful intervention for women with heart disease shown to improve physical and psychosocial functioning. The study will assess the impact of an innovative asthma management program based on principles of self- regulation and tailored to unique needs of women with asthma. It is expected that when compared to women randomly assigned to the treatment group will exhibit fewer gender-related asthma management problems, higher levels of physical functioning, fewer days of missed work, increased satisfaction with their quality of life, less frequent symptoms, and reduced use of health services. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EFFECTS OF AGE ON HYPOTHALAMIC/PITUITARY/OVARIAN ACTIVITY IN NORMAL WOMEN Principal Investigator & Institution: Evans, William S.; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF DIET ON GROWTH HORMONE-IGF-1 AXIS Principal Investigator & Institution: Boyd, Norman F.; Ontario Cancer Institute 610 University Ave Toronto, Timing: Fiscal Year 2001; Project Start 19-SEP-2001; Project End 31-AUG-2003 Summary: The specific aim of this proposal is to determine whether In premenopausal and postmenopausal women blood levels of Insulin like Growth Factor-I, Insulin like Growth Factor Binding Protein -3 and Growth hormone are influenced by a low-fat high- carbohydrate diet. The general method to be employed will be to perform assays for growth factors and hormone on blood samples, and nutrient analysis of food records, collected from subjects taking part in our ongoing multicentre randomized dietary intervention trial. This trial is designed to test the hypothesis that intervention with a low-fat high-carbohydrate diet will, in women with extensive mammographic densities, over a 10 year period reduce the incidence of breast cancer by 29 percent. The trial is explanatory in that it seeks to determine if there is a biological effect of dietary fat reduction in terms of a reduction in breast cancer incidence. To meet this goal we have selected as participants highly motivated subjects who are at increased risk of breast cancer, we have provided them with a high level of assistance in making a dietary alteration, we follow them carefully to ensure the maintenance of dietary change and the correct identification of subjects who develop breast cancer, and we plan to analyse the results according to study group and dietary compliance. Recruitment of the 4615 subjects required for the trial was completed in November 1998. (A total of 4693 were

Studies 47

randomized). Blood samples and food records from subjects enroled in the trial will be used to test the hypotheses given below about the effects of dietary intervention on growth factors and hormones associated with breast cancer risk. Modulation of these factors by dietary intervention would indicate potential mechanisms by which diet may influence risk of breast cancer. Although not the purpose of the research proposed here, the long term nature of the trial, the complete follow-up of all subjects, and the complete ascertainment of breast cancer, will ultimately allow any changes in blood markers found in the present research to be examined in relation to changes in breast cancer incidence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: DEPLETION

EFFECTS

OF

ESTROGEN

ON

DEPRESSION--TRYPTOPHAN

Principal Investigator & Institution: Epperson, Neill; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: The overall aim of this study is to examine whether estrogen will protect remitted depressed menopausal women from the transient relapse of depression after acute TRP depletion. Previous research has suggested that: 1) Peripheral and central measures of 5-HT activity are altered in depression: 2) SSRIs are effective in the treatment of depression: 3) estrogen has neuroregulatory activity on 5-HT function: 4) estrogen improves depressed mood. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EFFECTS METABOLISM

OF

OVARIAN

SUPPRESSION

ON

SUBSTRATE

Principal Investigator & Institution: Toth, Michael J. Assistant Professor; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, VT 05405 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Aging is associated with increased risk for heart disease, diabetes and physical disability. In women, the incidence of these age-related conditions increases dramatically after menopause. This has led to the hypothesis that ovarian hormone deficiency contributes to these adverse health outcomes. However, the effect of ovarian hormone deficiency, per se, on risk factors for disease and disability has not been clearly defined. Thus, the primary goal of the proposed studies is to characterize the effect of ovarian hormone deficiency on glucose, insulin, fat and protein metabolism. Our overall hypothesis is that ovarian hormone deficiency alters substrate turnover and utilization in a manner that increases the risk for developing chronic disease and disability. Specifically, alterations in glucose, insulin and fat metabolism increase the risk for developing heart disease and diabetes and changes in protein metabolism reduce lean tissue mass which, in turn, promotes disability. To address our hypothesis, we will measure substrate metabolism using stable isotope tracer methodology in healthy, premenopausal women before and after pharmacological ovarian suppression. Women will be randomized to receive the gonadotropin-releasing hormone agonist leuprolide acetate or placebo. Measurements of substrate metabolism will be performed during both the follicular and luteal phases of the menstrual cycle prior to treatment and 2 months after the initiation of treatment. This experimental paradigm will enable us to investigate the effect of ovarian hormone deficiency, per se, on substrate metabolism without the confounding factors present in prior cross-

48 Menopause

sectional, longitudinal and hormone replacement studies. This application consists of 3 separate experiments that will employ this model of ovarian suppression. Experiment I will investigate the effect of ovarian hormone deficiency on the glucose and insulin response to hyperglycemia. Experiment 2 will examine the role of ovarian hormone deficiency in the regulation of whole-body lipolysis under postabsorptive and epinephrine-stimulated conditions. Experiment 3 will examine the effect of ovarian hormone deficiency on whole-body protein metabolism under postabsorptive and simulated-postprandial conditions. Our findings will have direct relevance to understanding the fundamental role of ovarian hormone deficiency in the physiologic and metabolic changes that occur with menopause. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EFFECTS OF PROGESTERONE & ESTROGEN ON SIV VAGINAL TRANSMISSION: MENOPAUSE Principal Investigator & Institution: Marx, Preston A. Professor; Tulane University of Louisiana New Orleans, LA 70118 Timing: Fiscal Year 2001 Summary: The objective is to search for mechanisms by which the female hormones, progesterone and estrogen, influence vaginal transmission and pathogenesis of Simian Immunodeficiency Virus (SIV) in rhesus macaques. Progesterone?s known effects on female physiology are numerous. They include thinning of vaginal epithelium and immune suppression. In a recent study, progesterone was shown to increase SIV vaginal transmission. Thinning the vaginal barrier to SIV infection is a potential cause of this increase, but immune suppression, possible increases in target cells in vaginal tissues or direct effects on in vivo SIV replication need study. Moreover, an important inference from the progesterone study was that estrogen, an antagonist of progesterone, may actually protect against SIV vaginal transmission. Two specific aims are proposed to identify and characterize the action of progesterone, estrogen and the anovulatory state in vaginal transmission and pathogenesis of SIV. Aim 1. To individually test the effects of progesterone and estrogen on SIV vaginal transmission and their effects on SIV pathogenesis and the SIV immune response. Aim 2. To test progesterone and estrogen on in vivo pathogenesis independent of vaginal mucosal changes through intravenous infection of hormone treated- macaques. In both aims, each hormone will be examined independently by testing virus load, clinical outcome and immune responses in ovariectomized macaques with and without progesterone and estrogen implants. Ovariectomy is a standard technique for individual in vivo study of the sex hormones. Natural states of elevated hormones or their absence as in menopause, bear on vaginal physiology and may therefore, influence vaginal transmission of human immunodeficiency virus (HIV). Moreover, drugs based on these hormones are used in female contraceptives. Because human epidemiologic studies are difficult to design and control, an understanding of hormones gained in the SIV model may help to elucidate the effects of these natural and drug-based co-factors on HIV vaginal transmission. FUNDING NIH (1R01 AI41952) PUBLICATIONS Sodora, D.L., A. Gettie, C.J. Miller and P.A. Marx. Vaginal transmission of SIV assessing infectivity and hormonal influences in macaques inoculated with cell-free and cell-associated viral stocks. AIDS Research and Human Retroviruses, 13:S1-S5. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies 49

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Project Title: EFFICACY OF FISH OIL AFTER MENOPAUSE Principal Investigator & Institution: Utian, Wulf H.; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: The high prevalence, morbidity and mortality of osteoporosis in women offers a unique opportunity for investigation into the pathogenesis and prevention of this problem during the phase of rapid bone loss occurring in the immediate years following menopause. The primary objective of this study is to demonstrate the efficacy of omega-3 fatty acids in preventing loss of bone mass in an at risk population. We hypothesize that post-menopausal women who decline hormone replacement therapy and, thus, are at increased risk for loss of bone mass will have no bone loss on omega-3 fatty acids nutrient supplementation compared to similar women in a placebo control group. To better understand the mechanism of omega-3 fatty acids in preventing loss of bone mass, there are two secondary objectives: One is to examine the impact of omega-3 fatty acids on markers of bone turnover and the second is to examine the impact of omega-3 on cytokine production. We further hypothesize that omega-3 fatty acids will decrease loss of bone mass in post-menopausal women by decreasing bone turnover, mainly by decreasing bone resorption. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENERGETIC ADAPTATION TO THE MENOPAUSE TRANSITION Principal Investigator & Institution: Matthews, Dwight E. Chairman/ Professor; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, VT 05405 Timing: Fiscal Year 2001; Project Start 15-SEP-1997; Project End 31-AUG-2004 Summary: Loss of ovarian function accelerates the risk of cardiovascular and metabolic disease, and heralds the onset of changes that can have far-reaching consequences on women's future health. We will examine the impact of the menopause transition on several metabolic and cardiovascular risk factors associated with declining health status in women. Our overall hypothesis is that women who experience a natural menopause transition will show - accelerated decline in daily energy expenditure, increase in total and Intra-abdominal body fat and decline in insulin sensitivity. In this 5-year longitudinal study, we will recruit 57 premenopausal women and examine their natural history as they traverse the menopause. Changes in energy expenditure, body composition, body fat distribution and insulin sensitivity will be measured annually (a total of five exams) to examine the time course of menopause and age-related changes in outcome variables. Our First Aim will examine the effects of the menopause transition on total daily energy expenditure, body fat distribution and insulin sensitivity. We will use: 1) doubly labeled water and indirect calorimetry to measure changes in total daily energy expenditure, resting metabolic rate, thermic effect of a meal and physical activity; 2) computerized tomography to assess changes in intraabdominal body fat and 3) euglycemic clamps to measure insulin sensitivity. Our Second Aim is to develop and cross-validate new models to predict daily energy requirements, as derived from biological markers of total daily energy expenditure in pre- and postmenopausal women and to compare them to current daily energy intake recommendations. Current recommendations for daily energy needs are based on outdated food intake data and have not considered the influence of menopause status, body composition and physical activity as determinants of daily energy needs. These limitations have led to the suggestion that prescription of daily energy requirements

50 Menopause

should be based on the measurement of total daily energy expenditure. Analyses of these data will characterize the biological and metabolic sequelae of changes in energy metabolism, body fat distribution and insulin sensitivity in women as they traverse the menopause. Furthermore, we will offer new guidelines to predict energy requirements during the menopause transition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EPIDEMIOLOGIC STUDY OF THE LATE REPRODUCTIVE YEARS Principal Investigator & Institution: Freeman, Ellen W. Research Professor; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 10-FEB-1996; Project End 31-JAN-2006 Summary: (Adapted from the Investigator's Abstract) This is a prospective study of ovarian aging in African American and Caucasian women in their late reproductive years, commencing at ages 35-47 and continuing to ages 45-52. The specific aims are to 1) compare hormone dynamics (FSFL estradiol, DHEAS) and the follicular product inhibin between African American and Caucasian women; 2) evaluate menopauserelated symptoms over the study period and compare their severity and changes between African American and Caucasian women; and correlate physical and psychological factors (body mass, hot flashes, depression, steep disturbance and others) with hormone levels, fluctuations and rates of change and compare the associations between the two racial groups. The study is conducted with a randomly-identified population-based sample of approximately 400 women. The second phase of the study has four annual follow-up periods, each with two assessments at 1-month intervals, for a total of eight visits to collect blood samples for hormone assays and questionnaire data. More than 8O percent of U.S. women experience physical or psychological symptoms in the transition to menopause with varying degrees of severity and disruption of normal functioning. Whether these symptoms commonly attributed to the menopause are associated with the hormonal changes of the waning reproductive years is not well understood. Symptoms that diminish quality of life are a significant problem for women who experience them, their relationships and their productivity. Poor understanding of the symptoms and their associations with biological and environmental factors is a problem for health care when distressed women seek medical relief. This study provides the first information on racial differences in the associations between symptoms and the changing hormonal milieu compared between African American and Caucasian women. The investigators state that the findings will also inform clinicians addressing fertility problems of women in the late reproductive years and will increase understanding of the role of reproductive aging in the increased morbidity and mortality of postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY AND GENETICS OF PARKINSON'S DISEASE Principal Investigator & Institution: Rocca, Walter A. Professor of Epidemiology and Neurology; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-JUN-1996; Project End 31-MAY-2006 Summary: (Adapted from applicant's abstract): Parkinson's disease (PD) is a common and disabling condition in the expanding elderly population of the US and worldwide. Its etiology remains unknown and both genetic and environmental factors have been suspected. The long-term goal of the proposed studies based in different sampling is to clarify the etiology of PD and to identify means to prevent it. Three independent but

Studies 51

related studies based on different sampling and measurement strategies are proposed. The hypotheses tested derive directly from our current work and preliminary findings. A case control study will include 800 cases of PD referred to the Mayo clinic from a 120 mile radius or from a 5 state region and 800 controls free pf PD and parkinsonism matched by age (+ 2 years), sex and region of residence. Controls from the general population will be identified from health care financial administration lists for cases aged 65 years or above and through random digit dialing for cases below 65 years. Exposures will be accessed through direct telephone interview, and will include tobacco, coffee, and alcohol use; markers of novelty seeking behavior; and, for women, use of estrogen replacement therapy after menopause and other reproductive and estrogen related factors. A first historical cohort study will test the association between unilateral and bilateral oophorectomy before menopause and PD in an established population based cohort. The study will include 2,533 women who underwent oophorectomy in 1950-1987 while residing in Olmsted County, MN and 2,533 women of the same age and residence who did not undergo oophorectomy. A second historical study will test the association between personality traits measured by the Minnesota Multiphasic Personality Inventory (MMPI) and PD in an established research cohort. This study will include 8,775 persons who underwent MMPI testing in 1962-1965 while residing in Minnesota. The proposed case-control study is strong because it has adequate statistical power to confirm our preliminary findings on the role of estrogen in PD and to explore the link between substance use and novelty seeking behaviors in PD. All interviews with case and controls will be direct, the proposed oophorectomy cohort study is strong because of its cohort design, its population-based sampling, its adequate statistical power, and because of the expected high rate of follow-up through both passive and active strategies. The proposed MMPI cohort study is strong because of its cohort design, its adequate statistical power and because of our extensive experience with tracing and interviewing individuals. These three studies will contribute greatly to understanding the causes and possible prevention of PD by exploring novel hypotheses and by using innovative methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EPIDEMIOLOGY AND MECHANISMS OF FECAL INCONTINENCE Principal Investigator & Institution: Bharucha, Adil E.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: Fecal incontinence (FI) is a socially devastating symptom in older women and may contribute to institutionalization. The epidemiology and pathophysiology of "idiopathic" FI is incompletely understood. Current concepts based on tertiary-care studies heavily emphasize the role of anal sphincter defects visualized by endoanal ultrasound. Preliminary studies suggest that the prevalence of FI in Olmsted County in women greater than or equal to 50 years is 17.8 percent with a median age of onset of 61 years. Obstetric events, diarrhea/urgency and obesity are risk factors for FI. Our novel "fluoroscopic" single-shot fast spin-echo MRI techniques visualize pelvic floor descent during defecation in real-time. In contrast to US, endoanal MRI depicts external sphincter defects and atrophy, puborectalis thinning and global pelvic floor laxity. The hypothesis is that fecal incontinence is not attributable to obstetric trauma alone, but the cumulative result of pelvic floor weakness caused by obstetric trauma, excessive straining, obesity, aging and menopause, compounded by diarrhea. This hypothesis will be addressed by combining the data infrastructure of the Rochester Epidemiology Project with state- of-the-art physiological measurements in a community-based sample.

52 Menopause

A questionnaire will be mailed to a cohort of approximately 1,000 women surveyed previously to ascertain the incidence and natural history of FI, and, a new sample of 5,000 women to determine the prevalence and frequency of FI. Putative risk factors for pelvic floor injury (obstetric trauma, chronic straining, obesity and estrogen depletion) and FI (diarrhea and rectal urgency) will be evaluated in a case-control study of approximately 200 patients with FI at least once a month and approximately 200 controls. approximately 100 patients with FI and approximately 100 controls will have MRI fluoroscopy to characterize the specific global pelvic floor abnormality (i.e., anal sphincter defects, sphincter atrophy, puborectalis thinning and pelvic floor laxity) associated with FI. These studies will refine our understanding of the epidemiology of FI, identify the obstetric risk factors responsible for delayed manifestations of pelvic floor injury, i.e. FI, underscore the importance of non- obstetric risk factors for FI and provide novel insights into the specific pattern of pelvic floor injury associated with FI in a community. These steps are necessary for reducing the incidence of pelvic floor damage by risk factor modification, identifying patients at higher risk of progressing to symptomatic FI, and designing appropriate interventions to halt this process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EPIDEMIOLOGY OF CARDIOVASCULAR RISK FACTORS IN WOMEN Principal Investigator & Institution: Kuller, Lewis H. Professor and Chair; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-APR-1988; Project End 31-AUG-2003 Summary: (Adapted from Investigator's Abstract) The primary aim of this renewal is to determine the risk factors for subclinical cardiovascular disease, and the determinants of progression, as estimated from change in coronary and aortic calcification measured by electron beam computerized tomography (EBCT) at 8 and 12 years after menopause, and from change in carotid plaque index at 5 and 8 years postmenopause, in 350 women. The investigators hypothesize that premenopausal measures of risk factors, particularly LDLc, HDLc, and smoking, will strongly predict progression of coronary and aortic calcification, and carotid disease. This is based on their preliminary data analyses which found a very strong relationship between high LDLc levels, low HDLc levels, and smoking in predicting coronary and aortic calcification at the 8th postmenopausal visit. Risk factors measured during premenopause were much more strongly related to subclinical disease than concurrently measured risk factors, or change in risk factors, suggesting a long 'incubation' phase. They believe that aortic calcification and carotid plaque are earlier manifestations of subclinical cardiovascular disease than coronary calcification, as these were much more frequent than coronary calcification at the 8th visit. They will test the hypothesis that incident coronary calcification at the 12th menopausal year is more likely to occur in women with prior aortic calcification or carotid plaque compared with women without calcification or plague at the 8th year. The Healthy Women Study has documented the evolution of cardiovascular risk factors and subclinical cardiovascular disease from premenopause through menopause in a cohort of 541 women, aged 42-50 at the time of their recruitment in 1983-84. Participation in this study continues to be very high with only 51% dropping out and 7 deaths prior to the 8th visit. Currently, most women are 6-12 years postmenopause. Risk factors, including lipids, insulin, glucose, fatness and fat distribution, endogenous sex-steroid hormones, hormone replacement therapy, and behavioral and psychosocial factors, have been studied in detail. The investigators note

Studies 53

that this will be the first study to tract progression of coronary and aortic calcification by EBCT, and carotid plaque and wall thickness, in younger postmenopausal women. They further note that the identification of early and modifiable risk factors for subclinical disease should lead to prevention or reduction of clinical cardiovascular disease among postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EPIDEMIOLOGY OF MENOPAUSE AND DEMENTIA IN DOWN SYNDROME Principal Investigator & Institution: Schupf, Nicole; Institute for Basic Res in Dev Disabil Developmental Disabilities New York, NY 10314 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: An epidemiologic study is proposed to test the hypothesis that reductions in estrogen, indicated by onset of menopause, are associated with onset of Alzheimer's disease (AD) in women with Down syndrome (DS). We further hypothesize that this association will be stronger in women who are genetically susceptible to AD because they carry the apolipoprotein E (apoE) epsilon4 allele. Prior studies in the general population suggest that declines in estrogen levels following menopause play an important role in the etiology AD and that the presence of the apoE epsilon4 allele is associated with earlier age at onset and increased risk of AD. The relationships between onset of menopause, apoE and onset of AD are difficult to study in women in the general population because of the extended time period between menopause and onset of AD. In contrast, women with DS have a very high risk of AD, with an average age at onset of AD between 50-55 years, 10-15 years earlier than in the general population. Thus, women with DS experience onset of AD more closely in time to onset of menopause than is typical in the general population, providing a unique cohort in which to study the relationship between menopause and AD. We hypothesize that earlier age at menopause will be associated with earlier age at onset of AD. We propose a 5-year longitudinal study of incident dementia in 350 women with DS, 45-52 years of age, followed at 18 month intervals. We will ascertain age a menopause by chart review, as menstrual cycles are regularly charted in nursing notes. We will supplement this measure with assays of reproductive hormones at each assessment. We will assess declines in cognitive and adaptive competence indicative of AD using a uniform neuropsychological test battery and neurological examination of those suspected to be affected and a sample of those not suspected, with ascertainment of other medical or psychiatric conditions that might cause dementia. We will use standardized criteria for dementia and the differential diagnosis of AD. We will determine DS karyotypes and apoE genotypes. The results of this study will provide important information about the role of estrogen in the etiology of AD and the optimal strategy for the development of clinical trials of hormone replacement therapy in women with DS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF OSTEOPOROSIS IN WOMEN WITH LUPUS MAMDC PROJECT Principal Investigator & Institution: Ramsey-Goldman, Rosalind; Northwestern University Office of Sponsored Programs Chicago, IL 60611

Professor;

Timing: Fiscal Year 2001 Summary: The specific aims to be addressed in this study are: 1) To estimate the differences in bone mineral density (BMD) at the hip and lumbar spine between 128

54 Menopause

Caucasian and 128 African-American women with lupus and a comparable control group matched by age, race, and menopause status; 2) To determine the association of lupus risk factors with low BMD in women with lupus, after controlling for traditional risk factors for low BMD; 3) To follow the subjects entered in the cross-sectional study over a two year period in order to estimate the difference in the rate of bone loss at the hip and lumbar spine between women with lupus and a comparable control group matched by age, race, and menopause status; and 4) To determine the association of lupus risk factors with increased rates of bone loss in women with lupus, after controlling for traditional risk factors for low BMD. The hypotheses to be examined in this study are: 1a) Women with lupus have lower BMD at the hip and spine than matched controls; 1b) the negative effect of lupus on bone mineral density at the hip and spine is greater in Caucasian than in African-American women; 2a) Traditional risk factors for low BMD (nulliparty and menopause status, irregular menstrual cycles or premature menopause, avoidance of oral contraceptives and/or hormone replacement therapy, lower physical activity level, and decreased vitamin D levels) are associated with lower BMD at the hip or lumbar spine in women with lupus; 2b) lupus risk factors (greater disease activity, greater disease severity, higher corticosteroid burden, use of anticonvulsant drugs, and the presence of renal disease) are associated with lower BMD at the hip or lumbar spine in women with lupus, after controlling for traditional risk factors forlow BMD; 3a) Women with lupus have accelerated bone loss at the hip and spine during two additional years of lupus disease compared with matched controls followed for two years; 3b) the effect of lupus on the rate of bone loss at the hip and spine is greater in Caucasian than in African-American women; 4a) Traditional osteoporosis risk factors (mentioned in 2a above) are associated with accelerated bone loss in women with lupus; and 4b) lupus risk factors (mentioned in 2b above) are associated with accelerated bone loss at the hip or lumbar spine in women with lupus, after controlling for traditional risk factors for low BMD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EPIDEMIOLOGY OF OVARIAN AGE Principal Investigator & Institution: Kline, Jennie K. Research Scientist; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 31-MAR-2004 Summary: (provided by applicant): The goal of this study is to identify factors that influence ovarian age. We define "ovarian age" as the size of oocyte pool. Ovarian follicle (oocyte) counts are highest before birth and decrease as women age; similarly, the number of follicles that develop during each menstrual cycle decreases as women age. At any particular chronologic age, women vary in both the size of their oocyte pools and the number of antral (developing) follicles. These variations may reflect differences in the size of the pool at its formation or in rates of oocyte atresia. Increasing numbers of women are deferring childbearing to the later years. Since ovarian aging is accompanied by conception delay and an increased risk of infertility and trisomic conception, the identification of risk factors for accelerated ovarian aging would have significant implications for reproductive research and primary prevention. The proposed study draws on data from two already completed studies to identify risk factors for ovarian age. In the first study, ovarian age is measured by age at onset of the menopausal transition and at menopause in 494 women. In the second study. ovarian age is measured shortly after an index pregnancy by counts of ovarian antral follicles and three hormonal indicators of ovarian age-follicle stimulating hormone, inhibin B and estradiol-in 173 women. Both studies include extensive data on maternal characteristics

Studies 55

and exposures that might influence ovarian aging. They thus provide an excellent and unique opportunity to (i) identify determinants of ovarian age in fertile women during natural cycles and (ii) examine whether determinants of ovarian age during the reproductive years differ from determinants during the menopausal transition. The specific aims are: 1. To examine whether maternal characteristics (e.g., body mass index) or exposures (e.g., smoking) are associated with ovarian age measured by (i) antral follicle counts, (ii) selected hormonal indicators, (iii) age at onset of the menopausal transition, and (iv) age at menopause. 2. To conduct exploratory studies, using data from the Oocyte study, to assess whether or not skewed X-inactivation is associated with advanced ovarian age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EPIDEMIOLOGY OF PRIMARY BILIARY CIRRHOSIS Principal Investigator & Institution: Gershwin, M. Eric. Professor of Medicine; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, CA 95616 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: Primary biliary cirrhosis (PBC) is an enigmatic autoimmune disease characterized by female predominance, high titer anti- mitochondrial antibodies (AMA), small bile duct destruction, and liver failure. Our group was the first to clone and identify the mitochondrial antigens, a family of phylogenetically conserved 2- oxo acid dehydrogenase proteins recognized by T and B cells in PBC. In addition, recent data has provided us with the basis for the following working hypotheses. We submit that PBC is most likely the result of an inappropriate or malcontrolled response to an environmental (either chemical or biological) insult. The initiating insult in PBC could be either a urinary tract infection (UTI) or an exposure to halogen containing chemicals. In the case of UTI's, there are high degrees of homology between the mitochondrial proteins present in micro-organisms that characteristically cause UTI's and their eukaryotic (i.e. human) analogs. Alternatively, the liver-based metabolism of halogenated hydrocarbons as xenobiotics generates activated halogen containing intermediates that react to form halogen modified proteins. In both, UTIs and halogenated chemical exposures, the introduction of these foreign proteins may initiate an immunological response that results in the immune system inappropriately targeting self proteins. These insults, which appear to be necessary but are not sufficient to elicit an autoimune response, given their widespread occurrence, needs to occur in conjunction with other disease associated contributory factors (i.e. genetic background) to produce PBC. We propose to take advantage of our strengths, including a nationwide network of PBC researchers, to accomplish this goal. We will collect and analyze data on demographics (race/ethnicity, socio-economic status, place of birth), medical history, reproductive history (parity, birth outcomes/complications, fertility problems, oral contraceptive use), menstrual history (age at menarche, age at menopause, average cycle length, cycle regularity) and lifestyle factors (smoking, physical activity, occupation and occupational exposures) using a questionnaire that we have tested in a preliminary study of 201 patients and 171 unaffected siblings. The project data will be collected from a sample of 2000 cases from 17 medical centers around the country and an equal number of matched (on age, gender and residence) random-digit dialed controls. The proposed study would be the first comprehensive epidemiologic study of PBC to be conducted in the United States, and directed at testing our thesis in the hope of improving our understanding of this serious disease and potentially identifying preventive measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSPORT

ESTROGEN

AND

AGING

EFFECTS

ON

TRANSVAGINAL

Principal Investigator & Institution: Gorodeski, George I. Associate Professor; Reproductive Biology; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2003; Project Start 01-JUN-1999; Project End 31-MAY-2008 Summary: (provided by applicant): Our long-term objective is to understand the mechanisms that regulate the permeability of epithelia of the female reproductive tract. We have discovered that estrogen modulates the Resistance of the Lateral Intercellular Space (R-LIS) of human normal ectocervical-vaginal epithelial cells (ECVE), and decreases the paracellular resistance. The geometry of the lateral intercellular space (and the R-LIS) is determined by the shape of epithelial cells that define this space, and depends on the rigidity of the cytoskeleton. Based on novel preliminary results we advance our Maior Hypothesis that estrogen decreases the rigidity of the cytoskeleton by remodeling the cortical acto-myosin frame. The study has four Specific Aims: (1) To understand how estrogen remodels the cytoskeletal cortical acto-myosin frame. Our Hypothesis-A is that formation of a rigid cortical frame depends on the interaction of nonmuscle myosin IIB with cortical actin. We propose that estrogen remodels the cytoskeleton into a flexible structure by inducing disassembly of nonmusele myosin lIB from the cortical actin ring. (2) To understand the structural basis of the cortical actomyosin cytoskeletal ring in epithelial cells. Our Hypothesis-B is that in epithelial cells the stability of the cortical myosin-actin ring depends on the interaction of actin with homodimerized nonmuscle myosin IIB filaments. We propose that dedimerization of nonmuscle myosin IIB heavy chains inhibits myosin MgATPase activity, and leads to disassociation of nonmuscle myosin IIB from the cortical acto-myosin frame. (3) To understand the mechanism by which phosphorylation of nonmuscle myosin IIB heavy chains regulates MgATPase activity. Our Hypothesis-C is that that phosphorylation of nonmuscle myosin IIB heavy chains inhibits homodimerization of myosin filaments and blocks myosin MgATPase. The alternative hypothesis is that MgATPase can be regulated independent of dimerization, by phosphorylation of nonmuscle myosin lIB heavy chains directly at the motor domain. (4) To understand the signaling pathway of the estrogen-induced phosphorylation of nonmuscle myosin IIB heavy chains. Our Hypothesis-D is that the effect of estrogen is initiated by activation of the EGFR-MAPK pathway, and it involves casein kinase II (CKII) as the terminal kinase. The extended hypothesis postulates involvement of multimolecular complexes, including Rho-kinase and an unidentified phosphatase, as modulators of CKII-induced phosphorylation of nonmuscle myosin IIB heavy chains. Experiments will utilize tissues of human ectocervix and vagina obtained from women undergoing surgery, and cultures of human ECVE cells grown on filters. Health relatedness of the project: The results of the study may provide novel data about estrogen regulation of the permeability of the female reproductive tract epithelia, and improve our understanding of the physiology of reproduction: the pathophysiology of inflammatory and infectious disease in the genital tract; and for improving woman's health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ESTROGEN AND BRAIN CONTROL OF BLOOD PRESSURE Principal Investigator & Institution: Clark, John T. Assistant Professor; Meharry Medical College 1005-D B Todd Blvd Nashville, TN 37208 Timing: Fiscal Year 2001

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Summary: The incidence of cardiovascular disease in women increases dramatically following menopause. This is, most likely, triggered by estrogen deprivation. The proposed collaborative project is designed to expand Dr. Clark's scientific armament so as to enable a successful transition to mainstream funding for his studies of neuroendocrine regulation of cardiovascular and sexual function during aging. Very few studies of neural control of the cardiovascular system have employed middle-aged rats that are most at risk for the hypertension and stroke, and none have carefully considered the potential collaborative contribution between the sympathetic nervous system and the cardiovascular system in the generation of stroke. This is especially important, because even a short term excess of vasoconstriction could greatly increase the mortality or morbidity associated with stroke. The proposed studies will test the hypothesis that the loss of normal and hypertensive female rats, thus allowing sympathetic nervous system response to increase. Further, the role of estrogen also increases the contractile responses of cerebral arteries to noradrenergic (sympathetic) stimulation. We hypothesize that these responses are potentiated in the stroke-prone rat. Our specific aims are to test the hypotheses that, in middle-aged female rats: [1] estrogen deprivation will result in decreased norepinephrine release in pre-optic- anterior hypothalamic area. This will be associated with increased blood pressure in normotensive and hypertensive female rats; [2] the interaction between estrogen and the nervous system occurs in specific areas relevant to blood pressure control, namely the organum vaculosum of the lamina terminalis, the subfornical organ, and the median pre-optic nucleus. Neuronal projections from these areas utilize angiotensin II and are responsive to estradiol; and [3] hypothalamic neurons, and in AT-1 gene expression in noradrenergic projections to the preoptic-anterior hypothalamic area. The antihypertensive effects of AT-1 receptor blockade will be attenuated in estrogen deprived middle-aged female rats. Taken together, these studies will provide important new information regarding the role of protective estrogens in neural regulation of blood pressure, and damage due to stroke, in stroke-prone hypertensive rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ESTROGEN AND DHEA SUPPLEMENTATION ON SERUM LIPIDS, MUSCLE MASS, STRENGTH, ENDURAN Principal Investigator & Institution: Barnhart, Kurt T. Assistant Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN AND EXERCISE--VASCULAR BENEFITS AFTER MENOPAUSE Principal Investigator & Institution: Brownley, Kimberly A. Psychiatry; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract) This application describes a 5-year career development training program for Dr. Kim Brownley. The program includes extensive research and pedagogical training designed to facilitate her growth as an independent researcher investigating combination modality therapies in high-risk cardiac patient populations. The plan is structured around a randomized placebocontrolled study of raloxifene and aerobic exercise training in hypertensive

58 Menopause

postmenopausal women. Dr. Kathleen Light, whose expertise is in cardiovascular stress responses, hypertension, and hormone (estrogen) replacement therapy (HRT), will serve as mentor. A collaborative support team is also in place, including: 1) Dr. James Blumenthal, who specializes in exercise training interventions in coronary heart disease (CHD); and 2) Alan Hinderliter, M.D. (Cardiology consultant), who will provide training in ultrasound measurement of cardiovascular function, and oversee data interpretation from a clinical perspective. The proposed study will investigate cardiovascular, neuroendocrine, and metabolic functioning in borderline and stage I hypertensive postmenopausal women. This patient group is at increased CHD risk due to elevations in blood pressure (BP), insulin resistance, and low-density lipoproteins. HRT and exercise training can offset these harmful effects by enhancing vasodilatory processes, and their effects may be additive when combined. HRT improves cardiovascular and neuroendocrine function; yet despite these benefits, HRT use and compliance are low because of added cancer risks in some women. Raloxifene, a secondgeneration nonsteroidal selective anti-estrogen, has beneficial lipid and osteogenic effects but does not confer added cancer risks. However, the cardiovascular effects of raloxifene are unspecified. Also, HRT has only modest BP-reducing effects and is thus insufficient antihypertensive therapy for hypertensive postmenopausal women. In contrast, exercise training has robust BP-reducing potential, especially in hypertensive individuals. Therefore, after all subjects complete a 3-month intervention with raloxifene alone, they will be randomized to either an additional 3-month treatment with raloxifene alone or treatment with raloxifene plus exercise training. Pre- and posttreatment assessments will include: 1) impedance cardiography measures of hemodynamic responses to laboratory challenge, 2) 24-hour ambulatory BP and impedance cardiography monitoring, 3) echocardiography assessment of left-ventricular geometry and function, 4) B-mode ultrasound assessment of flow-mediated brachial artery dilatation, 5) assay of neuroendocrine and lipid levels at rest and in response to laboratory stress, and 6) euglycemic insulin clamp to assess insulin sensitivity. Implementation of this training will provide a unique and highly advantageous opportunity for Dr. Brownley to work with this team of senior scientist- practitioners within the collaborative environments of the University of North Carolina and Duke University. This investigation, coupled with the didactic experiences outlined in this plan, will lay the foundation for her future endeavors as a scientific advocate for the systematic investigation of underlying mechanisms of hypertensive heart disease, and for the delivery of effective combination behavioral and pharmacological interventions for stress- related cardiovascular disorders in patients at increased risk for CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ESTROGEN AND HIPPOCAMPAL CIRCUITRY Principal Investigator & Institution: Morrison, John H. Professor; Mount Sinai School of Medicine of Cuny New York, NY 10029 Timing: Fiscal Year 2001 Summary: In human, estrogen replacement therapy (ERT) improves memory performance in ovariectomized (OVX) and post-menopausal women and is thought to decrease the risk of Alzheimer's disease. Changes in circulating levels of estrogen in rat affect the synaptic properties of hippocampal circuits that mediate memory, and these effects appear to be NMDA receptor-dependent. In addition, a high degree of NMDA receptor plasticity occurs in response to aging and estrogen manipulations in hippocampus that is cell class- and circuit-specific. In collaboration with the other four Projects and Core A, this Project will employ both rat and non-human primate models

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to develop a comprehensive animal model of the impact of estrogen depletion and ERT on NMDA receptors and hippocampal circuits with respect to memory performance. The degree to which the impact of estrogen on these circuits is comparable in young and old female rats and monkeys will also be investigated. Several relevant neurobiological parameters will be analyzed and compared in ovariectomized (OVX) animals with and without ERT, as well as in aged monkeys that are pre- and post-menopausal. In Specific Aims 1-3, morphologic parameters such as neuron number, dendritic arbor, and spine density will be analyzed, as well as quantitative confocal microscopy, and postembedding immunogold electron microscopy will be used to de3velop a quantitative database of these parameters in OVX versus OVX with ERT in old and young adult females of both species. In Specific Aim 4, the most robust and functionally relevant morphologic and neurochemical attributes that are responsive to estrogen in S.A.s 1-3 will be considered in relation to behavioral parameters in monkeys that have been tested for memory performance and attention in Project 5. In collaboration with Project 2, Specific Aim 3 will investigate the most robust morphologic and neurochemical effects of OVX and ERT in animals 25-28 years old that are either still cycling or postmenopausal, in order to drawl parallels between surgically induced and naturally occurring menopause. This comprehensive approach will delineate the interactions among estrogen levels, hippocampus, NMDA receptors, memory, and aging and lay the groundwork for more informed approaches to ERT in humans with respect to the neurologic and behavioral manifestations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ESTROGEN AND SELECTIVE MODULATOR ON THYROID FUNCTION

ESTROGEN

RECEPTOR

Principal Investigator & Institution: Braverman, Lewis E. Chief, Section of Endocrinology,; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001 Summary: To evaluate the effect of estrogen and selective estrogen receptor modulator, both of which increase thyroxine binding globulin concentration, on thyroid in menopausal women who are at risk to develop hypothyroidism and hypothyroid menopausal women on L-T4 replacement therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ESTROGEN VASOCONSTRICTION

AND

SYMPATHETICALLY

MEDIATED

Principal Investigator & Institution: Fadel, Paul J. Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2002; Project Start 01-FEB-2002 Summary: (provided by applicant): Women are less susceptible than men to cardiovascular disease until they reach menopause, when cessation of ovarian hormone production is accompanied by an accelerated risk for atherosclerosis, coronary artery disease, and vascular dysfunction. Although several mechanisms by which estrogen may confer vascular protection have been proposed it remains unclear as to how estrogen exerts its beneficial effects on the vasculature. The main goal of this proposal is to examine the influence of estrogen on the regulation of sympathetic vasoconstriction in contracting skeletal muscle. To accomplish this goal complementary experiments will be performed in conscious humans and anesthetized rats. In pre and post-menopausal women changes in forearm muscle oxygenation and muscle sympathetic nerve activity

60 Menopause

will be measured during lower body negative pressure (LBNP) at rest and the responses will be compared to LBNP performed during rhythmic handgrip exercise. Studies will be performed when estrogen levels are high and again when estrogen concentrations are reduced to determine the impact of estrogen on sympathetically mediated vasoconstriction. In rats, the effect of lumbar sympathetic nerve stimulation on femoral blood flow and hind limb muscle oxygenation will be examined in resting and contracting hind limb of ovariectomized and sham rats. Further studies will examine influences of estrogen levels on neuronal nitric oxide synthase expression in skeletal muscle to determine its possible role in mediating a beneficial effect of estrogen on peripheral hemodynamics during muscle contraction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ESTROGEN DEFICIENCY AND RENAL DISEASE IN AGING WOMEN Principal Investigator & Institution: Striker, Liliane J. Professor; Medicine; University of Miami Box 016159 Miami, FL 33101 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2003 Summary: The incidence of endstage renal disease due to glomerulosclerosis rises with aging in women, especially in minority populations. Women are relatively protected prior to menopause (F/M ratio =0.5), but after menopause this protection is lost (F/M ratio=1.0). Based on these data, we propose that estrogen deficiency after menopause is an important contributor to the development of progressive glomerulosclerosis, particularly in minority women. Glomerulosclerosis, defined as an excess deposition of extracellular matrix, is due to increased matrix synthesis and/or decreased degradation. Matrix metalloproteinases decrease deposition of matrix in vitro, and are linked to decreased glomerulosclerosis in vivo. We will use in vivo and in vitro mouse models of glomerulosclerosis, and human mesangial cell lines developed in our laboratory, as models of the kidney disease in majority (sclerosis-resistant) and minority (sclerosisprone) women. We recently found that mesangial cells, the major source of sclerotic tissue in glomeruli, express estrogen receptors and that estrogen increases matrix metalloproteinase-2 (MMP-2) activity. We have additional preliminary data showing that the MMP-2 response to estrogen supplementation is blunted in sclerosis-prone mice. These data linking matrix turnover and estrogen response lead us to propose that estrogen retards glomerulosclerosis due, in part, to its stimulatory effect on matrix metalloproteinase-2 activity. A corollary proposal is that appropriate estrogen replacement would decrease the incidence of endstage renal disease in postmenopausal women. These proposals will be tested by identifying and characterizing estrogen receptor subtypes (ERalpha and ERbeta) and receptor activity in mesangial cells from women and sclerosis-prone and sclerosis-resistant mice, using a reporter construct under the transcriptional control of an estrogen responsive element. Mesangial cell MMP expression will be studied under conditions of estrogen deficiency, supplementation and antiestrogen treatment. The response to estrogen of cis-acting elements in the MMP-2 promoter will be studied in mesangial cells using MMP-2 promoter constructs. In addition, glomerular lesions and glomerular MMPs and collagen mRNA levels will be studied in ovariectomized mice in the presence of estrogen deficiency or supplementation and antiestrogen treatment. These data will provide data as to whether estrogen retards the progression of glomerulosclerosis in postmenopausal women. It may also provide tools to evaluate replacement therapy by estrogen analogues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN DEPENDENCY OF UTERINE LEIOMYOMA Principal Investigator & Institution: Al-Hendy, Ayman; Obstetrics and Gynecology; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2003; Project Start 24-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Uterine leiomyoma arise from the uterine smooth muscle compartment (myometrium) and are the most common gynecologic tumor in premenopausal women, occurring in up to 77% of all women. They are all significant cause of pelvic pain, menorrhagia, infertility, and pregnancy-related complications. These estrogen-dependent tumors are the leading indication for hysterectomy in reproductive age women. Currently, no medicinal therapy exists. Prolonged use of GnRH agonists, which can shrink tumors but induce a chemical menopause, is restricted due to serious side effects. The hormone-dependent phenotype of uterine leiomyoma suggests that interventions targeting the estrogen receptor (ER)-signaling pathway may have therapeutic efficacy. Proof-of-principal experiments have now established that treatment with anti-estrogen medications (e.g., tamoxifen and raloxifene) can significantly reduce tumor incidence, size, and proliferative index in the Eker rat, the only animal model known to acquire spontaneous uterine leiomyoma. Adenovirus-mediated delivery of a mutated dominant-negative ER (Ad-ER-DN) inhibited cell proliferation and induced apoptosis in human and rat leiomyoma cell lines. In a pilot experiment, Ad-ER-DN injected directly intratumor in nude mice with pre- existing fibroids induced immediate arrest and regression of tumor growth due to extensive apoptosis. explants in nude In this project, we will (Specific Aim 1) determine if Ad-ER-DN transduction inhibits endogenous ER signaling in estrogen-responsive rat and human leiomyoma cells, (Specific Aim 2) expand pilot results and evaluate the ability of Ad-ER-DN to ablate pre-established subcutaneous leiomyoma mice, and (Specific lira 3) conduct a pre-clinical trial to assess the ability of Ad-ER-DN to ablate uterine leiomyoma when delivered by direct intratumor injection in the immunecompetent Eker rat. Tumor response will be correlated to proliferative and apoptotic indices, to markers of tumor angiogenesis, and to several estrogen-regulated genes. We will examine immune response and the safety of single vs. repeated recombinant adenovirus treatment alone or in combination with SERM (Raloxifene). Evident therapeutic potential aside, this project will add to our understanding of the molecular mechanisms of estrogen-dependence in this common uterine tumor. It will also show, in a well-characterized natural rat model, the effects of specific perturbing of ER signaling on several cellular functions (i.e., angiogenesis, apoptosis, and cell cycle). This knowledge will impact many other estrogen-related conditions (e.g., breast and endometrial cancer, cardiovascular disease, osteoporosis). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN EFFECTS ON CHOLINERGIC FUNCTION IN OLDER WOMEN Principal Investigator & Institution: Newhouse, Paul A. Professor; Psychiatry; University of Vermont & St Agric College 340 Waterman Building Burlington, VT 05405 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The primary goal of this proposal is to examine in detail the effects of estrogen, estrogen antagonists, and progesterone on cognitive functions that are affected by cholinergic systems of the brain in postmenopausal women. These systems have critical relevance for the development of age-related cognitive and behavioral changes as well as the symptoms of dementing disorders such

62 Menopause

as Alzheimer's disease. Changes in estrogen levels after surgical and natural menopause are associated with negative changes in cognitive and behavioral functioning, which are preventable by estrogen administration. Administration of estrogen after menopause is associated with a lower risk of Alzheimer's disease. Specifically, these studies will examine the effects of estrogen and related gonadal steroids on the cholinergic system of the human brain that is thought to be critical for attention, learning, memory, and psychomotor performance. These studies will utilize a well-established method for probing the integrity of central cholinergic mechanisms utilizing cholinergic (muscarinic and nicotinic) antagonists. Preliminary data suggest that short-term administration of estrogen partially protects women from the negative cognitive effects of cholinergic antagonists. This effect could be mediated by trophic effects of estrogen on central cholinergic neurons. Estrogen has a substantial effect on the expression and activity of trophic factors such as Nerve Growth Factor (NGF) and its receptors, thereby directly producing neuroprotective and trophic effects. Estrogen also appears to have signaltransduction modulating properties. These effects are observed particularly in cholinergic neurons of the basal forebrain. However, women are now often taking agents, which may antagonize or modify estrogen effects such as the gonadal steroid progesterone and the anti-estrogen tamoxifen. Studies in this proposal will examine the acute vs. chronic effects of estrogen on anti-cholinergic induced cognitive changes, effects of combined estrogen-progesterone treatment on cholinergic integrity, and the effects of the estrogen antagonist tamoxifen on the cholinergic system. These studies will provide knowledge regarding the magnitude and type of effects of estrogen on cholinergic system integrity and will contribute to an understanding of the potential use of estrogen in late life for maintenance of cognitive functioning during normal aging and the prevention and/or treatment of age-related cognitive disorders such as mild cognitive impairment and Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ESTROGEN EFFECTS ON GROWTH HORMONE RELEASE Principal Investigator & Institution: Blank, Margot; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN ENHANCEMENT OF ENDOTHELIAL VASODILATORY FACTORS Principal Investigator & Institution: Rahimian, Roshanak; Physiology and Pharmacology; University of the Pacific-Stockton 3601 Pacific Ave Stockton, CA 95211 Timing: Fiscal Year 2003; Project Start 16-DEC-2002; Project End 30-NOV-2005 Summary: (provided by applicant): The risk of myocardial infarction and stroke increases dramatically in women after menopause. Loss of endogenous estrogen associated with menopause contributes to this increased cardiovascular risk. An important, recently established vasoprotective function of estrogen is enhancement of endothelial nitric oxide (NO) secretion which promotes vasodilation and antagonizes thrombosis. NO secreted by the endothelium is regulated through Ca2+ activation of endothelial NO synthase (eNOS). The objective of my research is to elucidate the cellular and molecular mechanisms whereby estrogen and raloxifene, a selective estrogen receptor modulator, enhance release of endothelial vasodilatory factors (EDRF)

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including NO, prostacyclin (PGI2), and endothelium-dependent hyperpolarizing factors (EDHF). I propose that after estrogen and raloxifene bind to their receptors, they alter gene expression and/or ion transport mechanisms raising [Ca2+]i through enhanced Ca2+ influx and/or decreased Ca2+ extrusion in endothelial cells. Aims: I will test which combination of the plausible target molecules (e.g., eNOS, EDHF) are affected by estrogen and raloxifene treatment. In addition, I will evaluate whether activation of nongenomic receptors by physiologically relevant concentrations of estrogen modulates calcium-dependent eNOS in endothelial cells. The knowledge gained is expected to provide new insight into the role of estrogen and raloxifene therapy in cardiovascular protection. Experiments will be performed in intact valvular endothelium and aortic rings taken from different groups of rats as well as in endothelial cells derived from human umbilical veins (HUVECs). EDRF release will be measured using Bioassay. Bioassay allows us to identify the nature of EDRF and its cellular action(s) in our preparation. The role of intracellular Ca2+ in stimulation of EDRF secretion will be determined using ratiometric fura- 2 fluorimetry. The extent of altered gene expression will be assessed by RT-PCR, Western blots, and immunohistochemistry. Understanding the mechanisms underlying the cardioprotective action of estrogen is expected to contribute significantly to the development of new therapeutic strategies, whereby the beneficial cardioprotective effects of synthetic estrogen analogues might be separated from the undesirable components of estrogen activity. The enhanced insight into these protective mechanisms is expected to eventually also be beneficial for the male population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ESTROGEN INFLUENCES ON NEUROENDOCRINE AGING Principal Investigator & Institution: Gore, Andrea C.; Mount Sinai School of Medicine of Cuny New York, NY 10029 Timing: Fiscal Year 2001 Summary: Reproductive aging is characterized by changes in estrogen levels; however, the brain itself is subject to age-related changes, some of which may be consequences of altered estrogen levels, and others which may be estrogen-independent. Therefore, the present proposal will examine the interactions of estrogen with hypothalamic neurons in the brain during reproductive senescence. Studies will focus on estrogen regulation of gonadotropin-releasing hormone (GnRH) neurons, the key cells regulating the reproductive axis, as well as the mediation of estrogen's effects on GnRH neurons by glutamatergic neurons, acting via the NMDA receptor. In order to better characterize effects of estrogen and hypothalamic aging, as well as their interactions, studies will be performed in the experimental model of ovariectomy (OVX), with or without estrogen replacement, as well as the natural model of ovarian- intact animals, at different stages of reproductive function and endogenous estrogen levels. Specific Aims 1 and 2 will investigate mechanisms for estrogen's effects on hypothalamic function during aging in young, middle-aged (MA) and old Sprague-Dawley OVX rats, given long-term or shortterm estrogen or vehicle replacement (Aim 1) or in ovarian-intact young, MA and old rats during the estrous cycle (Aim 2). For Aim 2, animals are utilized on pro-estrus the day of the pre-ovulatory GnRH/LH surge, with high estrogen levels, or on diestrus I, a day of low estrogen levels. Acyclic rats will be utilized on persistent estrus (high estrogen) or persistent estrus (high estrogen) or persistent diestrus (low estrogen). In both of these aims, effects of estrogen on GnRH and NMDA receptor subunit mRNAs and proteins will be quantitated by RNase protection assay and Western blots, respectively. The localization of NMDA receptor subunits on GnRH neurons, and their

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regulation by estrogen and aging, will be determined. The responsiveness of the GnRH neurosecretory system to administration of an NMDA receptor agonist will also be assessed. Specific Aims 3 and 4 will investigate the physiological changes in estrogen regulation of hypothalamic neurons, using the rhesus monkey, with its 28 day menstrual cycle, as an experimental model. Aim 3 will examine changes in hypothalamic GnRH and glutamate release and the regulation of GnRH release by NMDA receptor activation in OVX young and old monkeys, with or without long-term or short-term estrogen replacement. Aim 4 will make similar measurements in ovarianintact young and old rhesus monkeys across the natural menstrual cycle during periods of high estrogen (late follicular phase) or low estrogen (late luteal phase); comparisons will be made with amenorrheic aged monkeys. Experiments are anticipated to provide insight into the neurobiological effects of an estrogen deficiency at menopause. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ESTROGEN REGULATED GENES AND NEURAL PROTECTION Principal Investigator & Institution: Sisk, Cheryl L. Professor; Microbiology and Public Health; Michigan State University 301 Administration Bldg East Lansing, MI 48824 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2002 Summary: Epidemiological studies indicate 6that estrogen hormone replacement therapy in postmenopausal women reduces the risk of Alzheimer's Disease. One mechanisms by which estrogen may reduce risk of Alzheimer's Disease is inhibition of beta-amyloid plaque formation and ensuing cell death in hippocampus and cortex, which are among the most severely affected brain regions in Alzheimer's Disease. Using cDNA array assays to screen for estrogen-regulated genes in a mouse model of menopause, three genes were identified that are both regulated by estrogen in the hippocampus and frontal cortex and are known to be involved in amyloid precursor protein (APP) processing, plaque formation, and apoptosis. These genes encode transthyretin precursor (TTR), presenilin 1 (PS1), and presenilin 2 (PS2). Presenilins promote neural degeneration by cleaving APP into plaque-forming beta-amyloid peptide fragments (Abeta42) and inducing apoptosis. In contrast, TTR impedes plaque formation by sequestering Abeta42. The cDNA array data suggest two novel mechanisms for neural protection by estrogen: 1) inhibition of PS1 and PS2 gene expression, and 2) stimulation of TTR gene expression. The goal of the proposed project is to confirm and extend the findings based on cDNA arrays. The Specific Aims are to 1) confirm and precisely quantify estrogen regulation of TTR, PS1, and PS2 mRNA and protein are regulated by estrogen using in situ hybridization histochemistry and immunocytochemistry. The proposed studies employed a newly developed in vivo mouse model of menopause in which tissue responses to estrogen are assessed and compared when hormone replacement therapy is begin in either early or late menopause. The long-term goal of this work is to contribute to the development of hormone replacement strategies for post-menopausal women that are optimally effective in delaying or preventing the progression of Alzheimer's Disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN, INSULIN AND REGIONAL LIPOLYSIS IN OLDER WOMEN Principal Investigator & Institution: Van Pelt, Rachael E. Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2007

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Summary: (provided by applicant): As women gain weight after the menopause fat is preferentially deposited in the abdominal, and particularly the intra- abdominal region. Risk of metabolic and cardiovascular disease also increases non-linearly after the menopause. The central theme of this research project is the study of the role of intraabdominal fat (IAF) and estrogen in the regulation of whole body and regional adipose tissue lipolysis in women. Three specific aims will address the following hypotheses in postmenopausal women: 1) IAF volume is associated with resistance to insulin suppression of lipolysis in whole body and regional adipose tissue, 2) regular use of estrogen attenuates this resistance to insulin suppression of lipolysis, and 3) a reduction in IAF will enhance the antilipolytic action of insulin. The applicant, Rachael E. Van Pelt, PhD, is currently supported by an individual NRSA from NHLBI and has demonstrated a consistent focus and record of research productivity in the study of age-, exercise-, and hormone-related changes in body composition, metabolism and cardiovascular disease risk. Her career goal is to become an independent scientist and to develop an extramurally-funded research program to continue her focus in gerontologic research. The K01 Mentored Research Scientist Development Award would provide Dr. Van Pelt protected research time to obtain the additional research skills and experience necessary to achieve this goal. In addition to addressing the specific aims of the proposal, an important goal of her training is to learn the technically challenging micro dialysis and hyperinsulinemic, euglycemic clamp procedures, and to acquire further experience in basic bench work and stable isotope kinetics. During the award period Dr. Van Pelt will take courses through the Certificate Program in Clinical Science in the School of Medicine. She will also attend and participate in weekly research seminars, journal clubs and grand rounds, as well as relevant annual scientific meetings. Dr. Van Pelt's sponsor, Wendy M. Kohrt, PhD, is an established investigator and mentor in aging research and has a well-funded laboratory in the division of Geriatric Medicine at the University of Colorado Health Sciences Center. She and the department will provide Dr. Van Pelt the rich learning environment, resources, and technical guidance necessary to successfully complete her training and career development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ESTROGENS DIFFERENTIATION

AND

OSTEOCLAST

RECRUITMENT

AND

Principal Investigator & Institution: Pike, J. Wesley. Professor; Biochemistry; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from the Investigator's Abstract): Loss of ovarian function following menopause results in a substantial increase in bone turnover and a critical imbalance between bone formation and resorption. This imbalance leads to progressive loss of trabecular bone mass and significantly increases the risk of atraumatic fracture during the aging process. Estrogen (E) treatment prevents bone loss following the menopause. The cellular targets of E action in bone include differentiated osteoblasts and osteoclasts as well as their bone marrow-derived respective mesenchymal and hematopoietic cell precursors. In this application the Principal Investigator proposes to examine the stromal cell-independent actions of estrogen to repress both lineage progression and osteoclast differentiation. In Specific Aim 1, the investigators will focus on E action in myeloid/lymphoid lineage progression, an effect that limits pools of cells capable of either becoming osteoclasts or of modulating osteoclastogenesis. They will characterize the anti-proliferative, pro-apoptotic effects of E on IL-3 and GM-CSF dependent proliferation of lymphoid and myeloid cells. They will utilize transcriptional

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responses to determine the nature of the signaling pathways that are E repression targets and identify the transcription factors involved. They will also assess the mechanisms by which ER mediates repression by defining the ER repression domains, determining the site of intervention within the activation pathway and assessing the nature of the molecular interactions that occur. Finally they will evaluate the actions of raloxifene and tamoxifen in this system. In Specific Aim 2, studies will focus on E action during osteoclast differentiation, examining E anti-differentiative, pro-apoptotic effects in primary murine cells and in M-CSF/RANKL dependent OC cell models. They will determine which components of the RANKL signaling pathway represent targets of E action using selected transcriptional responses and then identify the transcription factors involved. They will characterize the mechanism of repression by determining whether E intervention is proximal to or distal to transcription and then define the molecular interaction. As in Specific Aim 1, the activity of SERMs in osteoclast differentiation will be evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EXERCISE & SLEEP: A CLINICAL TRIAL IN MENOPAUSAL WOMEN Principal Investigator & Institution: Davis, Jean E. Center for Health Research; Wayne State University 656 W. Kirby Detroit, MI 48202 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 30-JUN-2006 Summary: (provided by applicant): An estimated 80 percent of the approximately 50 million postmenopausal women in the United States have complaints of disrupted sleep patterns characterized by sleep loss. Several studies show that a relative lack of estrogen interferes with optimal sleep and exogenous estrogen replacement improves sleep maintenance. However, it has been reported that less than 15 percent of postmenopausal women use estrogen replacement therapy. A growing body of evidence demonstrates that exercise improves self-reported sleep quality in postmenopausal women. The longrange goal of this research is to develop an exercise prescription that will improve the sleep of postmenopausal women. The specific objective of this research application is to determine the effects of a moderate intensity, home-based exercises program on objective sleep parameters, self-reported sleep quality, and daytime sleepiness. The central hypothesis is that a regular exercise program will improve the sleep architecture and sleep continuity patterns, subjective sleep quality, and daytime sleepiness in estrogen-deficient postmenopausal women. Employing an experimental, repeated measures, randomized treatment control group design, forty postmenopausal women who are estrogen deficient, sedentary, and have a sleep maintenance disorder will be randomly assigned to one of two conditions; an exercise group or a control group. The exercise will be home-based, moderate intensity walking with a frequency of 5 times per week and a duration of 30 minutes per session. Measurements of sleep architecture, sleep continuity, sleep quality and daytime sleepiness will be obtained at baseline and after the 16-week exercise or non-exercise period. Data on potential mediating variables of estradiol and circadian core body temperature rhythm will also be collected. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FEMALE HYPERTENSION

GENDER

&

EXPRESSION

OF

RISK

GENES

IN

Principal Investigator & Institution: Seely, Ellen W. Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-FEB-1996; Project End 31-JAN-2006

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Summary: (Adapted from the applicant's abstract) Hypertension is a major contributor to cardiovascular disease, the leading cause of death in US women. Most studies of hypertension have focused on men. Women have a lower incidence of hypertension until age 50 at which time, the incidence of hypertension in women becomes greater than that in men. Since age 50 is the average age of menopause in US women, this observation suggests that ovarian steroids, present in the premenopausal state, mask genetic predisposition to hypertension and that with loss of these steroids at menopause, genetic predisposition to hypertension becomes manifest. Earlier studies by these workers have shown that a specific intermediate phenotype of essential hypertension is associated with polymorphism of the angiotensinogen gene which result in greater tissue activity of the renin-angiotensin- aldosterone system (RAAS) as a possible cause of hypertension. This phenotype is uncommon in premenopausal Caucasian women compared to age-matched men but the frequency of this phenotype increased at menopause becoming equal in men and women. Estradiol has major effects on many of the genes of the RAAS and therefore is a prime candidate for modulating the expression of genotype and being responsible for the change in phenotype frequency in pre- versus postmenopausal women. The overall objectives of this proposal are to: 1) demonstrate a difference in frequency of specific polymorphism of genes of the RAAS in premenopausal hypertensive women as compare to hypertensive postmenopausal women and men, 2) test the hypothesis that the administration of estrasiol to postmenopausal hypertensive women with these specific polymorphism in RAAS genes will alter the intermediate phenotype and lower blood pressure, and 3) examine activity of the tissue RAAS according to specific genotypes in these three groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: FEMALE REPRODUCTIVE OUTCOMES AND TCDD EXPOSURE Principal Investigator & Institution: Eskenazi, Brenda; Professor; None; University of California Berkeley Berkeley, CA 94720 Timing: Fiscal Year 2001; Project Start 01-JAN-1996; Project End 30-APR-2002 Summary: (Adapted from applicant's abstract): The proposed project is a continuation of the Seveso Women's Health Study (SWHS), ongoing since 1996 (R01ES07171). The original purpose of the SWHS was to investigate the relationship of 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and endometriosis in a nested casecontrol study embedded in a cohort of women exposed to extremely high levels of dioxin as a result of a chemical plant explosion in 1976 in Seveso, Italy. In order to identify cases and controls, the cohort of women aged 0 to 40 years at the time of accident, and who lived in Zone A (n=234) or Zone B (n=1,039) were interviewed extensively about their reproductive and pregnancy histories. Assessments included a blood draw, a pelvic examination, and transvaginal ultrasound. Participants were also asked to complete a menstrual diary. A unique strength of the study is that individual body burden TCDD levels can be measured in sera collected soon after the accident. More than 95% of the women were located twenty years after the accident and roughly 80% of the members of the cohort have participated. The current plan is to analyze the data collected in the SWHS to examine reproductive endpoints other than endometriosis, and to analyze the sera for TCDD necessary to examine these endpoints. In particular, the project will investigate the relationship of TCDD levels in sera with menstrual cycle characteristics (e.g. cycle length and flow), age of menarche, fetal loss, birthweight, clinical infertility, time to conception, and age at menopause. These endpoints were chosen, based on extensive rodent and rhesus monkey data, indicating

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that exposed animals experience higher rates of fetal mortality and resorption, smaller litter size, lower birthweight, lowered fecundity rates and, more recently, menstrual irregularities, reduced ovulation, delayed onset of puberty, and early onset of menopause. It is because of these animal data that the U.S. Environmental Protection Agency (EPA) is reassessing the allowable exposure levels of TCDD, which is ubiquitous in industrialized areas. There are also concerns that the non-cancer effects of this chemical may be the even more urgent threat to humans. The proposed investigation will be the first comprehensive reproductive health study conducted in human populations exposed to TCDD. If the findings in this highly exposed cohort with well-characterized individual exposure data do not confirm the animal findings, there can be less concern about human health effects, thereby having important policy implications for the regulation of TCDD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: FRET-BASED MODULATORS

HTS

ASSAY

FOR

ESTROGEN

RECEPTOR

Principal Investigator & Institution: De, Siddhartha; Luna Innovations, Inc. 2851 Commerce St Blacksburg, VA 24060 Timing: Fiscal Year 2003; Project Start 15-JAN-2003; Project End 31-JUL-2003 Summary: (provided by applicant): Hormone replacement therapy has been used for many years to delay or treat the changes that accompany menopause. However, epidemiologic and clinical research has revealed significant long-term risks and unintended side effects. Selective estrogen receptor modulator (SERM) were developed mimic the advantageous properties of estrogens without the negative side effects. Knowledge of SERMs, such as Tamoxifen and Raloxifene, has led to the development of novel drugs to treat a variety of conditions. While the success of these early SERMs is encouraging, their application is still limited and many still result in negative side effects. The critical task now presented to researchers and the pharmaceutical industry is the identification of more specific compounds with more important therapeutic applications while maximizing the risk/benefit ratio. To revolutionize this process, the Luna team proposes to develop a fluorescence resonance energy transfer (FRET)-based high throughput screening (HTS) assay for SERMs. The critical advantage of the proposed assay is direct detection with minimal false positives. Direct detection not only result in lower cost and greater efficiency in screening of new SERMs, it also presents the capability for detecting new SERMs not previously identified due to the nature of the competitive assays that are currently used. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: FUNCTIONALLY BASED TREATMENT OF STRESS INCONTINENCE Principal Investigator & Institution: Borello-France, Diane F.; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001 Summary: The long-term efficacy of pelvic floor exercise (PFE) as a treatment for urinary incontinence is threatened by patient compliance. To enhance compliance, PFE needs to be effective, while reducing the time burden placed on the patient. Our longterm objectives are to 1) validate a physiologically based, task-specific approach to PFE and 2) determine the exercise frequency needed to preserve muscle strength. Our specific aims are to determine: 1) the effectiveness of an individualized, physiologically based PFE regimen, 2) if a treatment progression to include exercise in upright postures

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is more effective than one performed in a lying position, and 3) if a low frequency exercise program is sufficient to preserve therapeutic gains over a six-month period. We will study 50 women, ages 40-70, with genuine stress incontinence. Based on symptom severity, we will randomly assign subjects to perform exercise either in upright postures or in a lying position. Subjects will attend 12 weekly physical therapy (PT) visits and perform a home exercise program (HEP) consisting of muscle strength, power, and endurance exercise. Using electromyography (an electrical recording of muscle activity), we will determine exercise progression using a protocol that individualizes exercise prescription based on muscle fatigue. At each weekly assessment, we will adjust the subject's HEP accordingly. Subjects assigned to the upright training group will perform one third of their exercises in the supine, sitting and standing positions. The other group will perform all exercises while in a lying position. At week 12, we will randomly assign subjects in each treatment group to either a low-(exercise once a week) or high-(exercises every other day) maintenance group. To determine treatment outcomes, we will compare group differences in the number of incontinent episodes, amount of urine lost during a psd test, a measure of urethral resistance (Valsalva leak point pressure), and scores on a quality of life measure. To determine the overall effectiveness of the treatment protocol, we will compare pre-to post-treatment changes in incontinent episodes to similar data reported in the literature. We will also examine the relationships between menopausal status, incontinence severity, and treatment outcomes. The results of this study may lead to a more effective exercise approach. Thus, future clients may benefit from fewer PT visits, greater pelvic muscle functions, and avoidance of surgery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GENDER AND MENOPAUSE ON NUTRIENT AND ENERGY METABOLISM Principal Investigator & Institution: Horton, Tracy J. Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 28-FEB-2004 Summary: The overall aim of the P.I.'s research is to better understand gender differences in energy and nutrient metabolism that related to the development and/or protection against disease. The health risks associated with a number of diseases including obesity and coronary heart disease are different between males and females. Knowledge of gender differences in energy and nutrient metabolism are required to fully understand the metabolic basis of these diseases. Studies in this proposal will begin to determine gender specific aspects of energy and nutrient metabolism and how these change at menopause. Specific aim number 1 will be to determine the sources of carbohydrate and lipid fuels utilized during exercise in males and females. This will be determined using indirect calorimetry and stable isotope techniques and muscle biopsies. Specific aim number 2 will be to determine the lipolytic response to catecholamines in males and females by using the pancreatic clamp technique in conjunction with catecholamine infusions and stable isotope measurements. Specific aim number 3 will be to determine whether males and females differ in their ability to remove exogenous lipid from the circulation and whether there are gender differences in the ability of insulin to suppress endogenous very-low density lipoprotein triglyceride (VLDL-TG) production. Triglyceride removal will be assessed in response to an intravenous fat tolerance test. Relative changes in VLDL-TG production will be measured following the radioactive labeling of VLDL-TG and measurement of VLDLTG kinetics under basal and hyperinsulinemic/euglycemic conditions. Specific aim

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number 4 will be to determine the effect of menopause and hormone replacement therapy on energy expenditure and resting substrate utilization. Free-living energy expenditure will be measured using the doubly labelled water technique and substrate utilization will be assessed using indirect calorimetry and stable isotope techniques. These studies will further our understanding of the metabolic basis for disease risk in males and females. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GENDER EFFECTS ON HIV BIOLOGY Principal Investigator & Institution: Greene, Warner C. Director; J. David Gladstone Institutes 365 Vermont St San Francisco, CA 94103 Timing: Fiscal Year 2001; Project Start 23-APR-2001; Project End 31-MAR-2006 Summary: (Abstract Provided by Applicant) In response to RFA HD-OO-006, "Women's HIV Pathogenesis Program", we propose a multidisciplinary program comprised of four interactive research projects and three supporting cores that thematically seeks to explore biological aspects of HIV infection and pathogenesis that are unique to women. Project I, led by Warner Greene, will study the molecular and cellular basis for HIV infection in the female genital tract using a cervical-vaginal organ culture model coupled with the use of fluorescently labeled virions to monitor the cellular targets and evolution of infection within this mucosal tissue. This project will also investigate the potential function of HIV Vpr as a transcriptional coactivator of the estrogen and progesterone nuclear hormone receptors and study the biological consequences of such a virus-host transcription factor interplay on HIV gene expression. Project II, led by Robert Grant, will explore whether the viral quasi-species present in the female genital tract of HIV infected women differs from that simultaneously circulating in the blood both prior to and after the administration of potent antiviral therapy. Other studies will assess potential defects in the ability of protease inhibitor resistant viruses to infect macrophages and dendritic cells. Project III, led by Marc Hellerstein, will examine the influence of sex hormones on T-helper cell turnover measured by a combination of flow based cell isolation and mass spectroscopy following deuterated glucose or 2H20 labeling in vivo. These studies will involve the analysis of hypogonadal women and men, postmenopausal women before and after estrogen replacement therapy, and children before and after puberty. Project IV, led by Leslie Benet, will determine the effect of hormonal changes occurring within the ovulatory cycle, during menopause, and after estrogen replacement on P-glycoprotein exporter and cytochrome p450 3A enzyme expression and functional activity. Changes in these two proteins will be monitored in the intestine, endometrium and PBMCs. This project will also assess how changes in these proteins may affect the response to HIV protease inhibitors that are all substrates for both proteins. Core A, led by Ruth Greenblatt. will provide clinical coordination of these projects, including recruitment, study visits, participant tracking and compensation. Core B, led by Robert Taylor, will provide reproductive endocrinology consultation, gonadal function assessments and ovulatory cycle staging, and tissue collection. Core C led by Warner Greene will provide overall scientific leadership, data entry and biostatistical analysis for all projects, and administrative support coupled with fiscally sound budget management. Together, these projects and cores combine to form a program that promises to yield new insights into the unique features that underlie gender specific differences in HIV infection and pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENDER-BASED OUTCOME DIFFERENCES IN NOSOCOMIAL PNEUMONIA Principal Investigator & Institution: Evans, Heather L. Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2002; Project Start 01-SEP-2002 Summary: (provided by applicant): Controversy exists regarding the effect of gender on differences in surgical infectious disease outcomes. Previously, our laboratory reported that the gender-based difference in mortality was greatest among critically ill patients who developed nosocomial pneumonia. Therefore, the proposed prospective, observational cohort study will concentrate on these hospital-acquired infections, stratifying patients not only by gender, but also by estrogen-status. Based on evidence that women who develop nosocomial pneumonia are at higher risk for death, especially if they are elderly, we hypothesize that estrogen-rich pre-menopausal women will be least likely to develop nosocomial pneumonia, while post-menopausal women will have the highest mortality. Thus, we hope to confirm our earlier findings of the incidence and mortality related to nosocomial pneumonia, and to further evaluate three areas of potential gender differences to account for the disparate outcomes: diagnosis, treatment and immune response. We believe that these areas are not only influenced by sex-based biologic and physiologic features, but also social factors. In the future, these data may lead to methods that facilitate either prevention, or earlier diagnosis and more efficacious treatment of nosocomial pneumonia, a disease which accounts for a substantial proportion of the lethal infections in surgical patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE-ENVIRONMENT INTERACTION IN COMPLEX DISEASE Principal Investigator & Institution: Bray, Molly M. Assistant Professor; Human Genetics Center; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2003; Project Start 05-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Cardiovascular disease (CVD), the number one cause of death in industrialized countries today is a complex disease with a multifactorial etiology involving many genetic and environmental factors. Public health prevention programs designed to reduce the risk and occurrence of CVD commonly focus on modifiable environments and behaviors such as diet and physical activity, with varied results among individuals. This heterogeneity in response to CVD interventions is at least in part of genetic origin. Although a number of candidate genes have been identified which appear to influence the development of CVD, little is known about how these genetic effects may vary within demographic (e.g., race and gender) and environmental (e.g., diet and exercise) contexts; thus, it is of utmost importance to determine how genes and environments interact to produce CVD. The purpose of this study is to characterize the environment-dependent effects of 87 biologic and positional candidate genes in a population-based sample of 11,625 African-American and Caucasian men and women from the Atherosclerosis Risk in Communities (ARIC) study. Candidate loci were selected based on confirmed functional significance, consistent association with CVD or its risk factors, and or identified as positional candidates in genome-wide linkage scans. Environmental contexts will focus on dietary measures (e.g., total kcals, Keys score, alcohol intake), obesity, measures of physical activity (sport, leisure, and work indices), smoking, and menopause status/hormone use (women only). Outcome variables will include measures of quantitative risk factors (e.g., total cholesterol, BMI, blood pressure), subclinical disease (carotid wall thickness),

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and clinical disease (incident CHD and stroke). Existing DNA samples will be used for genotyping of candidate loci, and no further contact with study participants will be necessary. The ARIC cohort, because of its large size and wealth of environmental and physiological measures, provides an ideal, timely, and efficient opportunity to evaluate the effects of modifiable environments on genetic variation which may influence CVD risk and disease outcomes with the ultimate goal of establishing more efficacious programs for the treatment and prevention of CVD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GENES AND CHEMICAL EXPOSURE ASSOCIATED WITH SLE RISK Principal Investigator & Institution: Fraser, Patricia A. Associate Professor; Cbr Institute for Biomedical Research 800 Huntington Ave Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 29-SEP-2003 Summary: Systemic lupus erythematosus (SLE) is an autoimmune, disabling, disfiguring systemic rheumatic disease that preferentially afflicts women and AfricanAmericans. The excess risk of SLE in African-Americans is not entirely explained by the genetic markers of susceptibility that have been identified to date. Sex hormones are immunomodulatory. During the interval between menarche and menopause women are exposed to significantly higher estrogen levels when compared to men of similar age. This gender difference in estrogen exposure may explain the gender imbalance in SLE risk. Similarly, African-Americans have higher levels of sex hormones than Caucasians. Genetic determinants of the observed ethnic differences in sex hormone levels may contribute to the ethnic differences in predisposition to SLE. Several polymorphic cytochrome P-450 genes encode enzymes in critical pathways of estrogen and androgen synthesis and degradation. Inter-relationships among these genes may be important genetic determinants of hormone levels that may also influence the hormonal effects on lupus susceptibility. Gene-hormone interactions affect hormone homeostasis of function and these, we hypothesize, can be affected by environmental agents. Through a variety of mechanisms, organochlorines in the environment such as 2,2bis(rho-chlorophenyl)-1,1,1- trichlorethane (DDT), and its long-lasting metabolite DDE may affect sex hormone homeostasis. We hypothesize that interactions of genes that affect sex hormone homeostasis and function (androgen receptor (AR) and estrogen receptors (ERs) and cytochrome P450 genes) with endogenous and/or exogenous estrogens and also with organochlorine exposures explain the gender and ethnic differences observed in SLE. The specific aims of this proposal are to: 1. Determine AR, ERs and cytochrome P450 genotypes in SLE subjects and controls by PCR based methodologies in a large SLE case/control study; 2. Determine the relative importance of genetic markers in Aim number 1 with endogenous and exogenous estrogens and with exposure to organochlorines in predicting risk of SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC & LIFE-STYLE FACTORS IN MENOPAUSAL BONE DENSITY Principal Investigator & Institution: Salamone, Loran M. Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 15-DEC-1997; Project End 30-NOV-2002 Summary: (Adapted from Investigator's Abstract) This is a revised submission of a FIRST Award. Bone mineral density (BMD) in later life is attributed to peak BMD attained in early adulthood and both menopause and age-related bone loss. There is

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compelling evidence to suggest that BMD and its subsequent loss are determined by a combination of genetic and environmental factors. The primary objective of this study is to gain a more comprehensive understanding of genetic and gene-environment interactions as correlates and determinants of BMD in a cohort of 535 healthy women (aged 44-50 years) enrolled in the NIH-funded Women's Healthy Lifestyle Project (WHLP; HL45167; Drs. Kuller and Wing, co-principal investigators). The study proposed will add two candidate genes for osteoporosis, the type I collagen gene and the estrogen receptor gene, using DNA isolated from the baseline examination. The second aim of this application is to examine the effect of a Lifestyle-Intervention aimed at weight loss across the menopause on BMD. The investigators will determine whether differences in BMD between Assessment and Intervention Groups can be explained by differences in markers of bone turnover, including serum osteocalcin and urinary Ntelopeptides. They state that this epidemiological study can improve our understanding of the individual variations in BMD and changes in BMD during the critical menopausal years, and the degree to which these differences are mediated by geneenvironment interactions. They further state that gaining insight into these mechanisms has important implications for effective prevention and more efficient identification of those individuals at the greatest risk of osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GENETIC EPIDEMIOLOGY OF BREAST CANCER--BRCA1 AND BRCA2 Principal Investigator & Institution: Neuhausen, Susan L. Professor; Medical Informatics; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 28-FEB-2003 Summary: (Adapted from the Investigator's Abstract) Many environmental, reproductive, and genetic factors have been associated with an increased risk of breast and ovarian cancers. A family history of breast cancer has been identified as a major risk factor for the development of the disease. A genetic predisposition likely accounts for 5 to 10 percent of breast cancer and ovarian cancer. Approximately 80 percent of inherited early onset breast cancer is attributed to the breast cancer genes, BRCA1 and BRCA2. Among families with the same BRCA1 (BRCA2) mutations, there are differences in agespecific penetrance, lifetime penetrance, proportions of breast and ovarian cancer, and risks of other cancers. This variability suggests there are environmental and genetic factors interacting with the BRCA1 and BRCA2 genes. The identification of predictors of phenotypic expression, not only in terms of type of cancer but also in modulating age at onset, has implications for screening and prevention strategies for women at significantly increased risk of breast and ovarian cancers due to the BRCA1 and BRCA2 genes. This is a proposal to examine the effects of reproductive and genetic factors which may modulate the incidence by age and overall incidence of breast and ovarian cancers in individuals with BRCA1 and BRCA2 mutations. The cohort is composed of Caucasian and African American BRCA1 and BRCA2 mutation carriers. We have already sampled 215 BRCA1 and 141 BRCA2 mutations carriers in our Utah kindreds and will continue to sample within these families to identify all mutation carriers. Little information is available regarding prevalence of BRCA1 and BRCA2 in African Americans, although for women less than 44 years of age, their incidence of breast cancer is higher than for Caucasians. With collaborators in Dallas and Chicago, we propose to contact African American families with a history of breast and/or ovarian cancer, to identify BRCA1 and BRCA2 mutations, and sample within those families to identify all mutations carriers. The cofactors to be examined in this cohort include ages

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at menarche and menopause, parity, age at first pregnancy, use of oral contraceptives, and hormone replacement therapy. The genetic factors to be investigated include the hRAS VNTR and carcinogen metabolizing genes GSTT1, GSTM1, CYP2D6, CYP1A1, and EPHX. Survival analysis models will be used to estimate cumulative incidence by age and overall incidence for breast and ovarian cancers stratified by the hormone, reproductive, and genetic factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GENETIC EPIDEMIOLOGY OF THE FMR1 GENE Principal Investigator & Institution: Sherman, Stephanie L. Professor of Human Genetics; Genetics; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2001; Project Start 05-MAY-1994; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract): The fragile X syndrome (FXS), a type of inherited mental retardation (MR), is due to the silencing of the FMR1 X-linked gene. In over 95 percent of the cases, the mutation is due to an expansion of an unstable CGG repeat sequence located in the 5' untranslated region of the gene. Once expanded to over 200 repeats, the FMR1 gene is hypermethylated and consequently no message is transcribed. In the previous grant, the investigators suggested that, in addition to this specific mutation and resulting MR, there may also be a phenotype associated with an increased number of CGG repeats, i.e., alleles with 41 to 100 repeats. Although not methylated, the mRNA of such FMR1 alleles may be altered or alter the binding properties of other proteins. Preliminary results suggest that an increased number of CGG repeats may influence an individual's cognitive and behavioral performance and, for females, affect the age at menopause. If confirmed, this gene may be one of the first clearly identified genes to affect cognitive and behavioral skills and will become one of the possible candidate genes that play a role in psychiatric and behavioral disorders. As the frequency of such FMR1 alleles is high in the population, about 3 percent, the impact on the population may be greater than that related to the mutation leading to the FXS. Moreover, a proportion of these high repeat alleles may be unstably inherited, although that proportion is unknown and factors that influence that instability are not fully understood. In this revised application, the researchers propose to survey a cross-section of the general population and FXS families to obtain a large sample of probands with high repeat alleles. First they will assess all probands with neuropsychological tests to confirm or refute the phenotype consequence of these alleles. Second, they will ascertain parents of probands and conduct a case control study to further examine the relationship between repeat number and the age at menopause in carriers with the high repeat alleles. Lastly, they will ascertain first degree relatives of probands to obtain an estimate of the proportion of unstable alleles in the general population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETICS & REGULATION OF HEPATIC LIPASE Principal Investigator & Institution: Deeb, Samir; Research Professor; Medicine; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: The long-term goals of this proposal are to define mechanisms of regulation of hepatic lipase (HL) levels and to determine how genetic variation at the HL gene locus modulates these levels under a variety of physiological and pathological states. HL plays a key role in lipoprotein metabolism by catalyzing the hydrolysis of triglycerides and phospholipids. A high level of HL is associated with two important

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metabolic risk factors for atherosclerosis: diminished concentrations of plasma high density lipoprotein cholesterol (HDL-C) and an increased prevalence of small, dense low density lipoprotein (LDL) particles. A significant proportion (20-30%) of the total variability in HL activity is explained by the common genetic variation in the regulatory sequences of the HL gene whereby, the variant form was observed to be associated with lower HL and higher HDL2 levels. Gender is another modulating factor since women have, on average, higher levels of HDL2 and lower levels of HL. The underlying hypotheses of this proposal are, first, that one or more of the observed regulatory sequence variants causes diminished HL gene expression which, in turn, results in increased HDL-C levels and expression is regulated by cholesterol and estrogens. Our preliminary in vitro studies indicate that sterols up-regulate and estrogens downregulate activity of the HL gene promoter, respectively. The specific aims are to: 1) Determine by association and linkage analysis whether the observed LIPC promoter variants underlie the observed interindividual variation in levels of hepatic lipase activity and HDL2 estrogens and sterols and assess the role of the regulatory sequence variants modulate the relationships between HL levels and gender, menopause status, estrogen replacement therapy and intra-abdominal fat deposits. The results of these studies will provide insights into the molecular genetic bases for interindividual variation in HL activity and the associated plasma lipoprotein profiles. This will open the door for novel pharmaceutical approaches that target modification of the lipoproteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEALTH AND MENOPAUSE IN HISPANIC WOMEN IN PUERTO RICO Principal Investigator & Institution: Romanguera, Josefina; University of Puerto Rico Med Sciences Medical Sciences Campus San Juan, PR 00936 Timing: Fiscal Year 2001 Summary: This proposal is for a two years cross-sectional study to monitor changes in health status during the midlife in Hispanic women living in Puerto Rico. With funding from this cross-sectional study, we propose to conduct preliminary analysis of crosssectional data to determine the average age at menopause and pattern of hysterectomy in Hispanic women in Puerto Rico. We will also estimate the prevalence of menopausal symptoms, hypertension, diabetes and osteoporosis by age in these women. The crosssectional data will come from a self- administered. questionnaire and a clinical visit offered to 300 female members of the Puerto Rican Teachers Association aged 35-80 years old, representative of six geographic sectors of Puerto Rico. We calculate to have 800 participants who will respond to the questionnaire and agree to participate in the study. The clinical exam will include measurement of blood pressure, height and weight, body composition by electrical impedance, and calcaneus DEXA to measure bone density as well as a blood draw. The blood sample will be used to measure lipids, blood glucose, glycosylated hemoglobin and follicle stimulating hormone. This study will be the first contemporary study of the health and functional status of Hispanic women living in Puerto Rico during the midlife and menopause It will have the advantage that it represents a specific Hispanic population. Most studies available to date include a diverse Spanish speaking population with different ethnic background such as Mexican, Cuban, Puerto Rican, etc. The study will include a mailed questionnaire and a clinical visit to this population in order to obtain estimates of annual disease incidence as well as to evaluate our ability to follow this population and estimate retention rates. These activities will permit us to determine the appropriate age

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groups to enroll, to determine the required sample size and make more accurate power calculations for a future longitudinal study. We will also develop the longitudinal questionnaire and manual of operations, will translate and pre-test scales which have not previously been used in this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HISTORY OF HORMONE REPLACEMENT THERAPY, 1960-2000 Principal Investigator & Institution: Watkins, Elizabeth S.; Individual Award--Watkins, Elizabeth Sie 6516 Northumberland St Pittsburgh, PA 15217 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The goal of this project is to produce the first sociocultural historical study of the changing rationales for prescribing hormone replacement therapy (HRT) for menopausal and post-menopausal women from the 1960s to the present. The resulting book will provide a historical perspective for contemporary debates about the health care and health policy implications of menopause, aging, and HRT. The study is driven by three main questions. 1) How and where do physicians and patients get their information about menopause, aging, and medical treatments? This project investigates the interactions among scientists, physicians, drug companies, government agencies, feminist health activists, the media, and the public in the construction, dissemination, and translation of medical information for midlife and older women. 2) In what ways have the phenomena of menopause and aging been both medicalized and de-medicalized? While menopause and its sequence, like other aspects of women's health (e.g., childbirth, birth control), have increasingly come under medical control in the 20th century, there has also been a parallel trend in recent decades to redefine menopause as a "natural" event. This project will analyze the differences and similarities between these two views and set them in the larger context of health policy making and the American pursuit of health. 3) What is the relationship between the medical treatment of menopause and cultural conceptions of aging? This project locates the use of HRT in the context of changing expectations and changing roles for older women in American society. Using historical methodologies to investigate the variety of actors engaged in disseminating information about menopause, aging, and medical treatment, this study will enrich our understanding of the practices, contexts, and meanings of aging and related health-care issues among American women. The primary product will be a book written for a broad audience, including historians, health policy makers, physicians, nurses, other health care providers, and the general public. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HOME VS CENTER-BASED WEIGHT LOSS & EXERCISE IN MENOPAUSE Principal Investigator & Institution: Dennis, Karen E. Nursing; University of Central Florida 4000 Central Florida Blvd Orlando, FL 32816 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Multi-faceted obesity treatment demonstrates the best weight loss (WL) outcomes, yet the most effective site and methods for treatment delivery and follow-up remain elusive. Compounding the persistent treatment enigmas, aging in women is associated with an increasingly sedentary lifestyle that reduces total daily energy expenditure, predisposing to obesity. Moreover, candidate genes that contribute to the heritability of body weight and body fat distribution also may influence the response to WL treatment. In a nation with an unrelenting epidemic of

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obesity, the need for treatment far exceeds the capacity of the health care system to provide care on an individual basis. The purpose of this study is to: 1) assess the effects of a multi-faceted HOME-versus CENTER-based WL program on WL, CVD risk factors, and psychosocial factors; 2) determine whether a multi-faceted HOME- or CENTERbased approach more effectively leads to sustained treatment enrollment; and 3) retrospectively determine whether women with one or more variants in selected obesity-energy expenditure or insulin-sensitivity candidate genes have different outcomes post-treatment and/or at follow-up than women without a genetic predisposition. Overweight or obese (BMI 25-40 kg/m2) women (n=100) at least one year postmenopausal but < 65 years of age will be randomized to receive CENTER- or HOME-based interventions for WL that include low intensity exercise (walking). All women will receive 2 weeks of orientation to CENTER or HOME programs onsite and have baseline data collected before 6-month CENTER or HOME-based programs begin. Evaluation will be in a stable diet and exercise status post intervention, and again after 6 months maintenance at CENTER or HOME. Multivariate analyses will be used to reduce error inflation from multiple comparisons, or Bonferonni corrections will be used when multivariate analyses are not possible. With its health promotion emphasis, nursing is an ideal discipline to conduct and translate research-based, lifestylemodification WL interventions into practice. WL interventions that postmenopausal women will accept and sustain are essential for promoting health and prevention disease during the period of major vulnerability in their lives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HORMONE REPLACEMENT AND RISK OF UTERINE FIBROID GROWTH Principal Investigator & Institution: Kjerulff, Kristen H. Epidemiology and Prev Medicine; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 07-APR-1997; Project End 31-DEC-2002 Summary: (Adapted from Applicant's Abstract). The disease of uterine fibroids is a common and significant public health problem, affecting women of all ages, racial backgrounds and socioeconomic levels. When women with fibroids reach the perimenopausal or postmenopausal periods, they face a troubling treatment dilemma. If they wish to preserve their uterus, they take an unknown risk of causing fibroid growth by taking HRT. On the other hand, the benefits of using HRT are substantial, particularly for women at risk for cardiovascular disease or osteoporosis. There are been little, if any, research done to examine the effect of HRT use on fibroid proliferation and growth among uterine fibroid patients. The proposed randomized, controlled, doubleblinded clinical trial will investigate the extent to which a commonly prescribed low dose, continuous estrogen-progestin HRT regimen stimulates fibroid growth and proliferation among black and white postmenopausal fibroid patients. Ultrasound assessments will be conducted for 300 postmenopausal fibroid patients at baseline, 6, 12 and 24 months, which will allow an examination of the extent to which fibroid growth occurs, and if so, whether growth continues or plateaus. The extent to which this HRT regimen affects menopause-related symptoms, fibroid-related symptoms and quality of life will also be examined. A risk-benefit analysis will be conducted, taking into account both uterine and non-uterine risks and benefits, based on the results of this study and reviews of other studies. The results of this study will be of significant value to a growing body of fibroid patients reaching the menopause and to the clinicians who treat these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REPLACEMENT THERAPY AND BREAST CANCER Principal Investigator & Institution: Paganini-Hill, Annlia; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001 Summary: Combination estrogen-progestogen therapy for postmenopausal women has become increasingly popular since the mid-1970s. Early on, clinicians widely believed that, in addition to reducing the risk of endometrial cancer associated with unopposed estrogen therapy, such therapy would reduce the risk of breast cancer. It was assumed that progestogens had an "anti-estrogen" effect on breast tissue comparable to that on the endometrium, with the results of a large prospective study of women receiving various modes of therapy widely quoted as supporting this view. However, the finding of an increased risk of breast cancer associated with combination oral contraceptive therapy given around the time of menopause and the observation that breast tissue mitotic activity peaks during the luteal phase of the menstrual cycle suggest estrogenprogestogen therapy may actually increase breast cancer risk in postmenopausal women. Experimental data support this notion, as does suggestive but inadequate data on use of progestogen-only contraceptives. One prospective epidemiologic study of combination therapy and breast cancer also suggests an increased risk but the number of cases was small. To determine the effect on breast cancer risk of combination estrogenprogestogen hormonal replacement therapy as well as of unopposed estrogen replacement therapy, we have been conducting a large case-control study. Preliminary analysis from 1355 cases and 884 controls indicate that unopposed estrogen therapy moderately increases breast cancer risk overall, but in a duration and dose-related fashion. The addition of a progestogen appears to enhance these estrogen-related effects and leads to a further increase in breast cancer risk. We wish to expand this study to address more adequately duration and latency effects, the possible interaction between use of hormone replacement therapy and other breast cancer risk factors, and to confidently assess differences in risk levels with use of combination versus unopposed replacement therapy. Breast cancer patients are English- or Spanish-speaking women aged 55 and over, of all races except Asian, born in 1923 or later, and identified by our population-based tumor registry over a six year period. Controls are individually matched to cases by age (+3 years), race and neighborhood of residence. A structured interview form supplemented by a comprehensive manual containing color photographs of all types of estrogen and progestogen pills is employed for the in-person interviews. Validation of hormone therapy is accomplished by a review of physician records. The 3000 case-control pairs to be interviewed will allow for the evaluation of the effects of estrogen and estrogen- progestogen therapy on breast cancer risk in the presence of possible confounding variables, such as age at and type of menopause and weight, and for testing for interactions between hormone therapy and other breast cancer risk factors, such as benign breast disease, and for careful evaluation of the effects of duration and latency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HRT DECISION SUPPORT FOR WOMEN WITH MOBILITY IMPAIRMENT Principal Investigator & Institution: Becker, Heather A. None; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, TX 78712 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2005

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Summary: (provided by applicant): Healthy People 2010, the American Nurses Association, and the American College of Physicians have all recommended that midlife women be counseled about the risks and benefits of hormone replacement therapy (HRT). Conflicting scientific evidence about long-term outcomes has made HRT use controversial. Menopausal women, however, cannot wait until the scientific evidence becomes more decisive to make this decision. In such an uncertain decision environment, nursing interventions are most needed to address the unsure and/or value sensitive nature of the risks and benefits associated with this decision (O'Connor, 1988). Women with mobility impairments face special challenges regarding HRT use. Because they enter menopause with decreased weight bearing and aerobic activity histories, they may be at greater risk for Osteoporosis and cardiovascular disease (Turk, Scandale, Rosenbaum, & Weber, 2001; Vandenakker & Glass, 2001). Women who experience temperature fluctuations as part of their disability may find the Vasomotor instability that can occur during menopause particularly troublesome. While HRT might be particularly beneficial to these women, they may also be at increased risk of thrombosis. Consequently, existing information about the risks and benefits associated with HRT use must be tailored to the special needs of this population. Previous research has indicated that, following use of a theoretically based decision support intervention, non-disabled women increased their HRT knowledge, congruence between personal values and choices, satisfaction with the decision, and decreased their decisional conflict (O'Connor, et al., 1998). The aim of this study is to test an adapted version of this intervention, designed to assist women with mobility impairments in making informed choices about HRT use. Two hundred mid-life women with mobility impairments will be randomly assigned either to a decision support intervention, which has been adapted to their special needs, or to a standard educational pamphlet. Multiple Analysis of Variance will be used to assess changes in decision outcomes from pre-intervention to immediate post-intervention and 6 months following the intervention. Findings from this study will assist nurses and other providers to counsel women with mobility impairments about key health care decisions during menopause. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HUNK AND PUNC FUNCTION IN MAMMARY EPITHELIAL BIOLOGY Principal Investigator & Institution: Chodosh, Lewis A. Associate Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 06-APR-2000; Project End 31-MAR-2005 Summary: The loss of growth control characteristic of carcinogenesis is uniformly accompanied by alterations in normal pathways of differentiation and development. This implies an intrinsic relationship between these processes. The existence of endocrine risk factors for breast cancer that are related to the timing of normal developmental events such as menarche, menopause and age at first full-term pregnancy epitomizes the relationship between development and carcinogenesis in the breast. Understanding the mechanism by which reproductive events influence breast cancer susceptibility will undoubtedly require a far better understanding of normal mammary development than currently exists, particularly with respect to identifying the genes that control proliferation and differentiation. Since major insights into the molecular mechanisms of differentiation, development, and carcinogenesis have been obtained in a variety of systems through studies of protein kinases, we have chosen to focus on this family of molecules. Several members of the protein kinase family have been shown to contribute to mammary carcinogenesis both in humans and in rodent

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model systems. Moreover, over-expression of genes encoding certain protein kinases, such as HER2/Neu, has been shown to provide prognostic information relevant to clinical outcome and response to therapy. As such, further studies of the function of protein kinases in the breast may reveal significant features of the relationship between development and carcinogenesis in this organ, as well provide insight into how the decision to proliferate or differentiate is made in mammary epithelial cells. We have identified two novel protein kinases, Hunk and Punc, that are: differentially regulated in the mammary gland during pregnancy; expressed in spatially restricted subsets of epithelial cells during specific stages of pregnancy; and differentially expressed in murine breast cancers induced by the Neu and c-myc oncogenes. Our studies suggest that Hunk and Punc may play a role in normal mammary development, may represent markers for biologically important subsets of epithelial cells in the breast, and may contribute to the process of mammary carcinogenesis. We hypothesize that Hunk and Punc play critical roles in mammary development by mediating pregnancy-induced changes in proliferation and differentiation. These hypotheses will be tested by using a tetracycline-inducible system to conditionally express Hunk and Punc in nontransformed mammary epithelial cells in vitro and in transgenic animals in vivo. Mice bearing targeted deletions of Hunk and Punc will be used to determine the impact of loss of function mutations in these kinases on mammary development, specifically with respect to changes in cellular proliferation, apoptosis, and programs of differentiation that occur during pregnancy. In this application we propose to investigate the role played by two novel protein kinases in normal mammary development as a step toward understanding the relationship between development and carcinogenesis in the breast. Beyond the further elucidation of this important relationship, we believe that these studies will yield an improved understanding of the regulation of mammary epithelial proliferation and differentiation during pregnancy, and will thereby help illuminate a stage of mammary development that contributes to the determination of breast cancer susceptibility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HYPOTHALAMIC AGING AND MENOPAUSE Principal Investigator & Institution: Reame, Nancy E. Professor; Center for Nursing Research; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2003 Summary: Adapted from the Applicant's Abstract): An early sign of reproductive aging in normal cycling women is the monotropic rise in FSH in the fact of preserved estradiol (E2) secretion. The mechanisms for this phenomenon are not know, but unlike the case in rodents, it is presumed to result from the incipient loss of negative feedback from ovarian inhibin, due to an accelerated decline in the pool of FSH-responsive follicles. Recently, this hypothesis has been challenged based on mounting evidence of altered pulsatile LH secretion well before the menopause, thus pointing to a contributory role for a decline in hypothalamic GnRH pacemakers in the onset of human ovarian failure. Through a detailed study of the ovarian negative feedback tone and sleep-induced changes in gonadotropin secretion (as a marker of the centrally-mediated GnRH signal generator), the goal is to determine the relative contribution of central aging effects to the onset of menopause in humans. Such information could assist in the development of improved strategies for menopause-related morbidity. Further, it perhaps could suggest therapies for the maintenance of follicular function and fertility in the 1 in every 100 women who will undergo premature ovarian failure and menopause before age 40.

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This proposal builds on a recent discovery using highly specific two-site assays that both inhibin B and Activin A (but no total and free follistatin or E2) are altered in aging, ovulatory women with magnified gonadotropin secretion. Whether such changes in ovarian function are a consequence or a cause of the menopausal transition remains to the determined. To separate the central and ovarian aspects of reproductive aging, plans are to assess pulsatile LH and FSH secretion for 1) follicular phase-dependent changes in the 24-hour dynamic secretory pattern (hypothalamic level) and 2) responsiveness to GnRH (pituitary level) in premenopausal, ovulatory women compared to younger controls and age-matched postmenopausal women; and 3) examine the individual effects of age and ovarian peptide feedback on gonadotropin dynamics by studying a comparative group of castrate women of different ages replaced with E2. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: IN VITRO STUDIES OF STEROID RECEPTORS IN NF1 Principal Investigator & Institution: Fishbein, Lauren M. Molecular Genetics & Microbiol; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2002; Project Start 31-JUL-2002 Summary: Neurofibromatosis type I (NF1), a common dominant condition, is characterized by abnormal proliferation of neural crest derived cells, including Schwann cells (thought to be the clonal element) in neurofibromas. The current therapy for neurofibromas is surgery, which is usually insufficient. Neurofibromas are often aggravated during puberty and pregnancy, suggesting an altered sensitivity to steroid hormones. NF1 patients and their physicians worry about this possible correlation when faced with decisions about hormone therapies for birth control, menopause, or disease treatments. To investigate this hypothesis, the type, relative quantity and localization of hormone receptors present in NF1 tumor Schwann cell cultures compared to normal Schwann cells will be measured through RT-PCR/Western blot and immunofluorescence, respectively. To investigate the functional role of these receptors, the tumor cultures will be assayed for increased proliferation and/or survival in response to these hormones. Expression of genes believed to be downstream targets of steroid hormones will also be analyzed. These studies will characterize the role of hormones in neurofibroma development, allowing for more educated medical decisions, as well as identifying potential targets for inhibiting tumor development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLUENCE OF SOY CONSUMPTION ON MENOPAUSE IN JAPAN Principal Investigator & Institution: Melby, Melissa K. Anthropology; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2002; Project Start 01-AUG-2002 Summary: (provided by applicant): For two decades, anthropologists have been aware that the experience and symptoms of menopause (i.e., hot flashes, night sweats) may not be universal. Several researchers have hypothesized that dietary factors such as phytoestrogens (plant estrogenic chemicals) in soy, which is consumed in great quantities by the Japanese, may play a role in their lower rate of menopausal symptoms. This dissertation project will test a biocultural, reproductive ecology model of whether and how soy consumption affects the menopausal transition (konenki) in Japan. Specifically, we hypothesize that: (1) Women with higher phytoestrogen exposure/intake will have less frequent or severe midlife symptoms; and (2) Variance in gonadotropins (FSH and LH) will be negatively correlated with phytoestrogen

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exposure. Two populations of Japanese women, aged 45-55, from the Tohoku and Kinki regions of Japan (which have the highest and lowest soy consumption respectively, providing a natural experiment in phytoestrogen exposure) will be sampled longitudinally for levels of E2, FSH, LH, SHBG, and the phoytoestrogens genistein and diadzein. This study will characterize the menopausal transition in Japan from multiple perspectives: (1) endocrinological/physiological; (2) ecological (diet), and (3) experimental. By combining new assays for measurement of phytoestrogens with our well-validated finger prick blood spot methods, this project will provide a biocultural characterization of menopause in Japan. These data are sorely needed to model crosscultural variation at the end of the reproductive lifespan, and the influence of the environment on endocrinology and experience over the menopausal transition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: INTERDISCIPLINARY RESEARCH CAREERS IN WOMEN'S HEALTH Principal Investigator & Institution: Ferguson, James E. Professor; Medicine; University of Kentucky 109 Kinkead Hall Lexington, KY 40506 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from applicant's description): The goals of this Program are to (1) provide junior faculty with state-of-the-art training in research relevant to women's health that will insure that they successfully establish independent research careers in the academic medicine and (2) facilitate and encourage ongoing and new collaborations in focused but interactive areas that are essential to improving women's health. The applicants will provide in- depth training in three focused and interacting areas of women's health: (1) regulation of the menopause and its repercussions on women's health, (2) nutrition-related illnesses and their impact on women, and (3) gender issues and drug abuse. The unique feature and critical strength of the BIRCWH Career Development Program outlined in this application is its multidisciplinary, crossdepartmental and interactive nature. Therefore, IWHR fellows will have in-depth and broad experiences with a primary mentor and many other faculty who will enrich their research experience and provide multiple role models to enhance their career development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LIFESTYLE CHANGE TO INCREASE BONE DENSITY IN TEEN GIRLS Principal Investigator & Institution: Debar, Lynn L.; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, CA 94612 Timing: Fiscal Year 2003; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: The annual cost of osteoporosis-related fractures in the US is $8 billion, most of which is borne by women in spite of an abundance of research on factors that might ameliorate the postmenopausal drop in bone mineral density (BMD). An important component of a lifelong prevention strategy would be to create methods for young women in the years 14-20 to maximize their bone mineral content and maintain it until menopause. This proposal will rigorously test two comprehensive lifestyle interventions, both oriented toward healthy diet and sustainable exercise, one based on individual counseling and the other on group intervention, against an attention control. The aim is to build bone and prevent bone loss among young women 14 to <16 years of age at recruitment. This trial draws upon our experience in 2 important studies of teens and nutrition--the Teen Lifestyle Project, DISC--and the ongoing fruit and vegetable

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study, DASH. The design is a parallel-group randomized clinical trial. with 300 participants equally divided among the groups, and measurements at baseline and three follow-ups to 27 months. This will provide power 0.90 to detect differences of l%-2% in TBBMD rates of change between groups. Secondary analysis will compare the achievement of the diet and exercise goals as compared to control, measured by objective markers (serum folate and carotenoids urinary sodium, lean body mass, accelerometer measure of physical activity) as well as by self-reports. The tertiary analysis will examine the same diet and exercise outcomes between the two intervention groups. and also in relation to process measures (adherence, evaluations, retention). The final analysis will explore potential causal pathways to bone mineral health involving a wider variety of factors, such as family history, biological and behavioral factors, hormonal influences and markers of bone metabolism. The investigators have a substantial amount of expertise in behavioral modification, research on teenage girls, nutrition and exercise interventions. They have substantial experience with assessment of bone mineral, body strength, exercise patterns, and diet, and with the biostatistical and qualitative research approaches required. The project will be carried out at the Kaiser Permanente Center for Health Research, a fully equipped research center with a mission of biomedical research in the public domain, in collaboration with the Oregon Health Sciences University. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MAMMOGRAPHIC DENSITY IN A MULTI-ETHNIC COHORT Principal Investigator & Institution: Habel, Laurel A.; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, CA 94612 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 30-JUN-2006 Summary: Mammographic density is one of the strongest known risk factors for breast cancer, yet it has been described as among the most undervalued and underutilized factors in studies of breast cancer etiology. While recently there has been interest in the potential value of mammographic density as an intermediate marker of breast cancer risk, several questions remain unanswered. A needed area of research is the identification of risk factors for breast cancer that are related to mammographic density, and may therefore act through a causal pathway reflected directly or indirectly by this feature. The aim of this study is to identify factors that are associated with mammographic density, with a special focus on race/ethnicity, circulating hormones (e.g., estradiol, progesterone, testosterone, sex hormone-binding globulin), bone mineral density, and modifiable factors such as diet (e.g., phytoestrogen, percent calories from fat,) and physical activity (e.g., recreational activity, occupational activity, and household activity). We will also look at how density changes as women transition through the menopause. This proposal seeks funding for obtaining and assessing mammograms on approximately 178 Chinese, 209 Japanese, 102 African-American, and 498 Caucasian women participating in SWAN (Study of Women's Health Across the Nation). We will request all mammograms performed as part of routine care during the SWAN follow-up period and request that women have a mammogram within six months of follow-up exam six. SWAN is a multi-site population-based study designed to investigate the menopausal transition in women of diverse ethnicities. At baseline and six annual follow-up exams, data are collected on a wide range of factors, including detailed anthropometry, bone mineral density, menstrual information (e.g., monthly calendars), and complete reproductive histories. In addition, blood is drawn, timed to the luteal phase of the menstrual cycle, for hormone analyses. An expert in assessing mammographic density will measure total area of the breast and area of dense tissue

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(for percent density) and classify mammograms according to parenchymal pattern (Wolfe system). This mammography information will be merged with data from SWAN to create analytic files. Repeated measures regression analysis will be used to examine the association between factors of interest and mammographic density. The SWAN study population provides a unique opportunity to efficiently examine the relationship between several established and suspected risk factors for breast cancer and mammographic density. The results will improve our understanding of a number of breast cancer risk factors and help determine whether mammographic density should be considered as a potential intermediate marker of breast cancer risk for intervention studies of several modifiable factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MARC PREDOCTORAL FELLOWSHIP Principal Investigator & Institution: Brisbon, Wendy; Anatomy and Physiology; Meharry Medical College 1005-D B Todd Blvd Nashville, TN 37208 Timing: Fiscal Year 2003; Project Start 29-AUG-2003; Project End 28-AUG-2006 Summary: (provided by applicant): My research focus is the role of estrogen in the neural control of blood pressure. Hypertension is a major health problem which greatly increases the risk of cardiovascular disease and stroke. In women, the incidence of cardiovascular disease and stroke increases dramatically following menopause. This is, most likely, due to estrogen depletion, which may trigger a slowly developing increase in blood pressure. Also, hypertension and diabetes mellitus are often seen as coexisting conditions. My working hypothesis is that aging, estrogen loss, and diabetes mellitus cause decreases in anterior hypothalamic norepinephrine release and decreased activation of alpha-2-adrenoceptors. This leads to decreased sympathoinhibition, increased blood pressure, and increased stroke risk. The specific hypotheses to be tested are: [1] Estrogen maintains lower blood pressure through mechanisms that involve alpha-2-adrenoceptors in the anterior hypothalamic nucleus; and [2] Estrogen depletion and diabetes are associated with increased blood pressure and stroke risk. The increase in blood pressure associated with diabetes involves a decreased activation of alpha-2adrenoceptors in the anterior hypothalamic nucleus. My studies will use middle-aged hypertensive rats and transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM ALZHEIMERS DISE

OF

ESTROGEN

NEUROPROTECTION

IN

Principal Investigator & Institution: Pike, Christian J. Assistant Professor; Gerontology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: (from applicant's abstract) Female gender is a risk factor for the development of Alzheimer's disease (AD). Accumulating evidence suggests that the massive reduction in estrogen levels that occurs in women following menopause appears to be the primary variable underlying this risk factor. Importantly, the clinical use of estrogen replacement therapy in postmenopausal women has been demonstrated to both delay the onset of AD and slow its progression. Because estrogen has many cellular effects potentially relevant to a protective role against AD, currently it is unclear what specific estrogen action(s) are salient to its inhibition of AD pathology. In this grant application, the applicants propose a novel neuroprotective mechanism of estrogen and predict that it functions to increase neuronal resilience against degenerative stimuli implicated in

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AD neurodegeneration. Based upon recent advances in the fields of endocrinology and oncology, they theorize that in estrogen responsive brain regions (e.g., hippocampus, entorhinal cortex, amygdala), estrogen activates its receptors, which initiates a genomic pathway that alters the expression of apoptosis- related proteins. In particular, their preliminary data suggest that estrogen significantly increases expression of the antiapoptotic protein Bcl-XL. As a consequence of its regulation of apoptosis-related proteins, they theorize that estrogen sways the balance of neuronal apoptotic pathways toward enhanced viability, thereby increasing the resistance of estrogen-responsive neurons to apoptotic degeneration. Thus, the loss of estrogen following menopause is predicted to decrease levels of an important endogenous modulator of neuronal viability, rendering estrogen-responsive brain regions vulnerable to apoptotic challenge. The applicants propose three aims to investigate this novel theory: (1) Using cell culture and in vivo paradigms, they will evaluate estrogen's ability to regulate neuronal expresssion of apoptosis-related proteins. They will identify estrogen target proteins, determine the role of receptor activation and differential receptor subtype response, and examine possible synergism with other apoptosis modulators; (2) They will investigate predictions that functional consequences of estrogen's regulatory actions include decreased activation of specific apoptotic pathways (e.g., caspase-mediated proteolysis) and increased neuronal viability; (3) They will use quantitative image analysis techniques to correlate findings made in experimental systems (Aims 1 and 2) to the normal aged and AD brain. The applicants anticipate that their novel hypotheses will generate new insight into the ability of estrogen to modulate neuronal viability throughout life, from neural development through age-related neurodegenerative disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MELATONIN FOR SLEEP DISTURBANCES DURING MENOPAUSE Principal Investigator & Institution: Suhner, Andrea G.; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 16-MAR-2003 Summary: Up to half of all women going through menopause report significant sleep disturbance. A number of factors contribute to these sleep problems, with hormonal imbalance and hot flashes being the most important. Estrogen replacement therapy can alleviate these symptoms, yet side effects and contraindications make the use of this hormone replacement therapy (HRT) problematic in many women. As such, alternatives to traditional HRT are needed. Previous work in our lab has indicated that not only low levels of sex steroids but also the marked increase of gonadotropins observed during the menopause transition may play an important role in disturbed sleep experienced by peri- and postmenopausal women. In particular, our studies have shown that elevated levels of luteinizing hormone (LH) or a high ratio of LH-to-estradiol were associated with low sleep- efficiency in postmenopausal women. Hormonal imbalance also induces changes in the thermoregulatory system. The result is hot flashes and sweats, which can adversely affect night-time sleep quality The proposed study will test the hypothesis that exogenous melatonin decreases LH levels and in so doing, increases sleep quality. Furthermore, we hypothesize that melatonin will reduce severity and number of hot flashes by virtue of its temperature-lowering effect. As a consequence, the number of awakenings due to nocturnal hot flashes and night sweats will be reduced, leading to improved sleep quality. To test these hypotheses, twelve symptomatic peri- or postmenopausal women between the ages of 45-55 will ingest a daily dose of 3 mg melatonin or placebo every evening at bedtime over a period of 14 days. Each subject

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will undergo both conditions. At the end of each treatment session, subjects will spend two consecutive nights in the sleep laboratory. Polysomnographic sleep variables and core body temperature will be recorded continuously on both nights. Hot flashes will be objectively identified by measuring distal skin temperature and proximal skin resistance. Over-night urine samples will be collected to assess LH levels. Sleep parameters, temperature data, number of hot flashes and LH levels will be compared across active and control condition. The current project is an important first step to identify and assess a promising alternative for sleep disturbances in menopause. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MENOPAUSAL TRANSITION, MENTAL HEALTH AND ETHNICITY Principal Investigator & Institution: Bromberger, Joyce T. Research Assistant Professor; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-AUG-2006 Summary: (provided by applicant): This competing renewal application is a revision of what was previously a Collaborative R0l three site prospective study of middle-aged women's mental health that is an ancillary study of the Study of Women' Health Across the Nation (SWAN). Due to difficulty with retention and feasibility issues at the other 2 sites they will be unable to continue the study. We are proposing to continue the study in Pittsburgh only. Our current sample consists of 412 African American and Caucasian women, aged 42-52 at the start of the study in 1996, who are beginning or will soon begin the menopausal transition. Women are interviewed annually with the Structured Clinical Interview (SCID) for DSM-IV Axis I Disorders. Our specific aims are: 1) to assess whether women will be more likely to develop a new (recurrent) syndromal or subsyndromal depression during the perimenopausal transition than before or after, 2) to determine if a history of major depression (MOD) is risk factor for the following during the transition: (a) syndromal or subsyndromal depression, (b) increased levels of perceived stress, somatic and psychological symptoms, or (c) decreased quality of life or functioning and 3) to compare rates of new (recurrent) syndromal or subsyndromal depression across the transition for African American and Caucasian women. The longitudinal nature of the SWAN biological and psychosocial data (e.g., medical morbidity, stressful events, lifestyle behaviors) will allow us to evaluate these as antecedents, correlates, and consequences of depression during the course of the study. By continuing to collect systematically psychiatric data in our cohort in conjunction with the continued collection of Core SWAN data, we have a unique opportunity to expand knowledge of women's mental health in midlife and beyond. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENOPAUSAL TRANSITION: A BIOBEHAVIORAL MODEL OF SYMPTOMS Principal Investigator & Institution: Mitchell, Ellen S. Family and Child Nursing; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2002; Project Start 01-SEP-1996; Project End 31-DEC-2006 Summary: More than 20 million U.S. women of the Baby Boomer cohort will make th transition to menopause between 2000 and 2010. Despite women's increasing search for information about menopause, little is known about the natural history of the menopausal transition, those years before menopause. Our recent description of an early, middle and late stage of the menopausal transition allows us to continue this 10-

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year longitudinal study of a group of midlife women with a focus on hormone changes, perceived stress, physiologic stress arousal, symptoms, and depressed mood during three stages of the menopausal transition. An additional focus will be to assess the effects of genetic polymorphisms of the estrogen receptor gene (ESR1 PvuII) and estrogen metabolic genes (CYP17, CYP19, EDH17B2, CYP1A1, CYP1b1 enzymes) on estradiol and estrone levels, age of onset of middle and late transition and menopause, and menstrual bleeding. It is estimated that by the end of this proposed 5-year study the majority of women would have reached late transition or be menopausal. Data collection will involve obtaining a single blood sample for estradiol, a single buccal cell scraping for DNA analysis, four urine samples a year assayed for estrone, FSH, testosterone, cortisol and catecholamines, four 3-day symptom diaries per year, questionnaires, and yearly menstrual calendar. T he results of this study will help inform women and clinicians about normal changes associated with three stages of the menopausal transition and about genetic factors influencing estrogen levels, age of onset of stages of the menopausal transition and menopause and menstrual bleeding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MENOPAUSE AND MIDLIFE AGING EFFECTS ON SLEEP DISORDERS Principal Investigator & Institution: Young, Terry B. Professor of Prventative Medicine; Preventive Medicine; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001; Project Start 15-JAN-1997; Project End 31-DEC-2001 Summary: A marked increase in the prevalence of sleep apnea, insomnia and hypersomnia in women has been noted during mid-life aging. Despite these observations and the biologic rationale that menopausal changes are likely to profoundly affect sleep, research on the pathogenesis of sleep disorders in women as they pass through menopause is lacking. The long-range goals of this longitudinal study of mid-life aging in women are to understand the role of menopause in the occurrence and progression of sleep apnea, insomnia and hypersomnolence and ultimately to formulate clinical strategies for intervention and prevention of the increased risk of theses dyssomnias in mid-life. Understanding the role of menopause in dyssomnia occurrence is particularly important because millions of women are exposed to menopausal changes yearly and because the hypothesized outcomes, particularly sleep apnea, are associated with cardiovascular and behavioral morbidity and mortality. The results of this study will have direct application o medical care for women in mid-life. The proposed study is designed to (1) definitively test the hypothesis that sleep apnea, insomnia and hypersomnia incidence and progression increase in peri and post menopause, relative to premenopause; (2) test the hypothesis that the association of sleep disorders and mid-life aging is attributable to menopause-related changes in body habitus; (3) test the hypothesis that peri and post menopausal women with hormonal replacement therapy, relative to those without, have lower incidence of dyssomnias; (4) determine the effect of type of menopause on dyssomnia occurrence in mid-life, and (5) establish a cohort of 150 women with data on menopausal status to be merged with ongoing data collected by the parent study on functional status, health care costs, cardiovascular and behavioral outcomes for future analyses. A robust prospective longitudinal study design with adequate power to address the above specific aims will be used. Semiannual home polysomnography studies and other measurement of dyssomnia during peri and post menopause will be conducted on a cohort of 150 women on whom up to 8 years of polysomnography data during premenopause have

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already been collected as part of the parent study, the Wisconsin Sleep Cohort Study. The specific aims, will be addressed using standard definition of menopause and dyssomnias, with longitudinal multivariate models able to control for confounding factors and to investigate interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MENOPAUSE EFFECT ON OBESITY, ENERGY BALANCE AND INSULIN Principal Investigator & Institution: Lovejoy, Jennifer C. Associate Professor; None; Lsu Pennington Biomedical Research Ctr 6400 Perkins Rd Baton Rouge, LA 70808 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-AUG-2004 Summary: Menopause has been associated with changes in body composition and increased cardiovascular risk factors in Caucasian women, although less information is available on the effects of menopause in African- American women. Changing levels of reproductive hormones are central to the physiological changes at menopause and, since these hormones have been related to body fat distribution, its likely that they play a role in body fat-related changes at this time of life. The overall goal of this proposal is to assess the influence of menopause on body composition and fat distribution, and to determine mechanisms they may influence body fat changes, in a prospectively followed cohort of Caucasian and African-American women. the studies outlined will address 4 general hypotheses. First, we hypothesize that menopause increases both total and visceral abdominal fat. Second, we hypothesize that the changes in body composition and body weight at menopause are mediated, at least in part by changes in 24-hour energy expenditure, physical activity and/or food intake. Third, we hypothesize that menopause results in decreased insulin sensitivity that may predispose certain women to develop diabetes later in life. These changes in insulin action may be connected to changing adiposity or may be independently related to hormonal changes. finally, we hypothesize that there may be a differential responsiveness to menopausal changes in African-American women, who end to have differences inn adioposity, insulin sensitivity, and reproductive hormone levels premenopausally compared to Caucasian women. Since health statistics for Africanamerican women are significantly worse than for the U.S. Caucasian population, understanding the effects of menopause on risk factors in african-American women is of great public health significance. In order to address these hypotheses related to the effects of menopause, a longtidudinal study is proposed where premenopausal women aged 47-52 year old will be assessed annually and changes in outcome variables in relation to aging and menopausal status will be determined. Major outcome variables include intra-abdominal far distribution by CT scan, body composition, 24-hr energy expenditure, food intake and activity, and insulin sensitivity by the Minimal Model method. Among the strengths of this design include the ability to address mechanisms of menopausal changes since sequential measurements will be taken over time in these outcome variables. The importance of this research was underscored in a recent consensus report from the National Institute on Ageing stating that "The need for longitudinal (observations) of women over time.. is essential.. to advance our knowledge of the natural history of menopause". Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENOPAUSE IN RHESUS MONKEYS Principal Investigator & Institution: Urbanski, Henryk F. Associate Professor; Oregon Health & Science University Portland, OR 972393098

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Timing: Fiscal Year 2001 Summary: In light of recent evidence from clinical studies that fewer postmenopausal women develop Alzheimer=s disease if they receive sex steroid replacement therapy, it has become important to examine the hypothesis that ovarian steroids can protect the brain from neurodegeneration. Interestingly, rhesus monkeys show many of the same aging-related cognitive impairments as do humans, and they also develop amyloid plaques in the same brain regions as do Alzheimer=s patients. The aim of this pilot project, therefore, was to determine whether female rhesus monkeys undergo true menopause, as do women, and if so to determine at what age this occurs. The results from this study clearly demonstrate that as female rhesus monkeys enter their third decade of life, they start to show irregular menstrual cycles which are associated with impaired ovarian steroidogenic function and a concomitant increase in circulating gonadotropin concentrations. The reproductive endocrine profiles of more th an twenty aged monkeys have been examined in detail, and the animals classified as having normal menstrual cycles, irregular cycles (perimenopausal) or as being acyclic (postmenopausal). These data clearly demonstrate that the aged rhesus monkey is a highly appropriate animal model in which to further investigate the potential neuroprotective effects of sex steroids. The data also provide a solid foundation for future studies using this valuable group of animals, including cognitive testing, hormone replacement, and ultimately neuropathology. FUNDING Alzheimer=s Research Alliance of Oregon PUBLICATIONS None Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MENOPAUSE INTERACTIVE DECISION AID SYSTEM (MIDAS) Principal Investigator & Institution: Col, Nananda F. Assistant Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2004 Summary: (provided by applicant): Most women are not satisfied with the counseling they receive about menopause. To improve menopausal counseling and help menopausal women more actively participate in the decision-making process, the applicant has developed a novel prototype web-based decision aid. The immediate goal of this project is to develop this prototype technology into a comprehensive Menopause Interactive Decision Aid System (MIDAS) that provides personalized feedback about menopausal symptoms, risks for common conditions, and the effects of different treatment options on the short- and long-term consequences of menopause. The main hypotheses of this study are that MIDAS can: 1) lead to better decisions and improve the quality of menopausal counseling; 2) improve compliance with a chosen menopausal plan; and 3) reduce medical errors associated with the use of menopausal therapies. The specific aims are to: 1) develop and optimize the utilization of MIDAS; 2) evaluate the impact of MIDAS on the decision-making process, including decisional conflict, knowledge, risk perception, anxiety, patient-physician communication, satisfaction with decision-making, the quality of menopause counseling, and medical errors related to menopausal therapy; and 3) evaluate the long-term impact of MIDAS on outcomes related to menopause. These endpoints include compliance with a chosen menopausal plan, quality of life, and providers' ability to manage menopausal patients. The applicant proposes a two-phase study conducted over three years. Phase I will transform the prototype application into a comprehensive MIDAS, completing its content and risk assessment instruments, and exploring its optimal design. This will be accomplished through conduct of focus groups and usability tests. Phase II will formally evaluate the impact of MIDAS in a randomized, controlled, multi-center clinical trial

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involving diverse patient populations and clinician settings. The impact of MIDAS on the decision-making process will be measured, as well as its effect on providers and outcome measures related to menopause, including compliance, quality of life, and medical errors related to menopausal therapy. Analyses will evaluate the extent to which the impact of MIDAS on these outcomes varies according to patient, practice, and physician characteristics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MENOPAUSE, IDDM, AND AUTOIMMUNITY--THE FAD STUDY Principal Investigator & Institution: Dorman, Janice S. Associate Professor; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2004 Summary: The Familial Autoimmune and Diabetes (FAD) Study has shown that the prevalence of Hashimoto's thyroiditis, defined by high titres of thyroid peroxidase or thyroglobulin autoantibodies, elevated TSH in the absence of medication, and/or a positive history or exam, is higher among adult women with type 1 diabetes than their non-diabetic sisters or mothers. These findings suggest that one's ability to maintain immunological self-tolerance may be lost prematurely among women with type 1 diabetes. This may also reflect one of the many chronic complications that occur at an early age among affected individuals. One would, therefore, expect that other indicators of advanced biological age may be common among women with type 1 diabetes. Selfreport data from the FAD Study support this hypothesis. The mean age at menopause for women with type 1 diabetes was nearly ten years younger than that for their nondiabetic sisters (41.6 vs. 49.9 years, p less than 0.05). To our knowledge, this is the first formal report of an association between type 1 diabetes and early menopause in the scientific literature. Moreover, the public health importance of these data, which must be confirmed, is enormous. Given the high incidence of cardiovascular disease and other complications known to be associated with long-term diabetes, an early natural menopause is likely to exacerbate the risk of myocardial infarction among young women with type 1 diabetes. We have the only defined cohort of type 1 diabetic women that is sufficiently large and of the appropriate age to address the following Specific Aims: 1) To validate the extremely important finding that menopause, defined by 12 months without menstruating and elevated FSH levels, occurs at a significantly younger average age among type 1 diabetic compared to non-diabetic women, 2) to evaluate potential differences in menstrual bleeding patterns, menopausal symptomatology and the determinants of age at menopause among type 1 diabetic compared to non-diabetic women, and 3) to evaluate the effect of the menopause transition on major cardiovascular disease risk factors and risk of autoimmune thyroid disease among type 1 diabetic compared to non-diabetic women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENOPAUSE, LPL GENOTYPE AND METABOLISM AFTER WEIGHT LOSS Principal Investigator & Institution: Goldberg, Andrew P. Professor; Medicine; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-JUL-2005 Summary: This research is designed to determine whether obese postmenopausal women with a common polymorphism in the lipoprotein lipase (LPL) PvuII gene, i.e.

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the (+) allele have less favorable metabolic responses to weight loss (WL) treatment than women without the LPL PvuII cut-site (-/-). The hypothesis is that the LPL PvuII genotype affects fasting muscle and adipose tissue and LPL activity and the metabolic responses to hypocaloric feeding-induced WL in a dose-dependent manner to affect the magnitude of the reduction of total and visceral fat, and improvements in glucose/insulin and lipoprotein lipid metabolism following WL in postmenopausal women. Specific aims determine whether obese women who are homozygous for the LPL PvuII (+) cut-site, i.e. the (+/+) genotype, have greater increases in adipose tissue LPL and decreases in muscle LPL activity and larger decreases in resting metabolic rate (RMR) and fat oxidation than heterozygotes during hypocaloric diets, that are associated with: 1) the loss of less total body and visceral fat; and 2) smaller improvements in lipid and glucose metabolism than women without the cut-site, i.e., (/-). We will study healthy, obese (Body Mass Index, 30-40 kg/m2) 50-60 year old women within 5 years of menopause. The statistical power to test our hypothesis is based on preliminary data showing differences in adipose tissue LPL responses to WL between LPL PvuII (+/+) and (-/-) genotypes, and requires 27 women/genotype. Subjects will be entered prospectively based on their LPL genotype to ensure a homogeneous group of obese menopausal women are studied to eliminate confounding factors of gender, age, duration from menopause and body composition on the metabolic responses to WL treatment. Metabolic studies are performed on prepared calculated weight maintaining eucaloric diets for 2-3 weeks at baseline and after 6-mo WL to ensure metabolic stability, and on hypocaloric diets after the short-term study to assess metabolic responses to negative energy balance. We will measure muscle and adipose tissue LPL activity, RMR, fat oxidation, total and visceral body fat (DXA and CT scans) lipoprotein lipids and. glucose/insulin responses during an oral glucose tolerance test. Following the post-WL metabolic evaluations, subjects enter a 6- mo follow-up period followed by metabolic testing to assess long- term metabolic adaptations and weight regain by genotype. Collectively, these findings will enhance our understanding of obesity by assessing the gene-metabolic mechanisms underlying the predisposition of some obese women to more favorable metabolic health benefits from WL. This would allow the targeting of WL treatments to women more likely to respond, and pharmacologic and other treatments to those less likely to respond to WL. This optimistic outcome would reduce prevalence of obesity and risk for CVD in older women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MENOPAUSE: DECISION-MAKING

ENHANCING

WOMEN'S

KNOWLEDGE

&

Principal Investigator & Institution: Sherman, Christy A. Research Associate; Oregon Center for Applied Science 1839 Garden Ave Eugene, OR 97403 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 29-FEB-2004 Summary: This project will develop an interactive multimedia program that (a) provides accurate and understandable information about menopause, (b) provides assistance in understanding and choosing among options for dealing with the effects of menopause, and (c) provides guidance and support for making collaborative decisions with health care providers for effective symptom management and long term risk prevention. The program will feature full interactivity, extensive video presentations, and animated examples. Extensive formative evaluation procedures will be employed to develop materials. Building on the successful Phase I prototype program that provided information about menopause, the Phase II product will expand this initial knowledge

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component and will develop additional components on (a) decision support and (b) decisional collaboration. The efficacy of the comprehensive program will be evaluated. PROPOSED COMMERCIAL APPLICATION: This program will be appropriate for use in homes, medical clinics, HMOs, libraries, women's centers and other educational resource centers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MENOPAUSE--MEANING AND EXPERIENCE IN OAXACA, MEXICO Principal Investigator & Institution: Ramirez, Michelle L. Anthropology; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): The broad long-term objective of the proposed study is to augment the existing anthropological research on menopause. Anthropologists have ascertained that cultural constructs, particularly gender roles and attitudes toward aging, affect the experience, symptomotology and perception of menopause. What has not received adequate attention in the field is how the meaning and experience of menopause varies within a cultural setting due to social and economic differentials. Thus, the specific aims of this project are to investigate in Oaxaca de Juarez, Mexico, how social class effects; a) gender roles, b) attitudes toward aging, c) the experience of menopause and d) various medical treatments used by women. The PI will also examine the medical and popular dissemination of information about menopause, analyzing what this reveals about contemporary prescriptions for appropriate womanhood. The PI will reside in Oaxaca de Juarez, Mexico from September 1999 to January 2001 to conduct this field study. A three page questionnaire developed by the PI contains questions regarding employment, education, household composition, income in order to ascertain social class. Open ended questions solicit the woman's knowledge, beliefs and experience of menopause. These interviews will be tape recorded and transcribed by the Pl, then later analyzed for the core meanings assigned to menopause. Participants will be recruited from the following sources; a) The NIMH Study, "Proyecto de Investigation Internacional Sobre Salud Comunitaria" (Grant MH51278), b) The PI will attend religious, community and social meetings and events that are primarily attended by women, c) Public and private clinics and d) Opportunisitc interviews in addition to snowball sampling. A two page questionnaire will be administered to 10 (each) of the following medical practitioners: gynecologists and family practitioners, homeopaths, naturistas, ethnomedical practitioners, pharmacists and mental health practitioners. The Oaxacan Yellow Pages and word-of-mouth sampling has been effective with these participants. After the field research has been completed (February 2001), the PI will return to the University of Iowa to write her dissertation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENTORED DEVELOPMENT AW

PATIENT

ORIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Carr, Molly C. Clinical Research Center; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 30-JUN-2005 Summary: PROPOSAL (Adapted from the applicant's abstract): Postmenopausal estrogen replacement therapy (ERT) has become an accepted intervention in aging women. The recent publication of the Heart and Estrogen and Progestin Replacement Study (HERS) has made the difficult decision to initiate postmenopausal ERT even more

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difficult for clinicians. Both small, dense low density lipoprotein (LDL) and plasminogen activator inhibitor Type 1 (PAI-1) are risk factors for coronary artery disease (CAD) that increase with menopause and may represent markers of future individual CAD risk. The primary objective of the proposed study is to investigate whether women who develop small, dense LDL across the menopause will selectively benefit from transdermal ERT. The mechanisms underlying the changes in LDL size will also be studied by measuring hepatic lipase activity, cholesteryl ester transfer protein (CETP) activity, triglyceride (TG) levels, body fat distribution and the hepatic lipase gene promoter polymorphism, all known to affect LDL size. The investigators will also determine whether women who develop small, dense LDL with menopause also have elevated PAI-1. This is a prospective, randomized non-blinded crossover trial comparing oral and transdermal ERT in two groups of postmenopausal women who have been followed since the premenopausal state. Twenty-three postmenopausal women who have developed small, dense LDL with menopause will be compared to 23 postmenopausal women who remain with large, buoyant LDL. They will be randomized to a six-month course of transdermal or oral ERT followed by a six-month washout period before the start of the second ERT course. This study will determine if there is a preferred method of postmenopausal ERT in the subset of women who develop small, dense LDL after menopause. They will also elucidate the mechanisms that underlie the shifts in LDL size with oral and transdermal ERT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MIDLIFE COGNITION: BIOPSYCHOSOCIAL MECHANISM Principal Investigator & Institution: Lachman, Margie E.; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2002; Project Start 01-JAN-2003; Project End 31-DEC-2008 Summary: The maintenanceof effectivecognitivefunctioningacross the lifespan is a crucial componentof an individual's well-beingandability to function independentlyin society.Althoughthere isa large literatureon cognitive performancein cider adulthood,there is limited nformation about cognitivefunctioning inmidlife. The proposed research will address that need by characterizing cognition across midlife and into old age on key domains that are hypothesizedto be sensitive to age effects, including verbal memory, working memory, executive function, reasoning,and speed of processing. Cognitive testing will be carried out through telephone interviews as part of the MIDUS II study. This will create a unique opportunity to examine the performance of middle-aged adults in a large-scale, nationally representative sample. In addition, the MIDUS study will provide a rich data base that will enable us to examine the relationship betweencognitive performance and a variety of biopsychosocial factors. The goal is to identify antecedents of effective cognitive function, in order to determine those factors that may serve a protective role in maintaining mental abilities, as well as those factors that serve as risk factors for exacerbating cognitive declines. We will investigate the links between cognitive performance and variables of interest, including SES, health, control beliefs, stressful life events, and menopausal status. Specifically, we predict that cumulative advantage (including high SES, good physical and mental health status, adaptive health behaviors, low stress, and a strong sense of mastery and control) will serve as a protective buffer against age decrements in cognitive performance in midlife and later life. Conversely, we expect that cumulative adversity (including low SES, chronic poor health, limited psychosocial resources) will be associated with greater vulnerability for cognitive deficits. We also will examine whether changes associated with the menopause are related to cognitive aging. A final goal is to carry out

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longitudinal analyses with an oversample from the Boston area, tested in 1996 on a multi-factor cognitive battery, stress reactivity measures, and control beliefs. This will provide valuable information on how changes over time in stress and psychosocial variables impact changes in cognitive performance during midlife. Understandingthe pathways to adaptive cognitive functioning in midlife may contribute to early detection and possible prevention of aging-related cognitive decline. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MODEL FOR PELVIC FLOOR DISORDERS Principal Investigator & Institution: Clark, Amanda L. Interim Director, Center for Women's Hea; Obstetrics and Gynecology; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001; Project Start 12-APR-2000; Project End 31-MAR-2005 Summary: Women's health is severely impacted by pelvic organ prolapse (pop), a highly prevalent condition that results from abnormal elongation and breaks of the connective tissue of the vaginal walls and its paravaginal attachments. The functional consequences of POP include vaginal protrusion, urinary incontinence, and voiding disorders, conditions that often demand surgical treatment. The underlying causes of POP are unknown, through hormonal deprivation, multiparity, and aging are all impacted. The work proposed addresses the role of steroid hormones, aging and parity in the rhesus macaque vagina. Preliminary data indicate that this model system is a valid and clinically relevant one for the study of pelvic floor disorders. The working hypothesis is that hormonal deprivation will lead to decreases in specific measurable endpoints, including steroid receptor levels, collagen density, elastin density and extracellular matrix components in the vaginal wall, and that these changes will be associated with decreases in biomechanical strength. Further aspects of the hypothesis are that matrix metalloproteinases will be up-regulated in hormonally deficient environments and that these degradative enzymes play a role in weakening the vaginal wall. Finally it is hypothesized that the degradative changes caused by hormonal deprivation can be reversed by appropriate hormonal replacement therapy, and that the response may vary with aging and parity. To examine these hypotheses the above mentioned endpoints will be measured in the vaginal fibromuscular wall and its paravaginal attachments and will be correlated with changes in biomechanical strength in both multiparous and nulliparous macaques. The specific aims will evaluate: 1) hormone replacement immediately after ovariectomy, 2) hormonal replacement after long term estrogen deprivation, 3) the rate of matrix metalloproteinase up-regulation after ovariectomy, and 4) properties of the vaginal wall in naturally aged macaques. Special attention will be paid to the effects of a SERM (raloxifene) as there are tow reports that experimental SERMs increase the incidence of POP. The SERM (raloxifene) as there are two reports that experimental SERMS increase the incidence of POP. The results will provide entirely novel data on the role of hormonal deprivation, parity and age on the anterior vaginal wall and its paravaginal attachments in a rigorously controlled primate model of direct clinical relevance to POP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODULATION OF VISCERAL FAT BY ESTROGENS AFTER MENOPAUSE Principal Investigator & Institution: Kohrt, Wendy M. Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508

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Timing: Fiscal Year 2001; Project Start 15-FEB-2000; Project End 31-JAN-2005 Summary: Excess abdominal visceral fat is associated with increased risk for coronary artery disease (CAD), Type 2 diabetes mellitus (DM), and hypertension. Although premenopausal women are largely protected against abdominal obesity, visceral fat accumulation increases after the menopause and there are concomitant deleterious changes in risk factors for CAD and Type 2 DM. Estrogen replacement attenuates increases in body weight and waist girth in postmenopausal women. However, it is not known whether estrogen use prevents or diminishes the visceral fat accumulation that occurs after menopause. It is possible that protective effects of estrogen on visceral fat metabolism contribute to the currently unknown component of the cardioprotective actions of estrogens. The specific aims of the proposed studies are to determine in postmenopausal women whether: 1) estrogen use augments reductions in visceral fat; 2) estrogen use attenuates increases in visceral fat; 3) changes in visceral adiposity are related to changes in whole body and regional resistance to the suppression of lipolysis by insulin and whether this relationship is altered by estrogens; and 4) changes in visceral adiposity are associated with changes in certain risk factors for CAD and Type 2 DM independent of an in addition to the effects of estrogen. An additional aim is to determine whether raloxifene exerts similar effects as estrogens on visceral fat. Faloxifene is a popular selective estrogen receptor modulator that is being promoted as a safer alternative to estrogen not only for its osteogenic effects but also for possible cardioprotective effects. To meet these aims, 108 healthy but overweight postmenopausal women, aged 50- 60 years, will be randomly assigned a placebo, estrogen, and weight reduction program and subsequent increases in adiposity will be measured through a 12-month follow-up period during which time the hormone/drug treatment will continue. Changes in risk factors for CAD and Type 2 DM (blood lipids and lipoproteins, glucose tolerance, insulin resistance) in response to reductions and gains in visceral adiposity will be measured. Because insulin resistance is a prominent characteristic of abdominal obesity, the effects of estrogen/raloxifene and of changes in visceral, adiposity on the glucoregulatory and anti-lipolytic actions of insulin will be evaluated during hyper-insulinemic, euglycemic clamp procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MUCOSAL IMMUNITY IN THE HUMAN FEMALE REPRODUCTIVE TRACT Principal Investigator & Institution: Wira, Charles R. Professor of Physiology; Physiology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001; Project Start 01-NOV-1993; Project End 28-FEB-2003 Summary: The overall goal of our multi-disciplinary Program Project is to understand the mucosal immune system in the human reproductive tract (FRT). The Program Project brings together endocrinologists and immunologists to characterize epithelial cell, myeloid cell and lymphocyte functions in the reproductive tract and obtain an integrated understanding of endocrine and cytokine control of the mucosal immune system in FRT. Our overall hypothesis is that the FRT is fully immunocompetent, and is regulated throughout the menstrual cycle and following menopause by sex hormones, cytokines and growth factors. The proposed studies focus on the presence and function of immune cells in reproductive tract issues from women undergoing hysterectomy. Sex hormone and cytokine regulation of reproductive architecture, antigen presentation, and myeloid cell and lymphocyte function will be investigated to obtain an integrated understanding of mucosal immune function in the Fallopian tube, uterus, cervix and vagina. Support the for 3 research projects will provided by 3 cores: Administrative,

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Tissue Procurement and Technical Support. The first Project will determine whether immune cell organization in the FRT varies with the stage of menstrual cycle and menopause. We will test the hypothesis that steroid hormones and cytokines differentially regulate the organization and function of immune cells with microenvironments of FRT tissues. The second Project will assess the inductive arm of the mucosal immune system in the FRT. The hypothesis to be tested is that epithelial cells, macrophages, dendritic cells and B cells throughout the FRT present antigen. We will assess how antigen presentation is influenced by endocrine balance and whether FRT antigen presentation can be enhanced by receptor (pIgR and FcR) targeting. The third project will define the response arm of the mucosal immune system in the FRT. The hypothesis to be tested is that lymphocytes provide protection against pathogens while maintain reproductive function. These studies will determine whether selective loss of CTL function in the uterus during the secretory phase of the menstrual cycle is down-regulated by FRT leukocytes. These studies will increase our presently limited understanding of immune protection of the female reproductive tract and should provide the basis of knowledge essential for the prevention of local infection in the genital mucosa, the management of sexually transmitted diseases, and insight into the heterosexual transmission of HIV-1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: NATURAL HISTORY OF MENOPAUSE IN HIV INFECTED DRUG USERS Principal Investigator & Institution: Schoenbaum, Ellie E. Professor; Montefiore Medical Center (Bronx, Ny) Bronx, NY 104672490 Timing: Fiscal Year 2001; Project Start 20-SEP-2000; Project End 31-AUG-2005 Summary: Description (from applicant's abstract): This proposal seeks to investigate the process of menopause among HIV-infected women. The specific aims are to describe: 1) the impact of HIV infection and drug use on menopausal symptoms and biologic markers; 2) attitudes and knowledge about menopause among HIV infected and drug using women, 3) the impact of H IV infection and drug use on bone mineral density before and after menopause: and 4) impact of HIV infection and antiretroviral therapy (HAART) on dyslipidemia, insulin resistance, and development of post-menopausal cardiovascular disease. The proposal is for a five-year prospective study of 750 middleaged women in the Bronx, half of whom are HIV infected, and half at risk for HIV infection. A significant number of the participants will come from existing cohorts HIV Epidemiologic Research Study (HERS) which is ending and HIV Epidemiologic Research on Outcomes Study (HEROS) which will continue until 2002. Women will be recruited from the community to complete the newly proposed cohort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NMR IMAGING AND STEREOLOGIC ANALYSIS OF TRABECULAR BONE Principal Investigator & Institution: Wehrli, Felix W. Professor; Radiology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-JAN-1993; Project End 31-MAR-2004 Summary: Most osteoporotic fractures occur at skeletal locations rich in cancellous (trabecular) bone. The most widely used criterion for risk assessment is bone mineral density (BMD). However, it is well known that BMD is not a satisfactory predictor of fracture risk. Indeed, there is now compelling theoretical, experimental and clinical

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evidence for the role of architecture as an additional predictor of the bone's mechanical competence. During the past cycles of this project we have shown both in the laboratory and in patient studies that magnetic resonance micro-imaging (mu-MRI), in conjunction with image analysis, can predict the trabecular bone's mechanical behavior and clinical outcome, respectively. In preliminary work we have conceived a new approach toward a complete quantification of cancellous bone architecture based on three-dimensional digital topological analysis and have shown that this techniques accurately describes the conversion of trabecular plates to rods, a process well known to occur during aging and, in particular, in osteoporosis. Paralleling these developments we have made significant progress in data acquisition, processing and analysis, which improved both sensitivity and precision of mu-MRI to the extent that longitudinal studies are now feasible. During the next phase of the project we propose (i) to further develop and evaluate digital topological analysis and additional structural analysis tools; (ii) to determine the precision of the mu-MRI-derived topological and scale parameters in specimens and representative patients; (iii) to assess the sensitivity of the method to detect architectural changes during early menopause in a pilot project involving women treated with estrogen and their controls; (iv) to compare sensitivity and precision of mu-MRI with DEXA and p-QCT. The overall hypothesis to be tested is that mu-MRI-based cancellous bone structural analysis is sensitive and reproducible and capable of detecting changes in cancellous bone architecture as they occur over time, either as a result of normal changes or in response to treatment. The long-term goal of the work proposed is to establish "virtual bone biopsy," analogous to physical bone biopsy, by three-dimensional architectural analysis of mu-MRI data collected in vivo, as a means to follow patients longitudinally, either as a method for assessing osteoporosis risk or for evaluating treatment efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: NORETHINDRONE PERIMENOPAUSE

WITH

ETHINYL

ESTRADIOL

IN

Principal Investigator & Institution: Berga, Sarah L. Professor and Chair; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001 Summary: The purpose of this investigation is to determine whether the continuous administration of FemHRT (CI-376) [1 mg norethindrone acetate (NA)/10 ug ethinyl estradiol (EE)] is an effective treatment for the symptoms associated with perimenopause. Currently, low-dose oral contraceptive (OCs) are prescribed to alleviate the symptoms of perimenopause. However, we hypothesize that the use of hormone replacement therapy (HRT), specifically FemHRT (CI-376), will also improve cycle control and provide symptom relief but at a lower estrogen exposure than oral contraceptives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: OBESITY PREVENTION AFTER SMOKING CESSATION IN MENOPAUSE Principal Investigator & Institution: Geiselman, Paula J. Associate Professor; None; Lsu Pennington Biomedical Research Ctr 6400 Perkins Rd Baton Rouge, LA 70808 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2003 Summary: The present proposal is an obesity prevention pilot study that addresses the high risk of weight gain associated with smoking cessation in postmenopausal women,

98 Menopause

especially African Americans. This proposal is innovative and unique in its analysis of at and other macronutrient intake as a target for individually tailored, weight control intervention following smoking cessation in women. This treatment program is designed for the primary prevention of weight gain that can lead to overweight in normal- weight women, that can progress to obesity in women who are already overweight (BMI=25.0-29.9), and for the prevention of additional weight gain in obese women with BMI's greater than or equal to 30.0. Postmenopausal African-American and Caucasian women aged 45-59 years will undergo the same standard two-week smoking cessation program followed by a 20-month, experimental or control follow-up intervention. Specific aim 1; To compare the relative effectiveness of following an empirically validated smoking cessation program with either 1) a group cessation maintenance program with standard exercise advice and food pyramid instructions for healthy eating or 2) a novel, individually tailored dietary-control and exercise, weightmanagement and cessation program in Caucasian and African-American postmenopausal women as assessed by weight change from baseline to post-cessation months 6, 12, and 20. It is hypothesized that our individually tailored, long-term, experimental intervention will effectively control dietary intake, particularly fat intake, thereby preventing weight gain post-cessation. Specific Aim 3: To assess whether there is differential responsiveness on the above measures in postmenopausal Caucasian versus African-American women. It is hypothesized that African-American women may respond differently from Caucasian women on the above measures. This pilot study is an extension of our research program with the long-term objective of developing individualized, multi-disciplinary, long-term interventions for the prevention of weight gain following smoking cessation in various subsets of women throughout the American population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: OFFICE BASED METHADONE PRESCRIBING II Principal Investigator & Institution: Drucker, Ernest; Montefiore Medical Center (Bronx, Ny) Bronx, NY 104672490 Timing: Fiscal Year 2001; Project Start 05-SEP-1997; Project End 31-MAR-2005 Summary: (Applicant's Abstract) This is the continuation and expansion of a study (RO1 DA11324) examining the practicality, safety, and clinical efficacy of the office based prescription of methadone by primary care practitioners. The current study population consists of a cohort of 150 women drawn from our Methadone program and randomly assigned to office based prescribing (OBP) or usual care in Methadone Maintenance Treatment Programs (MMTP). At 12 months follow-up, we have found that OBP produces equivalent treatment retention and reductions in illicit drug use, compared to the controls in MMTP. Over 50% of our 12,000 current MMTP patients meet the eligibility criteria for OBP-at least 6 months in MMTP, a stable dose of methadone, and some "take home" privileges. As was found in prior observational studies outside the U.S., it appears feasible to integrate methadone prescribing into office-based medical practice. In the continuation of this study, we propose to follow the current cohort of 150 women for an additional 24 months (for a total of 36 months), to "crossover" 50% of the female controls into OBP, and to add 100 male patients to the randomized design (50 OBP and 50 MMTP). By increasing the size and diversity of the cohort and following them for a total of 3 years, we will both increase the generalizability of our preliminary findings. We will initiate a health services component to study the integration of methadone prescribing within routine medical practice-evaluating patient and provider experiences and satisfaction, the patients' utilization and costs of primary and specialty

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medical care (with special attention to Hepatitis C, HIV/AIDS, and menopause). Secondary outcome measures (subsidiary or pilot studies) will continue to examine evidence of the use of other drugs (e.g., cocaine), and social adjustment (i.e. work home, criminal activity) In addition, as part of our exploration of alternative models of Methadone treatment, we propose to conduct a pilot study of community pharmacy dispensing of methadone for a sub- group of 20 stable patients (in both OBP and MMTP) who have been in the study for at least 12 month. Both the sponsoring medical institutions' methadone and medical care programs and the group of 15 primary care and specialist physicians currently prescribing Methadone and providing medical care for these patients have agreed to continue participating in the study and to expanding the number of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ORGANIZATION OF THE IMMUNE SYSTEM IN THE HUMAN FEMALE REPRODUCTIVE TRACT Principal Investigator & Institution: Fanger, Michael W. Professor of Microbiology & Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001 Summary: The tissues of the human female reproductive tract (FRT) exhibit defined and organized microenvironments that influence immune cell function. Furthermore, the sex steroid hormones, estradiol and progesterone, have a controlling influence on both the afferent and the efferent arms of the immune system. To date, studies of the human mucosal immune system have largely relied on the study of isolated cells, an approach which does not allow evaluation of the influence of tissue architecture and microenvironment. Moreover, relatively few studies of the immune system of the human FRT have been carried out. Thus, our current understanding of the organization and function of the immune system in this critically important organ system is clearly inadequate, as is our understanding of the endocrine influences on immunity in these tissues. The proposed studies will use novel in situ techniques, which utilize viable tissue sections, to test the hypothesis that sex hormones regulate immune cell organization and function in the different microenvironments of the uterine endometrium (EM) of the FRT. In particular, we postulate that during the menstrual cycle, sex hormones and cytokines act in concern to regulate the organization and function of immune cells within the EM of the FRT. More specifically, we will: 1) Determine the organization of T and B lymphocytes and myeloid cells within the different microenvironments of the EM of the FRT and how this varies with stage of the menstrual cycle. 2) Identify the mechanisms responsible for the regulation of architectural remodeling in the EM with regard to the role of cell proliferation, apoptosis, cytokines and adhesion molecules. 3) Determine the role of sex hormones and cytokines on cytotoxic T cell and myeloid cell function in the different microenvironments of the EM. The results of these studies should provide valuable insights into the organization and function of the immune system of the FRT, which in turn will enhance our understanding of the susceptibility of the FRT to sexually transmitted diseases, and be of value in the rational design of regimens for immunization against these diseases. These studies will also contribute important information useful for the evaluation of the mechanisms leading to gynecological malignancies and other diseases of the FRT, including endometriosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OSTEOGENIC MECHANICAL STIMULI-PREVENT/REVERSE BONE LOSS Principal Investigator & Institution: Kiel, Douglas P. Associate Professor; Hebrew Rehabilitation Center for Aged 1200 Centre St, Roslindale Boston, MA 02131 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 31-AUG-2003 Summary: Therapies which increase bone formation are highly desirable, yet few are available, and those under investigation, have significant disadvantages. Extremely low magnitude (less than 10 microstrain) biomechanical stimuli, intended to supplant the deterioration of muscle dynamics which parallel the aging process, can be introduced non-invasively into the skeleton as a non-pharmacologic means of increasing bone mass and strength. In animal studies, we have demonstrated that short periods (less than 30 min) of mechanical loading, applied at a relatively high frequency (15-90 Hz), will increase trabecular volume and number, mineral apposition rate and labeled surface, and will decrease trabecular spacing. Moreover, a one-year double-blind placebo controlled clinical trial of mechanical stimulation in 55 post- menopausal women, exposed to short duration (20 minute), low magnitude (0.2 g), 30 Hz mechanical stimuli demonstrated that lumbar spine bone mineral density (BMD), normalized for body weight, declined by 3.3 percent BMD in the control group compared to only 0.8 percent in the treated group. Similarly, in the trochanter region of the hip, a 2.8 percent loss was observed in the control group while the treated group experienced a 0.4 percent gain. Stratified for body mass index, it was clear that the efficacy of treatment was greatest in thinner women (BMI less than 24 K g/m2). The biomechanical stimulation was very well tolerated. The central hypothesis of this proposal is that osteogenic mechanical stimulation (0.3g at 30 Hz for 10 minutes daily) will effectively inhibit the rapid bone loss that immediately follows the menopause, and will serve to reverse bone loss in a population of frail elderly women. These two principal hypotheses will be addressed in a prospective, double blind, multi-center trial in which two experimental groups will be studied: women 1-6 years past the menopause (100 subjects), and women greater than 70 years of age (50 subjects). The recently menopausal women will have a hip T-score (TOTAL, neck, trochanter or intertrochanter) between -0.5 and -1.5 while the elderly participants will have T-scores less than -1.5. All women will be of thin body stature (body mass index below 26 kg/m2). In the feasibility trial, described above, it was women of this body and BMD status that were most responsive to the biomechanical treatment. The primary outcome variable, bone mineral density at the hip, will be measured at baseline and at 12-month intervals for three years. Secondary outcome variables will include BMD at the spine, and indices of bone formation and resorption, as well as the effect of these interventions upon postural stability, another key risk factor for fracture. We anticipate that the results of this study will demonstrate the attributes of a unique osteogenic biomechanical therapy for osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OVARIAN ASPECTS OF CALORIC RESTRICTION Principal Investigator & Institution: Zelinski-Wooten, Mary B. Affiliate Assistant Scientist; None; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Caloric restriction (CR) extends the life span, slows aging and retards age-related disease processes in short-lived mammalian species. Reproductive aging encompasses a life-long continuum of follicle depletion in the ovary that leads to decreased fecundity in older women and culminates in menopause, the

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cessation of ovarian/menstrual cyclicity, and its associated health-related risks. Caloric restriction delays the onset of ovarian follicular loss in rodents. Whether ovarian senescence is likewise suspended during CR in primates is not well understood. Using young and old female rhesus monkeys undergoing acute and long-term CR and their age-matched controls (CON), we propose to assess whether CR alters ovarian aging by determining: 1 ) the patterns and levels of gonadotropin and steroid hormones as well as inhibin-related proteins during spontaneous menstrual cycles and the perimenopausal period; 2) the responsiveness of somatic cells of the ovarian follicle, i.e. granulosa cells, to exogenous gonadotropin or "fertility" treatment, and resultant follicular growth and maturation; and 3) gene expression in luteinizing granulosa cells and localization of protein factors involved in the pro- or anti-apoptotic (cell death) pathways in the ovarian follicle. Hormonal profiles will be measured in daily samples during 3 consecutive menstrual cycles in all animals, and frequent sampling will be done over a 6-hour period during the early follicular phase of 21 cycles to determine gonadotropin pulsatility in acute CON and CR animals. AII animals will receive recombinant human gonadotropins to stimulate the growth of multiple pre-ovulatory follicles followed by a bolus of hCG to induce peri-ovulatory events. Progesterone production by luteinizing granulosa cells in the presence or absence of hCG in vitro will be measured, and global gene expression will be assessed by microarray technology. Ovarian morphology and protein localization will be examined with histochemical and immunocytochemical analyses in acute CON and CR animals. These studies will provide valuable insight into the potential impact of CR on the mechanisms of ovarian aging in primates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: OVARIAN FAILURE AMONG HYSTERECTOMIZED WOMEN Principal Investigator & Institution: Moorman, Patricia G. Assistant Professor; Community and Family Medicine; Duke University Durham, NC 27706 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Early menopause may increase the risk of osteoporosis, cardiovascular disease, and all-cause mortality. For approximately 20% of the female population, age at menopause is unknown because they had a hysterectomy without bilateral oophorectomy before their menstrual periods ended. There is some evidence to suggest that hysterectomized women who retain their ovaries are likely to experience ovarian failure earlier that women who go through natural menopause, however most prior studies had important limitations, including small sample size, lack of comparison group, and imprecise measures of menopausal status. In the proposed 5year study, we will investigate whether hysterectomized women who retain at least one ovary are more likely to experience ovarian failure than women of similar age who have an intact uterus and ovaries. We will recruit 500 premenopausal women aged 30 to 47 years who are undergoing hysterectomy without bilateral oophorectomy at Duke University Medical Center or Durham Regional Hospital, and 500 non-hysterectomized, premenopausal women frequency matched on age and race from gynecology practices in the Durham, North Carolina area. At baseline, all women will have a blood sample drawn and complete an interview focusing on reproductive, hormonal, and lifestyle characteristics that may be related to ovarian function. Serum samples will be analyzed for follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol. Women will be recontacted annually to have another blood sample drawn and update questionnaire information, particularly menopausal symptoms and hormone use. Menopausal status at each follow-up will be determined for all women using an

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algorithm based on measurements of FSH, estradiol, and LH. The primary goals of the study are: 1) to determine whether the risk of ovarian failure during the approximate 4 years of follow-up is greater for hysterectomized women than non-hysterectomized women, and 2) to evaluate the associations between medical, reproductive, and lifestyle characteristics and early ovarian failure. Hysterectomy is the most common nonobstetrical surgery in the United States, with over 600,000 procedures performed each year. The proposed study will contribute greatly to our understanding of the long-term effects of hysterectomy on ovarian function. It should have considerable public health impact given the high frequency of the procedure and the important health consequences of early ovarian failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: OVARIAN FOLLICULAR ACTIVATION AND GROWTH IN VITRO Principal Investigator & Institution: Cushman, Robert A. Biomedical Sciences; Cornell University Ithaca Office of Sponsored Programs Ithaca, NY 14853 Timing: Fiscal Year 2001; Project Start 01-FEB-2001 Summary: The mammalian ovary contains a large reservoir of non-growing primordial follicles. Very little is understood about the mechanisms governing activation of these follicles into the pool of growing follicles and growth of early preantral follicles. We have developed a culture system that supports activation of primordial follicles in organ cultures of bovine and baboon ovarian cortex; however, very few of these follicles grow to the secondary stage even after 20 days in culture. We have also developed a method for grafting cortical pieces beneath the chorioallantoic membrane (CAM) of 6-day-old chick embryos. The CAM grafts are quickly vascularized and spontaneous activation is inhibited. These two unique experimental models provide exciting opportunities to investigate the mechanisms that control activation of primordial follicles and preantral follicle growth. Therefore, I propose to further characterize ovarian cortical culture and CAM grafts as models for studying follicular activation and early growth (Specific Aim #1). I will also use these two exciting experimental models to determine whether kit ligand stimulates activation of primordial follicles (Specific Aim #2), and to examine the roles of growth hormone and growth differentiation factor-9 in growth of early preantral follicles (Specific Aim #3). The ultimate goals of this research are to elucidate fundamental mechanisms that may lead to new contraceptive technologies, new methods for alleviating infertility, and a better understanding of mechanisms of follicle depletion (menopause). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PLASTICITY

OVARIAN

STEROID

HORMONES

AND

HIPPOCAMPAL

Principal Investigator & Institution: Desmond, Nancy L. Psychologist; Neurological Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001; Project Start 15-APR-2001; Project End 31-MAR-2005 Summary: adapted from applicant's abstract) Hippocampal function is modulated by changing levels of the ovarian steroids, estradiol and progesterone, in adult females. Of particular interest here are the observations that 1) estradiol modulates long-term potentiation (LTP) and long-term depression (LTD) of the CA3-CA1 synapses and 2) estradiol increases the excitability of CAl pyramidal neurons. We hypothesize that these two observations are not independent and that the increased neuronal excitability underlies the estradiol-dependent changes in synaptic plasticity. Thus the long-term

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goal of this new R01 application is to understand how changing levels of estradiol modulate the excitability of the hippocampal CA1 region and thereby the long-term synaptic modification that occurs at the CA3-CA1 synapses. Here the focus of study is the hypothesis that estradiol increases recurrent CA 1-CA 1 connectivity. Using electrophysiological and pharmacological methods in hippocampal CA1 mini-slices from adult, ovariectomized (OVX) rats pretreated with estradiol or vehicle, Aim 1 characterizes the magnitude of this changed excitability and tests hypotheses concerning the proximal causes of this enhanced excitability. Aim 2 addresses the physiological significance of this enhanced excitability using CAl mini-slices from normally cycling rats across the estrous cycle. We will also determine whether the time course of the increase in excitability across the estrous cycle correlates with the time course of the changes of synaptic plasticity (LTP and LTD) at the CA3-CA 1 synapses. Aim 3 uses morphological methods to explore the hypothesis that this estradiol-dependent increase in the excitability of CAl pyramidal neurons involves the formation of recurrent excitatory CAl-CAl synapses. We will determine if the local axonal arborizations of CAl pyramids increase with estradiol treatment of OVX rats. Aim 4 tests the hypothesis that this estradiol-dependent increase in hippocampal excitability requires the action of genomic estrogen receptors. These studies will help us to understand better how estrogens modulate the hippocampal function and thus its cognitive functions in females. Moreover, these are likely to provide important insights for understanding the biological basis of memory problems that can occur with menopause. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: OVARY INTACT MURINE MODEL FOR MENOPAUSE Principal Investigator & Institution: Hoyer, Patricia B. Professor; Physiology; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-MAR-2008 Summary: (provided by applicant): By the year 2025, 19.5% of the population of the U.S. will be post-menopausal aged women. Many health risks are associated with menopause, thus, research into menopause and aging in women is of prime interest. Investigations of menopause-associated disorders in a relevant animal model would be particularly useful. The occupational chemical 4-vinylcyclohexene diepoxide (VCD) has been well characterized and found to induce pre-mature ovarian failure in mice and rats by accelerating the natural process of atresia (apoptosis). More recently, preliminary data have demonstrated that VCD-induced follicle loss in mice can cause depletion of primordial follicles within 15 days of daily dosing. This results in complete ovarian failure within 46 days of the onset of dosing, and the animals retain residual ovarian tissue. Physiological end points related to several menopause-associated disorders, including osteoporosis, cardiovascular disease, and ovarian cancer have been observed in VCD-treated mice. The majority of women enter menopause by a gradual depletion of ovarian function and they retain residual ovarian tissue. Thus, a follicle-deplete, ovary-intact animal would most closely mimic the natural progression through perimenopause and into the post-menopausal stage of life. It is proposed here to conduct studies to more completely characterize the physiological end points that have already been seen. The hypothesis to be tested is that the VCD-treated mouse will serve as a highly relevant animal model for studies aimed at understanding many of the facets of menopause. Four Specific Aims have been proposed: Specific Aim 1: To determine events surrounding the period of impending ovarian failure (model for perimenopause) Specific Aim 2: To investigate mechanisms by which osteocalcin levels are elevated (model for osteoporosis) Specific Aim 3: To characterize the development of

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aortic lesions (model for cardiovascular disease) Specific Aim 4: To evaluate changes resulting from proliferation of the ovarian surface epithelium (model for ovarian cancer). The studies proposed here will provide evidence in the follicle-deplete, ovaryintact mouse as to what aspects of menopausal physiology and pathology are particularly relevant for designing future studies aimed at mechanistic or therapeutic issues. Characterization of the VCD-treated mouse will, therefore, make a profound contribution to the study of menopause-related pathologies and, therefore, to women's health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PATHOLOGY OF AGING Principal Investigator & Institution: Didier, Peter J.; Tulane University of Louisiana New Orleans, LA 70118 Timing: Fiscal Year 2001 Summary: The objectives of this pilot project are to evaluate changes in ovarian morphology, serum estrogen, bone density, and DNA deletions over time in female rhesus monkeys. Preliminary results indicate that bone strength from young monkeys 35 years of age and aged monkeys 22-25 years is different and that breaking strength of femurs decreases substantially with age. Young monkey femur strength was 13.5 MPa (comparable to a previous report by Yamada, 1970) while aged monkey femur strength averaged 9.7 MPa, about 70% less. Thickness of cortical and trabecular bone decrease with age while the number of trabecular intersections increases. Similar measurements using the wing of the pelvis (iliem) failed to demonstrate these correlations. Recent work has concentrated on development of more sensitive measurements of bone strength. Precisely machined specimens of femur and lumbar vertebrae have recently been tested by ash content, ultrasonic mapping, compression and three point bending tests usin g a mechanical testing system (MTS Systems Corporation, Minneapolis). Using a threepoint bending test on specimens from the femur the average ultimate strength in the oldest age group (25-30 yr.) was significantly lower (p<0.05) than in all other age groups except the youngest (0-5 yr.)(p=0.076). We plan to evaluate the effect of activity level and age on bone strength (using housing history of coral vs. inside cage) but as yet, we do not have enough specimens to make this comparison. Using ultasonic equipment (digitizing oscilloscope, function generator, and piezoelectric crystal transducers) density tends to be less in older femur groups while elastic moduli (a measure of bone strength) peak at age 15 (11.9 Gpa). Young animals and very old animals have very similar elastic moduli (4.6 and 5.3 Gpa, respectively). A significant relationship has been established between ash density and compressive strength of lumbar bone but no significant difference amoung age groups and ultimate s trength measurements (range 8.3-11.1 Mpa). Enumeration of eggs, primary follicles and cystic follicles in histologic sections of ovaries showed substantial decreases with age. The results could provide the basis for future studies on effects of aging in females from puberty through menopause in response to exercise and dietary treatments. FUNDING Base Grant, Venture Research PUBLICATIONS None Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PERIMENOPAUSAL ACUPUNCTURE

SYMPTOMS

MANAGEMENT

WITH

Principal Investigator & Institution: Cohen, Susan M.; Yale University 47 College Street, Suite 203 New Haven, CT 065208047

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Timing: Fiscal Year 2001 Summary: We propose to test the use of acupuncture for menopausal symptom relief for women who experience menopause following treatment for breast cancer. The study is designed to test the effect of acupuncture on the menopausal symptom of hot flashes, explore the anticipated treatment benefit of acupuncture on menopausal symptoms of mood changes, sleep disturbances, loss of concentration, joint pain, headache and nervousness as well as changes in ovarian hormones and quality of life, and increase the knowledge base concerning the effectiveness of alternative/complementary health practices. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: P-GLYCOPROTEIN EXPRESSION AND FUNCTION IN HIV+ WOMEN Principal Investigator & Institution: Benet, Leslie Z. Professor; J. David Gladstone Institutes 365 Vermont St San Francisco, CA 94103 Timing: Fiscal Year 2001; Project Start 23-APR-2001; Project End 31-MAR-2006 Summary: Description (Abstract Provided by Applicant): We hypothesize that gender, ovulatory function and disease may affect P-glycoprotein (P-gp) expression in the intestine and other organs such as the liver, endometrium and lymphocytes, thereby modulating the effectiveness of protease inhibitors (PIs) in HIV+ women. P-gp expression and function varies with ovulatory function and phase. The highest levels occur during menopause and in the midluteal phase of the cycle; the severity of disease can also influence P-gp activity in various tissues in women (liver, gut, lymphocytes and endometrium). This in turn can affect the pharmacokinetics and pharmacodynamics of protease inhibitors (PIs) as well as the progression of HIV disease. While differences in pharmacokinetics of drugs that are cytochrome P4503A (CYP3A) and P-gp substrates, such as the PIs, are manifested as differences in metabolism, we believe that this end result is regulated by differences in P-gp function and activity rather than by differences in CYP3A expression across the population. Project IV has five specific aims: I) to determine if the intestine, like the liver and endometrium, exhibits variable levels of transporter and enzyme that are regulated by progestins and/or estrogen, (which will also serve as a measure as to how well commonly used cell lines, e.g., liver and endometrium, exhibit characteristics that may be useful in testing the hypothesis); 2) to learn whether an assay in lymphocytes might be used as a simple model for what occurs in the endometrium, intestine and liver; 3) to test whether known differences in P-gp between premenopausal and postmenopausal women translate into differences in PI drug levels; 4) to correlate ovulatory cycle phase (early follicular, midluteal and postmenopausal) and/or P1 levels with markers of viral resistance; and 5) to determine the effects of four parameters: (a) stage of ovulatory cycle phase (early follicular. midluteal or postmenopausal), (b) ethnicity (particularly African American vs. Caucasian), (c) presence vs. absence of HIV infection, and (d) CD4 count strata on P-gp expression, as measured by quantitative analysis of P-gp in tissue biopsies (intestinal cells, endometrium and peripheral blood mononuclear cells) and P-gp function, as measured by PT pharmacokinetic profiles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHARMACOLOGIC STUDIES OF SOY PHYTOESTROGENS Principal Investigator & Institution: Clarkson, Thomas B. Professor; Wake Forest University 2240 Reynolda Rd Winston-Salem, NC 27106

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Timing: Fiscal Year 2001 Summary: (Adapted from Applicant's Abstract) During the last program project period, the investigators obtained experimental evidence to support the conclusion that soy phytoestrogens (isoflavones) may be a useful alternative to traditional hormone replacement therapy for females, protecting against atherosclerosis without deleterious effects on the breast and endometrium. The investigators also found in a study with preand peripubertal cynomolgus males that the soy isoflavones were cardioprotective and did not affect the reproductive system. These studies increased the investigators' awareness of the public health importance of the simultaneous potential protective effects against coronary heart disease and hormone dependent cancers. In Project 1, the investigators propose to intensify their pharmacologic studies of the soy phytoestrogens using surgically menopausal female and mature male monkeys in a series of short-term Latin Square designs to assess the effects of varying doses, forms, and ratios of the phytoestrogens on intermediate outcomes (Aims 1, 2, 3). Aim 4 will be a longer-term comparison of "optimal" (best protein, isoflavone ratio, and dose) and control treatments. This project will assess treatment effects on cardiovascular disease risk factors and reproductive system of both genders and bone endpoints in females. The questions to be addressed are: 1. Is the high molecular weight fraction or the 7S peptide component in soy protein more effective than soy protein isolate on improving lipid metabolism and is one of these fractions required for the isoflavones to have their effect? 2. Are there different effects on disease markers with soy phytoestrogen preparations that are predominately genistein or predominately daidzein? 3. What is the relationship between dose of soy phytoestrogens and disease markers? 4. What are the longer-term effects of the optimal soy treatment on disease markers? This project relates directly to the central theme of the program project, specifically, to better understand the cardioprotective benefits of the soy phytoestrogens. The data to be obtained in this project should contribute to the understanding of data obtained in Projects 2 and 3 while Projects 2 and 3 will provide pathologic outcomes to support the intermediate endpoints used in this project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PHYSIOLOGY OF ESTROGEN'S MOOD EFFECT IN MENOPAUSAL WOMEN Principal Investigator & Institution: Joffe, Hadine; Instructor Massachusetts General Hospital 55 Fruit St Boston, MA 02114

in

Psychiatry;

Timing: Fiscal Year 2003; Project Start 07-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This Mentored Patient-Oriented Career Development Award focuses on developing expertise in the interdisciplinary field of perimenopausal depression. Menopause is universal in women, and depressive disorders occur in 10% of perimenopausal women. This project will dissect the mechanisms by which estrogen replacement therapy (ERT) treats depression in menopausal women. We hypothesize that ERT improves mood by a direct CNS effect, rather than by simply treating hot flushes and sleep disruption. A physiologic intervention study will compare the mood effect of ERT with that of a hypnotic agent in depressed perimenopausal women. The direct neuromodulatory effect of ERT on mood will be unmasked by controlling for ERT's effect on sleep. Polysomnographic (PSG) studies will be used to explore changes in sleep architecture that occur with ERT and the hypnotic agent zolpidem. This study will: (1) identify the elements critical to estrogen's antidepressant benefit; (2) characterize subpopulations of perimenopausal women whose depression can be treated with non-hormonal therapies and those who require

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treatment with ERT; and (3) define optimal management of depression in perimenopausal women. Understanding the components of ERT's effect on mood will also advance the field of hot-flush research by examining the impact of hot flushes on sleep, mood, and quality-of-life. This is critical for the development of novel estrogen alternatives and putative hot-flush therapies increasingly used in women with breast cancer and others unable or unwilling to take ERT. ENVIRONMENT: The proposed study will be based at Massachusetts General Hospital (MGH), with outstanding interdisciplinary sponsorship and consultant input. PSG studies will be performed at McLean Hospital. I will receive mentorship from Lee Cohen, M.D., in the Department of Psychiatry, and Janet Hall, M.D., in the Reproductive Endocrinology Unit of the Department of Medicine at MGH. Both sponsors are internationally recognized in their respective fields and have exceptional track records as effective research mentors. Their combined expertise will shape my career development in this interdisciplinary field. CAREER DEVELOPMENT PLAN: Physiologic investigation of mood disturbance in menopausal women requires that I acquire knowledge of (1) sleep medicine; and (2) research methods for healthoutcomes assessment and clinical intervention studies using physiologic measures. I will receive formal training in each of these specific research areas under the supervision of expert consultants. Such training will lay the foundation for a career of clinical investigation into the physiology of perimenopausal depression and the impact of hot flushes on sleep, mood, and quality-of-life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PILOT--CORONARY DISEASE: POST MENOPAUSE DISEASE MARKERS Principal Investigator & Institution: Hoff, Julie A.; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: (from applicant's Abstract) Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among women in the U.S. It accounts for nearly 500,000 deaths annually with coronary artery disease (CAD) accounting for more than half of the deaths. Conventional CAD risk factors are cigarette smoking, dyslipidemias, hypertension, diabetes, and obesity. Oral contraceptive use, menopause, and postmenopausal hormone replacement therapy status have been shown to be unique CAD risk factors for women. CAD primary prevention efforts for both men and women focus on the identification and management of CAD risk factors, yet studies have shown that risk factors predict less than 50 percent of all cardiovascular events and 50 percent of all myocardial infractions occur in individuals with normal plasma lipid levels. In an effort to better identify and stratify risk of atherosclerotic events in healthy populations several new markers of CAD risk have been proposed for use in screening they are: lipoprotein (a) [Lp(a)], homocysteine (tHcy), C-reactive protein (CRP), particle size and various concentrations of low density lipoproteins (LDL) and high density lipoproteins (HDL). This proposal seeks to conduct a pilot study that will explore the prevalence of new markers of CAD risk and clinically measured CAD risk factors among a cohort of self-referred, post-menopausal women who have subclinical CAD as measured by electron beam tomography (EBT) and self-report the absence of conventional CAD risk factors. EBT allows for noninvasive detection and quantification of coronary artery calcium, a subclinical marker for CAD. The results of this pilot study will serve as preliminary data for a future NIH study in post-menopausal women that will investigate the association of new CVD markers and subclinical CAD as measured by EBT. In addition, longitudinal follow-up of a larger cohort will enable the determination

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of those CAD factors and CVD markers that are most predictive of CAD risk in postmenopausal women. Considering that nearly 50 million American women are now more than 50 years of age, there is not a more important health issue than the primary prevention of CVD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: POPULATION STUDY OF PREGNANCY AND PELVIC FLOOR DISORDERS Principal Investigator & Institution: Luber, Karl M. Director, Section of Urogynecology; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, CA 94612 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2005 Summary: The prevalence, natural history and risk factors for female pelvic floor disorders (PFD) are poorly understood. These disorders, which include urinary incontinence, anal incontinence and pelvic organ prolapse, have a profound effect upon women's lives and impact a large percentage of the adult female population in the United States. Despite years of research, the fundamental question of the effects of pregnancy versus parity versus aging alone on the development of these disorders remains unanswered. The primary aims of this study are to (1) to determine whether the effects of pregnancy, vaginal delivery or aging act as independent risk factors for the development of PFD, (2) to establish the prevalence of individual PFDs across a full age spectrum of a multi-ethnic population, and, (3) to validate and implement a multifaceted questionnaire for large population screening that includes information related to urinary incontinence (stress and urge), anal incontinence, and prolapse symptomatology. In order to control for potential confounders, race/ethnicity, socioeconomic status, physical activities, smoking, menopause, hormone use, and comorbid medical conditions will be measured and their relative contributions to PFD will be evaluated. The association between prolapse symptoms and incontinence symptoms will also be examined. Validation of a questionnaire to evaluate PFD will be done with female patients recruited from the Gynecology and Female Pelvic Medicine clinics in Kaiser Permanente's San Diego Service Area. The subjects for the population-based study will be drawn from approximately one million female members of Kaiser Foundation Health Plan that reside in the Southern California region who are between the ages of 25 and 84 years. For the population-based study, women will be invited to complete a self-administered, mailed questionnaire after receiving an introductory letter in the mail explaining the study. Responses from the questionnaire will be analyzed to ascertain the impact of age, pregnancy, and vaginal birth on PFD. It remains unknown whether vaginal delivery increases the risk of PFD independent of other risk factors, specifically pregnancy and aging. To answer these questions, large population based studies on the prevalence of these disorders among women of all ages and various reproductive histories, specifically nulliparas, those delivered by elective cesarean section alone and those with a history of vaginal delivery, are needed. The answer to these questions will direct future research in both treatment and prevention of PFDs, and enable physicians to counsel their patients on the risk of vaginal delivery as it relates to PFD particularly for women with a history of cesarean section delivery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POST ABDOMINAL FAT

MENOPAUSAL

HORMONE

THERAPY

AND

INTRA

Principal Investigator & Institution: Gower, Barbara A.; University of Alabama at Birmingham Uab Station Birmingham, AL 35294

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Timing: Fiscal Year 2001 Summary: Background: Hormonal and metabolic changes associated with the menopause may confer increased risk for cardiovascular disease (CVD). Data indicate that the postmenopausal period is associated with increases in total and central ("android") body fat; increases in the atherogenic components of the blood lipid profile; and deterioration of glucose tolerance - all risk factors for CVD. Changes in lipid and glucose metabolism may be secondary to accumulation of central fat, particularly intraabdominal fat (IAF), the compartment associated with dyslipidemia and insulin resistance. Hormone replacement therapy has positive effects on the lipid profile in postmenopausal women, and may affect regional fat deposition. However, the extent to which the beneficial effects of hormone therapy on disease risk factors are mediated by changes in fat distribution is not known. Few studies have examined the effects of hormone replacement therapy on body composition and fat distribution, and non have examined the effect of exogenous hormones on IAF, the adipose compartment most closely associated with disease risk. Objective: To test the hypothesis that hormone replacement therapy (HRT, combined estrogen-progestin) in postmenopausal women decreases risk by limiting IAF deposition. The proposed research will examine the effect of HRT on total, regional, and intra-abdominal fat deposition, and on the relationships between adiposity, the plasma lipid profile, and glucose metabolism. Design: Longitudinal cohort study of 140 early postmenopausal women using or not using HRT. A baseline assessment (within the first year of hormone use) and one 2-year follow-up assessment will be conducted. Total body fat will be assessed with dual-energy X-ray absorptiometry, hydrodensitometry, and deuterium dilution; and regional adiposity (thigh, abdominal, intra-abdominal) will be quantified with computed tomography. Circulating levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides will be determined. Insulin sensitivity and glucose tolerance will be assessed with the tolbutaminde-modified, frequently-sampled, intravenous glucose tolerance test and minimal modeling. Significance: HRT reduces risk and incidence of CVD in postmenopausal women. This study will determine if HRT reduces disease risk by influencing fat distribution and decreasing IAF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: POSTMENOPAUSAL HORMONAL REPLACEMENT THERAPY Principal Investigator & Institution: Vongpatanasin, Wanpen; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2007 Summary: (provided by applicant): Hypertension incidence rises sharply after menopause, implicating a beneficial effect of estrogen on blood pressure (BP) regulation. However, there still are large gaps in the understanding of the underlying mechanisms and treatment of postmenopausal hypertension. Using intraneural microelectrodes to record postganglionic SNA in normotensive postmenopausal women, the applicant recently provided direct evidence for a major sympathoinhibitory effect of estrogen. Chronic estrogen replacement decreased SNA by 30% and caused a small decrease in 24-hour ambulatory BP. The most fascinating aspect of the work is that these effects were much more robust with transdermal than oral estrogen. She now wants to investigate: 1) the clinical importance of her findings by studying postmenopausal hypertension; and 2) underlying mechanism causing a greater effect of transdermal than oral estrogen on SNA and BP. She hypothesizes that the mechanism involves first-pass hepatic metabolism of oral estrogen leading to decreased hepatic production of insulin-like growth factor and excessive deposition of fat in the liver and

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around the abdominal viscera, factors which are likely to stimulate SNA and negate a primary sympathoinhibitory action of estrogen. To test her mechanistic hypothesis, she will need to acquire new research skills including euglycemic clamps and nuclear magnetic resonance measurements of regional fat distribution. She will use these techniques in exploring other clinical factors, such as concomitant administration of androgenic progestins, that are likely to engage some of the same adverse metabolic mechanisms and negate the antihypertensive effect of estrogen replacement. Finally, the applicant will learn to perform complementary experiments in a conscious rat model to determine the extent to which decreased activity of the sympathetic nervous system causes the antihypertensive effect of estrogen. The long-term goal of her work would be the discovery the most effective estrogen preparation that can prevent or treat hypertension in women after menopause. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PREDICTING ONSET AGE AND LENGTH OF MENOPAUSAL TRANSITION Principal Investigator & Institution: Keenan, Daniel M. Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (Applicant s abstract) Because of the greater life expectancy of today, menopause and its physiological consequences are having an enormous impact on the well-being of the older female. The present research is concerned with identifying, elucidating, and quantifying the ovarian and neuroendocrine mechanisms underlying menopause. In particular, to establish that there is a specific sequential pattern of five phases that occurs during the menopausal transition, and to construct statistical predictors of the onset age and duration of the menopausal transition. Moreover, such a predictor will also allow for the estimation of a given subject's hormonal- reproductive age, not chronological age, which has enormous implications for the infertility consequences of aging. For example, based upon certain endocrine reproductive measurements taken from say a given 40 year-old female, methods will be constructed by which to predict her age of perimenopause onset and its length, and at same time to state whether she is hormonally that of a 40 year-old, or more like a 45 or 35 year-old. The ability to predict the age and length of the menopausal transition is clinically important because early menopause has associated with it increased risk of cardiovascular disease and osteoporosis, whereas late menopause has associated with it an increased risk of breast cancer and endometrial cancer. This research consists of three components. First, five prospective and cross-sectional clinical studies specifically designed for the above aims will be conducted at the University of Virginia GCRC, using pre-, peri-, and postmenopausal subjects. Second, a biomathematical model for the aging hypothalamic-pituitary- ovarian axis will be developed which includes its several feedback/feed forward interactions, the dynamical onset and shutdown of the LH surge and ovulation, as well as its eventual cessation. Third, based upon the preceding two, hypotheses concerning the five phases will be tested, and predictors of onset age and duration constructed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREMATURE MENOPAUSE IN SURVIVORS OF CHILDHOOD CANCER Principal Investigator & Institution: Sklar, Charles A. Associate Member; SloanKettering Institute for Cancer Res New York, NY 10021

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Timing: Fiscal Year 2002; Project Start 05-SEP-1998; Project End 31-JUL-2003 Summary: (Applicant's Description) Advances in the treatment of childhood cancer have resulted in markedly improved survival rates. However, with these advancements, cancer survivors now face the long-term consequences of treatment with intensive, multimodality therapies. While the majority of prepubertal girls and adolescent females retain or recover ovarian function during or immediately after completing cancer therapy, preliminary data indicate that many of these young women are at risk for premature menopause in the future. We propose to study, in a cohort of young adult survivors of cancer diagnosed during childhood/adolescence, the prevalence of early menopause, risk factors for the development of early menopause, the impact of an early menopause on quality of life and psychosexual functioning. The study cohort will consist of 5,500 young adult female survivors of cancer diagnosed during childhood and adolescence, selected from a larger population of survivors of childhood cancer, the Childhood Cancer Survivor Study (CCSS), and 3,000 sibling controls. Data will be collected using a self-administered questionnaire and will include the following topics: menstrual history and menopause status, covariates of menopause, health-related outcomes associated with premature menopause, and standardized instruments which measure quality of life and psychosexual functioning. Detailed information concerning cancer diagnosis and treatment, including cumulative drug dosages and radiation fields/doses, will be known for all study participants, facilitating the study of endpoints of interest. The large size of the study population, the heterogeneity of diagnoses and exposures, combined with the extensive treatment data, will allow assessment of interaction between the major risk factors of interest. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PREVALENCE ATHEROSCLEROSIS

&

PROGRESSION

OF

SUBCLINICAL

Principal Investigator & Institution: Tyrrell, Kim S. Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 18-SEP-2000; Project End 31-JUL-2004 Summary: (Adapted from the Investigator's Abstract) Subclinical atherosclerosis will be evaluated in 728 women (305 African American, 423 Caucasian) enrolled in the Pittsburgh and Chicago sites of the Study of Women's Health Across the Nation (SWAN), a multicenter study characterizing the biological and psychosocial antecedents and sequellae of menopause. The extent to which diminishing ovarian function affects vascular function and accelerates the development of atherosclerosis in the coronary arteries, aorta and carotid arteries will be evaluated. Serial measures of coronary and aortic calcification (by EBCT), carotid atherosclerosis, endothelial function and aortic stiffening will be performed two years apart. The prevalence and progression of subclinical atherosclerosis will be evaluated in relation to serial measures of ovarian function, psychosocial and behavioral factors, markers of clotting and inflammation as well as traditional cardiovascular risk factors, all collected in SWAN. Decreased ovarian function and premenopausal obesity are likely the primary determinants of early coronary atherosclerosis as measured by calcification on EBCT. Aortic calcification occurs earlier than coronary calcification, may predict coronary calcification, and is expected to be the best marker of risk associated with traditional factors in these younger women. Preliminary data indicate that changes in coronary and aortic calcification can be observed over short periods of time in these women. A period of diminishing estrogen levels is the optimum time to observe changes in endothelial function which likely precede measurable atherosclerosis and thus may be the earliest

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markers for disease potential. Vascular stiffness, a marker for the biologic aging of the vascular system, is highly correlated with measures of insulin sensitivity which is altered in women at mid-life in conjunction with increases in central adiposity. Racial differences in disease prevalence and the relative importance of certain risk factors are likely. The investigators state that in summary, this application will allow a detailed elucidation of how diminishing ovarian function affects cardiovascular disease, which can only be done within the context of a careful prospective study of the menopausal transition such as SWAN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SURVIVORS

PREVENTION

OF

OSTEOPOROSIS

IN

BREAST

CANCER

Principal Investigator & Institution: Waltman, Nancy L. Adult Health and Illness; University of Nebraska Medical Center Omaha, NE 681987835 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-DEC-2006 Summary: Osteoporosis can be a major debilitating, expensive, long term, irreversible condition, and breast cancer survivors are particularly at risk for osteoporosis. As a result of some chemotherapy agents, many of these women experience premature ovarian failure. At least 60% of women with breast cancer have estrogen receptor positive tumor status; thus, they are not candidates for hormone replacement therapy. Without estrogen, bone loss occurs rapidly the first five years of menopause and continues over time but at a slower rate. The purpose of this study is to test whether strength/weight training exercises enhance the effectiveness of risedronate (5 mg/day), calcium (1200 mg/day), and vitamin D (400 IU/day) in improving bone mineral density (BMD) in post-menopausal breast cancer survivors. The sample will be 218 subjects recruited within a 100 mile radius of r sites across Nebraska (Omaha, Lincoln, Kearney and Scottsbluff). Post-menopausal women with a history of stage O (in situ), stage I or II breast cancer, with a BMD DEXA T-score of -1.0 SD or lower at any of 3 sites (hip, spine, forearm) will be stratified by time since menopause (5 yrs or less: > 5 years) and randomly assigned to one of two treatment groups (G1 and G2), with approximately 109 per group. Differences in tamoxifen, smoking, intake of calcium, and body mass index (BMI) between the two groups at baseline will be examined; if differences exist they will be controlled statistically. Both groups will receive risedronate, calcium and vitamin D; G1 also will receive strength/weight training exercises for upper and lower extremities and spine. Facilitative strategies based on Bandura's (1997) Self-Efficacy Theory are designed and used to encourage long-term adherence for both groups. The multicomponent intervention is 24 months with follow-up at 30 and 36 months. The primary outcome measure is BMD of the hip, spine and forearm (via DEXA): secondary outcome measures are muscle strength and fractures. The impact of the multi-component intervention on outcomes will be assessed using General Estimating Equation methodology Measurement of outcomes will occur at 6 and/or 12 month intervals through 36 months. In addition, relationships will be examined between level of confidence in goal accomplishment and adherence to intervention components over time. This study may provide evidence of an effective alternative to HRT for treatment of osteoporosis in breast cancer survivors who are not candidates for HRT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROFILE-BASED, INTERNET-LINKED, OBESITY PREVENTION TRIAL Principal Investigator & Institution: Going, Scott B. Professor; Nutritional Sciences; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: The increasing prevalence of obesity and its co-morbidities and the limited success of previous weight loss/maintenance interventions argues the need for new approaches to prevent obesity. Peri-menopausal women are t high risk to develop overweight and obesity. Around that period, physiological and behavioral factors contribute to changes in energy expenditure which promote energy surfeit and progressive gain of total and abdominal fat, often exacerbated by loss of lean tissue Thus, we propose to develop and test an innovative individualized weight loss/maintenance program for overweight peri-menopausal women, driven by frequent assessment of subjects' biopsychosocial profiles (allowing timely intervention response to individual needs), and delivered through extensive use of new communication technologies (primarily and Internet-CD-ROM hybrid package) which have been largely unexplored in behavioral and biological research. To this end, overweight/obese perimenopausal (aged 45 to 55 years) women will be randomized to intervention (n=50) or control (n=50) after completing a 3-month core curriculum exercise, diet, and cognitivebehavior therapy. After a 3 months transition with computer training (intervention group only), intervention (15 months) will proceed via the internet only, except for laboratory measurements (intervention and control groups). Increased physical activity (approximately 1500 kcal/week), healthy eating and modest calorie restriction with adequate nutrients will be targeted, with special emphasis on promotion of self-directed behavior. Biopsychosocial "weight loss profiles" will be monitored through questionnaires on the web site and used to individualize intervention, respond to change needs, and assess their relationship with changes in body weight and composition measured by dual energy x-ray absorptiometry. We contend the internet/web site technology represents a potentially low cost and effective means for providing the continuous education, encouragement and social support to foster sustained behavior change and weight loss/maintenance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RALOXIFENE EFFECTS ON COGNITION IN EARLY MENOPAUSE Principal Investigator & Institution: Upchurch, Margaret B. Professor; Psychology; Transylvania University 300 N Broadway Lexington, KY 40508 Timing: Fiscal Year 2001; Project Start 15-MAY-2001; Project End 30-APR-2004 Summary: Applicant?s Hormone replacement therapy (HRT) in women is commonly used to diminish the physical symptoms of menopause and to reduce the risk of disorders such as osteoporosis, heart disease, and atherosclerosis. HRT may have by its own risks, in particular, an increased chance of developing endometrial or breast cancer. In an effort to reduce these risks, some physicians are prescribing the selective estrogen receptor modulator (SERM) raloxifene (trade name Evista) for the prevention of osteoporosis. Estrogen also has cognition-enhancing capabilities in postmenopausal women and may serve to prevent or delay the onset of Alzheimer?s disease. Because raloxifene can function as either an agonist or antagonist at estrogen receptors, it is not known whether it too may affect cognitive function. The goals of this study are to examine the cognitive function of women in the perimenopausal period and to compare the effects of estrogen replacement and raloxifene treatment on cognitive function. The

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women in the two replacement groups will be compared with same-aged women who are still menstruating and to same-aged postmenopausal women who are not on HRT. The research will therefore compare the function of age-matched women with cyclic variation in estrogen levels (premenopausal), consistently high estrogen levels (postmenopausal, HRT-estrogen), consistently high SERM levels (postmenopausal, HRT-raloxifene), and consistently low estrogen levels (postmenopausal, no HRT). The tests will assess verbal recall and mental rotation skills, cognitive abilities that are influenced by estrogen levels. Digit span and Trail-Making Test performance, skills for which there is little evidence of an estrogen effect, will also be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: REGIONAL FAT METABOLISM AND MENOPAUSE TRANSITION Principal Investigator & Institution: Tchernof, Andre; University of Vermont & St Agric College 340 Waterman Building Burlington, VT 05405 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF ESTRADIOL LEVELS IN THE BREAST Principal Investigator & Institution: Chatterton, Robert T.; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2001 Summary: Long-term exposure of the breast endogenous estradiol (E2) is widely to be an important in determining a women's risk of developing breast cancer. Previous studies have shown that breast fluid (BF) obtained from nipple aspirates has many times the concentration of estradiol in serum, and that the concentration is not reduced significantly after menopause when blood levels have declined. The purpose of the present study is to ascertain the factors and mechanisms by which estradiol levels are maintained in the breast and the biological activity associated with those levels. We will determine whether salivary estradiol, an estimate of diffusible estradiol, is more closely related to BF 32 than serum E2 in both pre- and postmenopausal women. We will determine whether adrenal androgen precursors can explain the maintenance of BF E2 in postmenopausal women. We will determine whether adrenal androgen precursors can explain the maintenance of BF E2 in postmenopausal women. We will determine whether BF E2 or blood levels of E2 are more closely associated with the concentration of an estrogen response gene product, pS2, and to the growth factor, EGF, in BF. From the ratios of steroid products in BF we will estimate the importance of the several potential precursors of BF E2 and the role of specific cytokines for biosynthesis of BF E2. Potential feedback effects of estrogen on the levels of BF 32 will be determined in women receiving ethinyl estradiol and in women taking the estrogen antagonist, tamoxifen. For these experiments we have developed specific and sensitive assays for salivary E2, BF E2, and BF EGF and a method for separating BF products in a highly efficient manner into phenolic (estrogen), neutral (androgen), and aqueous fractions so that many more substances can be measured from a small volume of BF. Additional assays will be developed according to established protocols. We have already collected samples from pre- menopausal women on a dietary intervention study, and we plan to recruit pre-menopausal women planning to start oral contraceptive use and women who will start tamoxifen treatment as well as a group of postmenopausal women for these studies. Being able to monitor the effect on BF E2 of factors involved in its

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biosynthesis and in its action in human subjects will give us insight into the ways in which one of the important determinants of breast cancer risk is regulated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: REGULATION OF OOCYTE VIABILITY BY GRANULOSA CELL CONTACT Principal Investigator & Institution: Peluso, John J. Professor of Physiology and Ob/Gyn; Physiology; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-MAY-2005 Summary: (provided by applicant): Menopause occurs once the number of primordial follicles is depleted. Moreover, a rapid depletion of primordial follicles is associated with the age-related decline in fertility and premature ovarian failure. It has been estimated that about 70% of these follicles are lost because of oocyte death. Other than this, extremely little is known about the mechanism by which these small follicles are maintained. Insight into the survival mechanisms that influence primordial follicles could come from understanding how these follicles are formed. During embryonic development, primordial germ cells (PGCs) migrate into the developing mammalian ovary, proliferate and then enter meiotic prophase. At this stage, many of the PGCs die via a specific pathway known as apoptosis. However, some PGCs establish contact with somatic cells (presumptive granulosa cells) to form primordial follicles. These PGCs, now referred to as oocytes, appear to be protected from undergoing apoptosis. This process occurs in all mammalian species including humans. While it has been known for decades that cell contact seems to protect oocytes from dying, the mechanism through which cell contact promotes oocyte survival is completely unknown. It is known that granulosa cell-oocyte interaction is mediated, in part, by the adhesion proteins, E- and N-cadherin. Based on our previous studies of granulosa cell apoptosis, we propose that E- and/or N-cadherin mediated cell contact stimulates phosphatidylinositol 3 kinase (PI3K) activity within the oocyte. It is further proposed that PI3K ultimately acts to maintain the viability of the oocyte. Understanding how granulosa cells interact with oocytes to preserve oocyte viability could provide important insights into various aspects of infertility and the mechanisms that control entry into menopause. Therefore, we will determine: 1) the effect of granulosa cell contact on the rate at which oocytes undergo apoptosis in vitro; 2) whether E- and/or N-cadherin mediated cell contact regulates oocyte viability; and 3) whether E- and/or N-cadherin mediated cell contact stimulates PI3K activity and thereby maintains oocyte viability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REPRODUCTIVE AGING AND THE HUMAN HYPOTHALAMUS Principal Investigator & Institution: Rance, Naomi E. Professor; Pathology; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2002; Project Start 01-JUN-1991; Project End 31-DEC-2006 Summary: Our overall goal is to characterize and understand the events that occur in the human central nervous system in response to menopause. We have found that human menopause is characterized by a striking hypertrophy of neurons within the hypothalamic infundibular nucleus. Postmenopausal neuronal hypertrophy occurs in a subpopulation of neurons containing estrogen receptor and neurokinin B (NKB) mRNA and is accompanied by a marked increase in tachykinin gene expression. GnRH gene expression also increases, but in a separate subpopulation of hypothalamic neurons.

116 Menopause

During our last funding period, we used animal models to provide strong evidence that the changes in NKB cell size and gene expression in postmenopausal women are due to removal of steroid negative feedback. In this renewal, we propose the first studies to elucidate the physiological relevance of the increase in NKB gene expression in postmenopausal women. In specific aim 1, we will test the hypothesis that NKB neurons participate in the hypothalamic circuitry regulating LH secretion in the rat using pharmacological tools and antisense oligodeoxynucleotide (ODN) knockdown techniques. In specific aim 2, we will characterize the anatomic relationship between arcuate NKB neurons and the reproductive axis. We will determine if arcuate NKB or NK3 receptor-immunoreactive neurons project to the preoptic-septal region (site of GnRH neurons) or the primary capillary plexus of the median eminence in the rat. We will also determine if GnRH neurons express NK3 receptor-immunoreactivity in the human or rat hypothalamus. In specific aim 3, we will attempt to gain a deeper understanding of the remarkable changes in the infundibular nucleus of postmenopausal women. We will determine if menopause is association with signs of cellular degeneration such as increased microglial cells or GFAP gene expression. We will also use the Golgi-method to determine if the neuronal hypertrophy is associated with expansion or regression of infundibular dendritic arbors. Our studies provide an exceptional opportunity to study human brain specimens and address basic biological, issues directly relevant to the physiology of postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: REPRODUCTIVE HORMONES AND PRE-CLINICAL CVD IN WOMEN Principal Investigator & Institution: Bairey Merz, C. Noel. Associate Professor and Medical Director; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, CA 90048 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Cardiovascular disease is the leading killer of women, yet prior research has failed to provide any clear understanding of the gender gap wherein women appear to be relatively protected from CVD while premenopausal, compared to men. Recent randomized trials of hormone replacement therapy (HRT), described below, have failed to demonstrate CVD benefit, and call into question the "estrogen protection" hypothesis. Alternative explanations for the gender gap, e.g., androgen exposure, have not been explored. This application, developed in response to the NHLBI's Innovative Research Grant Program Request for Application HL-01-016 and using existing data sets and biological specimens, is designed to support collaborative feasibility research in an innovative and high impact area relevant to CVD in women. The overall aim of this application is to use the existing data and stored blood samples from the NHLBI-sponsored Los Angeles Atherosclerosis Study (LAAS, HL-490-10) to explore new and innovative hypotheses with regard to reproductive hormones and progression of pre-clinical cardiovascular disease (CVD), measured by carotid intima-media thickness (IMT), in the 269 women (45% minority) in the Los Angeles Atherosclerosis Study (LAAS), an ongoing NHLBI-sponsored study of employed utility workers in Southern California without CVD at study entry. Hormonal assays will be performed on stored samples by a NHLBI Reproductive Hormone Core Laboratory, and subsequent analyses will characterize relationships to carotid IMT measured by the LAAS Ultrasound Core Laboratory. The following hypotheses will be test ed: 1) Reproductive hormonal profiles characterized by a relative estrogen deficiency and/or relative androgen excess will be directly correlated with increased

Studies 117

baseline carotid IMT and predict greater carotid IMT progression over time in women; 2) Reproductive hormone effects on carotid IMT progression will be observed dominantly in situations of intimal injury, e.g. cigarette smoking, hypercholesterolemia, hypertension or diabetes in women. Innovative aspects of this application include evaluation of reproductive hormones repeatedly and prospectively in women across the spectrum of menopause (pre-, peri- and post-) using innovative methodologies including the sensitive reproductive hormonal assays used in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) core laboratory, and a newer quantitative carotid intimal media thickness (carotid IMT) protocol from the NHLBIsponsored LAAS. The current application represents an opportunity to gain feasibility pilot data in the area of the role of reproductive hormones and CVD in women using novel measures and a collaborative approach in order to plan further investigation, if warranted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: REPRODUCTIVE PHYSIOLOGY OF OVARIAN FAILURE Principal Investigator & Institution: Santoro, Nanette F. Professor and Director; Ob/Gyn & Women's Health; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2001; Project Start 15-AUG-1994; Project End 31-MAR-2004 Summary: Our group has previously reported striking increases in estrogen secretin and excretion in women in the early stage of the menopause transition. The causes of he shortened follicular phases, increased whole cycle estrogen, and decreased progesterone in perimenopause, as well as the consequences of this altered reproductive hormonal environment on the hypothalamic-pituitary and endometrial axes are the focus of this continuing renewal. We propose 3 Specific Aims: Aims 1 will determine the association of elevated FSH in the perimenopause with decreased inhibin A and B, and with increases in circulating activin A. In Aim 2, we will test the hypothesis that increased estrogen secretion in perimenopausal cycles will caused increased menstrual bleeding. We will also determine whether increased estradiol exposure causes increased endometrial angiogenesis and proliferation as assessed immunohistochemically. We will test the hypothesis that abundance and location of ER alpha and beta subtypes differ between perimenopausal and mid-productive aged women's endometrium. Aim 3 will test the hypothesis that perimenopausal anovulation is caused by LH surge failure secondary to supraphysiologic estradiol stimulation. We will administer physiologic and supraphysiologic estradiol by infusion and test the resulting LH surge. We will also test directly pituitary sensitivity to exogenous LH in estradiol primed perimenopausal women to determine if there id reduced positive feedback sensitivity in perimenopausal women to determine if there is reduced positive feedback sensitivity in perimenopausal women. In this manner, we hope to elucidate the critical mechanisms that may cause or be the consequence of the hormonal dynamics of the early stages of the menopausal transition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RISK FACTORS FOR HOT FLASHES IN MID-LIFE Principal Investigator & Institution: Flaws, Jodi A. Associate Professor; Epidemiology and Prev Medicine; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: Many perimenopausal women experience hot flashes during mid-life. Hot flashes often have serious consequences, including fatigue, irritability, and acute

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physical discomfort that affects work and quality of life. Despite the high prevalence and importance of hot flashes, little is known about their risk factors. The proposed project will test the hypotheses that smoking, genetic polymorphisms in cytochrome P450 (CYP450) enzymes, and low serum estrogen levels are associated with an increased risk of hot flashes. It also will assess the hypothesis that smoking and CYP45O polymorphisms are associated with hot flashes via mechanisms that lower estrogen levels. The specific aims are to: 1) determine whether cigarette smoking is associated with risk of hot flashes, 2) evaluate whether CYP45O polymorphisms are associated with risk of hot flashes, 3) assess whether low levels of serum estrogens are associated with risk of hot flashes, and 4) determine whether women exposed to both smoking and genetic polymorphisms have a different risk of hot flashes than women exposed to one or none of these risk factors. To complete the study, 400 perimenopausal women (45-54 years) with hot flashes (200 cases) or without hot flashes (200+ controls) will be recruited from Baltimore and the surrounding areas. Each participant will complete a questionnaire that assesses hot flash and smoking history, other potential risk factors, and potential confounders. Participants also will provide blood samples for analysis of estrogen levels and CYP450 genetic polymorphisms. Associations between hot flashes, smoking, estrogen levels, and CYP450 polymorphisms then will be assessed using appropriate statistical and analytic methods. The results of this study will provide information about risk factors for perimenopausal hot flashes, particularly the influence of smoking, CYP450 polymorphisms, and serum estrogen levels. These results ultimately may be useful for future studies on the prevention and/or treatment of hot flashes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: RISK FACTORS FOR UTI IN POST MENOPAUSAL WOMEN Principal Investigator & Institution: Fihn, Stephan D. Professor of Medicine and Health Service; Medicine; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 01-MAR-1991; Project End 30-JUN-2004 Summary: UTI is one of the commonest infections i women, occurring in nearly 20% during their lifetime and costing nearly $1 billion annually. Research on the epidemiology and aetiology of UTI has concentrated on two groups of women: the young and healthy and the elderly and debilitated. In younger women, general debility, voiding problems, diabetes, and possibly, estrogen deficiency are risk factors. Little is known about risk factors for UTI in women soon after menopause, even though there are 56 million women aged 50 to 75. The main goal of this project is to prospectively determine the incidence of acute UTI and to assess risk factors for this problem in postmenopausal women, aged 50 to 75, living in the community. The primary aims will be to learn the relative effects of diabetes, postmenopausal estrogens, urine incontinence or increased post-void residual urine, and sexual activity on the risk of UTI. There are also plans to determine whether changes in the vaginal bacterial flora predispose to UTI in this age group and how risk factors, such as diabetes and estrogen therapy affect the vaginal flora. A prospective cohort study of community-dwelling, postmenopausal women is proposed. Participants will be 900 women randomly selected from the Group Health Cooperative of Puget Sound (GHC) enrollment database, along with 110 agematched women, randomly selected from the GHC Diabetes Registry. Information about sexual activity,estrogen use, history of UTI, urinary continence and other exposures of interest will be obtained by interview. Urine and vaginal introital cultures along with measurement of the fasting serum glucose and the post-void residual urine volume will be performed at a clinic visit. Follow-up interviews and examinations will

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be performed annually for two years. Diabetic patients will be followed with glycosylated hemoglobin at least annually. Patients will monitor their urine monthly at home with leukocyte esterase/nitrite dipsticks and make a clinic visit if they test positive. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ROLE OF NO AND ESTRADIOL IN AGING AND ATHEROGENESIS Principal Investigator & Institution: Chaudhuri, Gautam; Professor; Obstetrics and Gynecology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: During aging in women, two important changes occur which affect the vascular system. The first is menopause which is associated with estrogen withdrawal and the other is endothelial dysfunction manifested by a decrease in endothelium dependent vasodilation, possibly a reflection of a decrease in NO production by endothelial cells. These two changes may be independent of each other or may be interlinked. We and others have demonstrated that estradiol (E2) increases NO production. Therefore, endothelial dysfunction seen during aging and menopause as manifested by a decrease in endothelium dependent vasodilation and decrease in NO production may be explained just on the basis of E2 withdrawal alone. Estrogen replacement to postmenopausal women has been utilized for potential benefits related to the cardiovascular system. However, the precise mechanism(s) by which estrogens exert a beneficial effect on the cardiovascular system is not known. On the other hand, a recent study indicates that administration of a combination of estrogen and a progestin to women with well-documented coronary artery disease was associated with an increase in the incidence of a second coronary event in the first year of the study compared to the placebo group. In this study, there was no group in which women received E2 alone. Therefore, the role of E2 in modulating atherogenesis, once the disease is established is not known. Similarly, post-menopausal women are occasionally administered testosterone (t) to increase their sexual function but the effect of T on atherogenesis is not known. The overall hypothesis to be tested is that "the mere withdrawal of E2 or T leads to a decrease in NO synthesis, and thereby, to a proinflammatory response of the vascular wall leading to changes seen early in atherogenesis. A corollary could be that the atherogenic process on the extreme might increase the production of OONO and under such conditions NO inhibition might actually be beneficial." We propose to mimic the postmenopausal state in experimental animals by ovariectomy (OVX). We propose to mimic endothelial dysfunction by pharmacological means by administering animals an inhibitor of NO synthesis. The hypothesis will be tested under three specific aims. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SCHOLARS IN WOMEN'S HEALTH RESEARCH ACROSS THE LIFESPAN Principal Investigator & Institution: Cassel, Christine K. Professor and Chair; None; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2002; Project Start 26-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The goal of the Oregon BIRCWH Development Program is to create a stimulating and nurturing environment for junior faculty to develop into leading Physician Scientists in Women's Health. The program recognizes

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that research can modify the course of disease at one point in a woman's lifespan and affect the rest of lifelong development and aging. The program pairs basic and clinical junior faculty scientists with established mentors from different backgrounds who have expertise in Women's Health Issues in order to enhance the scholar's research capabilities. The mix of career paths and backgrounds will be integral to increasing collaboration and invigorating research in Women's Health across the lifespan. The extensive intellectual and research resources at the Oregon Health & Science University (OHSU) are available and committed to developing BIRCWH scholars. Integration is interdepartmental and will enhance existing collaborations in Women's Health between scientists in the Center for Women's Health, the Heart Research Center, the Primate Research Center and the Cancer Institute. Sophisticated research core laboratories specializing in Molecular Biology, Cell Culture, DNA analysis, Imaging, Statistics, Assisted Reproductive Techniques, Endocrine Assays, Laboratory Animal, Transgenic and Molecular Genetics Cores, among others, have already been established and will be available to the BIRCWH Scholars. Advanced training in designing clinical studies and statistical evaluation for clinician scientists will be coordinated through the highly successful SOM Human Investigations Program. The mentors of this BIRCWH Program are funded scientists who will provide diverse and in-depth mentorship for scholars in areas of women's health that extend across the lifespan. Six major areas of focus will constitute the initial BIRCWH program: fetal environment in programming lifelong gender differences in cardiovascular function; reproduction and health which includes ovulation, normal/abnormal parturition, hormonal effect upon pelvic floor function and menopause; neurobiology and gender differences; substance abuse in women; cancers of women; aging and end of life research in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SERUM ATHEROSCLEROSIS

SEX

HORMONE

LEVELS

AND

SUBCLINICAL

Principal Investigator & Institution: Gapstur, Susan M. Associate Professor; Preventive Medicine; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Throughout their lifetime, men are at higher risk of coronary heart disease (CHD) than women, however, after menopause this difference is attenuated. This observation suggests that endogenous sex hormones could be associated with CHD risk. There is some evidence indicating that the effect of sex hormones on CHD risk could be mediated, in part, by alterations in lipid levels or other CHD risk factors. However, other evidence supports an independent relationship of circulating hormone levels with CHD risk. For example, we recently reported a significant positive association between serum total testosterone concentration and the presence of subclinical coronary artery calcium (CAC) in young adult men that was independent of other CHD risk factors. Conversely, we showed an independent inverse association between total testosterone concentration and carotid intimal-medial wall thickness (IMT) in women. Overall, these results suggest that the influence of the hormonal milieu on subclinical atherosclerosis may not be the same in men compared to that in women. The overall objective of the proposed project is to examine the associations of serum sex hormone concentrations with the presence and progression of subclinical atherosclerosis in 3,259 male and 2,802 postmenopausal female participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Subclinical atherosclerosis will be identified using both CAC and carotid IMT. Progression will be identified by the change in CAC over 3.5 years. Circulating concentrations of total (and free) testosterone (T),

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dehydroepiandrosterone (DHEA), 17 beta-estradiol (E2), and sex hormone binding globulin (SHBG) in stored serum samples collected at the MESA baseline exam will be assessed. Laboratory results will be merged with existing demographic, anthropometric, lifestyle, CHD risk factor, and subclinical disease data collected in MESA. Crosssectional and prospective methods of statistical analysis will be used to assess the proposed associations. MESA is particularly well suited for disentangling the effects of hormonal factors and CHD risk factors on subclinical atherosclerosis because of the availability of high-quality data, serum samples, and CAC and IMT measurements in a large multi-ethnic population of men and women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SEX STEROID, HPA REGULATION, AND FAT PATTERNING Principal Investigator & Institution: Purnell, Jonathan Q. Associate Professor; Medicine; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Central (visceral) obesity contributes to an excess risk of diabetes, dyslipidemia, and death from coronary heart disease in women. Women typically express central obesity during menopause but the mechanisms causing this change in fat distribution are poorly understood. Preliminary data presented here support a role for estrogen regulation of the hypothalamic-pituitaryadrenal (HPA) axis in the expression of visceral obesity in postmenopausal women. The first aim of this grant is to complete a pilot study and to test the ability of estrogen to decrease HPA activity and cortisol levels on a prospective basis in postmenopausal women. These studies will provide pilot data for studies of estrogen regulation of the HPA axis activity and subsequent changes in body fat distribution in women transitioning through the menopause. In addition, evidence indicates subjects with central (visceral) obesity have ectopic triglyceride deposition in muscle and fat, and that this deposition plays an etiological role in insulin resistance in these tissues. Magnetic resonance spectroscopy (MRS) is a novel, noninvasive imaging technique used to quantify intramyocellular (IMCL) and intrahepatic fat (IHF) and has been increasingly used in human studies of glucose metabolism. This technique therefore offers a unique opportunity to prospectively test mechanisms that might result in ectopic fat deposition. As part of my current K23, I am testing whether cortisol replacement across a normal physiological range increases visceral fat mass and insulin resistance, independent of changes in total body weight, in subjects with complete adrenal failure. To test whether increased cortisol secretion may commonly promote central obesity and ectopic triglyceride deposition, in my second and third aims I propose to establish MRS protocols measuring IMCL and IHF in humans and to apply this technique to this prospective cortisol dosing study. Funding from this R03 will build on the data I have generated to date for use in future grant applications. By providing salary support for a coinvestigator with expertise in MRS methods and a research study coordinator for subject recruitment and scheduling, this award will help me to maintain productivity and establish independence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP DISTURBANCE IN MENOPAUSE Principal Investigator & Institution: Freedman, Robert F. Professor; Psychiatry & Behav Neuroscis; Wayne State University 656 W. Kirby Detroit, MI 48202 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006

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Summary: At present, over 35% of the women in the United States have reached the median age of menopause, 51 years. Hot flashes (HFs) are the most common symptom of the climacteric and occur in the vast majority of postmenopausal women. Sleep disturbance has also been reported to be highly prevalent in this population. Yet, the causal links, if any, between these 2 phenomena are I not known. In the studies proposed here, we will attempt to discern the relationships among Hfs and objective and subjective sleep disturbance. In Study 1, we will record sleep and HF parameters in postmenopausal women with HFs, those without HFs, and age-matched premenopausal women without HFs. We will perform quantitative EEG analyses, use an objective test of daytime sleepiness (MSLT) and assess subjective sleep quality with established instruments. HF frequency increases with ambient temperature. If HFs produce arousals and thereby disrupt sleep, then reducing ambient temperature should improve sleep and increasing temperature should worsen it (Study 2). Increased arousal frequency has been found in postmenopausal women with HFs. If this accounts for reports of poor sleep, then experimental sleep disruption in asymptomatic women should produce reports of poor sleep, as well. In Study 3, we will use yoked groups of symptomatic and asymptomatic women and disrupt sleep of the latter group based on recordings from the former group. We will do this using a stimulus specific to HFs (ambient heating). Despite the common use of hormone replacement therapy, its effects on sleep have not been established. In Study 4, we will systematically manipulate ambient temperature during sleep in symptomatic women before and during estrogen replacement and in a placebo-control group. In Study 5, we will determine the effects of elevated sympathetic activation on HFs and sleep using a stimulus that does not, by itself, disrupt sleep (orthostasis). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SLEEP DURING THE PERI-MENOPAUSE IN A MULTI-ETHNIC COHORT Principal Investigator & Institution: Gold, Ellen B. Director; Epidemiology and Prev Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, CA 95616 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 30-SEP-2005 Summary: (provided by applicant) This interactive Research Project Grant (IRPG) will characterize the relationship between menopausal characteristics and sleep in a sample of 430 women: 200 Caucasian, 150 African-American, and 80 Chinese. Although sleep disruptions, insomnia and the incidence of sleep disordered breathing increase in midlife women, little is known about the relationship between menopause and sleep. The impact of vasomotor symptoms and hormone replacement therapy on sleep suggests that the sleep-menopause relationship is not merely a function of age. A greater understanding of the causes of sleep disturbances in mid-life women is important, given the impact of sleep on mental and physical health. Sleep disturbances are associated with a host of negative health outcomes including losses in productivity and quality of life, psychiatric morbidity, immunosuppression, and increased vulnerability to illness and disease. The study aims of this IRPG are to: 1) characterize sleep disturbances in a large, multi-ethnic sample of mid-life women; 2) characterize relationships among menopausal characteristics and sleep disturbances; 3) evaluate the influence of relevant psychobiological factors on the sleep-menopause relationship; and 4) establish baseline data for a future longitudinal study. Four of seven study sites from the ongoing Study of Women s Health Across the Nation (SWAN) will collaborate to recruit a sample of preand peri-menopausal women from the SWAN cohort. Once enrolled in the Sleep Study,

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participants will begin the protocol at the start of a new menstrual cycle. Ambulatory polysomnography will be conducted in participants homes during days 1-3 of the protocol. Sleep diary, actigraphy, and event monitor recordings of vasomotor symptom data will be collected throughout the cycle. Data will also include five years of Core SWAN study data on menopausal characteristics (bleeding patterns, vasomotor symptoms, hormone levels) and related psychobiological factors. Regression techniques will be used to model relationships among menopausal characteristics, sleep, and related psychobiological factors. The Pittsburgh site will train study personnel in the use of sleep monitoring equipment and will be responsible for processing, scoring, and archiving all sleep data. All sleep study data, as well as relevant data from the Core SWAN study, will be merged and analyzed by the Michigan site. The Chicago and UC Davis PIs will co-chair the Sleep Study Steering Committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SLEEP DURING THE PERIMENOPAUSE IN A MULTI-ETHNIC COHORT Principal Investigator & Institution: Hall, Martica; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 30-SEP-2006 Summary: This Interactive Research Project Grant (IRPG) will characterize the relationship between menopausal characteristics and sleep in a sample of 430 women: 200 Caucasian, 150 African- American, and 80 Chinese. Although sleep disruptions, insomnia and the incidence of sleep disordered breathing increase in mid- life women, little is known about the relationship between menopause and sleep. The impact of vasomotor symptoms and hormone replacement therapy on sleep suggests that the sleep- menopause relationship is not merely a function of age. A greater understanding of the causes of sleep disturbances in mid- life women is important, given the impact of sleep on mental and physical health. Sleep disturbances are associated with a host of negative health outcomes including losses in productivity and quality of life, psychiatric morbidity, immunosuppression, and increased vulnerability to illness and disease. The study aims of this IRPG are to: 1) characterize sleep disturbances in a large, multi-ethnic sample of mid-life women; 2) characterize relationships among menopausal characteristics and sleep disturbances; 3) evaluate the influence of relevant psychobiological factors on the sleep-menopause relationship; and 4) establish baseline data for a future longitudinal study. Four of seven study sites from the ongoing Study of Women's Health Across the Nation (SWAN) will collaborate to recruit a sample of preand peri-menopausal women from the SWAN cohort. Once enrolled in the Sleep Study, participants will begin the protocol at the start of a new menstrual cycle. Ambulatory polysomnography will be conducted in participants' homes during days 1-3 of the protocol. Sleep diary, actigraphy, and event monitor recordings of vasomotor symptom data will be collected throughout the cycle. Data will also include five years of Core SWAN study data on menopausal characteristics (bleeding patterns, vasomotor symptoms, hormone levels) and related psychobiological factors. Regression techniques will be used to model relationships among menopausal characteristics, sleep, and related psychobiological factors. The Pittsburgh site will train study personnel in the use of sleep monitoring equipment and will be responsible for processing, scoring, and archiving all sleep data. All sleep study data, as well as relevant data from the Core SWAN study, will be merged and analyzed by the Michigan site. The Chicago and UC Davis PIS will co-chair the Sleep Study Steering Committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP IN OLDER WOMEN--EFFECTS OF ESTROGEN Principal Investigator & Institution: Moe, Karen E. Psychiatry and Behavioral Scis; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 31-OCT-2003 Summary: (adapted from investigator's abstract): Sleep complaints increase significantly with age in both men and women, but the increase is especially striking in women. Older women experience more nighttime awakenings, longer sleep onset latencies, and "lighter" sleep. Insomnia, disrupted sleep, and consequent daytime drowsiness are associated with an increased risk of accidents, increased utilization of health care and sedative-hypnotic medications, and a reduced quality of life. Older women receive a disproportionate number of prescriptions for sedative-hypnotics, which can exacerbate sleep apnea and lead to daytime carryover effects such as sedation, falls and subsequent fractures, and cognitive impairment. A better understanding of the sleep changes experienced by older women is sorely needed. One contributing factor may be agerelated changes in sex steroids such as estrogen. The very low levels of estrogen that occur post-menopause have wide-ranging chronic effects, from increased cardiovascular risk factors to possible effects on memory. Sleep changes in older women may also be related to this dramatic change in hormonal milieu. Several studies have shown that ERT can improve the sleep of peri-menopausal women, and our preliminary data shows that the use of ERT is associated with better sleep in older post-menopausal women. Estrogen acts on several brain areas important for sleep and circadian rhythms (e.g., the suprachiasmatic nucleus, the hypothalamic pre-optic area, and the pineal gland). Previous studies of ERT effects on sleep were based on peri-menopausal women who were experiencing hot flashes and/or other menopausal symptoms including depression. All but a few of these studies were based on brief subjective sleep ratings. No published studies have examined the effect of ERT on the sleep of post-menopausal women., i.e., women who are several years past menopause, menopausal symptoms, and menopause-related hormone fluctuations. The proposed study will employ laboratory-based polysomnography and a randomized, placebo-controlled withinsubjects design to assess the effect of six months ERT or placebo on the sleep and circadian rhythms of post-menopausal women. The results will help determine the role of age-related estrogen decline in the decreased sleep quality of older women. This study is the first step in a research program investigating the relationship between sex steroids and sleep in older individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SOY AND LIPOPROTEINS IN POSTMENOPASUAL WOMEN Principal Investigator & Institution: Allen, Jerilyn K. Associate Professor; None; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Cardiovascular disease (CVD) remains the leading cause of mortality and disability in postmenopausal women. Menopause alters serum lipids and lipoproteins to produce a more atherogenic lipid profile that may contribute significantly to the increased risk for the development of CVD over the lifetime of women. Clinical trials have demonstrated a beneficial effect of soy protein containing isoflavones (soy) on plasma lipids and lipoproteins; however, these studies included small numbers of postmenopausal women and virtually none included sufficient African-American women. In addition, no published data exist on the impact of soy on atherogenic lipoprotein subclasses in postmenopausal women. Therefore, the primary

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aim of this study is to determine the effects of soy on lipids, lipoproteins and lipoprotein subclass in a sample of African-American and white postmenopausal women with lowdensity lipoprotein (LDL) cholesterol elevations that may increase their lifetime risk for CVD but would not qualify for definite pharmacotherapy under current guidelines. The secondary aims are to assess the impact of soy on menopausal quality of life, including menopausal symptoms, and to examine racial/ethnic differences in quality of life, acceptability, adherence to, and lipoprotein response to the soy supplementation. The proposed study is a double blind, parallel group, randomized clinical trial. A total of 160 healthy postmenopausal women (50 percent African-American) with LDL cholesterol between 130 mg/dL and 190 mg/dL will be enrolled. Following a pre-randomization run-in period on a NCEP Step I diet, women will be randomized to receive soy containing isoflavones or casein dietary supplements for 3 months. Major outcome variables will be assessed in both groups at baseline and again at 3 months. It is hypothesized that soy supplementation will result in significantly greater reduction in LDL cholesterol, LDL particle concentration, and prevalence of dense LDL particles and improvement in menopausal quality of life compared with placebo and that these effects will be comparable in African-Americans and whites. This will be the first study to determine whether a natural plant product can ameliorate the unfavorable changes in known and novel lipid risk factors that are a consequence of menopause in both African-American and white women. The unique transitional outcomes explored in this study will add substantially to the limited body of knowledge of the effects of soy. Evaluation of this nutritional alternative to hormone replacement therapy (HRT) that may provide a beneficial effect on lipid risk factors and menopausal symptoms but would be free of the adverse effects on triglycerides, the breast and uterus, and thrombotic events associated with HRT could have significant public health implications for postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SOY DIETARY SUPPLEMENT IN VASOMOTOR SYMPTOM THERAPY Principal Investigator & Institution: Creinin, Mitchell B.; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001 Summary: Perimenopause is the period of time before actual menopause occurs and is often characterized by irregular menstrual cycles due to fluctuating estrogen levels. Hot flushes (warmth that begins on the face and radiates to the neck and chest, often accompanied by red flush) are experienced by approximately 80% of women once circulatory estrogen levels are decreased. Certain plant chemicals called phytoestrogens can modify or mimic the action of reproductive hormones in humans and whose biological actions suggest that they may provide natural protection for women from symptoms such as hot flushes. This study will test two doses of isoflavones, a phytoestrogen in a soy dietary supplement for the treatment of hot flushes in perimenopausal and menopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANCER

SPIRIT:REPRODUCTIVE

PEER

COUNSELING FOR

BREAST

Principal Investigator & Institution: Schover, Leslie R. Behavioral Science; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030

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Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Reproductive health problems are the most troublesome and long-term sequellae of breast cancer treatment. African-American women are at increased risk for breast cancer diagnosis before age 45, and have higher mortality in general compared to Caucasian women. Research is just beginning to examine the impact of ethnicity and socioeconomic status on cancer survivorship, The goal of this project is to evaluate the effectiveness of a peer counseling program to improve the reproductive health knowledge and outcomes (menopause symptoms, sexuality problems, distress about infertility/pregnancy and health of offspring, concern about cancer risk in the family) in African-American breast cancer survivors. The peer counseling program has been highly valued by participants in a pilot feasibility study and produced significant gains in knowledge. We will train 30 peer counselors and 7 regional coordinators in an intensive, 40-hour workshop. Monthly teleconferences will facilitate project communication and quality control thereafter. Nine hundred AfricanAmerican women will be recruited by 20 chapters of Sisters Network, Inc., a national advocacy organization for African-American breast cancer survivors. Women will be randomized using minimization to receive either the full, 3-session individual peer counseling program or a minimal contact version including just workbook and 30 minutes or less of optional phone contact with the counselor. Questionnaires assessing medical and demographic factors, spiritual well-being, sexual function, menopause symptoms, distress about childbearing issues, relationship satisfaction or dating concerns, knowledge about reproductive health after breast cancer, emotional distress, and utilization of reproductive health services will be sent to women in the mail at baseline, post-treatment, and at 6 and 12 months' follow-up. We hypothesize that both programs will be effective, but the full program will be superior. Secondary goals of the project are to identify correlates of reproductive health outcomes at baseline, including cancer treatment variables, age, menopausal status, socioeconomic status, emotional distress, relationship status and distress, and spiritual well-being. We will also examine the impact of these mediating variables on the effectiveness of the intervention conditions. In addition, we will conduct 50 semi-structured, qualitative phone interviews with survivors diagnosed under age 45, to better identify and characterize concerns of this young, at-risk group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: STAGING REPRODUCTIVE AGING IN FIVE COHORT STUDIES Principal Investigator & Institution: Harlow, Sioban D. Assistant Professor; Epidemiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The menopause marks a period of critical change in women's biology and health status. Unlike puberty, no staging system for reproductive aging has been established. A staging system for reproductive aging would facilitate development of health interventions, enable providers to better counsel women about menopausal symptoms and preventative therapy, and permit researchers to better classify women's reproductive status. In July 2001, NIA and other organizations held a workshop to propose a staging system for reproductive aging (STRAW). Although STRAW's recommendations built upon emerging results from cohort studies of midlife women and represent an expert consensus, they were not database driven. STRAW's bleeding criteria for the early and late transition stages, although conceptually consistent with prior definitions, include important departures from current clinical and research

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practice. Also, STRAW did not provide unambiguous operational definitions for these bleeding criteria. The goal of this application is to empirically evaluate 5 proposed bleeding criteria for onset of the early menopausal transition and 4 proposed bleeding criteria for onset of the late transition that served as the basis for the STRAW recommendations. We will use menstrual calendar, hormone and symptom data accumulated from five of the large and comprehensive cohort studies of the menopausal transition (the Tremin Trust, Melbourne Women's Midlife Health Project, Seattle Midlife Women's Health Study, Michigan Bone Health Study and the multi-site, multi-ethnic Study of Women's Health Across the Nation). We propose to assess 1) how frequently each criterion is well defined (i.e., are we able to categorize women by reproductive stage using the criterion?), 2) whether the age at transition differs among the criteria within and across cohorts, 3) the relationship between age at transition and age at menopause, and 4) whether prediction of age at menopause is improved by including predictors such as FSH, or hot flash, and whether it varies by ethnicity, smoking status or body mass index. This study will provide empirical evidence regarding which criteria are broadly representative across populations and across the range of menopausal ages, furthering efforts to establish staging criteria for the menopausal transition. This information will help clarify our understanding of ovarian aging, permit researchers to more adequately control for menopausal status, and facilitate decision-making among women and their providers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: STRESS AND MEMORY FORMATION ACROSS THE FEMALE LIFESPAN Principal Investigator & Institution: Shors, Tracey J. Professor; Psychology; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, NJ 08901 Timing: Fiscal Year 2003; Project Start 01-SEP-1998; Project End 31-MAY-2008 Summary: (provided by applicant): It has become increasingly clear that males and females differ even more dramatically than we previously thought. Not only do they exhibit differing responses to stress and environmental experience, but they can also respond in opposite directions. In rats, exposure to an acute stressful event enhances associative learning in males while dramatically impairing performance in females (Wood et al 2001, Wood & Shors 1998; Shors et al., 1998, 2002). These opposite effects of stress on memory formation are accompanied by similarly opposite effects on the presence of dendritic spines in the hippocampal formation (Shors et al 2001). Moreover, these opposite effects of stress are mediated by different hormonal systems between the sexes (Wood et al 2001, Beylin & Shors 2002). Sex differences usually arise from activational and organizational effects of sex hormones which fluctuate across the lifespan, especially in females. The experiments described in this competing continuation capitalize on hormonal fluctuations and changes in emotionality that occur during very early development, puberty, post-partum and menopause. They are designed to associate and dissociate changes in learning ability and responses to stressful experience with changes in hormones and density of dendritic spines in the hippocampal formation. Finally, experiments are designed to explore a potential relationship between sex differences in learning and the expression of growth hormone (GH) in the hippocampus, a gene that is preferentially induced by learning (Donahue et al., 2002). Techniques include trace eyeblink conditioning in the rat, Golgi impregnation and light microscope analysis, real-time polymerase chain reaction, in situ hybridization, radioimmunoassay, and surgical manipulation of glucocorticoids and ovarian hormones. Overall, these studies will identity the neuronal and hormonal

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mechanisms that underlie sex differences in learning and opposite responses to stressful experience in males versus females. Because mental disorders often emerge or are exacerbated during these life changes, the studies will provide insight into sex differences in mental illness, especially those experienced so frequently by women: posttraumatic stress disorder (PTSD), unipolar, post-partum and post-menopausal depression, as well as Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: STRESS RESPONSE DIFFERENCES IN FEMALES: ESTRADIOL'S ROLE Principal Investigator & Institution: Faraday, Martha M.; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, MD 20852 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): In response to stress, pre-menopausal women are more likely to become depressed than are men, suggesting that being female and exposure to cycling female sex hormones may constitute part of depression vulnerability. Only some women develop depressive illness, however, indicating that women differ in stress sensitivity and depression vulnerability. Rodent models of depression that examine responses of stress-vulnerable vs. stress-resistant females would be valuable to understand the biologic basis of differential stress and depression vulnerability in women but models of depression generally have used male rats as subjects. Preliminary data indicate that Sprague-Dawley female rats are markedly more sensitive to stress than are Long-Evans female rats across several behaviors and biologic indices, including a behavioral model of depression and hypothalamo-pituitaryadrenocortical (HPA) axis responses. These differences in response to stress could be the result of many factors, including actions of estradiol on brains that are different and line differences in how stress affects estradiol levels or estrus cycling. Estradiol is the major sex hormone with behavioral and biologic actions in females. Estradiol interacts with stress-sensitive brain systems (i.e., serotonergic, dopaminergic) that control the behaviors under study. Estradiol also interacts with the HPA axis. Therefore, examining estradiol's role in stress responding of stress-sensitive female rats (Sprague-Dawley) and stress-resistant female rats (Long-Evans) is a critical step toward understanding why some females are more vulnerable to stress and depression than others. Behavioral and corticosterone responses of Sprague-Dawley and Long-Evans females that are intact, ovariectomized, or ovariectomized with estradiol replacement will be evaluated in response to daily restraint stress. Responses also will be compared with intact male rats. To determine whether female line differences in response to stress are the result of changes in estrus cycling or line differences in estradiol levels, estrus cycle and estradiol levels of intact females also will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDIES OF THE FATE OF THE OSTEOCLAST Principal Investigator & Institution: Boyce, Brendan F. Professor; Pathology and Lab Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2001; Project Start 01-JUN-1995; Project End 31-AUG-2003 Summary: Osteoclasts are required for the normal development of bone during endochondral osification and for the resorption of worn-out bone in the adult skeleton during normal bone remodeling. They also mediate the increased bone loss that occurs in association with inflammation in bone and estrogen deficiency following menopause.

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Recent studies indicate that expression of M-CSF and RANK (receptor activation of NFkappaB) ligand is required for osteoclast formation and that activation of genes regulated by the transcription factors, c-fos, PU.1 and NF-kappaB is also necessary. NFkappaB regulates the expression of the osteoclastogenic cytokines, IL-6, IL-1, and TNF whose expression is up-regulated in inflammatory bone diseases and in response to estrogen deficiency. These cytokines also prevent osteoclast apoptosis, and the increased bone resorption seen after the menopause may in part be due to prolongation of osteoclast life spans on bone surfaces. NF-kappaB has also been shown to prevent TNFand FAS ligand-induced apoptosis of some cell types and therefore may be involved in the regulation of osteoclast life span. Thus, NF-kappaB may regulate not only the formation of osteoclasts in normal bone remodeling, but also the increased production and prolonged life spans after the menopause. However, the molecular mechanisms whereby NF-kappaB mediates these activities in osteoclasts in osteoclasts are largely unknown and are likely to involve multiple signaling pathways in osteoclasts and their precursors and osteoblasts. We propose to use a combination of in vitro and in vitro approaches to study the role of NF- kappaB in osteoclast formation, activity and survival. Our specific aims are to determine the role of NF-kappaB in 1) osteoclast formation 2) the up- regulation of osteoclastogenesis induced by cytokines and estrogen deficiency and 3) the regulation of osteoclast apoptosis Our underlying hypothesis is that NF-kappaB is required for the activation of genes encoding cytokines which are essential for 1) the progression of osteoclast precursors along a differentiation pathway to form mature osteoclasts; 2) the up-regulation of osteoclastogenesis following estrogen withdrawal; and 3) for the survival of osteoclasts by preventing them from undergoing apoptosis. Understanding the role of NF-kappaB in osteoclastogenesis and survival could lead to the development of new therapeutic agents designed specifically to inhibit bone resorption in conditions, such as postmenopausal osteoporosis, in which it is increased. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: STUDY OF WOMEN'S HEALTH ACROSS THE NATION INTERIM COORD Principal Investigator & Institution: Matthews, Karen A. Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-1994; Project End 30-NOV-2003 Summary: (provided by applicant): The Study of Women's Health Across the Nation (SWAN) is a multicenter, multiethnic, community based, longitudinal study designed to characterize the biological and psychosocial changes that occur during the menopausal transition and to assess their effect on women's health. Current and past funding (SWAN I and II) support six years of follow-up, at the end of which 60% of observable transitions to postmenopause will have occurred. Together, this competitive renewal application (SWAN HI) and a separate competitive supplement application request funding to complete a total of 10 cohort follow-up visits, allowing us to capture 91% of observable transitions to postmenopause and thus providing a more representative sample. The additional data will permit a focus on the late perimenopausal and early postmenopausal periods that have not been well studied in the literature. As women reach the end of early postmenopause (two years following the final menstrual period), we will shift from an annual to a bi-annual follow-up schedule with mail and telephone contact in the alternating years. This will set the stage for cost-effective and less intensive follow-up beyond SWAN lB. We will continue our current observations as well as undertake new science in each of the four scientific project areas (ovarian aging;

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symptoms, risk factors, functioning and aging; cardiovascular risk factors; and determinants and outcomes of bone mass). The new science includes measurement of vascular stiffness to assess early cardiovascular disease, salivary cortisol levels, vertebral morphometry using newly developed DEXA technology, and circulating androgens and total bioactive estrogens using an assay system developed by SWAN investigators. In addition, we will focus on linking the menopause and midlife experiences to age-related outcomes and chronic diseases, including physical and cognitive function. The additional follow-up will contribute to and expand the SWAN biological specimen repository (annual blood and urine samples as well as DNA and immortalized cells), a separately funded component that broadens the opportunities to address future hypotheses about health, disease and aging. With SWAN llI, many of the original goals of SWAN will be brought to fruition. We will build upon the rich foundation developed during SWAN I and II, and ultimately, link these data to subsequent age-related health outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: STUDY SUPPLEMENT

OF

WOMEN'S

HEALTH

ACROSS

THE

NATION-

Principal Investigator & Institution: Mathews, Karen A. Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-1994; Project End 30-NOV-2003 Summary: (provided by applicant): This supplement to the Study of Women's Health Across the Nation (SWAN) II is designed to provide funds for the on time fielding of the seventh follow-up clinic visit for the SWAN cohort. SWAN is a multicenter, multiethnic, community based, longitudinal study to characterize the biological and psychosocial changes that occur during the menopausal transition and to assess their effect on women's health. Current and past funding (SWAN I and II) support six years of followup, at the end of which 60% of observable transitions to postmenopause will have occurred. This application requests funding for 10 months, for the timely initiation of the seventh follow-up clinical visit. A separate SWAN Iii application requests funds to finish the seventh follow-up and complete a total of 10 follow-up visits, so that the study can capture 91% of observable transitions to postmenopause and thus provide a more representative sample. The additional data will permit a focus on the late perimenopausal and early postmenopausal periods that have not been well studied in the literature. As women reach the end of early postmenopause (two years following the final menstrual period), we will shift from an annual to a bi-annual clinic visit with mail and telephone contact in the alternating years. This will set the stage for cost-effective and less intensive follow-up beyond SWAN Iii. We will continue our current observations as well as undertake new science in each of the four scientific project areas (ovarian aging; symptoms, risk factors, functioning, and aging; cardiovascular risk factors; and determinants and outcomes of bone mass). The new science includes measurement of: vascular stiffness to assess early cardiovascular disease, salivary cortisol levels, vertebral morphometry using newly developed DEXA technology, and circulating androgens and total bioactive estrogens using an assay system developed by SWAN investigators. In addition, we will focus on linking the midlife experience to agerelated outcomes and chronic diseases, including physical and cognitive function. The additional follow-up will also contribute to and expand the SWAN biological specimen repository (annual blood and urine samples as well as DNA and immortalized cells), a separately funded component that broadens the opportunities to address future hypotheses about health, disease, and aging. With SWAN Iii, many of the original goals

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of SWAN will be brought to fruition. We will build upon the rich foundation developed during SWAN I and II, and ultimately, link these data to subsequent age-related health outcomes. INTEGRATIVE SCIENCE AND THE NEXUS TO AGING (OVERVIEW AND INTEGRATIVE). (provided by applicant): SWAN is exceptional in the breadth of data that are being collected across scientific areas. In the scientific projects that are encompassed in the subsequent 100 pages of this application, specific study hypotheses relating to each of the primary scientific areas are presented. However, by approaching scientific areas individually, we are in danger of over-simplifying the biological and social processes involved. A great strength of SWAN is our ability to approach the study of women at mid-life from a multi-disciplinary perspective. An Integrative Committee has been formed and charged with fostering the development of multidisciplinary lines of investigation. The Integrative Committee will also link the data collected in SWAN to the larger body of knowledge related to aging. At the outset of SWAN III, the mean age of the cohort will be almost 53 years of age and 884 women will have transitioned to postmenopause. This maturation of the study population invites explicit consideration of the nexus between the menopausal transition and chronological aging. The Integrative Committee will focus on the interface between menopause and aging, taking advantage of the unique cohort and breadth of data being collected. While a number of integrative lines of investigation will be pursued, in the following brief section, we preview one integrative approach to aging and menopause from conceptualization through data collection and analysis. As will be described in this preview, to gain a more comprehensive perspective of the biology and implications of the menopausal transition, ultimately we must move beyond the simplistic concept of estrogen deficiency. This will require a shift to a new paradigm. As an illustration of how this can be accomplished in SWAN, the following section develops an exploratory approach that represents a new way to pull together information across scientific disciplines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SYMPTOMATIC ARRHYTHMIA IN PERIMENOPAUSAL WOMEN &HORMONE Principal Investigator & Institution: Kaufman, Elizabeth S.; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: Despite anecdotal reports of palpitations associated with menopause, there is no medical literature describing the types of arrhythmias which occur or their timecourse or response to hormone replacement therapy. The purpose of this study is to test the hypotheses that there is a high prevalence of palpitation during menopause; these correspond to frequent premature atrial and ventricular complexes; these arrhythmias are mediated in part by changes in autonomic control of the heart; and symptoms, arrhythmias and autonomic changes improve after hormone replacement therapy. Women who plan to start hormone replacement therapy will be recruited. Subjects will be asked to fill out a questionnaire about symptoms characteristic of menopause and palpitations and to wear a 24-hour holter monitor twice before and twice after initiating hormone replacement therapy.This study is important because complaints of palpitation are prevalent among perimenopausal women, frequently leading to expensive evaluations. It is important to establish the normal range of symptoms and arrhythmias in this populaton in order to reduce unnecessary testing and to provide reassurance to women whose symptoms are within normal limits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TARGETED DELIVERY OF ESTROGEN IN MENOPAUSE Principal Investigator & Institution: Subbiah, Ravi M. Prof. of Exper. Medicine & Path. Molecular Diagnostics Laboratories, Inc. 3130 Highland Ave, Ste 3315 Cincinnati, OH 45219 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2004 Summary: (provided by applicant): In postmenopausal women, coronary artery disease (CAD) is the leading cause of death. Estrogen replacement therapy appears to offer considerable protection against CAD in postmenopausal women. However, there is great concern about risk for breast and endometrial cancer after long-term estrogen use in these women. The activation of estrogen receptors and subsequent genomic effects in terms of cell growth appears to play a significant role in estrogen-related carcinogenesis. Our laboratory has been interested in achieving a differential effect of estrogens by differential delivery to cells. We hypothesize that desired cardioprotective benefits of estrogens (without carcinogenic effects) can be achieved either through a) macrophages targeted for preferential delivery of hydrophobic estrogen acetylated LDL (ac-LDL) complexes to atherosclerotic tissues or b) by conjugating these estrogens into lipid microspheres or by coating lipoprotein/estrogen complexes with functionalized (Fc) dextran, both of which have been used for preferential uptake by endothelial cells. Phase I will determine a) whether i.v. administered hydrophobic estrogens will associate with LDL; b) tissue distribution and the feasibility of macrophage-targeted (MT) and endothelium-targeted (ET) liposomal preparation of hydrophobic estrogen derivatives for differential delivery to macrophages or endothelium and c) whether ET and MT are functionally active. Phase II will deal with their in vivo effects on atherogenic indices and suitable lipoprotein-like carriers and enhancers for use as transdermal patch. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TELOMERES AND VASCULAR AGING Principal Investigator & Institution: Aviv, Abraham; Professor; Hypertension Research Center; Univ of Med/Dent Nj Newark Newark, NJ 07103 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: The use of chronological age in clinical practice and in aging research is based on the premise that biological aging proceeds at an identical pace for all human beings. Such an approach overlooks the pnncipals of biological diversity. The central hypothesis of this project is that telomere length, as expressed in white blood cells, provides an account additional to chronological age, of variation in vascular aging among human beings. This hypothesis will be tested in the Offspring Study cohort of the Framingham Heart Study. The project will also seek through genome-wide search for genetic regions with large effects on telomere length. The specific aims of this project are: 1. To examine the relations between telomere length and indices of arterial aging in the previously phenotyped/genotyped Offspring Study cohort of the Framingham Heart Study. The indices of arterial aging include: brachial pulse pressure, central pulse pressure, augmentation index, and carotid-femoral, carotid-radial and carotid-brachial pulse wave velocities; 2. To assess heritability of telomere length and identify genetic loci that explain variation in telomere length. Results would lead to a better understanding of the heterogeneity of vascular aging, test the concept that telomere length may serve as an index of biological aging, and provide information on genetic determinants of telomere length in human beings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE DICHOTOMY OF ESTROGENS IN THE CARDIOVASCULAR SYSTEM Principal Investigator & Institution: Eyster, Kathleen M. Basic Biomedical Sciences; University of South Dakota 414 E Clark St Vermillion, SD 57069 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 14-FEB-2004 Summary: Estrogen is a fascinating hormone with seemingly paradoxical effects in the cardiovascular system. On the one hand, estrogen appears to be protective to the cardiovascular system of pre-menopausal women. Prior to the menopause have a lower incidence of cardiovascular disease than men. After the menopause, the incidence increases rapidly to reach and even exceed that of men. It has been widely assumed, form anecdotal evidence, as ell as several early studies, that replacement of estrogen would return the cardiovascular system of the post-menopausal woman to its premenopausal protected state. However, the early data from the Women's Health Initiative does not support the assumption; rather, these data suggest an increase in cardiovascular events in the first two years of hormone replacement therapy with estrogen. Estrogen remains the most likely cardiovascular protective factor for premenopausal women. Thus we propose that the failure to observe a protective effect of estrogen on cardiovascular function is the result of administering an estrogen that is an incomplete agonist in cardiovascular tissues, or that is administered in inappropriate mode. This project is designed to test the hypothesis that the dichotomous effects of estrogen on the cardiovascular system are due to differential Gene expression responses to different estrogen formulations and modes of administration. Two specific aims have been developed to test this hypothesis. Specific aim #1: To develop a profile of genes expressed in response to estradiol 17beta in vascular tissues and to examine the effect of estrogen formulation on the vascular reactivity of the mesenteric arteries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE EFFECT OF BLACK COHOSH EXTRACT ON THE HUMAN BREAST Principal Investigator & Institution: Sauter, Edward R. Surgery; University of Missouri Columbia 310 Jesse Hall Columbia, MO 65211 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Over 40 million women in the US have reached menopause, and 40% will experience symptoms significant enough to seek medical attention. Hormone replacement therapy, prescribed to ameliorate menopausal symptoms, has been associated with an increased risk of developing breast cancer. Many women use herbal preparations for menopausal complaints, believing them to be safe. Black cohosh extract (BCE) is the largest selling herbal dietary supplement in the United States used to alleviate menopausal symptoms. The mechanism of action by which BCE acts to treat menopausal symptoms of estrogen deficiency is not clear, with some data supporting a central nervous system effect, while other studies demonstrate a proestrogenic effect. The primary aim of this study is to determine if BCE administered to symptomatic postmenopausal women results in estrogenic stimulation of the breast as measured by changes in nipple aspirate fluid (NAF) levels of estradiol, pS2, follicle stimulating hormone (FSH), leutenizing hormone (LH) and prostate-specific antigen (PSA), as well as NAF cytology. Secondary aims are to 1) evaluate if BCE saponins, the proposed active constituents in BCE, are detectable in the NAF of women receiving BCE, 2) determine if BCE leads to a reduction in clinical symptoms of menopause, and 3) determine if the biomarker effects persist after stopping BCE. As the American

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population ages there are an increasing number of menopausal women. Interest in herbal therapies is rapidly growing among these women, including breast cancer survivors, to treat the disruptive symptoms associated with menopause. BCE binds to the estrogen receptor and in some studies stimulates breast cells. It is therefore important to demonstrate that BCE does not increase the risk of estrogen-related cancers. We have chosen biomarkers proven to be estrogen responsive proteins which are readily measured in both NAF and blood. Although prior studies failed to correlate clinical response to BCE with changes in serum levels of LH, FSH, or estradiol, it is critical to measure these markers in the breast itself, not diluted by the contribution from other organs. The findings should allow us to design a high quality R01 submission involving a larger, randomized study of longer duration which should provide some answers on the potential role of BCE in breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: THE IGF-I RECEPTOR IN AGING Principal Investigator & Institution: Baserga, Renato L. Professor; Kimmel Cancer Center; Thomas Jefferson University Office of Research Administration Philadelphia, PA 191075587 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: (adapted verbatim from the investigator's abstract) The Central Nervous System (CNS) is a primary target of biological aging, from a loss of neurons to decreased brain function, all the way to devastating diseases like Alzheimer's Disease (ALD). The IGF system (especially the IGF-I receptor, activated by its ligands) is known to play a significant role in mitogenesis, differentiation and protection from apoptosis (survival). All these functions of the IGF system are active during the development of the CNS, with the last two, differentiation and survival, becoming more prominent in adult life and aging. Aging in both sexes and menopause in women are also accompanied by a decrease in IGF-I levels in the plasma. Although the literature on the IGF system and the CNS is by now abundant, the present proposal aims at a different target, specifically the mechanism(s) by which the IGF-I receptor (IGF-IR) regulates the differentiation and/or survival of neurons (with the IR only involved in survival). The main model system is based on a neuronal cell line, immortalized by a temperature-sensitive SV40 T antigen. These cells, designated as H19-7 cells, grow quite well in growth medium at the permissive temperature of 340, but they growth-arrest, and differentiate when incubated with bFGF, at the restrictive temperature of 39o. Our preliminary results indicate that, in the presence of IGF-I, a modestly over-expressed IGF-I receptor can induce differentiation, in the absence of any other growth factor. We can therefore carry out in this cell line a mutational analysis of the IGF-IF in differentiation and survival (as we have already done for mitogenesis and transformation), which will provide us with the basic information to elucidate the pathway(s) involved in these processes. Finally, we have recently developed neuronal (and fibroblastic) cell lines from mice homozygous for targeted disruptions of both the IGF-IR and IGF-II receptor genes. These cell lines (also immortalized by a tsA SV40 T antigen) will be extremely useful in elucidating insulin receptor signaling in cell survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE YUCATAN MICROPIG CARDIOVASCULAR MODEL OF MENOPAUSE Principal Investigator & Institution: Goodrich, James A. Comparative Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425

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Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Menopause in women is an understudied normal aspect of the aging process that is associated with a loss of estrogen production and increased risk of cardiovascular disease and other health problems. Estrogen is generally considered to be cardioprotective. There are currently unprecedented numbers of women, about 50 million, in the United States reaching menopause; cardiovascular disease is the number one killer of postmenopausal women. Animal models provide a means of performing critical studies of the biological mechanisms and responses to existing and emerging therapies for this condition (i.e. soy protein/isoflavones). A nonprimate animal model of menopause is needed to provide a research tool that is: 1) readily available to many researchers; 2) low in risk for zoonotic disease; 3) domesticated; 4) a low cost rapidly renewable resource; 5) possess a similar coronary artery anatomy; and 6) atherosclerotic lesion to that of women. The ovariectomized Yucatan Micropig has the potential to fill this void, and will serve the interests of both the NIA and NHLBI. The overall objective of this application is to develop, characterize, and improve the Yucatan Micropig Model of Menopause for use in cardiovascular studies. This will be approached by Aim 1 clarifying the cardioprotective effects of soy protein in this model by measuring the extent of the reduction in coronary artery atherosclerosis, serum lipids, inflammatory risk factors (C-reactive Protein, Interleukin6) and blood pressure among soy, control, and conjugated equine estrogen treated groups. Establishing that soy protein can reduce coronary artery atherosclerosis in Micropigs, like it does in monkeys, would provide foundation data helpful to future soy isoflavone mechanistic studies in the Micropig model. Studies to determine how soy isoflavones and soy protein interact to reduce serum cholesterol and subsequently coronary artery atherosclerosis are needed. The next step is Aim 2, to examine the effects of these treatments on reproductive tissue. The investigators approach this aim by comparing uterine weights, and mammary and uterine immunohistology among these groups. The third step Aim 3, is to determine if and to what extent there is a natural female cardioprotection in the Yucatan Micropig. The investigators will approach this by comparing groups of male, ovariectomized female, and intact female Micropigs fed an atherogenic diet. The end points will be identical to those of the first aim. Finally, Aim 4, is to determine if and to what extent ovariectomized female Yucatan Micropigs experience vasomotor symptoms or hot flashes related to estrogen deficiency. This will be approached through continuous telemetric monitoring of skin temperature spikes before and after ovariectomy and then with and without estrogen replacement therapy. The future plans for this model are to use it to study the cardiovascular benefits/risks of new progestins, selective estrogen receptor modulators, tissue selective estrogens, and isoflavone products, as well as the mechanism by which soy protein lowers serum cholesterol and coronary artery atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: THERAPEUTIC DECISIONS AT MENOPAUSE--A MULTISITE STUDY Principal Investigator & Institution: Obermeyer, Carla M. Population & Interntl Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, MA 02460 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: URINARY INCONTINENCE: MOLECULAR MECHANISM&MATRIXBASED T Principal Investigator & Institution: Lue, Tom F. Professor of Urology; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: It is estimated that 100 million men and women are affected by urinary incontinence (UI). The prevalence of UI is generally higher in women than in men, women being between two (older age groups) and four times (younger and middleaged) more likely to be incontinent than men. In the past 3 years, supported by an NIH grant, we have studied the effect of pregnancy, delivery, birth trauma, ovariectomy and aging on the ultrastructure and function of the continence mechanism. We have learned that the final common pathway of stress urinary incontinence in the rat model is the alteration of nervous, vascular, and muscular components of the continence mechanism. We therefore propose to further study the molecular mechanism involved in the pathogenesis of female stress urinary incontinence. We hypothesize that pregnancy/delivery, birth trauma, and hormonal deficiency (menopause) alter the gene and protein expression of many factors. We propose to use the state-of-the-art technique such as gene microarray, realtime PCR, multiple PCR etc to identify genes that are associated with female stress urinary incontinence and to further study the molecular mechanism. Further more, we have obtained encouraging results from using organ specific acellular matrix as a scaffold for the repair of bladder and ureteral defects in our lab. We propose to study whether the acellular matrix with or without growth factors can be used for the treatment of stress urinary incontinence. The hypotheses will be tested by completing the following specific aims. Specific aim 1: To identify gene that are associated with stress incontinence and to elucidate the molecular mechanism of stress urinary incontinence associated with pregnancy/delivery, birth trauma, and ovariectomy. Specific aim 2: To identify the best growth factor combinations that can enhance angiogenesis, neural growth and urethral smooth/striated muscle proliferation in a novel in vitro assay system. Specific aim 3: To apply acellular matrix with or without growth factors identified from specific aim 2 to animals with stress urinary incontinence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VARIABILITY IN ESTROGEN METABOLISM POSTMENOPAUSE Principal Investigator & Institution: Goldner, Deborah N.; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001 Summary: Women spend one third of their lives after menopause. Estrogen replacement therapy and hormone replacement therapy (estrogen and progesterone) have been shown to decrease morbidity and mortality, the symptoms of menopause, the severity of osteoporosis, the risk of coronary artery disease and possibly affect the onset of Alzheimer's disease in postmenopausal women (1)(2). Estrogen replacement therapy has been shown to increase the incidence of endometrial hyperplasia and endometrial carcinoma w/a less well defined effect on the incidence of breast cancer. Various forms of estrogen are some of the most frequently prescribed drugs, however, there is relatively little information regarding factors that affect the metabolism of estrogen. The purpose of this pilot study is to investigate various drugs that may alter the metabolism of estrogen. To determine the effect of an inhibitor (erythromycin) and an inducer (rifampin) of P4503A4 on the pharmacokinetics of estradiol.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: VITAMIN D SUPPLEMENTATION IN POSTMENOPAUSAL WOMEN Principal Investigator & Institution: Aloia, John F.; Winthrop-University Hospital 259 1St St Mineola, NY 11501 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-JUL-2003 Summary: (Adapted from the Applicant's Abstract): The long-term goal of this project is to develop strategies for the prevention of osteoporotic fractures in black women. Most studies have excluded black women because of the mistaken belief that osteoporosis is not a major health problem in this population. It is true that black women have a higher bone density, protective anatomic geometry of the femur, and a larger muscle mass compared to white women. Nonetheless, the incidence of hip fracture in black women is as great as 40% of that in white women. As the black population ages, osteoporosis will become even a greater health problem for this ethnic minority. Black women have lower levels of calcidiol and higher levels of parathyroid hormone (PTH) than white women. Since black women have lower indices of bone turnover, they also appear to have a relative resistance to the effect of PTH. Dietary supplementation with vitamin D3 has been shown to safely reduce bone loss and prevent hip fractures in postmenopausal white women. The strategy of vitamin D3 supplementation to prevent osteoporosis is even more cogent in black postmenopausal women compared to white women because (a) they have lower calcidiol levels, (b) they have evidence of secondary hyperparathyroidism, (c) the long-term effects and risks of hormonal replacement therapy have not been evaluated in black women, and (d) because of their higher bone mass, low risk strategies are more appropriate. There are less black women with osteoporosis at menopause, so that a modest reduction in bone loss could have a great impact on prevention of osteoporosis. The specific aim of this project is to determine if daily dietary supplementation with 800 IU (20 ug) of vitamin D3 will reduce bone loss in postmenopausal black women. A secondary aim is to evaluate the changes in the vitamin D-endocrine system and indices of bone turnover that result from long term vitamin D3 augmentation. A positive response would provide a safe, inexpensive and acceptable strategy for prevention of osteoporotic fractures in black women. If this randomized clinical trial demonstrates a positive effect on prevention of bone loss, a large scale multi-centered trial with fracture prevention as an endpoint will have merit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: WEIGHT CONTROL IN PERI- AND EARLY POSTMENOPAUSAL WOMEN Principal Investigator & Institution: Racette, Susan B. Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Obesity is a preventable condition that contributes significantly to morbidity and mortality. A women's risk for obesity, as well as cardiovascular disease and osteoporosis, increases dramatically with menopause due to normal and lifestyle changes. Furthermore, many perimenopausal women are already at risk for obesity based upon current overweight or obesity, former obesity, or a family history of obesity. In light of much evidence that reversal of obesity generally is difficult and unsuccessful long-term, a preventive approach that emphasizes modest lifestyle modifications may be superior in promoting long-term behavioral changes and weight control with advancing age. Therefore, the primary aim of this study is to assess the effectiveness of a

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modest lifestyle intervention program or preventing gains in body weight, whole body bat mass, and abdominal adipose tissue during a 2-year period in perimenopausal and early postmenopausal women who are at risk for obesity. A second aim is to determine the effects of the intervention on daily physical activity, which will be calculated from total daily expenditure and resting metabolic rate, as determined by the doubly labeled water method and indirect calorimetry, respectively. A randomized, controlled trial will be used to evaluate the intervention in female employees of a large Midwestern medical center. The intervention is a modest lifestyle modification program that will focus on teaching participants ways to modify their dietary habits and incorporate additional physical activity, as a means of altering daily energy balance to prevent weight gain during the 2-year intervention period. The 4 components of the intervention include: 1) reducing dietary fat intake; 2) increasing daily physical activity; 3) two consecutive days per month of low-fat, low-calorie meals prepared either in the metabolic kitchen of the General Clinical Research Center or by the participant; and 4) a "study- buddy" system, in which each participant is paired with a buddy with whom she is to keep in the frequent contact, discuss goals and progress, and motive. The results of this project are intended to provide valuable information regarding lifestyle programs that may assist women in controlling body weight at a time when weight gain is common. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: WEIGHT MGT & NUTRITION FOR PRE-/PERIMENOPAUSAL BREAST CANCER SURVIVORS Principal Investigator & Institution: Wylie-Rosett, Judith; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2001 Summary: More than half of premenopausal breast cancer survivors gain weight during the first postsurgical year. A greater than average weight gain has been associated with an increased risk for breast cancer recurrence weight gain during menopause is greatest during its first decade.and death. Adult weight gain also increases the risk of postmenopausal breast cancer. It is estimated that weight gain during menopause is greatest during its first decade. There is increasing evidence that elevated plasma free estradiol, the portion of estradiol not bound to plasma proteins, is associated with both weight gain and an increased risk for breast cancer. There has been very limited research on whether free estradiol can be modulated through dietary or body fat changes. Therefore, we will also evaluate in this protocol the impact that a reduction in dietary fat, an increase in dietary fiber, weight loss and a change in body fat percentage or body fat distribution has on plasma free estradiol. The aims of this pilot study are to conduct a randomized controlled clinical trial with 72 breast cancer survivors (36 to the intervention group and 36 to the control group). The sample will be stratified evenly between pre/peri menopausal and post-menopausal subjects. Participants in the intervention group will be offered 13 nutrition education sessions. The goals of the nutrition intervention are to help paritipants: a) Reduce fat intake to 15% of calories (with the calorie level set to maintain or achieve a healthy weight); b) Increase fiber intake to 40 grams per day by consuming a diet rich in fruits, vegetables and unprocessed complex carbohydrates and c) Establishing or maintaining an exercise pattern of at at least 1000 kilocalories/week. The primary hypothesis is that the intervention group will have a significantly greater reduction in the percentage of plasma free estradiol than the control group. A secondary hypothesis is that the intervention group will have significantly fewer women than the control group who have a net weight gain since breast cancer surgery of five or more pounds. Other

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variables of interest are whether the intervention results in changes in the body fat percentage, the ratio of upper to lower body fat, and in the lipid profile. We will also assess whether the intervention hormonal patterns differently between pre, peri and postmenopausal women. Additionally, we will compare the effect of the dietary intervention on the percentage of plasma free estradiol to another potential biomarker for breast cancer risk, the ratio of 2-hydroxyestrone to 16-alpha-hydroxyestrone. Secondary questions include how changes in dietary intake, physical activity, and weight-related parameters are related to the quality of life, perception of risk from breast cancer, and participants' satisfaction with the protocol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: WOMANS HEALTH ACROSS THE NATION MGH Principal Investigator & Institution: Finkelstein, Joel S. Massachusetts General Hospital 55 Fruit St Boston, MA 02114

Associate

Professor;

Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 30-NOV-2003 Summary: This application is to continue the Study of Women's Health Across the Nation (SWAN) for a second five year funding cycle. SWAN II is poised to contribute substantive new knowledge on the menopause transition through its prospective design, multi-ethnic/racial composition, representativeness of defined populations, and comprehensive measurement and power. No other recent or ongoing study is in a position to respond to the breadth of identified gaps in scientific knowledge on the menopause transition, either because sample sizes or follow-up data are insufficient, the multidisciplinary data are lacking or are restrictive, or because the samples are homogeneous. This application serves as the primary scientific application for SWAN. There are also companion applications being submitted by the Coordinating Center (NERI) and the Central Endocrine Laboratory (CLASS). This executive summary serves as the overall summary and progress report for SWAN I and as an introduction to the four substantive project applications which follow. The four project applications each provide a detailed proposal to address one of four major objectives originally identified in the RFA (number AG-94-002), from which the Study of Women's Health Across the Nation (SWAN I), was funded in September 1994 by the National Institute on Aging with support from the National Institute of Nursing Research and the Office of Research on Women's Health. The objectives from the original RFA and the project applications which follow this executive summary are: 1) To collect and analyze data on demographics, health and social characteristics, race/ethnicity, reproductive history, pre-existing illness, physical activity (includes activity limitations), health practices (includes diet, smoking, use of OTC) as potential predictor variables and to describe the multiethnic community-based samples of mid-life women. (Risk Factor Project); 2) To elucidate factors that differentiate symptomatic from asymptomatic women during the [menopausal] transition. (Risk Factor Project); 3) To identify and utilize appropriate markers of ovarian aging or aging of the ovarian-hypothalamo-pituitary axis and relate these markers to alterations in menstrual characteristics as women approach and traverse menopause. (Ovarian Aging Project); 4) To elucidate factors that differentiate women most susceptible to long-term pathophysiological consequences of ovarian hormone deficiency from those who are protected. (Cardiovascular Project and Bone Project) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: WOMEN IN TRANSITION: THE CRUCIAL YEARS BEFORE MENOPAUSE Principal Investigator & Institution: Wurzburg, Gerardine; President; State of the Art, Inc. 4455 Connecticut Ave Nw, Ste B-2 Washington, DC 20008 Timing: Fiscal Year 2001; Project Start 20-SEP-1998; Project End 31-JAN-2004 Summary: The proposed project is a preventive health promotion campaign for women 40-55 about the health risks they face in perimenopause and what they can do to decrease mortality rates and increase well being. In Phase I, the creative plans for the materials were developed and researched for effectiveness. Phase ll products will include: two videotapes and accompanying print booklets, one set for a general audience of women 40- 55 and one set for an African American audience of women 4055; a daily health planner and a website for all women 40-55. Production of the Phase II products will incorporate Phase I findings into the production of two broadcast quality videotapes, design and printing of the two booklets and daily health planner and creation of the interactive website Before completion, these materials will be reviewed by the Board of Advisors and focus group tested with the target audiences and health professionals to ensure that each product meets the informational as well as the supportive needs of women 40-55. The video, print and website materials will then be quantitatively tested with women from diverse backgrounds to measure effectiveness and impact on overall well being and preventive lifestyles. PROPOSED COMMERCIAL APPLICATION: The complete educational packages will be marketed to women through hospitals with women's health centers, advocacy groups and churches, doctors, HMO's and video distributors who specialize in health care media. State of the Art has successfully marketed several other videotape/print packages to this market and already has contacts and established relationships to assist in the marketing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: WOMEN'S HEALTH ACROSS THE NATION - ENDOCRINE LAB Principal Investigator & Institution: Mcconnell, Daniel S. Epidemiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2003; Project Start 30-SEP-1994; Project End 30-NOV-2003 Summary: (provided by applicant): This one year competing renewal is submitted as one of a set of nine component applications (including seven clinic sites, the Coordinating Center and a Central Endocrinology Laboratory) to augment the last year of the current five-year renewal (SWAN II) of the nine originally funded applications in response to RFA AG-94-002, "Menopause and Health in Aging Women." The purpose of this renewal is to complete a sixth annual follow-up visit on approximately 2470 women across clinical sites and a final annual cycle of daily urine collections on approximately 550 women. Each of these data collection activities requires a two-year period for completion. The SWAN II application included funding to finish Visit 02 to the Visit 00 and Visit 01 data collections, to undertake Visits 03, 04 and 05 data collections and to spend the final year on analyses. Preliminary data now available from Visits 00-03 indicate that the original and continuing aims of this important study cannot be addressed with the currently funded five years of follow-up observation as the number of menopause transitions will be insufficient. Projections indicate that nine years of follow up will be required. Bridging funding (this supplement application) is needed so that a one year gap in cohort follow-up to complete a Visit 06 can be closed. A competing renewal for five years (SWAN III) must be predicated on continuing data collection so that cohort retention, follow-up integrity and certified staff availability is

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assured. Hence there is a need to obtain this supplemental funding to bridge the time in the SWAN II that was planned for closeout and data analysis. To assess endocrine changes in midlife women, the University of Michigan?s Central Ligand Assay Satellite Services (CLASS) laboratory will continue to support SWAN by using state-of-thescience, automated assays for all the major reproductive axis hormones (LH, FSH, E2, P, and T), adrenal markers of aging (DHEAS), other endocrine markers (TSH, SHBG) and new ovarian markers which have the potential to allow us to hormonally define the menopausal transition and the postmenopause with greater precision (inhibin B, estrone). In order to continue to support the Daily Hormone Study, CLASS will utilize sensitive and specific urinary assays for LH, FSH and the principal urinary metabolites of estradiol and progesterone, estrone conjugates and pregnanediol glucuronide, respectively. To assess endocrine changes in midlife women, the University of Michigan?s Central Ligand Assay Satellite Services (CLASS) laboratory will continue to support SWAN by using state-of-the-science, automated assays for all the major reproductive axis hormones (LH, FSH, E2, P, and T), adrenal markers of aging (DHEAS), other endocrine markers (TSH, SHBG) and new ovarian markers which have the potential to allow us to hormonally define the menopausal transition and the postmenopause with greater precision (inhibin B, estrone). In order to continue to support the Daily Hormone Study, CLASS will utilize sensitive and specific urinary assays for LH, FSH and the principal urinary metabolites of estradiol and progesterone, estrone conjugates and pregnanediol glucuronide, respectively. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: WOMENS HEALTH ACROSS THE NATION--CC Principal Investigator & Institution: Mckinlay, Sonja M. President; New England Research Institutes, Inc. 9 Galen St Watertown, MA 02472 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 30-NOV-2003 Summary: The study of Women's Health Across the Nation (SWAN I) was funded on September 1994 by the National Institutes on Aging in response to RFA AG-94-002 entitled "Menopause and Health in Aging Women." The RFA identified four primary objectives and called for a Coordinating Center, Clinical Sites and a central endocrinology laboratory. This Coordinating Center application is a component of a set of applications, including seven clinic sites and central endocrinology laboratory, to continue SWAN for an additional five years. SWAN II proposes to continue the science begun under the current awards, building on the experience gained to further enhance the scientific contribution of the study to our knowledge of the role of menopause and aging on health in mid-aged and older women. To facilitate addressing the scientific goals of this renewal, the Coordinating Center (CC) will meet the following four goals. 1. The CC will maintain and continue to enhance the current distributed data management system (DMS) to collect, integrate, quality control and document for analysis data collected directly from the clinic sites and from the central laboratories. 2. The CC will continue to support the development and implementation of all core and sub-core SWAN protocols, including scientific input, forms design, manuals of operation, training and certification of site staff and on-going quality control and standardization of measurement through site visits, regular conference calls and review of data. 3. The CC will continue to provide, in collaboration with site statisticians, statistical experience in study design and analytic approach, coordinate the development of and maintain all analytic data sets and complete analyses for manuscripts and presentations. Administratively, the CC will continue to coordinate and support the SWAN administrative structure through conference call and meeting

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support, and by maintaining Steering Committee (SC) and Executive Committee (EC) minutes, assisting with Advisory Panel (AP) minutes, maintaining the study directory, committee lists and the SWAN Web Site. The CC will also maintain all study protocol documentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: WOMENS HEALTH ACROSS THE NATION--NEW JERSEY Principal Investigator & Institution: Weiss, Gerson; Professor and Chair; Ob/Gyn & Women's Health; Univ of Med/Dent Nj Newark Newark, NJ 07103 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 30-NOV-2003 Summary: This application is to continue the Study of Women's Health Across the Nation (SWAN) for a second five year funding cycle. SWAN II is poised to contribute substantive new knowledge on the menopause transition through its prospective design, multi-ethnic/racial composition, representativeness of defined populations, and comprehensive measurement and power. No other recent or ongoing study is in a position to respond to the breadth of identified gaps in scientific knowledge on the menopause transition, either because sample sizes or follow-up data are insufficient, the multidisciplinary data are lacking or are restrictive, or because the samples are homogeneous. This application serves as the primary scientific application for SWAN. There are also companion applications being submitted by the Coordinating Center (NERI) and the Central Endocrine Laboratory (CLASS). This executive summary serves as the overall summary and progress report for SWAN I and as an introduction to the four substantive project applications which follow. The four project applications each provide a detailed proposal to address one of four major objectives originally identified in the RFA (number AG-94-002), from which the Study of Women's Health Across the Nation (SWAN I), was funded in September, 1994, by the National Institute on Aging with support from the National Institute of Nursing Research and the Office of Research on Women's Health. The objectives from the original RFA and the project applications which follow this executive summary are: 1) To collect and analyze data on demographics, health and social characteristics, race/ethnicity, reproductive history, pre- existing illness, physical activity (includes activity limitations), health practices" (includes diet, smoking, use of OTC) as potential predictor variables and to describe the multiethnic community-based samples of mid-life women. (Risk Factor Project); 2) To elucidate factors that differentiate symptomatic from asymptomatic women during the [menopausal] transition. (Risk Factor Project); 3) To identify and utilize appropriate markers of ovarian aging or aging of the ovarian-hypothalamo-pituitary axis and relate these markers to alterations in menstrual characteristics as women approach and traverse menopause. (Ovarian Aging Project); 4) To elucidate factors that differentiate women most susceptible to long-term pathophysiological consequences of ovarian hormone deficiency from those who are protected. (Cardiovascular Project) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: WOMENS HEALTH ACROSS THE NATION--UCLA Principal Investigator & Institution: Greendale, Gail A. Associate Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 30-NOV-2003 Summary: This application is to continue the Study of Women's Health Across the Nation (SWAN) for a second five year funding cycle. SWAN II is poised to contribute

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substantive new knowledge on the menopause transition through its prospective design, multi-ethnic/racial composition, representativeness of defined populations, and comprehensive measurement and power. No other recent or ongoing study is in a position to respond to the breadth of identified gaps in scientific knowledge on the menopause transition, either because sample sizes or follow-up data are insufficient, the multidisciplinary data are lacking or are restrictive, or because the samples are homogeneous. This application serves as the primary scientific application for SWAN. There are also companion applications being submitted by the Coordinating Center (NERI) and the Central Endocrine Laboratory (CLASS). This executive summary serves as the overall summary and progress report for SWAN I and as an introduction to the four substantive project applications which follow. The four project applications each provide a detailed proposal to address one of four major objectives originally identified in the RFA (number AG-94-002), from which the Study of Women's Health Across the Nation (SWAN I), was funded in September, 1994, by the National Institute on Aging with support from the National Institute of Nursing Research and the Office of Research on Women's Health. The objectives from the original RFA and the project applications which follow this executive summary are: 1) To collect and analyze data on demographics, health and social characteristics, race/ethnicity, reproductive history, pre-existing illness, physical activity (includes activity limitations), health practices" (includes diet, smoking, use of OTC) as potential predictor variables and to describe the multiethnic community-based samples of mid-life women. (Risk Factor Project); 2) To elucidate factors that differentiate symptomatic from asymptomatic women during the [menopausal] transition. (Risk Factor Project); 3) To identify and utilize appropriate markers of ovarian aging or aging of the ovarian-hypothalamo-pituitary axis and relate these markers to alterations in menstrual characteristics as women approach and traverse menopause. (Ovarian Aging Project); 4) To elucidate factors that differentiate women most susceptible to long-term pathophysiological consequences of ovarian hormone deficiency from those who are protected. (Cardiovascular Project and Bone Project). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: WOMEN'S HEALTH AND AGING: RESEARCH & LEADERSHIP TRAINING Principal Investigator & Institution: Carnes, Mary L. Associate Professor; Medicine; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-APR-2004 Summary: Women's health research has been emphasized in the NIH strategic plan and one of the mandates of the NIH Office of Research in Women's Health established in 1990 by Congressional mandate is to enhance research in Women's Health. The National Institute of Aging has a precedent of funding innovative research on Women's Health and Aging including menopause. The proposed Women's Health and Aging: Research and Leadership Training Grant focuses on training researchers in Women's Health and Aging. Research faculty cluster along themes of the Biology of Menopause and Postmenopausal Diseases (9 faculty) or Clinical Research in Mid to Late Life Aging Women (7 faculty). All research training faculty are currently principal investigators to NIH-funded research programs. To ensure mentoring, the Training Grant also has a Leadership Core of four senior women faculty committed to nurturing the careers of future academicians. An Advisory Committee of selected faculty from each theme and three additional faculty will assist the director and Co-Directors in overseeing recruitment, selection, and monitoring of trainees. This training program is for

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postdoctoral PhD or physician scientists who desire a research career in Women's Health and Aging. Support is requested for two positions in year one and four positions in subsequent years. The training program incorporates the following: 1) apprenticeship with a research mentor, 2) course work, lectures, and seminars which include instruction in grant writing, teaching, women's health, aging, leadership skills, mentoring, ethical conduct in research, and issues of aging among special populations, 3) and close tracking and mentoring by the Advisory Committee, the Leadership Core, and the individual research mentor. An Evaluation Plan is proposed for the trainees, faculty and training program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: WOMEN'S HEALTH IN CYSTIC FIBROSIS Principal Investigator & Institution: Billings, Joanne L. Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 05-JUL-2001; Project End 30-JUN-2006 Summary: Dr. Billings is a fourth year pulmonary and critical care fellow at the University of Minnesota who will become an Instructor of Medicine on July 1, 2000. Her long term goal is to develop an independent academic career combining clinical research with clinical medicine. Her primary research and clinical field will be in cystic fibrosis (CF). The proposed career development plan combines an intense interdisciplinary patient-- oriented research experience in association with a comprehensive structured didactic curriculum. The candidate is particularly interested in the health of women with CF. Data from patients seen at the University of Minnesota CF Center demonstrate greater mortality in women compared to men which appears to increase near the time of puberty. Dr. Billings will explore the hypothesis that estrogen and progesterone may have a negative impact on CF lung disease. The present study will examine lung function during the follicular and luteal phases of the menstrual cycle in normally menstruating young women with CF. Lung function of women with CF on birth control pills will be compared to those who are not. Pilot information on the effect of menopause on lung function, bone health, lipid levels and cardiovascular disease will also be obtained. If there is evidence of hormonal influence on pulmonary function, there may be future therapeutic implications and the potential to improve survival in women with CF. The Mentored Patient-Oriented Development Award affords the opportunity for the PI to translate existing knowledge of cohort study design into the practical application of study conduct and implementation. The applicant will pursue additional courses in the School of Public Health in the areas of clinical research, biostatistics and ethics. She will have the opportunity to expand her knowledge of endocrinology and metabolism as well as research methodology with this study of women's health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National

3

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

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Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “menopause” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for menopause in the PubMed Central database: ·

3-day course of ofloxacin versus cefalexin in the treatment of urinary tract infections in postmenopausal women. by Raz R, Rozenfeld S. 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163499

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Debate: The potential role of estrogen in the prevention of heart disease in women after menopause. by Johnson RR, Sweeney ME. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59620

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Debate: The potential role of estrogen in the prevention of heart disease in women after menopause. by Rossouw JE. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59619

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Effect of Surgical Menopause and Estrogen Replacement on Cytokine Release from Human Blood Mononuclear Cells. by Pacifici R, Brown C, Puscheck E, Friedrich E, Slatopolsky E, Maggio D, McCracken R, Avioli LV. 1991 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51826

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Grandmothering, menopause, and the evolution of human life histories. by Hawkes K, O'Connell JF, Jones NG, Alvarez H, Charnov EL. 1998 Feb 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18762

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Hormone replacement therapy use dramatically increases breast oestrogen receptor expression in obese postmenopausal women. by Lawson JS, Field AS, Tran DD, Houssami N. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=57804

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International versions of the Menopause Rating Scale (MRS). by Heinemann LA, Potthoff P, Schneider HP. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=183844

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Ovarian antibodies as detected by indirect immunofluorescence are unreliable in the diagnosis of autoimmune premature ovarian failure: a controlled evaluation. by Novosad JA, Kalantaridou SN, Tong ZB, Nelson LM. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153539

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Population based case-control study of sick leave in postmenopausal women before diagnosis of hyperparathyroidism. by Lundgren E, Szabo E, Ljunghall S, Bergstrom R, Holmberg L, Rastad J. 1998 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31094

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With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Prevalence of Bacterial Vaginosis and Vaginal Flora Changes in Peri- and Postmenopausal Women. by Cauci S, Driussi S, De Santo D, Penacchioni P, Iannicelli T, Lanzafame P, De Seta F, Quadrifoglio F, de Aloysio D, Guaschino S. 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=130764

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Pulse pressure and age at menopause. by Luoto R, Sharrett AR, Eigenbrodt M, Arnett D. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117223

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What type of exercise prevents cardiovascular disease in postmenopausal women? by Rivet C. 2003 Feb 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140475

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with menopause, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “menopause” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for menopause (hyperlinks lead to article summaries): ·

A comparison of endothelial function in Caucasian and Chinese women before and after the menopause. Author(s): McCrohon JA, Woo KS, Celermajer DS. Source: Maturitas. 2000 April 28; 35(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802397&dopt=Abstract

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A critical ethnography of Korean Canadian women's menopause experience. Author(s): Elliott J, Berman H, Kim S. Source: Health Care for Women International. 2002 June; 23(4): 377-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12148915&dopt=Abstract

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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A decision aid for women considering hormone therapy after menopause: decision support framework and evaluation. Author(s): O'Connor AM, Tugwell P, Wells GA, Elmslie T, Jolly E, Hollingworth G, McPherson R, Bunn H, Graham I, Drake E. Source: Patient Education and Counseling. 1998 March; 33(3): 267-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9731164&dopt=Abstract

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A feminist analysis of the menopause discourse. Author(s): Loppie C, Keddy B. Source: Contemp Nurse. 2002 February; 12(1): 92-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12013524&dopt=Abstract

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A longitudinal study of the effects of menopause on mammographic features. Author(s): Boyd N, Martin L, Stone J, Little L, Minkin S, Yaffe M. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 October; 11(10 Pt 1): 1048-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376506&dopt=Abstract

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A longitudinal study of weight and the menopause transition: results from the Massachusetts Women's Health Study. Author(s): Crawford SL, Casey VA, Avis NE, McKinlay SM. Source: Menopause (New York, N.Y.). 2000 March-April; 7(2): 96-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10746891&dopt=Abstract

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A mouse model to study the effects of hormone replacement therapy on normal mammary gland during menopause: enhanced proliferative response to estrogen in late postmenopausal mice. Author(s): Raafat AM, Hofseth LJ, Li S, Bennett JM, Haslam SZ. Source: Endocrinology. 1999 June; 140(6): 2570-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10342844&dopt=Abstract

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A polymorphism of the Nos3 gene and age at natural menopause. Author(s): Hefler LA, Worda C, Huber JC, Tempfer CB. Source: Fertility and Sterility. 2002 December; 78(6): 1184-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477509&dopt=Abstract

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A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition. Author(s): Burger HG, Dudley EC, Cui J, Dennerstein L, Hopper JL. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 August; 85(8): 2832-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10946891&dopt=Abstract

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A prospective study of menopause in women with Down's syndrome. Author(s): Seltzer GB, Schupf N, Wu HS. Source: Journal of Intellectual Disability Research : Jidr. 2001 February; 45(Pt 1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11168771&dopt=Abstract

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A randomized comparison of continuous combined transdermal delivery of estradiolnorethindrone acetate and estradiol alone for menopause. CombiPatch Study Group. Author(s): Archer DF, Furst K, Tipping D, Dain MP, Vandepol C. Source: Obstetrics and Gynecology. 1999 October; 94(4): 498-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10511348&dopt=Abstract

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A review of bone mineral density scans referred by a community-based menopause clinic in 1997. Author(s): Miles A, Weaver KE, Glasier A. Source: Br J Fam Plann. 2000 July; 26(3): 136-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10920288&dopt=Abstract

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A review of the effectiveness of Cimicifuga racemosa (black cohosh) for the symptoms of menopause. Author(s): Lieberman S. Source: Journal of Women's Health / the Official Publication of the Society for the Advancement of Women's Health Research. 1998 June; 7(5): 525-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9650153&dopt=Abstract

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A role for melatonin in breast disease and the menopause. Author(s): Oosthuizen GM, Joubert G, du Toit RS. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2001 July; 91(7): 576-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11544972&dopt=Abstract

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A survey of menopause content in BSN curricula. Author(s): Carlson ES, Holm K, Dooling SL. Source: The Journal of Nursing Education. 2000 December; 39(9): 412-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11138747&dopt=Abstract

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A validation study on status and age of natural menopause reported in the E3N cohort. Author(s): Clavel-Chapelon F, Dormoy-Mortier N. Source: Maturitas. 1998 June 3; 29(2): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9651898&dopt=Abstract

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A woman's hell? Medical perceptions of menopause in preindustrial Europe. Author(s): Stolberg M. Source: Bulletin of the History of Medicine. 1999 Fall; 73(3): 404-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500337&dopt=Abstract

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Ability of peripheral DXA measurements of the forearm to predict low axial bone mineral density at menopause. Author(s): Pouilles JM, Tremollieres FA, Martinez S, Delsol M, Ribot C. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(1): 71-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305086&dopt=Abstract

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Aboriginal women and menopause. Author(s): Webster RW. Source: J Obstet Gynaecol Can. 2002 December; 24(12): 938-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464991&dopt=Abstract

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Active and passive smoking and the occurrence of natural menopause. Author(s): Cooper GS, Sandler DP, Bohlig M. Source: Epidemiology (Cambridge, Mass.). 1999 November; 10(6): 771-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10535795&dopt=Abstract

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Acute menopause symptoms during adjuvant systemic treatment for breast cancer: a case-control study. Author(s): McPhail G, Smith LN. Source: Cancer Nursing. 2000 December; 23(6): 430-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11128122&dopt=Abstract

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Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis. Author(s): Goodwin PJ, Ennis M, Pritchard KI, McCready D, Koo J, Sidlofsky S, Trudeau M, Hood N, Redwood S. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 January; 17(1): 120-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458225&dopt=Abstract

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Age and distance from the surface but not menopause reduce osteocyte density in human cancellous bone. Author(s): Qiu S, Rao DS, Palnitkar S, Parfitt AM. Source: Bone. 2002 August; 31(2): 313-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151084&dopt=Abstract

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Age and menopause-related changes in phalangeal bone density of Japanese women, measured by a digital image processing method. Author(s): Zhang H, Kitazawa A, Kushida K, Nagano A. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2000; 5(5): 431-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180898&dopt=Abstract

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Age at menarche and age at menopause in relation to hepatocellular carcinoma in women. Author(s): Mucci LA, Kuper HE, Tamimi R, Lagiou P, Spanos E, Trichopoulos D. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2001 March; 108(3): 291-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281471&dopt=Abstract

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Age at menopause and childbearing patterns in relation to mortality. Author(s): Cooper GS, Baird DD, Weinberg CR, Ephross SA, Sandler DP. Source: American Journal of Epidemiology. 2000 March 15; 151(6): 620-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10733044&dopt=Abstract

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Age at menopause and prevalence of its different types in contemporary Greek women. Author(s): Adamopoulos DA, Karamertzanis M, Thomopoulos A, Pappa A, Koukkou E, Nicopoulou SC. Source: Menopause (New York, N.Y.). 2002 November-December; 9(6): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439104&dopt=Abstract

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Age at menopause as a marker of reproductive ageing. Author(s): te Velde ER, Dorland M, Broekmans FJ. Source: Maturitas. 1998 October 12; 30(2): 119-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9871906&dopt=Abstract

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Age at menopause in women with type 2 diabetes mellitus. Author(s): Lopez-Lopez R, Huerta R, Malacara JM. Source: Menopause (New York, N.Y.). 1999 Summer; 6(2): 174-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10374226&dopt=Abstract

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Age at menopause, body mass index, and the risk of colorectal cancer mortality in the Dutch Diagnostisch Onderzoek Mammacarcinoom (DOM) cohort. Author(s): van Wayenburg CA, van der Schouw YT, van Noord PA, Peeters PH. Source: Epidemiology (Cambridge, Mass.). 2000 May; 11(3): 304-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10784248&dopt=Abstract

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Age at natural menopause and all-cause mortality: a 37-year follow-up of 19,731 Norwegian women. Author(s): Jacobsen BK, Heuch I, Kvale G. Source: American Journal of Epidemiology. 2003 May 15; 157(10): 923-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746245&dopt=Abstract

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Age at natural menopause and mortality. Author(s): Cooper GS, Sandler DP. Source: Annals of Epidemiology. 1998 May; 8(4): 229-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9590601&dopt=Abstract

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Age at natural menopause and risk of cardiovascular disease. Author(s): Hu FB, Grodstein F, Hennekens CH, Colditz GA, Johnson M, Manson JE, Rosner B, Stampfer MJ. Source: Archives of Internal Medicine. 1999 May 24; 159(10): 1061-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10335682&dopt=Abstract

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Age at natural menopause and the risk of epithelial ovarian cancer. Author(s): Schildkraut JM, Cooper GS, Halabi S, Calingaert B, Hartge P, Whittemore AS. Source: Obstetrics and Gynecology. 2001 July; 98(1): 85-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430962&dopt=Abstract

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Age at natural menopause and total mortality and mortality from ischemic heart disease: the Adventist Health Study. Author(s): Jacobsen BK, Knutsen SF, Fraser GE. Source: Journal of Clinical Epidemiology. 1999 April; 52(4): 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10235170&dopt=Abstract

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Age at natural menopause in Beirut, Lebanon: the role of reproductive and lifestyle factors. Author(s): Reynolds RF, Obermeyer CM. Source: Annals of Human Biology. 2001 January-February; 28(1): 21-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11201328&dopt=Abstract

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Age at onset of dementia and age of menopause in women with Down's syndrome. Author(s): Cosgrave MP, Tyrrell J, McCarron M, Gill M, Lawlor BA. Source: Journal of Intellectual Disability Research : Jidr. 1999 December; 43 ( Pt 6): 461-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10622361&dopt=Abstract

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Age, pattern and symptoms of menopause among rural women of Lahore. Author(s): Yahya S, Rehan N. Source: J Ayub Med Coll Abbottabad. 2002 July-September; 14(3): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476855&dopt=Abstract

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Ageing of the skin during menopause. Author(s): Broniarczyk-Dyla G, Joss-Wichman E. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2001 September; 15(5): 494-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763406&dopt=Abstract

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Aging, menopause, and free radicals. Author(s): Schwenke DC. Source: Semin Reprod Endocrinol. 1998; 16(4): 281-308. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10101810&dopt=Abstract

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An Australian study on the sociocultural context of menopause: directions for contemporary nursing practice. Author(s): Berger G, Forster E. Source: Contemp Nurse. 2001 December; 11(2-3): 271-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924626&dopt=Abstract

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An earlier menopause as clinical manifestation of granulosa-cell tumor: a case report. Author(s): Hiroi H, Momoeda M, Yamauchi N, Abe Y, Yoshikawa H, Tsutsumi O, Taketani Y. Source: The Journal of Obstetrics and Gynaecology Research. 2000 February; 26(1): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10761324&dopt=Abstract

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An evaluation of a health education intervention for mid-aged women: five year follow-up of effects upon knowledge, impact of menopause and health. Author(s): Hunter M, O'Dea I. Source: Patient Education and Counseling. 1999 November; 38(3): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10865690&dopt=Abstract

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An event history analysis of age at last menstrual period: correlates of natural and surgical menopause among midlife Wisconsin women. Author(s): Shinberg DS. Source: Social Science & Medicine (1982). 1998 May; 46(10): 1381-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9665569&dopt=Abstract

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Androgen and SHBG serum concentrations in late post-menopause women. Author(s): Skalba P, Wojtowicz M, Sikora J. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 March; 9(3): Cr152-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640346&dopt=Abstract

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Androgen cotherapy in menopause: evolving benefits and challenges. Author(s): Bachmann GA. Source: American Journal of Obstetrics and Gynecology. 1999 March; 180(3 Pt 2): S30811. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10076169&dopt=Abstract

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Androgen deficiency: menopause and estrogen-related factors. Author(s): Sarrel PM. Source: Fertility and Sterility. 2002 April; 77 Suppl 4: S63-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12007905&dopt=Abstract

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Androgen metabolism and the menopause. Author(s): Longcope C. Source: Semin Reprod Endocrinol. 1998; 16(2): 111-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9711675&dopt=Abstract

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Androgen replacement in menopause. Author(s): Burd ID, Bachmann GA. Source: Curr Womens Health Rep. 2001 December; 1(3): 202-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112971&dopt=Abstract

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Androgens and women at the menopause and beyond. Author(s): Morley JE, Perry HM 3rd. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 May; 58(5): M409-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730248&dopt=Abstract

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Anticipating menopause: observations from the Seattle Midlife Women's Health Study. Author(s): Woods NF, Mitchell ES. Source: Menopause (New York, N.Y.). 1999 Summer; 6(2): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10374225&dopt=Abstract

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Anticipations and experiences of menopause in a Danish female general population cohort born in 1936. Author(s): Koster A, Eplov LF, Garde K. Source: Archives of Women's Mental Health. 2002 August; 5(1): 9-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503069&dopt=Abstract

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Anxiety and depression before and after the menopause. Author(s): Sagsoz N, Oguzturk O, Bayram M, Kamaci M. Source: Archives of Gynecology and Obstetrics. 2001 January; 264(4): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205708&dopt=Abstract

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Apoptosis, cellular proliferation and expression of p53 in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause. Author(s): Wu X, Blanck A, Olovsson M, Moller B, Favini R, Lindblom B. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2000 May; 79(5): 397-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10830768&dopt=Abstract

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Appraising the menopause Web. Five top sites worth exploring. Author(s): Learn CD. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 1998 August; 2(4): 40-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9791336&dopt=Abstract

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Are changes in sexual functioning during midlife due to aging or menopause? Author(s): Dennerstein L, Dudley E, Burger H. Source: Fertility and Sterility. 2001 September; 76(3): 456-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532464&dopt=Abstract

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Ask the doctor. I take a statin because of high cholesterol. Now that I'm past menopause, my doctor thinks I need to take a medication to protect my bones. I've read that statins prevent osteoporosis, so do I really need another pill? Author(s): Lee TH. Source: Harvard Heart Letter : from Harvard Medical School. 2003 June; 13(10): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835155&dopt=Abstract

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Ask the doctor. I've been taking estrogen since I reached menopause seven years ago, and it really helped my hot flashes and other symptoms. When I started these drugs, I was told they would lower my risk for osteoporosis and heart attacks, but I ve been reading lots of negative articles about how they may increase risk for heart problems. Should I stop them? Author(s): Lee TH. Source: Harvard Heart Letter : from Harvard Medical School. 2001 October; 12(2): 7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684494&dopt=Abstract

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Ask the doctor. I've been taking tamoxifen for several months after completing treatment for breast cancer. My doctor prescribed it primarily to lower my risk of developing cancer in my unaffected breast. As a result of chemotherapy, I underwent menopause abruptly. Tamoxifen has worsened my symptoms, especially hot flashes and vaginal dryness. Other than stopping the tamoxifen, are there ways to deal with the side effects? Author(s): Nicholson CR. Source: Harvard Women's Health Watch. 1999 May; 6(9): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10198465&dopt=Abstract

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Assessment of digit preference in self-reported year at menopause: choice of an appropriate reference distribution. Author(s): Crawford SL, Johannes CB, Stellato RK. Source: American Journal of Epidemiology. 2002 October 1; 156(7): 676-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244037&dopt=Abstract

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Assessment of menopause-induced myocardial changes by integrated backscatter during inotropic stimulation and atropine injection. Author(s): Ho YL, Lin LC, Yen ML, Wu CC, Chow SN, Huang PJ. Source: Ultrasound in Medicine & Biology. 2002 July; 28(7): 889-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208331&dopt=Abstract

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Assignment to menopausal status and estimation of age at menopause for women with missing or invalid data--a probabilistic approach with weighting factors in a large-scale epidemiological study. Author(s): Kroke A, Schulz M, Hoffmann K, Bergmann MM, Boeing H. Source: Maturitas. 2001 October 31; 40(1): 39-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684371&dopt=Abstract

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Association of diet and other lifestyle with onset of menopause in Japanese women. Author(s): Nagata C, Takatsuka N, Inaba S, Kawakami N, Shimizu H. Source: Maturitas. 1998 June 3; 29(2): 105-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9651899&dopt=Abstract

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Association of diet with the onset of menopause in Japanese women. Author(s): Nagata C, Takatsuka N, Kawakami N, Shimizu H. Source: American Journal of Epidemiology. 2000 November 1; 152(9): 863-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11085398&dopt=Abstract

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Associations with age at natural menopause in Blackfeet women. Author(s): Johnston SL. Source: American Journal of Human Biology : the Official Journal of the Human Biology Council. 2001 July-August; 13(4): 512-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400222&dopt=Abstract

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Attitude toward menopause among married middle-aged adults. Author(s): Papini DR, Intrieri RC, Goodwin PE. Source: Women Health. 2002; 36(4): 55-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555802&dopt=Abstract

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Attitudes to menopause and hormone replacement therapy among Asian and Caucasian women general practitioners. Author(s): Gupta S, Forbes N, Kirkman R. Source: Maturitas. 2001 August 25; 39(2): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514115&dopt=Abstract

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Attitudes toward menopause and aging across ethnic/racial groups. Author(s): Sommer B, Avis N, Meyer P, Ory M, Madden T, Kagawa-Singer M, Mouton C, Rasor NO, Adler S. Source: Psychosomatic Medicine. 1999 November-December; 61(6): 868-75. Erratum In: Psychosom Med 2000 January-February; 62(1): 96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10593640&dopt=Abstract

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Attitudes toward menopause and hormone therapy among women with access to health care. Author(s): Woods NF, Saver B, Taylor T. Source: Menopause (New York, N.Y.). 1998 Fall; 5(3): 178-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9774765&dopt=Abstract

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Attitudes towards menopause in a group of women followed in a public service for menopause counseling. Author(s): Betti S, Orsini MR, Sciaky R, Cristini C, Cesa-Bianchi G, Zandonini GF. Source: Aging (Milano). 2001 August; 13(4): 331-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11695502&dopt=Abstract

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Awareness of and attitudes toward menopause and hormone replacement therapy in an African community. Author(s): Mashiloane CD, Bagratee J, Moodley J. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 January; 76(1): 91-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818104&dopt=Abstract

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Awareness of personal healthcare and menopause in menopausal women in Israel. Author(s): Vinker S, Yogev Y, Kitai E, Ben-Haroush A, Kaplan B. Source: Isr Med Assoc J. 2003 January; 5(1): 31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592955&dopt=Abstract

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Between childbearing & menopause. Contraceptive options for women over 40. Author(s): Long VE. Source: Adv Nurse Pract. 1998 December; 6(12): 52, 54-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9934012&dopt=Abstract

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Bias in breast cancer analyses due to error in age at menopause. Author(s): Rockhill B, Colditz GA, Rosner B. Source: American Journal of Epidemiology. 2000 February 15; 151(4): 404-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695599&dopt=Abstract

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Biochemical markers as predictors of rates of bone loss after menopause. Author(s): Rogers A, Hannon RA, Eastell R. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2000 July; 15(7): 1398-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10893690&dopt=Abstract

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Biochemical markers of bone turnover after surgical menopause and hormone replacement therapy. Author(s): Peris P, Alvarez L, Monegal A, Guanabens N, Duran M, Pons F, Martinez de Osaba MJ, Echevarria M, Ballesta AM, Munoz-Gomez J. Source: Bone. 1999 September; 25(3): 349-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10495139&dopt=Abstract

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Biochemical markers of bone turnover do not decline after menopause in healthy women. Author(s): Takahashi M, Kushida K, Hoshino H, Ohishi T, Inoue T. Source: British Journal of Obstetrics and Gynaecology. 1999 May; 106(5): 427-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10430192&dopt=Abstract

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Birth weight and age at menopause in Australian female twin pairs: exploration of the fetal origin hypothesis. Author(s): Treloar SA, Sadrzadeh S, Do KA, Martin NG, Lambalk CB. Source: Human Reproduction (Oxford, England). 2000 January; 15(1): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10611188&dopt=Abstract

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Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study. Author(s): Delmas PD, Balena R, Confravreux E, Hardouin C, Hardy P, Bremond A. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1997 March; 15(3): 955-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9060533&dopt=Abstract

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Blood and nerves revisited: menopause and the privatization of the body in a Newfoundland postindustrial fishery. Author(s): Davis DL. Source: Med Anthropol Q. 1997 March; 11(1): 3-20; Discussion 21-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9138768&dopt=Abstract

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Blood pressure and metabolic profile after surgical menopause: comparison with fertile and naturally-menopausal women. Author(s): Casiglia E, Ginocchio G, Tikhonoff V, D'Este D, Mazza A, Pizziol A, Pavei A, Ambrosio GB, Piccoli A, Pessina AC. Source: Journal of Human Hypertension. 2000 December; 14(12): 799-805. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11114696&dopt=Abstract

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Body composition characteristics after menopause. Author(s): Kirchengast S, Grossschmidt K, Huber J, Hauser G. Source: Coll Antropol. 1998 December; 22(2): 393-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9887595&dopt=Abstract

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Body fat distribution, the menopause transition, and hormone replacement therapy. Author(s): Tchernof A, Poehlman ET, Despres JP. Source: Diabetes & Metabolism. 2000 February; 26(1): 12-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10705099&dopt=Abstract

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Body mass index in mid-life women: relative influence of menopause, hormone use, and ethnicity. Author(s): Matthews KA, Abrams B, Crawford S, Miles T, Neer R, Powell LH, Wesley D. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2001 June; 25(6): 863-73. Erratum In: Int J Obes Relat Metab Disord 2002 August; 26(8): 1150. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11439301&dopt=Abstract

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Bone density patterns after normal and premature menopause. Author(s): Hadjidakis DJ, Kokkinakis EP, Sfakianakis ME, Raptis SA. Source: Maturitas. 2003 April 25; 44(4): 279-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697368&dopt=Abstract

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Bone loss and bone size after menopause. Author(s): Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 327-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878739&dopt=Abstract

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Bone loss in hyperthyroid patients and in former hyperthyroid patients controlled on medical therapy: influence of aetiology and menopause. Author(s): Jodar E, Munoz-Torres M, Escobar-Jimenez F, Quesada-Charneco M, Lund del Castillo JD. Source: Clinical Endocrinology. 1997 September; 47(3): 279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9373448&dopt=Abstract

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Bone loss in relation to menopause: a prospective study during 16 years. Author(s): Ahlborg HG, Johnell O, Nilsson BE, Jeppsson S, Rannevik G, Karlsson MK. Source: Bone. 2001 March; 28(3): 327-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11248665&dopt=Abstract

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Bone mineral density in natural and surgically-induced menopause. Author(s): Chittacharoen A, Theppisai U, Sirisriro R. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1999 August; 66(2): 193-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468352&dopt=Abstract

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Bone preservation and the menopause. Author(s): Fraser WD. Source: Br J Hosp Med. 1997 March 5-18; 57(5): 212-4. Review. No Abstract Available. Erratum In: Br J Hosp Med 1997 April 2-15; 57(7): 352. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9176601&dopt=Abstract

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Bone resorption versus estrogen loss following oophorectomy and menopause. Author(s): Ohta H, Makita K, Komukai S, Nozawa S. Source: Maturitas. 2002 September 30; 43(1): 27-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270579&dopt=Abstract

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Bone-mass peak in multiparity and reduced risk of bone-fractures in menopause. Author(s): Cure-Cure C, Cure-Ramirez P, Teran E, Lopez-Jaramillo P. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 March; 76(3): 285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880132&dopt=Abstract

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Breastfeeding, menopause, and epithelial ovarian cancer. Author(s): Siskind V, Green A, Bain C, Purdie D. Source: Epidemiology (Cambridge, Mass.). 1997 March; 8(2): 188-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9229212&dopt=Abstract

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Breathing during sleep in menopause: a randomized, controlled, crossover trial with estrogen therapy. Author(s): Polo-Kantola P, Rauhala E, Helenius H, Erkkola R, Irjala K, Polo O. Source: Obstetrics and Gynecology. 2003 July; 102(1): 68-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850609&dopt=Abstract

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British-Asian women's views on and attitudes towards menopause and hormone replacement therapy. Author(s): Sethi K, Pitkin J. Source: Climacteric : the Journal of the International Menopause Society. 2000 December; 3(4): 248-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910584&dopt=Abstract

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By the way, doctor. I went through menopause about 10 years ago and have been taking estrogen therapy ever since. My uterus was removed because of fibroids, so there is no risk of endometrial cancer, which is why I am taking estrogen without progesterone. Should I have a bone density scan? A lot of my friends are having them, but I'm not sure how this test could alter my therapy. Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2000 March; 25(5): 7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10677201&dopt=Abstract

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By the way, doctor. I'm 47 and my menstrual periods are quite irregular, so my doctor started me on birth control pills. How will I know when I enter menopause and when to switch to HRT? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 1999 November; 7(3): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10521920&dopt=Abstract

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By the way, doctor. I'm one year into menopause and really bothered by hot flashes and vaginal dryness. I'd like to take hormone replacement therapy, but I'm worried about increasing my risk of getting breast cancer. My doctor said I can take HRT at a dose longer than what's usually prescribed. What do you think? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 September; 9(1): 7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11572838&dopt=Abstract

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By the way, doctor.. I'm 70. I took hormone therapy for a while after menopause, but stopped taking it long ago. My memory definitely isn't as good as it used to be. If I started taking estrogen again, would my memory improve? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2000 December; 26(2): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11114876&dopt=Abstract

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By the way, doctor..I'm a few years past menopause, and I take a statin because of high cholesterol. My doctor has broached the subject of whether I might need to take something else to lower my risk for osteoporosis, but I've read that statins help prevent that problem. Can't I tell the doctor I don't need another pill? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2001 May; 26(7): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11424275&dopt=Abstract

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Can menopause be considered an independent risk factor for cardiovascular disease? Author(s): Mercuro G, Zoncu S, Cherchi A, Rosano GM. Source: Ital Heart J. 2001 October; 2(10): 719-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721715&dopt=Abstract

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Canadian menopause study-I: Understanding women's intentions to utilise hormone replacement therapy. Author(s): Fisher WA, Sand M, Lewis W, Boroditsky R. Source: Maturitas. 2000 November 30; 37(1): 1-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11099868&dopt=Abstract

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Cancer treatment-induced menopause: meaning for breast and gynecological cancer survivors. Author(s): Davis CS, Zinkand JE, Fitch MI. Source: Can Oncol Nurs J. 2000 Winter; 10(1): 14-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10887860&dopt=Abstract

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Cardiovascular changes and cardiac morbidity of menopause. Effects of hormone replacement therapy. Author(s): Bassan R. Source: Arquivos Brasileiros De Cardiologia. 1999 January; 72(1): 85-98. Review. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10347915&dopt=Abstract

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Cardiovascular effects of testosterone: implications of the “male menopause”? Author(s): Channer KS, Jones TH. Source: Heart (British Cardiac Society). 2003 February; 89(2): 121-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527649&dopt=Abstract

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Care during menopause: comparison of a women's health practice and traditional care. Author(s): Ryan CA, Ghali WA, Boss RD, Moskowitz MA, Freund KM. Source: Journal of Women's Health & Gender-Based Medicine. 1999 December; 8(10): 1295-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10643838&dopt=Abstract

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Carotid atherosclerosis in premenopausal and postmenopausal women and its association with risk factors measured after menopause. Author(s): Sutton-Tyrrell K, Lassila HC, Meilahn E, Bunker C, Matthews KA, Kuller LH. Source: Stroke; a Journal of Cerebral Circulation. 1998 June; 29(6): 1116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9626281&dopt=Abstract

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Carotid intima-media thickness in surgical menopause: women who received HRT versus who did not. Author(s): Mihmanli V, Mihmanli I, Atakir K, Kantarci F, Aydin T, Sengun Y, Uysal O. Source: Maturitas. 2002 May 20; 42(1): 37-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020978&dopt=Abstract

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Carotid pulsatility indices in surgical menopause. Author(s): Mihmanli V, Mihmanli I, Kantarci F, Aydin T, Yilmaz MH, Ogut G. Source: Archives of Gynecology and Obstetrics. 2002 April; 266(2): 96-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049304&dopt=Abstract

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Carrying on: the experience of premature menopause in women with early stage breast cancer. Author(s): Knobf MT. Source: Nursing Research. 2002 January-February; 51(1): 9-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11822573&dopt=Abstract

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Cartilage turnover assessed with a newly developed assay measuring collagen type II degradation products: influence of age, sex, menopause, hormone replacement therapy, and body mass index. Author(s): Mouritzen U, Christgau S, Lehmann HJ, Tanko LB, Christiansen C. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 332-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634232&dopt=Abstract

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Catamenial epilepsy and menopause. Author(s): Bauer J. Source: Epilepsia. 2001 April; 42(4): 572. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440355&dopt=Abstract

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Causality, the menopause, and depression. Review did not fully examine the evidence. Author(s): Petticrew M. Source: Bmj (Clinical Research Ed.). 1997 February 22; 314(7080): 608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9055749&dopt=Abstract

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CD3+ CD8+ CTL activity within the human female reproductive tract: influence of stage of the menstrual cycle and menopause. Author(s): White HD, Crassi KM, Givan AL, Stern JE, Gonzalez JL, Memoli VA, Green WR, Wira CR. Source: Journal of Immunology (Baltimore, Md. : 1950). 1997 March 15; 158(6): 3017-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9058841&dopt=Abstract

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Cessation of reproduction: an analytic view of menopause. Author(s): Spencer RP. Source: Medical Hypotheses. 2002 October; 59(4): 406-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208179&dopt=Abstract

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Change in psychological and vasomotor symptom reporting during the menopause. Author(s): Hardy R, Kuh D. Source: Social Science & Medicine (1982). 2002 December; 55(11): 1975-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406465&dopt=Abstract

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Changes in body mass index around menopause: a population study of Chilean woman. Author(s): Blumel JE, Castelo-Branco C, Rocangliolo ME, Bifa L, Tacla X, Mamani L. Source: Menopause (New York, N.Y.). 2001 July-August; 8(4): 239-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449080&dopt=Abstract

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Changes in bone mineral density in the hip and spine before, during, and after the menopause in elite runners. Author(s): Tomkinson A, Gibson JH, Lunt M, Harries M, Reeve J. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 July; 14(6): 462-8. Epub 2003 April 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730740&dopt=Abstract

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Changes in enzymatic antioxidant defense system in blood and endometrial tissues of women after menopause. Author(s): Gurdol F, Oner-Yyidothan Y, Yalcyn O, Genc S, Buyru F. Source: Res Commun Mol Pathol Pharmacol. 1997 July; 97(1): 38-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9507566&dopt=Abstract

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Changes in hemodynamics and left ventricular structure after menopause. Author(s): Hinderliter AL, Sherwood A, Blumenthal JA, Light KC, Girdler SS, McFetridge J, Johnson K, Waugh R. Source: The American Journal of Cardiology. 2002 April 1; 89(7): 830-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11909568&dopt=Abstract

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Changes in muscle strength in women following the menopause: a longitudinal assessment of the efficacy of hormone replacement therapy. Author(s): Greeves JP, Cable NT, Reilly T, Kingsland C. Source: Clinical Science (London, England : 1979). 1999 July; 97(1): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10369797&dopt=Abstract

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Changes in physical symptoms during the menopause transition. Author(s): Brown WJ, Mishra GD, Dobson A. Source: International Journal of Behavioral Medicine. 2002; 9(1): 53-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112996&dopt=Abstract

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Changes in proinflammatory cytokine activity after menopause. Author(s): Pfeilschifter J, Koditz R, Pfohl M, Schatz H. Source: Endocrine Reviews. 2002 February; 23(1): 90-119. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844745&dopt=Abstract

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Changes in prolactin levels with the menopause: the effects of estrogen/androgen and calcitonin treatment. Author(s): Balint-Peric LA, Prelevic GM. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 1997 August; 11(4): 275-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9272425&dopt=Abstract

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Changes in serum levels of type I collagen-related proteins after surgically induced menopause and correlations with bone loss in the lumbar spine. Author(s): Yasumizu T, Fukada Y, Hoshi K. Source: Endocr J. 1999 April; 46(2): 337-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10460020&dopt=Abstract

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Changes in sexual behavior in Bulgarian women after the menopause. Author(s): Borissova AM, Kovatcheva R, Shinkov A. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 December; 14(6): 448-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228067&dopt=Abstract

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Changing estrogen and progesterone receptor patterns in breast carcinoma during the menstrual cycle and menopause. Author(s): Pujol P, Daures JP, Thezenas S, Guilleux F, Rouanet P, Grenier J. Source: Cancer. 1998 August 15; 83(4): 698-705. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9708933&dopt=Abstract

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Chemicals and menopause: effects on age at menopause and on health status in the postmenopausal period. Author(s): Silbergeld EK, Flaws JA. Source: Journal of Women's Health / the Official Publication of the Society for the Advancement of Women's Health Research. 1999 March; 8(2): 227-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10100136&dopt=Abstract

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Chemotherapy for gestational trophoblastic tumours hastens menopause by 3 years. Author(s): Bower M, Rustin GJ, Newlands ES, Holden L, Short D, Foskett M, Bagshawe KD. Source: European Journal of Cancer (Oxford, England : 1990). 1998 July; 34(8): 1204-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849480&dopt=Abstract

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Chemotherapy-induced menopause: a literature review. Author(s): Poniatowski BC, Grimm P, Cohen G. Source: Cancer Investigation. 2001; 19(6): 641-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486707&dopt=Abstract

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Chinese midlife women's perceptions and attitudes about menopause. Author(s): Chen YL, Voda AM, Mansfield PK. Source: Menopause (New York, N.Y.). 1998 Spring; 5(1): 28-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9689192&dopt=Abstract

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Chlormadinone acetate versus micronized progesterone in the sequential combined hormone replacement therapy of the menopause. Author(s): Pelissier C, Maroni M, Yaneva H, Brin S, Peltier-Pujol F, Jondet M. Source: Maturitas. 2001 October 31; 40(1): 85-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684377&dopt=Abstract

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Clinical and biological characteristics of breast cancers in post-menopausal women receiving hormone replacement therapy for menopause. Author(s): Salmon RJ, Ansquer Y, Asselain B, Languille O, Lesec G, Remvikos Y. Source: Oncol Rep. 1999 May-June; 6(3): 699-703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10203618&dopt=Abstract

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Clinical challenges in osteoporosis. Case 1: screening for osteoporosis in early menopause. Author(s): Watts NB. Source: Seminars in Arthritis and Rheumatism. 2002 February; 31(4): 284-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11836662&dopt=Abstract

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Clinical decision-making with the woman after menopause. Author(s): Bidikov I, Meier DE. Source: Geriatrics. 1997 March; 52(3): 28-35; Quiz 36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9068621&dopt=Abstract

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Clinical presentation and management of menopause in Lagos, Nigeria. Author(s): Odum CU, Anorlu RI, Ohaya NI. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1999 September; 66(3): 285-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580677&dopt=Abstract

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Cognitive function at menopause: neuroendocrine implications for the study of the aging brain. Author(s): Costa A, Nappi RE, Sinforiani E, Bono G, Poma A, Nappi G. Source: Funct Neurol. 1997 May-August; 12(3-4): 175-80. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9218973&dopt=Abstract

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Cognitive function in nondemented older women who took estrogen after menopause. Author(s): Jacobs DM, Tang MX, Stern Y, Sano M, Marder K, Bell KL, Schofield P, Dooneief G, Gurland B, Mayeux R. Source: Neurology. 1998 February; 50(2): 368-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484355&dopt=Abstract

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Combination therapy in the treatment of major depressive disorder complicated by fibromyalgia and menopause. Author(s): Clayton AH, Kaltsounis-Puckett J. Source: Psychosomatics. 2002 November-December; 43(6): 491-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444233&dopt=Abstract

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Comparative cardiovascular effects of different progestins in menopause. Author(s): Rosano GM, Fini M. Source: Int J Fertil Womens Med. 2001 September-October; 46(5): 248-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720197&dopt=Abstract

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Comparison of bone and total alkaline phosphatase activity on bone turnover during menopause and in patients with established osteoporosis. Author(s): Takahashi M, Kushida K, Hoshino H, Miura M, Ohishi T, Inoue T. Source: Clinical Endocrinology. 1997 August; 47(2): 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9302392&dopt=Abstract

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Comparison of serum and urinary C-terminal telopeptide of type I collagen in aging, menopause and osteoporosis. Author(s): Kawana K, Takahashi M, Hoshino H, Kushida K. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 February; 316(1-2): 109-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11750280&dopt=Abstract

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Concentration of insulin-like growth factor (IGF)-I and -II in iliac crest bone matrix from pre- and postmenopausal women: relationship to age, menopause, bone turnover, bone volume, and circulating IGFs. Author(s): Seck T, Scheppach B, Scharla S, Diel I, Blum WF, Bismar H, Schmid G, Krempien B, Ziegler R, Pfeilschifter J. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 July; 83(7): 2331-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9661604&dopt=Abstract

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Concentration of sex steroids in adipose tissue after menopause. Author(s): Szymczak J, Milewicz A, Thijssen JH, Blankenstein MA, Daroszewski J. Source: Steroids. 1998 May-June; 63(5-6): 319-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9618794&dopt=Abstract

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Concentration of transforming growth factor beta in human bone tissue: relationship to age, menopause, bone turnover, and bone volume. Author(s): Pfeilschifter J, Diel I, Scheppach B, Bretz A, Krempien R, Erdmann J, Schmid G, Reske N, Bismar H, Seck T, Krempien B, Ziegler R. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1998 April; 13(4): 716-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9556072&dopt=Abstract

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Conceptual models for women's health research: reclaiming menopause as an exemplar of nursing's contributions to feminist scholarship. Author(s): Andrist LC, MacPherson KI. Source: Annu Rev Nurs Res. 2001; 19: 29-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11439785&dopt=Abstract

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Conceptualizing menopause and midlife: Chinese American and Chinese women in the US. Author(s): Adler SR, Fosket JR, Kagawa-Singer M, McGraw SA, Wong-Kim E, Gold E, Sternfeld B. Source: Maturitas. 2000 April 28; 35(1): 11-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802395&dopt=Abstract

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Consanguinity and the age of menopause in the United Arab Emirates. Author(s): Bener A, Rizk DE, Ezimokhai M, Hassan M, Micallef R, Sawaya M. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1998 February; 60(2): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9509954&dopt=Abstract

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Continuous hormone replacement therapy for menopause combining nomegestrol acetate and gel, patch, or oral estrogen: a comparison of amenorrhea rates. Author(s): Blanc B, Cravello L, Micheletti MC, d'Ercole C, Zartarian M. Source: Clinical Therapeutics. 1998 September-October; 20(5): 901-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9829442&dopt=Abstract

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Continuous-combined treatment of the menopause with combinations of oestradiol valerate and dienogest - a dose-ranging study. Author(s): Graser T, Muller A, Mellinger U, Muck AO, Lippert TH, Oettel M. Source: Maturitas. 2000 June 30; 35(3): 253-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936742&dopt=Abstract

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Contraception and the menopause. Author(s): Pitkin J. Source: Maturitas. 2000 January; 34 Suppl 1: S29-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10759062&dopt=Abstract

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Controversial aspects of hormone replacement therapy upon cardiovascular mortality and morbidity of women in menopause. Author(s): Rosano GM, Mercuro G. Source: G Ital Cardiol. 1999 September; 29(9): 999-1003. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10514956&dopt=Abstract

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Controversial issues in climacteric medicine (I) Cardiovascular disease and hormone replacement therapy. International Menopause Society Expert Workshop, 13-16 October 2000, Royal Society of Medicine, London, UK. Author(s): Genazzani AR. Source: Maturitas. 2001 May 30; 38(3): 263-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358643&dopt=Abstract

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Controversial issues in climacteric medicine I. Cardiovascular disease and hormone replacement therapy. International Menopause Society Expert Workshop. 13-16 October 2000, royal society of medicine, London, UK. Author(s): Genazzani AR, Gambacciani M; International Menopause Society. Source: Climacteric : the Journal of the International Menopause Society. 2000 December; 3(4): 233-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910582&dopt=Abstract

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Controversial issues in climacteric medicine II. Hormone replacement therapy and cancer. International Menopause Society Expert Workshop. 9-12 June 2001, Opera del Duomo, Pisa, Italy. Author(s): Genazzani AR, Gadducci A, Gambacciani M. Source: Climacteric : the Journal of the International Menopause Society. 2001 September; 4(3): 181-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588941&dopt=Abstract

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Conventional and ambulatory blood pressure and menopause in a prospective population study. Author(s): Staessen JA, Ginocchio G, Thijs L, Fagard R. Source: Journal of Human Hypertension. 1997 August; 11(8): 507-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9322832&dopt=Abstract

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Coronary and aortic calcification among women 8 years after menopause and their premenopausal risk factors : the healthy women study. Author(s): Kuller LH, Matthews KA, Sutton-Tyrrell K, Edmundowicz D, Bunker CH. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1999 September; 19(9): 218998. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10479662&dopt=Abstract

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Coronary artery disease--is menopause a risk factor? Author(s): Gohlke-Barwolf C. Source: Basic Research in Cardiology. 2000; 95 Suppl 1: I77-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192358&dopt=Abstract

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Coronary heart disease risk factors and menopause: a study in 1684 French women. Author(s): Tremollieres FA, Pouilles JM, Cauneille C, Ribot C. Source: Atherosclerosis. 1999 February; 142(2): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10030394&dopt=Abstract

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Correlates of age at natural menopause: a community-based study in Alexandria. Author(s): Hidayet NM, Sharaf SA, Aref SR, Tawfik TA, Moubarak II. Source: East Mediterr Health J. 1999 March; 5(2): 307-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10793807&dopt=Abstract

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Correlates of the age at natural menopause in Morocco. Author(s): Reynolds RF, Obermeyer CM. Source: Annals of Human Biology. 2003 January-February; 30(1): 97-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519657&dopt=Abstract

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Correlation of serum osteocalcin fractions with bone mineral density in women during the first 10 years after menopause. Author(s): Knapen MH, Nieuwenhuijzen Kruseman AC, Wouters RS, Vermeer C. Source: Calcified Tissue International. 1998 November; 63(5): 375-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9799820&dopt=Abstract

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Could institutional clinical trials exist in Europe? EUTERP Pilot Study Group. European Trial of Estrogen/progestin Replacement treatment in Post-menopause. Author(s): Cornu C, Cano A, Pornel B, Melis GB, Boissel JP. Source: Lancet. 1999 January 2; 353(9146): 63-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10023967&dopt=Abstract

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Cross-cultural attitudes to the menopause and the ageing female. Author(s): Mercer C. Source: Age and Ageing. 1999 September; 28 Suppl 2: 12-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10560003&dopt=Abstract

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Current attitudes toward hormone replacement therapy (HRT) prescribed during menopause. Author(s): Kaplan B. Source: Clin Exp Obstet Gynecol. 2002; 29(3): 167-71. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519035&dopt=Abstract

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Current diet does not relate to bone mineral density after the menopause. The Nottingham Early Postmenopausal Intervention Cohort (EPIC) Study Group. Author(s): Earnshaw SA, Worley A, Hosking DJ. Source: The British Journal of Nutrition. 1997 July; 78(1): 65-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9292760&dopt=Abstract

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Cyclical behavior of bone remodeling and bone loss in healthy women after menopause: results of a prospective study. Author(s): Mazzuoli G, Marinucci D, D'erasmo E, Acca M, Pisani D, Rinaldi MG, Bianchi G, Diacinti D, Minisola S. Source: Bone. 2002 December; 31(6): 718-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531568&dopt=Abstract

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Dealing with the devastating effects of early menopause. Author(s): Abernethy K. Source: Community Nurse. 1997 March; 3(2): 48-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9451118&dopt=Abstract

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Decline in lung function in lymphangioleiomyomatosis: relation to menopause and progesterone treatment. Author(s): Johnson SR, Tattersfield AE. Source: American Journal of Respiratory and Critical Care Medicine. 1999 August; 160(2): 628-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10430739&dopt=Abstract

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Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DS) as therapeutic options in menopause. Author(s): Katz S, Morales AJ. Source: Semin Reprod Endocrinol. 1998; 16(2): 161-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9711682&dopt=Abstract

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Dental hygienists' knowledge of menopause and its potential oral manifestations. Author(s): Murray DL, Fried J. Source: Journal of Dental Hygiene : Jdh / American Dental Hygienists' Association. 1999 Winter; 73(1): 22-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634118&dopt=Abstract

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Depression and the menopause. Oestrogens improve symptoms in some middle aged women. Author(s): Studd J. Source: Bmj (Clinical Research Ed.). 1997 March 29; 314(7085): 977-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9099139&dopt=Abstract

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Depression during the transition to menopause: a guide for patients and families. Author(s): Kahn DA, Moline ML, Ross RW, Altshuler LL, Cohen LS. Source: Postgraduate Medicine. 2001 March; (Spec No): 114-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11501001&dopt=Abstract

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Depression often culprit in male menopause. Author(s): Nash PA. Source: Adv Nurse Pract. 2001 March; 9(3): 21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400318&dopt=Abstract

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Depression, menopause and estrogens: is there a correlation? Author(s): Birkhauser M. Source: Maturitas. 2002 April 15; 41 Suppl 1: S3-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955789&dopt=Abstract

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Dermatologic problems of the menopause. Author(s): Graham-Brown R. Source: Clinics in Dermatology. 1997 January-February; 15(1): 143-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9034662&dopt=Abstract

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Desaturation function does not decline after menopause in human females. Author(s): Liu YW, Medeiros LC, Revesz E, O'Dorisio TM. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2000 January; 32(1): 26-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10727010&dopt=Abstract

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Determinants of age at menopause in Italy: results from a large cross-sectional study. ICARUS Study Group. Italian Climacteric Research Group Study. Author(s): Meschia M, Pansini F, Modena AB, de Aloysio D, Gambacciani M, Parazzini F, Campagnoli C, Maiocchi G, Peruzzi E. Source: Maturitas. 2000 February 15; 34(2): 119-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714906&dopt=Abstract

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Determinants of body mass index in women around menopause attending menopause clinics in Italy. Author(s): Progetto Menopausa Italia Study Group. Source: Climacteric : the Journal of the International Menopause Society. 2003 March; 6(1): 67-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776693&dopt=Abstract

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Determinants of elevated blood pressure in women around menopause: results from a cross-sectional study in Italy. Author(s): Amigoni S, Morelli P, Parazzini F, Chatenoud L. Source: Maturitas. 2000 January 15; 34(1): 25-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10687879&dopt=Abstract

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Determinants of self rated menopause status. Author(s): Taffe J, Garamszegi C, Dudley E, Dennerstein L. Source: Maturitas. 1997 July; 27(3): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9288694&dopt=Abstract

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Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. VirgilioMenopause-Health Group. Author(s): Pasquali R, Vicennati V, Bertazzo D, Casimirri F, Pascal G, Tortelli O, Labate AM. Source: Metabolism: Clinical and Experimental. 1997 January; 46(1): 5-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9005961&dopt=Abstract

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Determinants of the first decade of bone loss after menopause at spine, hip and radius. Author(s): Reeve J, Walton J, Russell LJ, Lunt M, Wolman R, Abraham R, Justice J, Nicholls A, Wardley-Smith B, Green JR, Mitchell A. Source: Qjm : Monthly Journal of the Association of Physicians. 1999 May; 92(5): 261-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10615481&dopt=Abstract

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Development of the menopause symptom list: a factor analytic study of menopause associated symptoms. Author(s): Perz JM. Source: Women Health. 1997; 25(1): 53-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9253138&dopt=Abstract

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Developments in the management of menopause and hormone replacement therapy: a presentation given at the symposium to honour the retirement of Professor Martin Vessey. Author(s): Barlow DH. Source: Pharmacoepidemiology and Drug Safety. 2001 January-February; 10(1): 29-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417063&dopt=Abstract

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DHEA as physiological replacement therapy at menopause. Author(s): Labrie F. Source: J Endocrinol Invest. 1998 June; 21(6): 399-401. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9699133&dopt=Abstract

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Diabetes and the menopause. Special considerations. Author(s): Phillips P. Source: Aust Fam Physician. 1998 January-February; 27(1-2): 59-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9503708&dopt=Abstract

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Differences in bone resorption after menopause in Japanese women with normal or low bone mineral density: quantitation of urinary cross-linked N-telopeptides. Author(s): Taguchi Y, Gorai I, Zhang MG, Chaki O, Nakayama M, Minaguchi H. Source: Calcified Tissue International. 1998 May; 62(5): 395-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9541516&dopt=Abstract

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Differences in the capacity of several biochemical bone markers to assess high bone turnover in early menopause and response to alendronate therapy. Author(s): Fink E, Cormier C, Steinmetz P, Kindermans C, Le Bouc Y, Souberbielle JC. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2000; 11(4): 295-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10928218&dopt=Abstract

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Differential effects of menopause and metabolic disease on trabecular and cortical bone assessed by peripheral quantitative computed tomography (pQCT). Author(s): Tsurusaki K, Ito M, Hayashi K. Source: The British Journal of Radiology. 2000 January; 73(865): 14-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10721315&dopt=Abstract

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Discourse about menopause in selected print media. Author(s): Shoebridge A, Steed L. Source: Aust N Z J Public Health. 1999 October; 23(5): 475-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10575768&dopt=Abstract

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Dispositional factors, coping and adaptation during menopause. Author(s): Caltabiano ML, Holzheimer M. Source: Climacteric : the Journal of the International Menopause Society. 1999 March; 2(1): 21-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910676&dopt=Abstract

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Distribution and fine structure of macrophages in the human ovary during the menstrual cycle, pregnancy and menopause. Author(s): Katabuchi H, Suenaga Y, Fukumatsu Y, Okamura H. Source: Endocr J. 1997 December; 44(6): 785-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9622293&dopt=Abstract

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Do flares of systemic lupus erythematosus decline after menopause? Author(s): Mok CC, Lau CS, Ho CT, Wong RW. Source: Scandinavian Journal of Rheumatology. 1999; 28(6): 357-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10665741&dopt=Abstract

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Do men experience menopause? Author(s): Fischman J. Source: U.S. News & World Report. 2001 July 30; 131(4): 47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11569458&dopt=Abstract

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Do mothers of dizygotic twins have earlier menopause? A role for fragile X? Author(s): Martin NG, Healey SC, Pangan TS, Heath AC, Turner G. Source: American Journal of Medical Genetics. 1997 March 3; 69(1): 114-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9066896&dopt=Abstract

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Does age at natural menopause affect mortality from ischemic heart disease? Author(s): Jacobsen BK, Nilssen S, Heuch I, Kvale G. Source: Journal of Clinical Epidemiology. 1997 April; 50(4): 475-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9179106&dopt=Abstract

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Does early growth influence timing of the menopause? Evidence from a British birth cohort. Author(s): Hardy R, Kuh D. Source: Human Reproduction (Oxford, England). 2002 September; 17(9): 2474-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202444&dopt=Abstract

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Does the menopause influence the risk of bacteriuria? Author(s): Hextall A, Hooper R, Cardozo L, Stringer C, Workman R. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 2001; 12(5): 332-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716001&dopt=Abstract

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Dose-response efficacy of a new estradiol transdermal matrix patch for 7-day application: a randomized, double-blind, placebo-controlled study. Italian Menopause Research Group. Author(s): Rovati LC, Setnikar I, Genazzani AR. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 August; 14(4): 282-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11075300&dopt=Abstract

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Drugs do not only relieve male menopause. Author(s): Hernandez-Lopez C. Source: Bmj (Clinical Research Ed.). 2000 August 12; 321(7258): 451. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10991600&dopt=Abstract

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Duration of menopause and behavior of malondialdehyde, lipids, lipoproteins and carotid wall artery intima-media thickness. Author(s): Signorelli SS, Neri S, Sciacchitano S, Di Pino L, Costa MP, Pennisi G, Ierna D, Caschetto S. Source: Maturitas. 2001 July 25; 39(1): 39-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451619&dopt=Abstract

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Early age at menopause and breast cancer: are leaner women more protected? A prospective analysis of the Dutch DOM cohort. Author(s): Monninkhof EM, van der Schouw YT, Peeters PH. Source: Breast Cancer Research and Treatment. 1999 June; 55(3): 285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10517172&dopt=Abstract

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Early cardiac changes after menopause. Author(s): Schillaci G, Verdecchia P, Borgioni C, Ciucci A, Porcellati C. Source: Hypertension. 1998 October; 32(4): 764-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9774377&dopt=Abstract

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Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964-1988 in Ontario, Canada. Author(s): Chiarelli AM, Marrett LD, Darlington G. Source: American Journal of Epidemiology. 1999 August 1; 150(3): 245-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10430228&dopt=Abstract

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Early menopause in a family carrying a fragile X premutation. Author(s): Driscoll G, Clark J, Elakis G, Turner G. Source: Aust N Z J Med. 2000 February; 30(1): 86-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10800887&dopt=Abstract

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Early menopause in women with Down's syndrome. Author(s): Schupf N, Zigman W, Kapell D, Lee JH, Kline J, Levin B. Source: Journal of Intellectual Disability Research : Jidr. 1997 June; 41 ( Pt 3): 264-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9219076&dopt=Abstract

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Early menopause presenting with mood symptoms in a student aviator. Author(s): Berg JS, Moore J. Source: Aviation, Space, and Environmental Medicine. 2000 March; 71(3): 251-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10716170&dopt=Abstract

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Early menopause: increased fracture risk at older age. Author(s): van Der Voort DJ, van Der Weijer PH, Barentsen R. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 July; 14(6): 525-30. Epub 2003 April 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730751&dopt=Abstract

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Early menopause? Author(s): Schuiling GA. Source: Journal of Psychosomatic Obstetrics and Gynaecology. 2001 June; 22(2): 123-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446153&dopt=Abstract

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Ease through menopause with homeopathic and herbal medicine. Author(s): Gardner C. Source: Journal of Perianesthesia Nursing : Official Journal of the American Society of Perianesthesia Nurses / American Society of Perianesthesia Nurses. 1999 June; 14(3): 139-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10603817&dopt=Abstract

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Effect of 1 alpha-hydroxyvitamin D3 on loss of bone mineral density immediately after artificial menopause. Author(s): Kato T, Chen JT, Katase K, Hirai Y, Hasumi K, Ogata E, Shiraki Y, Shiraki M. Source: Endocr J. 1997 April; 44(2): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9228466&dopt=Abstract

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Effect of age and menopause on serum concentrations of pentosidine, an advanced glycation end product. Author(s): Takahashi M, Oikawa M, Nagano A. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2000 March; 55(3): M137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10795725&dopt=Abstract

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Effect of amlodipine and hormone replacement therapy on blood pressure and bone markers in menopause. Author(s): Zacharieva S, Shigarminova R, Nachev E, Kamenov Z, Atanassova I, Orbetzova M, Stoynev A, Doncheva N, Borissova AM. Source: Methods Find Exp Clin Pharmacol. 2003 April; 25(3): 209-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743626&dopt=Abstract

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Effect of ipriflavone--a synthetic derivative of natural isoflavones--on bone mass loss in the early years after menopause. Author(s): Gennari C, Agnusdei D, Crepaldi G, Isaia G, Mazzuoli G, Ortolani S, Bufalino L, Passeri M. Source: Menopause (New York, N.Y.). 1998 Spring; 5(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9689189&dopt=Abstract

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Effect of menopause and different combined estradiol-progestin regimens on basal and growth hormone-releasing hormone-stimulated serum growth hormone, insulinlike growth factor-1, insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3 levels. Author(s): Cano A, Castelo-Branco C, Tarin JJ. Source: Fertility and Sterility. 1999 February; 71(2): 261-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9988395&dopt=Abstract

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Effect of menopause on cognitive performance in women with Down syndrome. Author(s): Patel BN, Seltzer GB, Wu HS, Schupf N. Source: Neuroreport. 2001 August 28; 12(12): 2659-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522943&dopt=Abstract

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Effect of menopause on low-density lipoprotein oxidation: is oestrogen an important determinant? Author(s): Wen Y, Doyle MC, Cooke T, Feely J. Source: Maturitas. 2000 March 31; 34(3): 233-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10717489&dopt=Abstract

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Effect of menopause on plaque morphologic characteristics in coronary atherosclerosis. Author(s): Burke AP, Farb A, Malcom G, Virmani R. Source: American Heart Journal. 2001 February; 141(2 Suppl): S58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11174360&dopt=Abstract

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Effect of natural menopause on serum levels of IGF-I and IGF-binding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women. Author(s): Nasu M, Sugimoto T, Chihara M, Hiraumi M, Kurimoto F, Chihara K. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1997 June; 136(6): 608-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9225724&dopt=Abstract

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Effect of non-weight-bearing body fat on bone mineral density before and after menopause. Author(s): Douchi T, Yamamoto S, Kuwahata R, Oki T, Yamasaki H, Nagata Y. Source: Obstetrics and Gynecology. 2000 July; 96(1): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10862834&dopt=Abstract

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Effect of raloxifene on the ovarian circulation in women after menopause. Author(s): Lidor AL, Cohen SB, Seidman DS, Novikov I, Rabinovici J, Mashiach S, Lipitz S. Source: American Journal of Obstetrics and Gynecology. 2002 May; 186(5): 984-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12015525&dopt=Abstract

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Effect of surgical menopause and Paget's disease of bone on the isomerization of type I collagen carboxyterminal telopeptide: evolution after antiresorptive therapy. Author(s): Peris P, Alvarez L, Monegal A, Guanabens N, Duran M, Echevarria M, Ros I, Ballesta AM, Munoz-Gomez J. Source: Journal of Bone and Mineral Metabolism. 2002; 20(2): 116-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862534&dopt=Abstract

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Effect of surgical menopause on cognitive functions. Author(s): Farrag AK, Khedr EM, Abdel-Aleem H, Rageh TA. Source: Dementia and Geriatric Cognitive Disorders. 2002; 13(3): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893842&dopt=Abstract

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Effects of age and menopause on spinal bone mineral density in Japanese women: a ten-year prospective study. Author(s): Zhang HC, Kushida K, Atsumi K, Kin K, Nagano A. Source: Calcified Tissue International. 2002 March; 70(3): 153-7. Epub 2002 January 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907711&dopt=Abstract

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Effects of age at menopause on serum cholesterol, body mass index, and blood pressure. Author(s): Akahoshi M, Soda M, Nakashima E, Tsuruta M, Ichimaru S, Seto S, Yano K. Source: Atherosclerosis. 2001 May; 156(1): 157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11369009&dopt=Abstract

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Effects of age, ethnicity and menopause on ambulatory blood pressure: JapaneseAmerican and Caucasian school teachers in Hawaii. Author(s): Brown DE, Sievert LL, Aki SL, Mills PS, Etrata MB, Paopao RN, James GD. Source: American Journal of Human Biology : the Official Journal of the Human Biology Council. 2001 July-August; 13(4): 486-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400219&dopt=Abstract

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Effects of age, menopause and osteoporosis on free, peptide-bound and total pyridinium crosslink excretion. Author(s): Del Campo MT, Gonzalez-Casaus ML, Aguado P, Bernad M, Carrera F, Martinez ME. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1999; 9(5): 449-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10550465&dopt=Abstract

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Effects of different hormone replacement regimens on postmenopausal women with abnormal lipid levels. Menopause Study Group. Author(s): Pickar JH, Wild RA, Walsh B, Hirvonen E, Lobo RA. Source: Climacteric : the Journal of the International Menopause Society. 1998 March; 1(1): 26-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913407&dopt=Abstract

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Effects of ethnicity and age or menopause on osteoblast function, bone mineralization, and osteoid accumulation in iliac bone. Author(s): Parfitt AM, Han ZH, Palnitkar S, Rao DS, Shih MS, Nelson D. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1997 November; 12(11): 1864-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9383691&dopt=Abstract

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Effects of ethnicity and age or menopause on the remodeling and turnover of iliac bone: implications for mechanisms of bone loss. Author(s): Han ZH, Palnitkar S, Rao DS, Nelson D, Parfitt AM. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1997 April; 12(4): 498-508. Erratum In: J Bone Miner Res 1999 Apr; 14(4): 660. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9101361&dopt=Abstract

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Effects of hormone replacement on hemostasis in spontaneous menopause. Author(s): Demirol A, Baykal C, Kirazli S, Ayhan A. Source: Menopause (New York, N.Y.). 2001 Summer; 8(2): 135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256874&dopt=Abstract

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Effects of hormone-replacement therapy on hemostatic factors, lipid factors, and endothelial function in women undergoing surgical menopause: implications for prevention of atherosclerosis. Author(s): Lip GY, Blann AD, Jones AF, Beevers DG. Source: American Heart Journal. 1997 October; 134(4): 764-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9351746&dopt=Abstract

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Effects of menopause and estrogen on cervical epithelial permeability. Author(s): Gorodeski GI. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 July; 85(7): 2584-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10902812&dopt=Abstract

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Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity. Author(s): Abbey M, Owen A, Suzakawa M, Roach P, Nestel PJ. Source: Maturitas. 1999 December 15; 33(3): 259-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10656504&dopt=Abstract

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Effects of menopause and nasal occlusion on breathing during sleep. Author(s): Carskadon MA, Bearpark HM, Sharkey KM, Millman RP, Rosenberg C, Cavallo A, Carlisle C, Acebo C. Source: American Journal of Respiratory and Critical Care Medicine. 1997 January; 155(1): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9001313&dopt=Abstract

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Effects of menopause and obesity on lipid profiles in middle-aged Taiwanese women: the Chin-Shan Community Cardiovascular Cohort Study. Author(s): Torng PL, Su TC, Sung FC, Chien KL, Huang SC, Chow SN, Lee YT. Source: Atherosclerosis. 2000 December; 153(2): 413-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164431&dopt=Abstract

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Effects of menopause on age-dependent bone loss in the axial and appendicular skeletons in healthy Japanese women. Author(s): Ito M, Nakamura T, Tsurusaki K, Uetani M, Hayashi K. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1999; 10(5): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10591835&dopt=Abstract

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Effects of menopause on bone mineral density in women with endemic fluorosis. Author(s): Yildiz M, Oral B. Source: Clinical Nuclear Medicine. 2003 April; 28(4): 308-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642710&dopt=Abstract

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Effects of menopause on intraindividual changes in serum lipids, blood pressure, and body weight--the Chin-Shan Community Cardiovascular Cohort study. Author(s): Torng PL, Su TC, Sung FC, Chien KL, Huang SC, Chow SN, Lee YT. Source: Atherosclerosis. 2002 April; 161(2): 409-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888525&dopt=Abstract

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Effects of menopause on seizures in women with epilepsy. Author(s): Abbasi F, Krumholz A, Kittner SJ, Langenberg P. Source: Epilepsia. 1999 February; 40(2): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9952268&dopt=Abstract

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Effects of sex steroid hormones and menopause on serum leptin concentrations. Author(s): Di Carlo C, Tommaselli GA, Nappi C. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 December; 16(6): 479-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626035&dopt=Abstract

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Effects of surgical menopause and estrogen replacement therapy on atrio-ventricular conduction and ventricular repolarization. Author(s): Siniscalchi M, De Franciscis P, Palomba S, Di Palo C, Colacurci N, Nappi C, Giugliano D. Source: Maturitas. 2001 October 31; 40(1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684372&dopt=Abstract

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Effects of the menopause transition on body fatness and body fat distribution. Author(s): Tchernof A, Poehlman ET. Source: Obesity Research. 1998 May; 6(3): 246-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9618130&dopt=Abstract

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Effects of the menopause, gender, and estrogen replacement therapy on vascular nitric oxide activity. Author(s): Majmudar NG, Robson SC, Ford GA. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 April; 85(4): 157783. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770200&dopt=Abstract

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Efficacy and safety of phospholipid liposomes in the treatment of neuropsychological disorders associated with the menopause: a double-blind, randomised, placebocontrolled study. Author(s): Rachev E, Nalbansky B, Kolarov G, Agrosi M. Source: Current Medical Research and Opinion. 2001; 17(2): 105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759177&dopt=Abstract

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Efficacy and tolerability of moexipril and nitrendipine in postmenopausal women with hypertension. MADAM study group. Moexipril as Antihypertensive Drug After Menopause. Author(s): Agabiti-Rosei E, Ambrosioni E, Pirelli A, Stimpel M, Zanchetti A. Source: European Journal of Clinical Pharmacology. 1999 May; 55(3): 185-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10379633&dopt=Abstract

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Efficacy of continuous sequential transdermal estradiol and norethindrone acetate in relieving vasomotor symptoms associated with menopause. Author(s): Notelovitz M, Cassel D, Hille D, Furst KW, Dain MP, VandePol C, Skarinsky D. Source: American Journal of Obstetrics and Gynecology. 2000 January; 182(1 Pt 1): 7-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10649149&dopt=Abstract

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Efficacy of raloxifene for treatment of menopause: a systematic review. Author(s): Boyack M, Lookinland S, Chasson S. Source: Journal of the American Academy of Nurse Practitioners. 2002 April; 14(4): 15065. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12001746&dopt=Abstract

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El cambio de vida: conceptualizations of menopause and midlife among urban Latina women. Author(s): Villarruel AM, Harlow SD, Lopez M, Sowers M. Source: Res Theory Nurs Pract. 2002 Summer; 16(2): 91-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12371435&dopt=Abstract

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Endometrial polyps during menopause: characterization and significance. Author(s): Dessole S, Capobianco G, Ambrosini G. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2000 October; 79(10): 902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11304982&dopt=Abstract

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Endometrial polyps during menopause: characterization and significance. Author(s): Orvieto R, Bar-Hava I, Dicker D, Bar J, Ben-Rafael Z, Neri A. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1999 November; 78(10): 883-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10577618&dopt=Abstract

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Endothelial function and menopause: effects of raloxifene administration. Author(s): Colacurci N, Manzella D, Fornaro F, Carbonella M, Paolisso G. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 May; 88(5): 2135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727966&dopt=Abstract

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Epidemiology, sleep, and menopause. Author(s): Rosenthal MB. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 4-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544670&dopt=Abstract

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Epilepsy and women's health: family planning, bone health, menopause, and menstrual-related seizures. Author(s): Liporace J, D'Abreu A. Source: Mayo Clinic Proceedings. 2003 April; 78(4): 497-506. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683703&dopt=Abstract

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Epilepsy in the menopause. Author(s): Lee MA. Source: Neurology. 1999; 53(4 Suppl 1): S41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487514&dopt=Abstract

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Estradiol-intranasal: a review of its use in the management of menopause. Author(s): Dooley M, Spencer CM, Ormrod D. Source: Drugs. 2001; 61(15): 2243-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772138&dopt=Abstract

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Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause. Author(s): Shlipak MG, Simon JA, Vittinghoff E, Lin F, Barrett-Connor E, Knopp RH, Levy RI, Hulley SB. Source: Jama : the Journal of the American Medical Association. 2000 April 12; 283(14): 1845-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770146&dopt=Abstract

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Estrogen receptor polymorphism predicts the onset of natural and surgical menopause. Author(s): Weel AE, Uitterlinden AG, Westendorp IC, Burger H, Schuit SC, Hofman A, Helmerhorst TJ, van Leeuwen JP, Pols HA. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 September; 84(9): 3146-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487678&dopt=Abstract

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Ethnicity and attitude toward menopause and hormone replacement therapy in Northern Israel. Author(s): Nir-Caein R, Nahum R, Yogev Y, Rosenfeld J, Fisher M, Kaplan B. Source: Clin Exp Obstet Gynecol. 2002; 29(2): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171325&dopt=Abstract

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Evaluation of late onset bipolar illness during menopause. Author(s): Ishimaru-Tseng TV. Source: Hawaii Med J. 2000 February; 59(2): 51-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10800252&dopt=Abstract

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Evaluation of patient information Internet web sites about menopause and hormone replacement therapy. Author(s): Reed M, Anderson C. Source: Maturitas. 2002 October 25; 43(2): 135-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385862&dopt=Abstract

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Evidence-based practice in women's health: hormone therapy for women at menopause. Author(s): Rousseau ME. Source: Journal of Midwifery & Women's Health. 2001 May-June; 46(3): 167-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480749&dopt=Abstract

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Evolution of the human menopause. Author(s): Shanley DP, Kirkwood TB. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. 2001 March; 23(3): 282-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11223885&dopt=Abstract

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Exercise at menopause: a critical difference. Author(s): Burghardt M. Source: Medscape Women's Health [electronic Resource]. 1999 January-February; 4(1): 1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10089554&dopt=Abstract

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Experiences at menopause of women in a non-English-speaking community: a qualitative study. Author(s): Komesaroff PA, Kafanelis B, Black C, Cable V, Sudhir K, Daly J. Source: Climacteric : the Journal of the International Menopause Society. 2002 March; 5(1): 78-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11974562&dopt=Abstract

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Expert panel unsure of HRT benefits for conditions other than menopause. Author(s): Lawrence DM. Source: Lancet. 2002 April 27; 359(9316): 1493. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11988255&dopt=Abstract

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Explaining women's intentions and use of hormones with menopause. Author(s): Lauver DR, Settersten L, Marten S, Halls J. Source: Research in Nursing & Health. 1999 August; 22(4): 309-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10435548&dopt=Abstract

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Exploring the discursive construction of menopause for Thai women. Author(s): Punyahotra S, Street A. Source: Nursing Inquiry. 1998 June; 5(2): 96-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9923303&dopt=Abstract

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Exponent of “male menopause” censured by GMC. Author(s): Dyer O. Source: Bmj (Clinical Research Ed.). 2002 July 13; 325(7355): 65B. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114231&dopt=Abstract

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Expression of basic fibroblast growth factor (bFGF), FGF receptor 1 and FGF receptor 2 in uterine leiomyomas and myometrium during the menstrual cycle, after menopause and GnRHa treatment. Author(s): Wu X, Blanck A, Olovsson M, Moller B, Lindblom B. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2001 June; 80(6): 497-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11380284&dopt=Abstract

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Expression of Bcl-2, Bcl-x, Mcl-1, Bax and Bak in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause. Author(s): Wu X, Blanck A, Olovsson M, Henriksen R, Lindblom B. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 January; 80(1): 77-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867266&dopt=Abstract

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Factors affecting a woman's intent to adopt hormone replacement therapy for menopause. Author(s): Wilhelm SL. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 2002 November-December; 31(6): 698-707. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465866&dopt=Abstract

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Factors affecting access to menopause information. Author(s): Domm JA, Parker EE, Reed GW, German DC, Eisenberg E. Source: Menopause (New York, N.Y.). 2000 January-February; 7(1): 62-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10646705&dopt=Abstract

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Factors associated with age at natural menopause in a multiethnic sample of midlife women. Author(s): Gold EB, Bromberger J, Crawford S, Samuels S, Greendale GA, Harlow SD, Skurnick J. Source: American Journal of Epidemiology. 2001 May 1; 153(9): 865-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11323317&dopt=Abstract

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Factors associated with early menopause. Author(s): Harlow BL, Signorello LB. Source: Maturitas. 2000 April 28; 35(1): 3-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802394&dopt=Abstract

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FDA insists that oestrogen products for menopause carry a warning. Author(s): Gottlieb S. Source: Bmj (Clinical Research Ed.). 2003 January 18; 326(7381): 126. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531839&dopt=Abstract

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Female depression and menopause. Author(s): Facchinetti F. Source: Psychotherapy and Psychosomatics. 2001 May-June; 70(3): 166-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340420&dopt=Abstract

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Female depression before and after menopause. Author(s): Benazzi F. Source: Psychotherapy and Psychosomatics. 2000 September-October; 69(5): 280-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10965293&dopt=Abstract

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Feminist ethics and menopause: autonomy and decision-making in primary medical care. Author(s): Murtagh MJ, Hepworth J. Source: Social Science & Medicine (1982). 2003 April; 56(8): 1643-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639581&dopt=Abstract

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For and against: The male menopause--does it exist? Author(s): Gould DC, Petty R, Jacobs HS. Source: Bmj (Clinical Research Ed.). 2000 March 25; 320(7238): 858-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10731186&dopt=Abstract

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Fractal analysis of trabecular bone texture on calcaneus radiographs: effects of age, time since menopause and hormone replacement therapy. Author(s): Lespessailles E, Poupon S, Niamane R, Loiseau-Peres S, Derommelaere G, Harba R, Courteix D, Benhamou CL. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 May; 13(5): 366-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086346&dopt=Abstract

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Fractures before menopause: a red flag for physicians. Author(s): Hosmer WD, Genant HK, Browner WS. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002; 13(4): 337-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030549&dopt=Abstract

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Fragile X premutations are not a major cause of early menopause. Author(s): Kenneson A, Cramer DW, Warren ST. Source: American Journal of Human Genetics. 1997 December; 61(6): 1362-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9399905&dopt=Abstract

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Frequency and effectiveness of self-care actions and menopause symptoms of middleaged working women. Author(s): Schott-Baer D, Kotal B. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 2000 December; 9(6): 302-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11904864&dopt=Abstract

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Frequency of anovulation and early menopause among women enrolled in selected adult AIDS clinical trials group studies. Author(s): Clark RA, Mulligan K, Stamenovic E, Chang B, Watts H, Andersen J, Squires K, Benson C. Source: The Journal of Infectious Diseases. 2001 November 15; 184(10): 1325-7. Epub 2001 October 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11679923&dopt=Abstract

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From in vitro fertilization (IVF) to menopause: physiologic hormone replacement adapted from donor egg IVF may be our best option for hormone therapy. Author(s): de Ziegler D, Meldrum DR. Source: Fertility and Sterility. 2003 September; 80(3): 485-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969682&dopt=Abstract

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Functional impact of unvarying exercise program in women after menopause. Author(s): Kerschan K, Alacamlioglu Y, Kollmitzer J, Wober C, Kaider A, Hartard M, Ghanem AH, Preisinger E. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 1998 July-August; 77(4): 326-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9715923&dopt=Abstract

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Gendered personality dispositions, hormone values, and hot flushes during and after menopause. Author(s): Overlie I, Finset A, Holte A. Source: Journal of Psychosomatic Obstetrics and Gynaecology. 2002 December; 23(4): 219-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520859&dopt=Abstract

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General and medical factors associated with hormone replacement therapy among women attending menopause clinics in Italy. Author(s): Progetto Menopausa Italia Study Group. Source: Menopause (New York, N.Y.). 2001 July-August; 8(4): 290-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449088&dopt=Abstract

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Genes control the cessation of a woman's reproductive life: a twin study of hysterectomy and age at menopause. Author(s): Snieder H, MacGregor AJ, Spector TD. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 June; 83(6): 1875-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9626112&dopt=Abstract

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Genetic analysis of the age at menopause by using estimating equations and Bayesian random effects models. Author(s): Do KA, Broom BM, Kuhnert P, Duffy DL, Todorov AA, Treloar SA, Martin NG. Source: Statistics in Medicine. 2000 May 15; 19(9): 1217-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10797518&dopt=Abstract

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Genetic and environmental influences on lipids, lipoproteins, and apolipoproteins: effects of menopause. Author(s): Middelberg RP, Spector TD, Swaminathan R, Snieder H. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 July 1; 22(7): 1142-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117729&dopt=Abstract

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Genetic influences on the age at menopause. Author(s): Treloar SA, Do KA, Martin NG. Source: Lancet. 1998 October 3; 352(9134): 1084-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9798581&dopt=Abstract

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Genetic variation in bone mineral density and calcaneal ultrasound: a study of the influence of menopause using female twins. Author(s): Hunter DJ, de Lange M, Andrew T, Snieder H, MacGregor AJ, Spector TD. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(5): 406-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11444090&dopt=Abstract

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Genetics of menopause-associated diseases. Author(s): Massart F, Reginster JY, Brandi ML. Source: Maturitas. 2001 November 30; 40(2): 103-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716989&dopt=Abstract

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Gonadotropins at menopause: the influence of obesity, insulin resistance, and estrogens. Author(s): Malacara JM, Fajardo ME, Nava LE. Source: Steroids. 2001 July; 66(7): 559-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11322964&dopt=Abstract

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Grandmothering, menopause, and the evolution of human life histories. Author(s): Hawkes K, O'Connell JF, Jones NG, Alvarez H, Charnov EL. Source: Proceedings of the National Academy of Sciences of the United States of America. 1998 February 3; 95(3): 1336-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9448332&dopt=Abstract

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Has psychosocial research on the menopause any clinical relevance? Author(s): Greene JG. Source: Climacteric : the Journal of the International Menopause Society. 2003 March; 6(1): 23-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725661&dopt=Abstract

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Headache at menopause and in hormone replacement therapy users. Author(s): Hodson J, Thompson J, al-Azzawi F. Source: Climacteric : the Journal of the International Menopause Society. 2000 June; 3(2): 119-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910652&dopt=Abstract

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Heart rate and its variability change after the menopause. Author(s): Brockbank CL, Chatterjee F, Bruce SA, Woledge RC. Source: Experimental Physiology. 2000 May; 85(3): 327-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825420&dopt=Abstract

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HEDIS 2000: strategies for successful menopause management. Author(s): Hammond CB. Source: Am J Manag Care. 2000 September; 6(14 Suppl): S738-41. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11184070&dopt=Abstract

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HEDIS measure for the management of menopause. Author(s): Andrews WC, Morrow TJ. Source: Am J Manag Care. 2000 September; 6(14 Suppl): S742-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11184071&dopt=Abstract

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Helping Asian women to understand the menopause. Author(s): Sarwar Z. Source: Community Nurse. 1998 April; 4(3): 12-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9763939&dopt=Abstract

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Hirsutism of recent onset with marked hyperandrogenaemia and ovarian hyperthecosis after the menopause. Author(s): Ayuk P, Stringfellow H, Donnai P, Beardwell C, Holt A, Laing I. Source: Annals of Clinical Biochemistry. 1998 January; 35 ( Pt 1): 145-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9463756&dopt=Abstract

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Homoeopathic treatment during the menopause. Author(s): Katz T. Source: Complementary Therapies in Nursing & Midwifery. 1997 April; 3(2): 46-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9432430&dopt=Abstract

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Hope on ice: reversing the menopause may be tougher than we think. Author(s): Motluck A. Source: New Scientist (1971). 1999 October 2; 164(2206): 5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186101&dopt=Abstract

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Hormonal changes in the menopause transition. Author(s): Burger HG, Dudley EC, Robertson DM, Dennerstein L. Source: Recent Progress in Hormone Research. 2002; 57: 257-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017547&dopt=Abstract

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Hormonal strategies of the menopause. Author(s): Damewood MD. Source: Md Med J. 1997 September; 46(8): 415-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9294948&dopt=Abstract

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Hormonal substitution during menopause: what are we treating? Author(s): Maartens LW, Leusink GL, Knottnerus JA, Pop VJ. Source: Maturitas. 2000 February 15; 34(2): 113-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714905&dopt=Abstract

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Hormonal therapy for menopause and ovarian cancer in a collaborative re-analysis of European studies. Author(s): Negri E, Tzonou A, Beral V, Lagiou P, Trichopoulos D, Parazzini F, Franceschi S, Booth M, La Vecchia C. Source: International Journal of Cancer. Journal International Du Cancer. 1999 March 15; 80(6): 848-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10074916&dopt=Abstract

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Hormone replacement and the menopause: a European position paper. Writing Group on Women's Health of the Fondazione Giovanni Lorenzini Medical Science Foundation. Author(s): Crosignani PG, Kenemans P, Paoletti R, Soma MR, Woodford FP. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1997 July; 74(1): 67-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9243206&dopt=Abstract

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Hormone replacement following early menopause. Author(s): Cooper GS. Source: Jama : the Journal of the American Medical Association. 2002 December 11; 288(22): 2824-5; Author Reply 2825. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472322&dopt=Abstract

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Hormone replacement therapy and menopause: a review of randomized, doubleblind, placebo-controlled trials. Author(s): Chang C, Lin CH. Source: Kaohsiung J Med Sci. 2003 June; 19(6): 257-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873034&dopt=Abstract

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Hormone replacement therapy and menopause: attitude, information, and compliance among Israeli nurses. Author(s): Kaplan B, Yogev Y, Gal B, Fisher M. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 June; 77(3): 251-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065139&dopt=Abstract

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Hormone replacement therapy for somatopause: risk-benefit analysis and precedents in the treatment of menopause. Author(s): Lamberts SW. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2000 April; 10 Suppl A: S523. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984295&dopt=Abstract

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Hormone replacement therapy in the menopause. Author(s): Sarrel PM. Source: Int J Fertil Womens Med. 1997 March-April; 42(2): 78-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9160217&dopt=Abstract

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Hormone replacement therapy increases ACTH/dehydroepiandrosterone sulfate in menopause. Author(s): Fonseca E, Basurto L, Velazquez S, Zarate A. Source: Maturitas. 2001 July 25; 39(1): 57-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451621&dopt=Abstract

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Hormone replacement therapy menopause with a better future--a survey of views on hormone replacement therapy (HRT). Author(s): Shafi S, Samad Z, Syed S, Sharif A, Khan MA, Nehal US, Siddiqui AR. Source: J Pak Med Assoc. 2001 December; 51(12): 450-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11850984&dopt=Abstract

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Hormone replacement therapy: effect of progestin dose and time since menopause on endometrial bleeding. Author(s): Archer DF, Pickar JH. Source: Obstetrics and Gynecology. 2000 December; 96(6): 899-905. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11084175&dopt=Abstract

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Hormone replacement therapy: the elixer for menopause? Author(s): Klein L. Source: J Med Assoc Ga. 1997 September; 86(3): 177-80. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9293168&dopt=Abstract

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Hormone therapy and heart disease after the menopause. Author(s): Skegg DC. Source: Lancet. 2001 October 13; 358(9289): 1196-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675050&dopt=Abstract

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Hormone therapy in menopause: the plot thickens. Author(s): Good AE. Source: Minn Med. 2003 January; 86(1): 32-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585557&dopt=Abstract

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Hormone therapy in women in the menopause transition. Randomised, double-blind, placebo-controlled trial of effects on body weight, blood pressure, lipoprotein levels, antithrombin III activity, and the endometrium. Author(s): Khoo SK, Coglan MJ, Wright GR, DeVoss KN, Battistutta D. Source: The Medical Journal of Australia. 1998 March 2; 168(5): 216-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9539899&dopt=Abstract

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Hormones after menopause? Author(s): Velkeniers B. Source: Acta Clin Belg. 2001 March-April; 56(2): 113-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383314&dopt=Abstract

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Hormones and mood: from menarche to menopause and beyond. Author(s): Steiner M, Dunn E, Born L. Source: Journal of Affective Disorders. 2003 March; 74(1): 67-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646300&dopt=Abstract

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Hormones and.. many symptoms of menopause means many therapies. Author(s): Levine S, Brink S, Hobson K, Carpenter B, Malrine A. Source: U.S. News & World Report. 2002 November 18; 133(19): 63, 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501477&dopt=Abstract

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Hormones, weight change and menopause. Author(s): Davies KM, Heaney RP, Recker RR, Barger-Lux MJ, Lappe JM. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2001 June; 25(6): 874-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11439302&dopt=Abstract

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How does menopause alter the primary care of women? Author(s): Onega T. Source: Jaapa. 2000 April; 13(4): 42-4, 47-8, 51-4 Passim. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11503384&dopt=Abstract

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How Japanese women talk about hot flushes: implications for menopause research. Author(s): Zeserson JM. Source: Med Anthropol Q. 2001 June; 15(2): 189-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452627&dopt=Abstract

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How to manage the menopause following therapy for breast cancer. is raloxifene a safe alternative? Author(s): Sismondi P, Biglia N, Roagna R, Ponzone R, Ambroggio S, Sgro L, Cozzarella M. Source: European Journal of Cancer (Oxford, England : 1990). 2000 September; 36 Suppl 4: S74-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11056328&dopt=Abstract

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How women experience menopause: the importance of social context. Author(s): Winterich JA, Umberson D. Source: J Women Aging. 1999; 11(4): 57-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10721689&dopt=Abstract

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HRT & menopause. A clinician's guide to understanding the dilemma. Author(s): DeMasters J. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2000 April-May; 4(2): 26-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11146923&dopt=Abstract

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HRT and its impact on the menopause, osteoporosis and breast cancer. Author(s): Torgerson DJ. Source: Expert Opinion on Pharmacotherapy. 2000 September; 1(6): 1163-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11249485&dopt=Abstract

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HRT in menopause. Author(s): Zurlinden J. Source: Nurs Spectr (Wash D C). 1997 June 30; 7(13): 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9431193&dopt=Abstract

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Hypersecretion of ovarian androgens may be gonadotrophin dependent many years after menopause. Author(s): Lindgren R, Gunnarsson C, Jakobsson A, Hammar M. Source: Maturitas. 2000 January 15; 34(1): 43-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10687881&dopt=Abstract

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Hypertension and obesity after the menopause. Author(s): Rappelli A. Source: Journal of Hypertension. 2002 May; 20 Suppl 2: S26-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183846&dopt=Abstract

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Hysterectomy, menopause, and estrogen use preceding Parkinson's disease: an exploratory case-control study. Author(s): Benedetti MD, Maraganore DM, Bower JH, McDonnell SK, Peterson BJ, Ahlskog JE, Schaid DJ, Rocca WA. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2001 September; 16(5): 830-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746612&dopt=Abstract

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I am a 54-year-old woman who has gone through menopause. Six months after starting HRT, I discovered I had gallstones, after suffering four attacks. I am not interested in having my gallbladder out, and I have drastically reduced the amount of fat in my diet, which has eliminated further attacks. However, I have also read that there is a link between estrogen and gallstone formation. Should I stop taking the estrogen? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 1998 October; 6(2): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9795606&dopt=Abstract

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Impact of calcitonin on urinary excretion of prostaglandins during menopause. Author(s): Akgul C, Vural P, Canbaz M. Source: Gynecologic and Obstetric Investigation. 1998; 46(3): 199-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9736804&dopt=Abstract

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Impact of menopause on the brain. Author(s): Wise PM. Source: Alzheimer Disease and Associated Disorders. 2003 April-June; 17 Suppl 2: S4850. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813208&dopt=Abstract

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Impact of menopause on the prevalence and severity of sleep apnea. Author(s): Dancey DR, Hanly PJ, Soong C, Lee B, Hoffstein V. Source: Chest. 2001 July; 120(1): 151-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451831&dopt=Abstract

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Implications of the FMR1 gene in menopause: study of 147 Spanish women. Author(s): Mallolas J, Duran M, Sanchez A, Jimenez D, Castellvi-Bel S, Rife M, Mila M. Source: Menopause (New York, N.Y.). 2001 Summer; 8(2): 106-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256870&dopt=Abstract

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Improvement of diagnostic accuracy of transvaginal ultrasound for identification of endometrial malignancies by using cutoff level of endometrial thickness based on length of time since menopause. Author(s): Tsuda H, Kawabata M, Kawabata K, Yamamoto K, Umesaki N. Source: Gynecologic Oncology. 1997 January; 64(1): 35-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8995544&dopt=Abstract

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Increased plasma homocysteine after menopause. Author(s): Hak AE, Polderman KH, Westendorp IC, Jakobs C, Hofman A, Witteman JC, Stehouwer CD. Source: Atherosclerosis. 2000 March; 149(1): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704628&dopt=Abstract

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Independent genetic factors determine the amount and distribution of fat in women after the menopause. Author(s): Samaras K, Spector TD, Nguyen TV, Baan K, Campbell LV, Kelly PJ. Source: The Journal of Clinical Endocrinology and Metabolism. 1997 March; 82(3): 781-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9062482&dopt=Abstract

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Infertility and premature menopause in childhood cancer survivors. Author(s): Byrne J. Source: Medical and Pediatric Oncology. 1999 July; 33(1): 24-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10401493&dopt=Abstract

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Influence of menopause on blood cholesterol levels in women: the role of body composition, fat distribution and hormonal milieu. Virgilio Menopause Health Group. Author(s): Pasquali R, Casimirri F, Pascal G, Tortelli O, Morselli Labate A, Bertazzo D, Vicennati V, Gaddi A. Source: Journal of Internal Medicine. 1997 March; 241(3): 195-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9104432&dopt=Abstract

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Influence of menopause on high density lipoprotein-cholesterol and lipids. Author(s): Kim CJ, Kim TH, Ryu WS, Ryoo UH. Source: Journal of Korean Medical Science. 2000 August; 15(4): 380-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10983684&dopt=Abstract

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Information needs regarding menopause. Results from a survey of women receiving cancer prevention and detection services. Author(s): Mahon SM, Williams M. Source: Cancer Nursing. 2000 June; 23(3): 176-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10851768&dopt=Abstract

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Information sources, menopause beliefs, and health complaints of midlife Filipinas. Author(s): Berg JA, Lipson JG. Source: Health Care for Women International. 1999 January-February; 20(1): 81-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10335158&dopt=Abstract

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Intake of selected foods and nutrients and breast cancer risk: an age- and menopausespecific analysis. Author(s): Braga C, La Vecchia C, Negri E, Franceschi S, Parpinel M. Source: Nutrition and Cancer. 1997; 28(3): 258-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9343834&dopt=Abstract

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International variability in ages at menarche, first livebirth, and menopause. World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives. Author(s): Morabia A, Costanza MC. Source: American Journal of Epidemiology. 1998 December 15; 148(12): 1195-205. Erratum In: Am J Epidemiol 1999 September 1; 150(5): 546. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9867266&dopt=Abstract

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International variability of ages at menarche and menopause: patterns and main determinants. Author(s): Thomas F, Renaud F, Benefice E, de Meeus T, Guegan JF. Source: Human Biology; an International Record of Research. 2001 April; 73(2): 271-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446429&dopt=Abstract

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Interventions for other risk factors: tobacco use, physical inactivity, menopause, and homocysteine. Author(s): Beto JA, Bansal VK. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1998 November; 32(5 Suppl 3): S172-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9820474&dopt=Abstract

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Introduction. Menopause disorders and other menopause related problems. Author(s): Schindler PA. Source: Maturitas. 2002 April 15; 41 Suppl 1: S1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955788&dopt=Abstract

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Ipriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH-agonists. Author(s): Gambacciani M, Cappagli B, Piaggesi L, Ciaponi M, Genazzani AR. Source: Calcified Tissue International. 1997; 61 Suppl 1: S15-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9263611&dopt=Abstract

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Is bleeding a predictor of endometrial hyperplasia in postmenopausal women receiving hormone replacement therapy? Menopause Study Group (United States, Italy, Netherlands, Switzerland, Belgium, Germany, and Finland. Author(s): Pickar JH, Archer DF. Source: American Journal of Obstetrics and Gynecology. 1997 November; 177(5): 117883. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9396916&dopt=Abstract

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Is incontinence associated with menopause? Author(s): Sherburn M, Guthrie JR, Dudley EC, O'Connell HE, Dennerstein L. Source: Obstetrics and Gynecology. 2001 October; 98(4): 628-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576579&dopt=Abstract

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Is menopause an independent cardiovascular risk factor? Evidence from populationbased studies. Author(s): Casiglia E, Tikhonoff V, Mormino P, Piccoli A, Pessina AC. Source: Journal of Hypertension. 2002 May; 20 Suppl 2: S17-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183844&dopt=Abstract

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Is open-angle glaucoma associated with early menopause? The Rotterdam Study. Author(s): Hulsman CA, Westendorp IC, Ramrattan RS, Wolfs RC, Witteman JC, Vingerling JR, Hofman A, de Jong PT. Source: American Journal of Epidemiology. 2001 July 15; 154(2): 138-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11447046&dopt=Abstract

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Is the age of menopause determined in-utero? Author(s): Cresswell JL, Egger P, Fall CH, Osmond C, Fraser RB, Barker DJ. Source: Early Human Development. 1997 September 19; 49(2): 143-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9226121&dopt=Abstract

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Is there a case for targeting hormone replacement therapy for osteoporosis at the menopause? Author(s): Stevenson JC. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1998; 8 Suppl 1: S47-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9682798&dopt=Abstract

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Is there an association between menopause status and sexual functioning? Author(s): Avis NE, Stellato R, Crawford S, Johannes C, Longcope C. Source: Menopause (New York, N.Y.). 2000 September-October; 7(5): 297-309. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10993029&dopt=Abstract

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Is there really a 'male menopause'? Whatever the term, midlife changes warrant attention. Author(s): Collins A. Source: Adv Nurse Pract. 2000 July; 8(7): 63-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11261040&dopt=Abstract

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Issues surrounding surgical menopause. Indications and procedures. Author(s): Reich H. Source: J Reprod Med. 2001 March; 46(3 Suppl): 297-306. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11304878&dopt=Abstract

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Italian-Canadian women's views of menopause: how culture may affect hormone use. Author(s): Bonetta C, Cheung AM, Stewart DE. Source: Medscape Women's Health [electronic Resource]. 2001 October; 6(5): 4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11698926&dopt=Abstract

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It's not only mammographies and menopause. Author(s): Freda MC. Source: The American Journal of Nursing. 1997 April; 97(4): 80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9103928&dopt=Abstract

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JAMA patient page. Perimenopause: beginning of menopause. Author(s): Torpy JM, Lynm C, Glass RM. Source: Jama : the Journal of the American Medical Association. 2003 February 19; 289(7): 940. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588280&dopt=Abstract

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Knowledge among German and Turkish women about specifically female bodily functions, contraception, preventative medical examinations and menopause. Author(s): David M, Borde T, Kentenich H. Source: Ethnicity & Health. 2000 May; 5(2): 101-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984828&dopt=Abstract

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Knowledge and attitude towards personal health care and menopause among women with ischemic heart disease undergoing coronary angiography. Author(s): Yogev Y, Nahum R, Sulkes J, Fisher M, Hertz I, Kaplan B. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2003 June; 17(3): 255-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857434&dopt=Abstract

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Knowledge of menopause and hormone replacement therapy use in low-income urban women. Author(s): Appling SE, Allen JK, Van Zandt S, Olsen S, Brager R, Hallerdin J. Source: Journal of Women's Health & Gender-Based Medicine. 2000 January-February; 9(1): 57-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10718507&dopt=Abstract

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Korean urban women's experience of menopause: new life. Author(s): Lee KH. Source: Health Care for Women International. 1997 March-April; 18(2): 139-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9119790&dopt=Abstract

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Laryngeal cytological aspects in women with surgically induced menopause who were treated with transdermal estrogen replacement therapy. Author(s): Caruso S, Roccasalva L, Sapienza G, Zappala M, Nuciforo G, Biondi S. Source: Fertility and Sterility. 2000 December; 74(6): 1073-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119730&dopt=Abstract

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Lay perceptions of a 'natural' menopause. Cross sectional study of the British Women's Heart and Health Study. Author(s): Lawlor DA, Adamson J, Ebrahim S. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 December; 109(12): 1398-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504978&dopt=Abstract

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Left-handed women have earlier age of menopause. Author(s): Dane S, Reis N, Pasinliogu T. Source: J Basic Clin Physiol Pharmacol. 1999; 10(2): 147-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10444716&dopt=Abstract

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Leptin levels in menopause: effect of estrogen replacement therapy. Author(s): Cento RM, Proto C, Spada RS, Napolitano V, Ciampelli M, Cucinelli F, Lanzone A. Source: Hormone Research. 1999; 52(6): 269-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10965205&dopt=Abstract

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Life after menopause. Author(s): Weisfeldt L. Source: J Gend Specif Med. 1999 March-April; 2(2): 16. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11252856&dopt=Abstract

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Lifetime cognitive function and timing of the natural menopause. Author(s): Richards M, Kuh D, Hardy R, Wadsworth M. Source: Neurology. 1999 July 22; 53(2): 308-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10430419&dopt=Abstract

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Lifetime estrogen exposure versus age at menopause as mortality predictor. Author(s): Jansen SC, Temme EH, Schouten EG. Source: Maturitas. 2002 October 25; 43(2): 105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385858&dopt=Abstract

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Lipid effects, effectiveness and acceptability of tibolone versus transdermic 17 betaestradiol for hormonal replacement therapy in women with surgical menopause. Author(s): Mendoza N, Suarez AM, Alamo F, Bartual E, Vergara F, Herruzo A. Source: Maturitas. 2000 November 30; 37(1): 37-43. Erratum In: Maturitas 2001 Nov 30; 40(2): 191. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11099872&dopt=Abstract

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Lipoproteins and BMI: a comparison between women during transition to menopause and regularly menstruating healthy women. Author(s): Hall G, Collins A, Csemiczky G, Landgren BM. Source: Maturitas. 2002 March 25; 41(3): 177-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886763&dopt=Abstract

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Longitudinal influence of age, menopause, hormone replacement therapy, and other medications on parotid flow rates in healthy women. Author(s): Ghezzi EM, Wagner-Lange LA, Schork MA, Metter EJ, Baum BJ, Streckfus CF, Ship JA. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2000 January; 55(1): M34-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10719771&dopt=Abstract

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Longitudinal research on the menopause-methodological challenges. Author(s): Collins A, Landgren BM. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 July; 81(7): 579-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190830&dopt=Abstract

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Longitudinal study of age- and menopause-related metacarpal index changes in Japanese adult females. Author(s): Huachou Z, Kitazawa A, Kushida K, Nagano A. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2001 Spring; 4(1): 43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11309519&dopt=Abstract

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Longitudinal study of bone density and its determinants in women in peri- or early menopause. Author(s): Picard D, Imbach A, Couturier M, Lepage R, Ste Marie LG. Source: Calcified Tissue International. 2000 November; 67(5): 356-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11136532&dopt=Abstract

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Longitudinal study of hormone levels and depression among women transitioning through menopause. Author(s): Avis NE, Crawford S, Stellato R, Longcope C. Source: Climacteric : the Journal of the International Menopause Society. 2001 September; 4(3): 243-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588948&dopt=Abstract

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Longitudinal study of menopause and sexuality. Author(s): McCoy NL. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 July; 81(7): 617-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190836&dopt=Abstract

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Lp(a) lipoprotein--an independent risk factor for coronary heart disease after menopause. Author(s): Futterman LG, Lemberg L. Source: American Journal of Critical Care : an Official Publication, American Association of Critical-Care Nurses. 2001 January; 10(1): 63-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11153187&dopt=Abstract

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Macronutrient intake and change in mammographic density at menopause: results from a randomized trial. Author(s): Knight JA, Martin LJ, Greenberg CV, Lockwood GA, Byng JW, Yaffe MJ, Tritchler DL, Boyd NF. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1999 February; 8(2): 123-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10067809&dopt=Abstract

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Maintaining sexual health after menopause. Author(s): Bartlik B, Goldstein MZ. Source: Psychiatric Services (Washington, D.C.). 2000 June; 51(6): 751-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10828105&dopt=Abstract

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Management of menopause. Author(s): Goolsby MJ. Source: Journal of the American Academy of Nurse Practitioners. 2001 April; 13(4): 14750. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930525&dopt=Abstract

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Management of menopause: a new HEDIS measure and an opportunity for health plans. Author(s): Cawood J, Morrow T. Source: Manag Care Interface. 2000 August; 13(8): 65-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11185178&dopt=Abstract

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Management of postmenopausal osteoporosis: position statement of the North American Menopause Society. Author(s): North American Menopause Society. Source: Menopause (New York, N.Y.). 2002 March-April; 9(2): 84-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875327&dopt=Abstract

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Management of the menopause in cancer survivors. Author(s): Clemons M, Clamp A, Anderson B. Source: Cancer Treatment Reviews. 2002 December; 28(6): 321-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470982&dopt=Abstract

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Managing menopause after breast cancer: balancing risks and benefits. Author(s): Moore HC. Source: Cleve Clin J Med. 2001 March; 68(3): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263852&dopt=Abstract

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Managing menopause: a critical feminist engagement. Author(s): Guillemin MN. Source: Scandinavian Journal of Public Health. 1999 December; 27(4): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10724470&dopt=Abstract

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Managing menopause: a qualitative analysis of self-help literature for women at midlife. Author(s): Lyons AC, Griffin C. Source: Social Science & Medicine (1982). 2003 April; 56(8): 1629-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639580&dopt=Abstract

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Marital status and age at natural menopause: considering pheromonal influence. Author(s): Sievert LL, Waddle D, Canali K. Source: American Journal of Human Biology : the Official Journal of the Human Biology Council. 2001 July-August; 13(4): 479-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400218&dopt=Abstract

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Measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx) in aging, menopause, and osteoporosis with fractures. Author(s): Takahashi M, Hoshino H, Kushida K. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1999 January; 279(1-2): 69-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10064119&dopt=Abstract

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Measurement-specific quality-of-life satisfaction during the menopause in an Arabian Gulf country. Author(s): Bener A, Rizk DE, Shaheen H, Micallef R, Osman N, Dunn EV. Source: Climacteric : the Journal of the International Menopause Society. 2000 March; 3(1): 43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910609&dopt=Abstract

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Measuring cognition in menopause research: a review of test use. Author(s): Rice K, Morse C. Source: Climacteric : the Journal of the International Menopause Society. 2003 March; 6(1): 2-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725660&dopt=Abstract

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Medico-social dimensions of menopause: a cross-sectional study from rural south India. Author(s): Aaron R, Muliyil J, Abraham S. Source: Natl Med J India. 2002 January-February; 15(1): 14-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11855585&dopt=Abstract

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Medroxyprogesterone-induced endocrine alterations after menopause. Author(s): Saaresranta T, Irjala K, Polo-Kantola P, Polo O. Source: Menopause (New York, N.Y.). 2002 July-August; 9(4): 288-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12082365&dopt=Abstract

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Menopause across cultures: a review of the evidence. Author(s): Obermeyer CM. Source: Menopause (New York, N.Y.). 2000 May-June; 7(3): 184-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10810964&dopt=Abstract

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Menopause after breast cancer: a survey on breast cancer survivors. Author(s): Biglia N, Cozzarella M, Cacciari F, Ponzone R, Roagna R, Maggiorotto F, Sismondi P. Source: Maturitas. 2003 May 30; 45(1): 29-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753941&dopt=Abstract

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Menopause and aging with disability. Author(s): Vandenakker CB, Glass DD. Source: Phys Med Rehabil Clin N Am. 2001 February; 12(1): 133-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11853033&dopt=Abstract

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Menopause and beyond. The wise woman way. Author(s): Weed SS. Source: Journal of Nurse-Midwifery. 1999 May-June; 44(3): 267-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10380445&dopt=Abstract

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Menopause and breast cancer: addressing the secondary health effects of adjuvant chemotherapy. Author(s): Ganz PA, Greendale GA. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 July 15; 19(14): 3303-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454876&dopt=Abstract

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Menopause and breast cancer: symptoms, late effects, and their management. Author(s): Ganz PA. Source: Seminars in Oncology. 2001 June; 28(3): 274-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11402437&dopt=Abstract

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Menopause and hormone replacement: Part 1. Evaluation and treatment. Author(s): Ratner S, Ofri D. Source: The Western Journal of Medicine. 2001 June; 174(6): 400-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11381008&dopt=Abstract

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Menopause and hormone-replacement therapy: Part 2. Hormone-replacement therapy regimens. Author(s): Ratner S, Ofri D. Source: The Western Journal of Medicine. 2001 July; 175(1): 32-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11431399&dopt=Abstract

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Menopause and ischaemic stroke: basic, clinical and epidemiological considerations. The role of hormone replacement. Author(s): Pines A, Bornstein NM, Shapira I. Source: Human Reproduction Update. 2002 March-April; 8(2): 161-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099631&dopt=Abstract

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Menopause and menarche in patients with primary blepharospasm: an exploratory case-control study. Author(s): Martino D, Livrea P, Giorelli M, Masi G, Aniello MS, Defazio G. Source: European Neurology. 2002; 47(3): 161-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914554&dopt=Abstract

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Menopause and perimenopause: the role of ovarian hormones in common neuroendocrine syndromes in primary care. Author(s): Vliet EL. Source: Primary Care. 2002 March; 29(1): 43-67, Vi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856658&dopt=Abstract

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Menopause and postmenopausal hormone use and risk of incident kidney stones. Author(s): Mattix Kramer HJ, Grodstein F, Stampfer MJ, Curhan GC. Source: Journal of the American Society of Nephrology : Jasn. 2003 May; 14(5): 1272-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707395&dopt=Abstract

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Menopause and risk of non-fatal acute myocardial infarction: an Italian case-control study and a review of the literature. Author(s): Fioretti F, Tavani A, Gallus S, Franceschi S, La Vecchia C. Source: Human Reproduction (Oxford, England). 2000 March; 15(3): 599-603. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10686203&dopt=Abstract

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Menopause and the characteristics of the large arteries in a population study. Author(s): Staessen JA, van der Heijden-Spek JJ, Safar ME, Den Hond E, Gasowski J, Fagard RH, Wang JG, Boudier HA, Van Bortel LM. Source: Journal of Human Hypertension. 2001 August; 15(8): 511-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494087&dopt=Abstract

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Menopause and the skin. Author(s): Wines N, Willsteed E. Source: The Australasian Journal of Dermatology. 2001 August; 42(3): 149-8; Quiz 159. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11488706&dopt=Abstract

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Menopause and the transmission of women's knowledge: African American and white women's perspectives. Author(s): Agee E. Source: Med Anthropol Q. 2000 March; 14(1): 73-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10812564&dopt=Abstract

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Menopause and weight. Author(s): Avis NE, Crawford SL. Source: Menopause (New York, N.Y.). 2001 July-August; 8(4): 230-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449078&dopt=Abstract

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Menopause as a measure of population health: an overview. Author(s): Sievert LL. Source: American Journal of Human Biology : the Official Journal of the Human Biology Council. 2001 July-August; 13(4): 429-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400214&dopt=Abstract

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Menopause in Blackfeet women--a life span perspective. Author(s): Johnston SL. Source: Coll Antropol. 2003 June; 27(1): 57-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974133&dopt=Abstract

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Menopause in Morocco: symptomatology and medical management. Author(s): Obermeyer CM, Schulein M, Hajji N, Azelmat M. Source: Maturitas. 2002 February 26; 41(2): 87-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11836039&dopt=Abstract

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Menopause in type 1 diabetic women: is it premature? Author(s): Dorman JS, Steenkiste AR, Foley TP, Strotmeyer ES, Burke JP, Kuller LH, Kwoh CK; Familial Autoimmune and Diabetes (FAD) Study. Source: Diabetes. 2001 August; 50(8): 1857-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11473049&dopt=Abstract

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Menopause is associated with reduced protection from postprandial lipemia. Author(s): van Beek AP, de Ruijter-Heijstek FC, Erkelens DW, de Bruin TW. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1999 November; 19(11): 2737-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10559019&dopt=Abstract

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Menopause is 'by no means confined to the woman,' doctor said. Author(s): Randal J. Source: Journal of the National Cancer Institute. 2002 August 7; 94(15): 1117. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165631&dopt=Abstract

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Menopause World Congress in Berlin. Author(s): Schneider HP. Source: Climacteric : the Journal of the International Menopause Society. 2002 March; 5(1): 90-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11974564&dopt=Abstract

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Menopause, coronary artery disease and antioxidants. Author(s): Krstevska M, Dzhekova-Stojkova S, Bosilkova G. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2001 July; 39(7): 641-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522113&dopt=Abstract

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Menopause, energy expenditure, and body composition. Author(s): Poehlman ET. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 July; 81(7): 603-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190834&dopt=Abstract

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Menopause, estrogen, and training effects on exercise hemodynamics: the HERITAGE study. Author(s): Green JS, Stanforth PR, Gagnon J, Leon AS, Rao DC, Skinner JS, Bouchard C, Rankinen T, Wilmore JH. Source: Medicine and Science in Sports and Exercise. 2002 January; 34(1): 74-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782651&dopt=Abstract

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Menopause, hormone replacement therapy and cancer. Author(s): La Vecchia C, Brinton LA, McTiernan A. Source: Maturitas. 2001 August 25; 39(2): 97-115. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514109&dopt=Abstract

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Menopause, hormone replacement therapy and tear function. Author(s): Evans I, Millar TJ, Eden JA, Willcox MD. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 1029-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614027&dopt=Abstract

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Menopause, hormone replacement therapy, and sleep-disordered breathing: are we ready for the heat? Author(s): Young T. Source: American Journal of Respiratory and Critical Care Medicine. 2001 March; 163(3 Pt 1): 597-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254506&dopt=Abstract

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Menopause, HRT and menopausal symptoms. Author(s): Kenemans P. Source: Journal of Epidemiology and Biostatistics. 1999; 4(3): 141-6; Discussion 146-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695956&dopt=Abstract

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Menopause, local biologies, and cultures of aging. Author(s): Lock M, Kaufert P. Source: American Journal of Human Biology : the Official Journal of the Human Biology Council. 2001 July-August; 13(4): 494-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400220&dopt=Abstract

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Menopause, oestrogens and arthritis. Author(s): Wluka AE, Cicuttini FM, Spector TD. Source: Maturitas. 2000 June 30; 35(3): 183-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936736&dopt=Abstract

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Menopause, oestrogens, SERM's and cardiovascular health in women. Author(s): Mijatovic V, van der Mooren MJ. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2000 November; 93(1): 5-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11000495&dopt=Abstract

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Menopause, sex hormones, and sleep. Author(s): Shin K, Shapiro C. Source: Bipolar Disorders. 2003 April; 5(2): 106-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680899&dopt=Abstract

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Menopause. A treatment algorithm. Author(s): Reddish S. Source: Aust Fam Physician. 2002 May; 31(5): 423-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043545&dopt=Abstract

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Menopause: Irish women's voices. Author(s): Carolan M. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 2000 July-August; 29(4): 397-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10929843&dopt=Abstract

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Menopause: new therapies. Author(s): Davis SR. Source: The Medical Journal of Australia. 2003 June 16; 178(12): 634-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797852&dopt=Abstract

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Menopause: social expectations, women's realities. Author(s): Stotland NL. Source: Archives of Women's Mental Health. 2002 August; 5(1): 5-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503068&dopt=Abstract

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Menopause-associated problems: types and magnitude. A study in the Ain Al-Basha area, Jordan. Author(s): Al-Qutob R. Source: Journal of Advanced Nursing. 2001 March; 33(5): 613-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11298197&dopt=Abstract

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Menopause-induced changes in lipid fractions and total fatty acids in plasma. Author(s): Maynar M, Mahedero G, Maynar I, Maynar JI, Tuya IR, Caballero MJ. Source: Endocrine Research. 2001 August; 27(3): 357-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678583&dopt=Abstract

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Menopause-related changes in body fat distribution. Author(s): Toth MJ, Tchernof A, Sites CK, Poehlman ET. Source: Annals of the New York Academy of Sciences. 2000 May; 904: 502-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10865795&dopt=Abstract

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Menopause-related differences in inflammation markers and their relationship to body fat distribution and insulin-stimulated glucose disposal. Author(s): Sites CK, Toth MJ, Cushman M, L'Hommedieu GD, Tchernof A, Tracy RP, Poehlman ET. Source: Fertility and Sterility. 2002 January; 77(1): 128-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779602&dopt=Abstract

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Menstrual-reproductive factors and age at natural menopause in Iran. Author(s): Ayatollahi SM, Ghaem H, Ayatollahi SA. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2003 March; 80(3): 311-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628535&dopt=Abstract

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Mental illness and menopause: a patient and family perspective. Author(s): Sajatovic M, Rosenthal MB, Plax MS, Meyer ML, Bingham CR. Source: J Gend Specif Med. 2003; 6(2): 31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814000&dopt=Abstract

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Methodological issues related to studies of lead mobilization during menopause. Author(s): Berkowitz GS, Moline JM, Todd AC. Source: Salud P'ublica De M'exico. 1999; 41 Suppl 2: S88-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850130&dopt=Abstract

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Midlife development and menopause in African American and Caucasian women. Author(s): Sampselle CM, Harris V, Harlow SD, Sowers M. Source: Health Care for Women International. 2002 June; 23(4): 351-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12148913&dopt=Abstract

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Migraine in a specialist menopause clinic. Author(s): MacGregor EA, Barnes D. Source: Climacteric : the Journal of the International Menopause Society. 1999 September; 2(3): 218-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910600&dopt=Abstract

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Migraine in the menopause. Author(s): Fettes I. Source: Neurology. 1999; 53(4 Suppl 1): S29-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487511&dopt=Abstract

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Migraine, menopause and hormonal replacement therapy. Author(s): Silberstein SD, de Lignieres B. Source: Cephalalgia : an International Journal of Headache. 2000 April; 20(3): 214-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997776&dopt=Abstract

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Modeling and simulation of pathways in menopause. Author(s): Tsavachidou D, Liebman MN. Source: Journal of the American Medical Informatics Association : Jamia. 2002 September-October; 9(5): 461-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223498&dopt=Abstract

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Models of intervention in menopause: proposal of a holistic or integral model. Author(s): Olazabal Ulacia JC, Garcia Paniagua R, Montero Luengo J, Garcia Gutierrez JF, Sendin Melguizo PP, Holgado Sanchez MA. Source: Menopause (New York, N.Y.). 1999 Fall; 6(3): 264-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10486798&dopt=Abstract

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Mood and the menopause. Author(s): Klein P, Versi E, Herzog A. Source: British Journal of Obstetrics and Gynaecology. 1999 January; 106(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10426252&dopt=Abstract

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Multisite quantitative ultrasound: precision, age- and menopause-related changes, fracture discrimination, and T-score equivalence with dual-energy X-ray absorptiometry. Author(s): Knapp KM, Blake GM, Spector TD, Fogelman I. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(6): 456-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446561&dopt=Abstract

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Natural menopause and ovarian toxicity associated with breast cancer therapy. Author(s): Knobf MT. Source: Oncology Nursing Forum. 1998 October; 25(9): 1519-30; Quiz 1531-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9802049&dopt=Abstract

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Natural options for menopause. Author(s): Norling S. Source: Minn Med. 1999 May; 82(5): 42-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10337138&dopt=Abstract

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Neuroendocrine influences and repercussions of the menopause. Author(s): Wise PM, Smith MJ, Dubal DB, Wilson ME, Krajnak KM, Rosewell KL. Source: Endocrine Reviews. 1999 June; 20(3): 243-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10368769&dopt=Abstract

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Neuroendocrine modulation of the “menopause”: insights into the aging brain. Author(s): Wise PM. Source: The American Journal of Physiology. 1999 December; 277(6 Pt 1): E965-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10600782&dopt=Abstract

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Neuropeptides, neurotransmitters, body weight, and menopause. Author(s): Brzezinski A, Benshushan A. Source: Menopause (New York, N.Y.). 2000 May-June; 7(3): 137-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10810956&dopt=Abstract

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Nonalcoholic compounds of wine: the phytoestrogen resveratrol and moderate red wine consumption during menopause. Author(s): Calabrese G. Source: Drugs Exp Clin Res. 1999; 25(2-3): 111-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10370872&dopt=Abstract

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Nonhuman primate models of menopause workshop. Author(s): Bellino FL, Wise PM. Source: Biology of Reproduction. 2003 January; 68(1): 10-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493689&dopt=Abstract

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Nonprimate animal models of menopause: workshop report. Author(s): Gorodeski GI. Source: Menopause (New York, N.Y.). 2000 January-February; 7(1): 1-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10646696&dopt=Abstract

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Nonprimate animal models of menopause: workshop report. Author(s): Bellino FL. Source: Menopause (New York, N.Y.). 2000 January-February; 7(1): 14-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10646699&dopt=Abstract

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Nulliparity and late menopause are associated with decreased cognitive decline. Author(s): McLay RN, Maki PM, Lyketsos CG. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Spring; 15(2): 161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724456&dopt=Abstract

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Number of years since menopause: spontaneous bone loss is dependent but response to hormone replacement therapy is independent. Author(s): Bjarnason NH, Alexandersen P, Christiansen C. Source: Bone. 2002 April; 30(4): 637-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934658&dopt=Abstract

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Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Author(s): Sorensen MB, Rosenfalck AM, Hojgaard L, Ottesen B. Source: Obesity Research. 2001 October; 9(10): 622-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595778&dopt=Abstract

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Older women's experience of the menopause. Author(s): Wright J. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 1998 August 12-18; 12(47): 46-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9752160&dopt=Abstract

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On call. My wife and I are both 62 and healthy. She started taking Prempro during her menopause eight years ago but has now decided to stop the hormones. I began taking DHEA five years ago, but I switched to AndroGel when my doctor gave me a prescription last year. Should I stay on AndroGel, go back to DHEA, or stop hormones? Author(s): Simon HB. Source: Harvard Men's Health Watch. 2003 January; 7(6): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543598&dopt=Abstract

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On mortality from ischemic heart disease in women with very late menopause. Author(s): Jacobsen BK, Heuch I, Kvale G. Source: Journal of Clinical Epidemiology. 2000 April; 53(4): 435-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10841665&dopt=Abstract

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On the role of menopause for sleep-endocrine alterations associated with major depression. Author(s): Antonijevic IA, Murck H, Frieboes RM, Uhr M, Steiger A. Source: Psychoneuroendocrinology. 2003 April; 28(3): 401-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573305&dopt=Abstract

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Onset of natural menopause in African American women. Author(s): Palmer JR, Rosenberg L, Wise LA, Horton NJ, Adams-Campbell LL. Source: American Journal of Public Health. 2003 February; 93(2): 299-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554590&dopt=Abstract

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Onset of natural menopause. Author(s): van Noord PA, Peeters PH, Grobbee DE, Dubas JS, te Velde E. Source: Journal of Clinical Epidemiology. 1999 December; 52(12): 1290-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580794&dopt=Abstract

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Oocyte apoptosis: prevention strategies, and implications for female aging and the menopause. Author(s): Tilly JL. Source: Annales D'endocrinologie. 2003 April; 64(2): 82-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773936&dopt=Abstract

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Optimal age for preventing osteoporosis after menopause depends on effects of stopping treatment. Author(s): Caulin F, Kanis JA, Johnell O, Oden A. Source: Bone. 2002 May; 30(5): 754-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996915&dopt=Abstract

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Oral bone loss associated with menopause. Author(s): Zachariasen RD. Source: J Gt Houst Dent Soc. 1999 August; 71(1): 19-21. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10686901&dopt=Abstract

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Oral contraceptive use in relation to age at menopause in the DOM cohort. Author(s): de Vries E, den Tonkelaar I, van Noord PA, van der Schouw YT, te Velde ER, Peeters PH. Source: Human Reproduction (Oxford, England). 2001 August; 16(8): 1657-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11473959&dopt=Abstract

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Oral manifestations and dental treatment in menopause. Author(s): Frutos R, Rodriguez S, Miralles-Jorda L, Machuca G. Source: Medicina Oral : Organo Oficial De La Sociedad Espanola De Medicina Oral Y De La Academia Iberoamericana De Patologia Y Medicina Bucal. 2002 January-February; 7(1): 26-30, 31-5. Review. English, Spanish. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788806&dopt=Abstract

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Oral symptoms at menopause--the role of hormone replacement therapy. Author(s): Tarkkila L, Linna M, Tiitinen A, Lindqvist C, Meurman JH. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001 September; 92(3): 276-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552144&dopt=Abstract

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Orally and transdermally replaced estradiol improves endothelial function equally in middle-aged women after surgical menopause. Author(s): Zegura B, Keber I, Sebestjen M, Borko E. Source: American Journal of Obstetrics and Gynecology. 2003 May; 188(5): 1291-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748500&dopt=Abstract

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Organochlorine exposure and age at natural menopause. Author(s): Cooper GS, Savitz DA, Millikan R, Chiu Kit T. Source: Epidemiology (Cambridge, Mass.). 2002 November; 13(6): 729-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410018&dopt=Abstract

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Orientation of the trabecular pattern of the distal radius around the menopause. Author(s): Geraets WG, Van der Stelt PF, Lips P, Elders PJ, Van Ginkel FC, Burger EH. Source: Journal of Biomechanics. 1997 April; 30(4): 363-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9075004&dopt=Abstract

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Osteoporosis and years since menopause. Author(s): Ide S, Hirota Y, Hotokebuchi T, Takasugi S, Sugioka Y, Hayabuchi H. Source: European Journal of Epidemiology. 1999 September; 15(8): 739-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10555618&dopt=Abstract

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Osteoporosis in relation to menopause. Author(s): Choo WL, Loh FH, Ng SC. Source: Ann Acad Med Singapore. 2002 January; 31(1): 30-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885493&dopt=Abstract

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Osteoporosis. Menopause and beyond. Author(s): MacLennan A. Source: Aust Fam Physician. 1997 February; 26(2): 123-5, 128-9, 131. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9046661&dopt=Abstract

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Ovarian autoimmunity: greater frequency of autoantibodies in premature menopause and unexplained infertility than in the general population. Author(s): Luborsky J, Llanes B, Davies S, Binor Z, Radwanska E, Pong R. Source: Clinical Immunology (Orlando, Fla.). 1999 March; 90(3): 368-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10075866&dopt=Abstract

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Ovaries, androgens and the menopause: practical applications. Author(s): Plouffe L Jr. Source: Semin Reprod Endocrinol. 1998; 16(2): 117-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9711676&dopt=Abstract

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P53 expression in spontaneous and estradiol-induced endometrial hyperplasia during menopause. Author(s): Maia H Jr, Maltez A, Athayde C, Coelho G, Coutinho EM. Source: Maturitas. 2003 March 28; 44(3): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648880&dopt=Abstract

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Paraurethral connective tissue in stress-incontinent women after menopause. Author(s): Falconer C, Ekman-Ordeberg G, Blomgren B, Johansson O, Ulmsten U, Westergren-Thorsson G, Malmstrom A. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1998 January; 77(1): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9492727&dopt=Abstract

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Patient profile 2: surgical menopause. Author(s): Sonder HM. Source: American Journal of Obstetrics and Gynecology. 1999 March; 180(3 Pt 2): S328. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10076174&dopt=Abstract

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Patients' understanding of risk: a qualitative study of decision-making about the menopause and hormone replacement therapy in general practice. Author(s): Walter FM, Britten N. Source: Family Practice. 2002 December; 19(6): 579-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429658&dopt=Abstract

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Pattern of bone loss in surgical menopause: a preliminary report. Author(s): Chittacharoen A, Theppisai U, Sirisriro R, Thanantaseth C. Source: J Med Assoc Thai. 1997 November; 80(11): 731-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9385771&dopt=Abstract

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Pelvic actinomycosis in menopause: a case report. Author(s): Cobellis L, Messalli EM, Pierno G. Source: Maturitas. 2001 July 25; 39(1): 79-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451624&dopt=Abstract

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Pelvic connective tissue resilience decreases with vaginal delivery, menopause and uterine prolapse. Author(s): Reay Jones NH, Healy JC, King LJ, Saini S, Shousha S, Allen-Mersh TG. Source: The British Journal of Surgery. 2003 April; 90(4): 466-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673750&dopt=Abstract

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Physical activity and weight gain and fat distribution changes with menopause: current evidence and research issues. Author(s): Astrup A. Source: Medicine and Science in Sports and Exercise. 1999 November; 31(11 Suppl): S564-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10593529&dopt=Abstract

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Physical and mental health: changes during menopause transition. Author(s): Mishra GD, Brown WJ, Dobson AJ. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2003 June; 12(4): 405-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797713&dopt=Abstract

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Physicians' perceptions of menopause and prescribing practices in Morocco. Author(s): Obermeyer CM, Sahel A, Hajji N, Schulein M. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2001 April; 73(1): 47-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336721&dopt=Abstract

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Physiologic aspects of natural and surgical menopause. Author(s): Bachmann G. Source: J Reprod Med. 2001 March; 46(3 Suppl): 307-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11310451&dopt=Abstract

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Phytoestrogens and the management of menopause. Author(s): Ramsey LA, Ross BS, Fischer RG. Source: Adv Nurse Pract. 1999 May; 7(5): 26-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10578731&dopt=Abstract

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Phytoestrogens and the menopause. Author(s): Eden J. Source: Baillieres Clin Endocrinol Metab. 1998 December; 12(4): 581-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10384814&dopt=Abstract

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Phyto-oestrogens get more attention at menopause meeting. Author(s): Newman L. Source: Lancet. 1999 October 2; 354(9185): 1184. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10513722&dopt=Abstract

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Pieter van Keep Memorial Lecture. Menopause--a modern perspective from a controversial history. Author(s): Utian WH. Source: Maturitas. 1997 March; 26(2): 73-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9089556&dopt=Abstract

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Plasma cholesterol esterification and transfer, the menopause, and hormone replacement therapy in women. Author(s): Lewis-Barned NJ, Sutherland WH, Walker RJ, Walker HL, De Jong SA, Edwards EA, Markham VH. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 October; 84(10): 3534-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10522991&dopt=Abstract

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Plasma cholesteryl ester fatty acid composition, insulin sensitivity, the menopause and hormone replacement therapy. Author(s): Lewis-Barned NJ, Sutherland WH, Walker RJ, de Jong SA, Walker HL, Edwards EA, Markham V, Goulding A. Source: The Journal of Endocrinology. 2000 June; 165(3): 649-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10828848&dopt=Abstract

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Polycystic ovary syndrome and implications for the menopause. Author(s): Norman RJ, McVeigh E. Source: Climacteric : the Journal of the International Menopause Society. 1999 June; 2(2): 141-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910667&dopt=Abstract

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Polycystic ovary syndrome, hyperthecosis and the menopause. Author(s): Rittmaster RS. Source: Clinical Endocrinology. 1997 February; 46(2): 129-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9135691&dopt=Abstract

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Population-based study of age at menopause and ultrasound assessed carotid atherosclerosis: The Tromso Study. Author(s): Joakimsen O, Bonaa KH, Stensland-Bugge E, Jacobsen BK. Source: Journal of Clinical Epidemiology. 2000 May; 53(5): 525-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10812326&dopt=Abstract

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Portraits of menopause in the mass media. Author(s): Gannon L, Stevens J. Source: Women Health. 1998; 27(3): 1-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9698634&dopt=Abstract

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Positive aspects of menopause: a qualitative study. Author(s): Hvas L. Source: Maturitas. 2001 July 25; 39(1): 11-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451616&dopt=Abstract

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Possibilities of sterility therapy in a patient with a premature menopause due to an Xchromosomal anomaly - a case report. Author(s): Nawroth F, Foth D, Stute P, Schmidt T, Romer T. Source: Maturitas. 2000 December 29; 37(2): 129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11137332&dopt=Abstract

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Postmenopausal estrogen use, type of menopause, and lens opacities: the Framingham studies. Author(s): Worzala K, Hiller R, Sperduto RD, Mutalik K, Murabito JM, Moskowitz M, D'Agostino RB, Wilson PW. Source: Archives of Internal Medicine. 2001 June 11; 161(11): 1448-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11386895&dopt=Abstract

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Post-menopause is the main risk factor for developing isolated pulmonary hypertension in systemic sclerosis. Author(s): Scorza R, Caronni M, Bazzi S, Nador F, Beretta L, Antonioli R, Origgi L, Ponti A, Marchini M, Vanoli M. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 238-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114278&dopt=Abstract

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Predictive factors of age at menopause in a large Australian twin study. Author(s): Do KA, Treloar SA, Pandeya N, Purdie D, Green AC, Heath AC, Martin NG. Source: Human Biology; an International Record of Research. 1998 December; 70(6): 1073-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9825597&dopt=Abstract

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Predictors of declining self-rated health during the transition to menopause. Author(s): Dennerstein L, Dudley EC, Guthrie JR. Source: Journal of Psychosomatic Research. 2003 February; 54(2): 147-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573736&dopt=Abstract

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Predictors of participation in health care at menopause. Author(s): Kroll J, Rothert M, Davidson WS 2nd, Schmitt N, Holmes-Rovner M, Padonu G, Reischl TM. Source: Health Communication. 2000; 12(4): 339-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063285&dopt=Abstract

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Premature menopause after cancer treatment. Author(s): Muscari Lin E, Aikin JL, Good BC. Source: Cancer Practice. 1999 May-June; 7(3): 114-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10352073&dopt=Abstract

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Premature menopause and psychological well-being. Author(s): Liao KL, Wood N, Conway GS. Source: Journal of Psychosomatic Obstetrics and Gynaecology. 2000 September; 21(3): 167-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11076338&dopt=Abstract

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Premature menopause and self-concept disjunctions. A case for crisis management. Author(s): Pasquali EA. Source: Journal of Psychosocial Nursing and Mental Health Services. 2002 September; 40(9): 20-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12235966&dopt=Abstract

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Premature menopause in a multi-ethnic population study of the menopause transition. Author(s): Luborsky JL, Meyer P, Sowers MF, Gold EB, Santoro N. Source: Human Reproduction (Oxford, England). 2003 January; 18(1): 199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525467&dopt=Abstract

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Premature menopause raises risks of fatal adrenal condition. Early diagnosis can lead to effective treatment for women. Author(s): Cockey CD. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2002 October-November; 6(5): 390-2, 394-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420381&dopt=Abstract

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Premature menopause. 'I feel like an alien'. Author(s): Farrell E. Source: Aust Fam Physician. 2002 May; 31(5): 419-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043544&dopt=Abstract

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Premature menopause: multiple disruptions between the woman's biological body experience and her lived body. Author(s): Boughton MA. Source: Journal of Advanced Nursing. 2002 March; 37(5): 423-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843980&dopt=Abstract

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Premature ovarian failure is not premature menopause. Author(s): Kalantaridou SN, Nelson LM. Source: Annals of the New York Academy of Sciences. 2000; 900: 393-402. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10818427&dopt=Abstract

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Premature ovarian failure: frequency and risk factors among women attending a network of menopause clinics in Italy. Author(s): Progetto Menopausa Italia Study Group. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 January; 110(1): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504937&dopt=Abstract

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Premenstrual syndrome and psychiatric morbidity at the menopause. Author(s): Novaes C, Almeida OP. Source: Journal of Psychosomatic Obstetrics and Gynaecology. 1999 March; 20(1): 56-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10212888&dopt=Abstract

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Preparation for menopause: prospective evaluation of a health education intervention for mid-aged women. Author(s): Liao KL, Hunter MS. Source: Maturitas. 1998 June 17; 29(3): 215-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9699192&dopt=Abstract

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Preprocessing histograms of age at menopause using the fast Fourier transform. Author(s): Greer W. Source: Maturitas. 2003 April 25; 44(4): 267-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697367&dopt=Abstract

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Prescribing of hormone therapy in menopause and postmenopause. Author(s): Hemminki E, Topo P. Source: Journal of Psychosomatic Obstetrics and Gynaecology. 1997 June; 18(2): 145-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9219111&dopt=Abstract

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Prevalence of climacteric symptoms according to years after menopause. Author(s): Sueblinvong T, Taechakraichana N, Phupong V. Source: J Med Assoc Thai. 2001 December; 84(12): 1681-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999814&dopt=Abstract

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Prevalence of sexual dysfunction in a cohort of middle-aged women: influences of menopause and hormone replacement therapy. Author(s): Castelo-Branco C, Blumel JE, Araya H, Riquelme R, Castro G, Haya J, Gramegna G. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 July; 23(4): 426-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881088&dopt=Abstract

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Profile of a menopause clinic in an urban population in Malaysia. Author(s): Damodaran P, Subramaniam R, Omar SZ, Nadkarni P, Paramsothy M. Source: Singapore Med J. 2000 September; 41(9): 431-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11193115&dopt=Abstract

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Progestins and menopause: epidemiological studies of risks of endometrial and breast cancer. Author(s): Pike MC, Ross RK. Source: Steroids. 2000 October-November; 65(10-11): 659-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108873&dopt=Abstract

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Progestins in the menopause. Author(s): Sitruk-Ware R. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1999 April-June; 69(1-6): 185-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10418992&dopt=Abstract

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Progestogens used in menopause. Side effects, mood and quality of life. Author(s): Sherwin BB. Source: J Reprod Med. 1999 February; 44(2 Suppl): 227-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392037&dopt=Abstract

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Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study. Author(s): Hak AE, Pols HA, van Hemert AM, Hofman A, Witteman JC. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 August; 20(8): 1926-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10938013&dopt=Abstract

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Prospective study of factors influencing the onset of natural menopause. Author(s): Kato I, Toniolo P, Akhmedkhanov A, Koenig KL, Shore R, ZeleniuchJacquotte A. Source: Journal of Clinical Epidemiology. 1998 December; 51(12): 1271-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10086819&dopt=Abstract

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Prospective study of the determinants of age at menopause. Author(s): Bromberger JT, Matthews KA, Kuller LH, Wing RR, Meilahn EN, Plantinga P. Source: American Journal of Epidemiology. 1997 January 15; 145(2): 124-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9006309&dopt=Abstract

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Psychologic distress and natural menopause: a multiethnic community study. Author(s): Bromberger JT, Meyer PM, Kravitz HM, Sommer B, Cordal A, Powell L, Ganz PA, Sutton-Tyrrell K. Source: American Journal of Public Health. 2001 September; 91(9): 1435-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527777&dopt=Abstract

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Psychological aspects of menopause management. Author(s): Deeks AA. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 17-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763510&dopt=Abstract

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Psychological consequences of surgical menopause. Author(s): Taylor M. Source: J Reprod Med. 2001 March; 46(3 Suppl): 317-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11304879&dopt=Abstract

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Psychological distress around menopause. Author(s): Becker D, Lomranz J, Pines A, Shmotkin D, Nitza E, BennAmitay G, Mester R. Source: Psychosomatics. 2001 May-June; 42(3): 252-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351115&dopt=Abstract

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Psychosexual effects of menopause: role of androgens. Author(s): Sarrel PM. Source: American Journal of Obstetrics and Gynecology. 1999 March; 180(3 Pt 2): S31924. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10076172&dopt=Abstract

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Psychosocial factors, attitude to menopause and symptoms in Swedish perimenopausal women. Author(s): Olofsson AS, Collins A. Source: Climacteric : the Journal of the International Menopause Society. 2000 March; 3(1): 33-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910608&dopt=Abstract

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Psychosocial, behavioral, and health factors related to menopause symptomatology. Author(s): Avis NE, Crawford SL, McKinlay SM. Source: Womens Health. 1997 Summer; 3(2): 103-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9332153&dopt=Abstract

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Pure Leydig cell tumour (hilus cell) of the ovary: a rare cause of virilization after menopause. Author(s): Baiocchi G, Manci N, Angeletti G, Celleno R, Fratini D, Gilardi G. Source: Gynecologic and Obstetric Investigation. 1997; 44(2): 141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9286731&dopt=Abstract

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Quality of life after the menopause: a population study. Author(s): Blumel JE, Castelo-Branco C, Binfa L, Gramegna G, Tacla X, Aracena B, Cumsille MA, Sanjuan A. Source: Maturitas. 2000 January 15; 34(1): 17-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10687878&dopt=Abstract

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Quality of life and hormone therapy in women before and after menopause. Author(s): Ekstrom H, Hovelius B. Source: Scandinavian Journal of Primary Health Care. 2000 June; 18(2): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10944068&dopt=Abstract

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Quality of life and menopause: the role of estrogen. Author(s): Freedman MA. Source: Journal of Women's Health (2002). 2002 October; 11(8): 703-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570037&dopt=Abstract

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Quantitative analysis of three-dimensional complexity and connectivity changes in trabecular microarchitecture in relation to aging, menopause, and inflammation. Author(s): Mawatari T, Miura H, Higaki H, Kurata K, Moro-oka T, Murakami T, Iwamoto Y. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 1999; 4(6): 431-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10664426&dopt=Abstract

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Race, menopause, health-related quality of life, and psychological well-being in obese women. Author(s): Laferrere B, Zhu S, Clarkson JR, Yoshioka MR, Krauskopf K, Thornton JC, PiSunyer FX. Source: Obesity Research. 2002 December; 10(12): 1270-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490671&dopt=Abstract

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Racial differences in menopause information and the experience of hot flashes. Author(s): Grisso JA, Freeman EW, Maurin E, Garcia-Espana B, Berlin JA. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 1999 February; 14(2): 98-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10051780&dopt=Abstract

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Racial differences in sex hormone levels in women approaching the transition to menopause. Author(s): Manson JM, Sammel MD, Freeman EW, Grisso JA. Source: Fertility and Sterility. 2001 February; 75(2): 297-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172830&dopt=Abstract

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Rapid changes of flow-mediated dilatation after surgical menopause. Author(s): Ohmichi M, Kanda Y, Hisamoto K, Morishige K, Takahashi K, Sawada K, Minekawa R, Tasaka K, Murata Y. Source: Maturitas. 2003 February 25; 44(2): 125-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590008&dopt=Abstract

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Reassuring the woman facing menopause: strategies and resources. Author(s): Cobb JO. Source: Patient Education and Counseling. 1998 March; 33(3): 281-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9731165&dopt=Abstract

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Regulation by human uterine cells of PBMC proliferation: influence of the phase of the menstrual cycle and menopause. Author(s): Prabhala RH, Fahey JV, Humphrey SL, Edkins RD, Stern JE, Wira CR. Source: Journal of Reproductive Immunology. 1998 October; 40(1): 25-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9862255&dopt=Abstract

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Relation of lifestyle factors to metacarpal bone mineral density was different depending on menstrual condition and years since menopause in Japanese women. Author(s): Ishikawa K, Ohta T, Hirano M, Yoshimoto K, Tanaka S, Inoue S. Source: European Journal of Clinical Nutrition. 2000 January; 54(1): 9-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694765&dopt=Abstract

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Relationship between diabetes mellitus, impaired glucose tolerance and age, menopause, pregnancy: a survey of 5153 women in Shenzhen. Author(s): Liu P, Li Y, Yu H. Source: Chin Med J (Engl). 1999 July; 112(7): 612-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11601254&dopt=Abstract

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Relationship between osteoarthritis of knee and menopause. Author(s): Nadkar MY, Samant RS, Vaidya SS, Borges NE. Source: J Assoc Physicians India. 1999 December; 47(12): 1161-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225216&dopt=Abstract

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Relationship between osteoarthritis of knee and menopause. Author(s): Mohan A. Source: J Assoc Physicians India. 2001 February; 49: 297-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225158&dopt=Abstract

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Relationship between psychosocial factors and health behaviours for women experiencing menopause. Author(s): Anderson D, Posner N. Source: International Journal of Nursing Practice. 2002 October; 8(5): 265-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225353&dopt=Abstract

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Relationship of blood and bone lead to menopause and bone mineral density among middle-age women in Mexico City. Author(s): Garrido Latorre F, Hernandez-Avila M, Tamayo Orozco J, Albores Medina CA, Aro A, Palazuelos E, Hu H. Source: Environmental Health Perspectives. 2003 April; 111(4): 631-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676627&dopt=Abstract

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Relationship of intra-abdominal adiposity and peripheral fat distribution to lipid metabolism in an island population in western Japan: gender differences and effect of menopause. Author(s): Manabe E, Aoyagi K, Tachibana H, Takemoto T. Source: The Tohoku Journal of Experimental Medicine. 1999 July; 188(3): 189-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10587011&dopt=Abstract

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Relationship of leptin concentration to gender, menopause, age, diabetes, and fat mass in African Americans. Author(s): Sumner AE, Falkner B, Kushner H, Considine RV. Source: Obesity Research. 1998 March; 6(2): 128-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9545019&dopt=Abstract

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Relationships of age, menopause and central obesity on cardiovascular disease risk factors in Chinese women. Author(s): Chang CJ, Wu CH, Yao WJ, Yang YC, Wu JS, Lu FH. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2000 December; 24(12): 1699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126227&dopt=Abstract

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Relative androgen excess and increased cardiovascular risk after menopause: a hypothesized relation. Author(s): Liu Y, Ding J, Bush TL, Longenecker JC, Nieto FJ, Golden SH, Szklo M. Source: American Journal of Epidemiology. 2001 September 15; 154(6): 489-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11549553&dopt=Abstract

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Relative contribution of aging and menopause to changes in lean and fat mass in segmental regions. Author(s): Douchi T, Yamamoto S, Yoshimitsu N, Andoh T, Matsuo T, Nagata Y. Source: Maturitas. 2002 August 30; 42(4): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12191853&dopt=Abstract

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Relevant results of the WHI study for the management of the menopause in Spain. Author(s): Palacios S, Calaf J, Cano A, Parrilla JJ; Spanish Menopause Society (AEEM). Source: Maturitas. 2003 January 30; 44(1): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568739&dopt=Abstract

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Reliability of reported age at menopause. Author(s): Hahn RA, Eaker E, Rolka H. Source: American Journal of Epidemiology. 1997 November 1; 146(9): 771-5. Erratum In: Am J Epidemiol 1999 January 15; 149(2): 201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9366625&dopt=Abstract

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Report on the 10th World Congress on the Menopause. 10-14 June 2002, Berlin, Germany. Author(s): Schneider HP. Source: Climacteric : the Journal of the International Menopause Society. 2002 September; 5(3): 219-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422899&dopt=Abstract

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Representations of menopause and their health care implications: a qualitative study. Author(s): Jones JB. Source: American Journal of Preventive Medicine. 1997 January-February; 13(1): 58-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9037343&dopt=Abstract

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Reproductive ageing and the menopause. Author(s): Finn CA. Source: Int J Dev Biol. 2001; 45(3 Spec No): 613-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417906&dopt=Abstract

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Reproductive surgery, menopause and breast cancer risk. Author(s): La Vecchia C. Source: European Journal of Cancer (Oxford, England : 1990). 1999 January; 35(1): 12-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211081&dopt=Abstract

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Resistance to glomerulosclerosis in B6 mice disappears after menopause. Author(s): Zheng F, Plati AR, Potier M, Schulman Y, Berho M, Banerjee A, Leclercq B, Zisman A, Striker LJ, Striker GE. Source: American Journal of Pathology. 2003 April; 162(4): 1339-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651625&dopt=Abstract

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Review of the International Position Paper on Women's Health and Menopause: a comprehensive approach. Author(s): Paoletti R, Wenger NK. Source: Circulation. 2003 March 11; 107(9): 1336-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628957&dopt=Abstract

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Risk factors of early menopause in two generations of gainfully employed French women. Author(s): Cassou B, Derriennic F, Monfort C, Dell'Accio P, Touranchet A. Source: Maturitas. 1997 April; 26(3): 165-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9147348&dopt=Abstract

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Risk of coronary heart disease in women after menopause. Author(s): Bulliyya G. Source: J Indian Med Assoc. 2001 September; 99(9): 478-80, 482. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018552&dopt=Abstract

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Risk of low bone density in women attending menopause clinics in Italy. Author(s): Progetto Menopausa Italia Study Group. Source: Maturitas. 2002 June 25; 42(2): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065169&dopt=Abstract

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Risk of menopause during the first year after breast cancer diagnosis. Author(s): Goodwin PJ, Ennis M, Pritchard KI, Trudeau M, Hood N. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 August; 17(8): 2365-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10561298&dopt=Abstract

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Role of androgens in surgical menopause. Author(s): Gelfand MM. Source: American Journal of Obstetrics and Gynecology. 1999 March; 180(3 Pt 2): S325-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10076173&dopt=Abstract

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Role of progestogen in hormone therapy for postmenopausal women: position statement of The North American Menopause Society. Author(s): North American Menopause Society. Source: Menopause (New York, N.Y.). 2003 March-April; 10(2): 113-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627037&dopt=Abstract

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Roundtable discussion.. are MCOs implementing programs to meet the challenges of baby-boomer women entering menopause? Author(s): Roglieri J, Joyce H, Tepper D, Harwood P, Kovak K, Klitzner T, Miller S, Strauss W, Forte H, Cherney B, Whittlesey D, Keitel C, Epstein LG. Source: Manag Care Interface. 2000; Suppl A: 32-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10788019&dopt=Abstract

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Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause. Author(s): Takahashi K, Okada M, Ozaki T, Kurioka H, Manabe A, Kanasaki H, Miyazaki K. Source: Human Reproduction (Oxford, England). 2000 May; 15(5): 1028-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10783346&dopt=Abstract

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Sarcopenia and muscle function during menopause and hormone-replacement therapy. Author(s): Dionne IJ, Kinaman KA, Poehlman ET. Source: J Nutr Health Aging. 2000; 4(3): 156-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936902&dopt=Abstract

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Screening for hypothyroidism at a menopause clinic. Author(s): Suchartwatnachai C, Thepppisai U, Jirapinyo M. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 April; 77(1): 39-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929657&dopt=Abstract

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Secular trend and intrapopulational variation in age at menopause in Spanish women. Author(s): Varea C, Bernis C, Montero P, Arias S, Barroso A, Gonzalez B. Source: Journal of Biosocial Science. 2000 July; 32(3): 383-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979231&dopt=Abstract

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Secular trends in menopause age. Author(s): Flint MP. Source: Journal of Psychosomatic Obstetrics and Gynaecology. 1997 June; 18(2): 65-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9219101&dopt=Abstract

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Self-awareness during the menopause. Author(s): Bloch A. Source: Maturitas. 2002 January 30; 41(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809344&dopt=Abstract

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Self-reported sexual symptoms in women attending menopause clinics. Author(s): Nappi RE, Verde JB, Polatti F, Genazzani AR, Zara C. Source: Gynecologic and Obstetric Investigation. 2002; 53(3): 181-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12053104&dopt=Abstract

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Semantics, menopause-related terminology, and the STRAW reproductive aging staging system. Author(s): Utian WH. Source: Menopause (New York, N.Y.). 2001 November-December; 8(6): 398-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723411&dopt=Abstract

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Sensitive skin at menopause; dew point and electrometric properties of the stratum corneum. Author(s): Paquet F, Pierard-Franchimont C, Fumal I, Goffin V, Paye M, Pierard GE. Source: Maturitas. 1998 January 12; 28(3): 221-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9571597&dopt=Abstract

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Serum inhibin A, inhibin B, and pro-alphaC levels are altered after surgically or pharmacologically induced menopause. Author(s): Cobellis L, Luisi S, Pezzani I, Reis FM, De Leo V, Petraglia F. Source: Fertility and Sterility. 2002 April; 77(4): 745-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937127&dopt=Abstract

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Serum inhibins, estradiol, progesterone and FSH in surgical menopause: a demonstration of ovarian pituitary feedback loop in women. Author(s): Muttukrishna S, Sharma S, Barlow DH, Ledger W, Groome N, Sathanandan M. Source: Human Reproduction (Oxford, England). 2002 October; 17(10): 2535-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351524&dopt=Abstract

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Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade past menopause. Author(s): Scheidt-Nave C, Bismar H, Leidig-Bruckner G, Woitge H, Seibel MJ, Ziegler R, Pfeilschifter J. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 May; 86(5): 2032-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344203&dopt=Abstract

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Serum interleukin-6, soluble interleukin-6 receptor and soluble gp130 exhibit different patterns of age- and menopause-related changes. Author(s): Giuliani N, Sansoni P, Girasole G, Vescovini R, Passeri G, Passeri M, Pedrazzoni M. Source: Experimental Gerontology. 2001 March; 36(3): 547-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11250125&dopt=Abstract

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Serum ionized magnesium and calcium in women after menopause: inverse relation of estrogen with ionized magnesium. Author(s): Muneyyirci-Delale O, Nacharaju VL, Dalloul M, Altura BM, Altura BT. Source: Fertility and Sterility. 1999 May; 71(5): 869-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10231048&dopt=Abstract

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Sex steroids and sleep: sleep disturbances in menopause. Author(s): Polo-Kantola P. Source: Annales D'endocrinologie. 2003 April; 64(2): 152-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773953&dopt=Abstract

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Sexual desire. Menopause and its psychological impact. Author(s): Deeks A. Source: Aust Fam Physician. 2002 May; 31(5): 433-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043547&dopt=Abstract

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Sexual function in menopause and postmenopause. Author(s): Nachtigall LE. Source: Curr Ther Endocrinol Metab. 1997; 6: 632-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9174820&dopt=Abstract

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Sexually and well-being in early menopause. Effect of transdermal estradiol therapy. Author(s): Rigano A, Rigano M, Cancellieri F, Pulle C. Source: Panminerva Medica. 2001 June; 43(2): 115-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449182&dopt=Abstract

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Should women with premature menopause be screened for FMR-1 mutations? Author(s): Taylor AE. Source: Menopause (New York, N.Y.). 2001 Summer; 8(2): 81-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256878&dopt=Abstract

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Sleep apnea in menopause. Author(s): Regestein QR. Source: Menopause (New York, N.Y.). 1999 Fall; 6(3): 186-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10486786&dopt=Abstract

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Sleep disruption and mood changes associated with menopause. Author(s): Baker A, Simpson S, Dawson D. Source: Journal of Psychosomatic Research. 1997 October; 43(4): 359-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9330235&dopt=Abstract

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Sleep disturbance in menopause. Author(s): Shaver JL, Zenk SN. Source: Journal of Women's Health & Gender-Based Medicine. 2000 March; 9(2): 109-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10746514&dopt=Abstract

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Sleep in menopause: differential effects of two forms of hormone replacement therapy. Author(s): Montplaisir J, Lorrain J, Denesle R, Petit D. Source: Menopause (New York, N.Y.). 2001 January-February; 8(1): 10-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11201509&dopt=Abstract

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Sleep in women across the life cycle from adulthood through menopause. Author(s): Moline ML, Broch L, Zak R, Gross V. Source: Sleep Medicine Reviews. 2003 April; 7(2): 155-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628216&dopt=Abstract

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Small low-density lipoprotein particles in women with natural or surgically induced menopause. Author(s): Ikenoue N, Wakatsuki A, Okatani Y. Source: Obstetrics and Gynecology. 1999 April; 93(4): 566-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10214834&dopt=Abstract

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Smoking and menopause. Author(s): Chiechi LM, Ferreri R, Granieri M, Lobascio A, Bianco G, Berardesca C, Loizzi P. Source: Clin Exp Obstet Gynecol. 1997; 24(1): 26-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9107452&dopt=Abstract

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Smoking cessation, weight gain, and changes in cardiovascular risk factors during menopause: the Healthy Women Study. Author(s): Burnette MM, Meilahn E, Wing RR, Kuller LH. Source: American Journal of Public Health. 1998 January; 88(1): 93-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9584041&dopt=Abstract

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So what's a woman to do about menopause? Author(s): Miller CA. Source: Geriatric Nursing (New York, N.Y.). 2003 May-June; 24(3): 190-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813441&dopt=Abstract

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Social and biological predictors of early menopause: a model for premature aging. Author(s): Nilsson P, Moller L, Koster A, Hollnagel H. Source: Journal of Internal Medicine. 1997 October; 242(4): 299-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9366808&dopt=Abstract

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Sociodemographic and clinical factors associated with HRT use in women attending menopause clinics in Italy. Author(s): Pansini F, Bacchi Modena AB, de Aloysio D, Gambacciani M, Meschia M, Parazzini F, Sciacchitano G, di Micco R, Peruzzi E, Maiocchi G; ICARUS Study Group. Source: Climacteric : the Journal of the International Menopause Society. 2000 December; 3(4): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910583&dopt=Abstract

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Statins and menopause. Author(s): Moghadasian MH. Source: Drugs. 2002; 62(17): 2421-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421100&dopt=Abstract

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Statistical techniques for the analysis of change in longitudinal studies of the menopause. Author(s): Lehert P, Dennerstein L. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 July; 81(7): 581-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190831&dopt=Abstract

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Stiffness index of the calcaneus measured by quantitative ultrasound and menopause among Japanese women: The Hizen-Oshima Study. Author(s): Yoshimi I, Aoyagi K, Okano K, Yahata Y, Kusano Y, Moji K, Tahara Y, Takemoto T. Source: The Tohoku Journal of Experimental Medicine. 2001 October; 195(2): 93-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846213&dopt=Abstract

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Strategies for effectively addressing women's concerns about the menopause and HRT. Author(s): Graziottin A. Source: Maturitas. 1999 November; 33 Suppl 1: S15-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10661611&dopt=Abstract

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Subcutaneous adipose tissue metabolism at menopause: importance of body fatness and regional fat distribution. Author(s): Mauriege P, Imbeault P, Prud'Homme D, Tremblay A, Nadeau A, Despres JP. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 July; 85(7): 2446-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10902792&dopt=Abstract

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Symptom reporting around the menopause in Beirut, Lebanon. Author(s): Obermeyer CM, Ghorayeb F, Reynolds R. Source: Maturitas. 1999 December 15; 33(3): 249-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10656503&dopt=Abstract

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Targeting of hormone replacement therapy immediately after menopause. Author(s): Johnell O, Kanis JA, Oden A, Redlund-Johnell I, Hasserius R, Sernbo I, Caulin F. Source: Bone. 2001 April; 28(4): 440-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336926&dopt=Abstract

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Testosterone “fix”: youth or consequences? Should we treat “male menopause”? Author(s): Utiger RD. Source: Health News. 2003 April; 9(4): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710389&dopt=Abstract

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The 1944-1945 Dutch famine and age at natural menopause--the value and validity of individual exposure assessment. Author(s): Elias SG, Van Noord PA, Peeters PH, Den Tonkelaar I, Grobbee DE. Source: Iarc Sci Publ. 2002; 156: 311-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484195&dopt=Abstract

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The association of menopause and physical functioning in women at midlife. Author(s): Sowers M, Pope S, Welch G, Sternfeld B, Albrecht G. Source: Journal of the American Geriatrics Society. 2001 November; 49(11): 1485-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890587&dopt=Abstract

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The biology, medical management, and podiatric implications of menopause. Author(s): Friedlander AH, Jones LJ. Source: Journal of the American Podiatric Medical Association. 2002 September; 92(8): 437-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237264&dopt=Abstract

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The contribution of menopause to changes in body-fat distribution. Author(s): Ijuin H, Douchi T, Oki T, Maruta K, Nagata Y. Source: The Journal of Obstetrics and Gynaecology Research. 1999 October; 25(5): 36772. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10533334&dopt=Abstract

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The effect of menopause and perimenopause on the course of epilepsy. Author(s): Harden CL, Pulver MC, Ravdin L, Jacobs AR. Source: Epilepsia. 1999 October; 40(10): 1402-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10528936&dopt=Abstract

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The effect of menopause on blood lipid and lipoprotein levels. The Icarus Study Group. Author(s): de Aloysio D, Gambacciani M, Meschia M, Pansini F, Bacchi Modena A, Bolis PF, Massobrio M, Maiocchi G, Peruzzi E. Source: Atherosclerosis. 1999 November 1; 147(1): 147-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10525136&dopt=Abstract

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The effect of menopause on the relation between weight gain and mortality among women. Author(s): Singh PN, Haddad E, Knutsen SF, Fraser GE. Source: Menopause (New York, N.Y.). 2001 September-October; 8(5): 314-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528356&dopt=Abstract

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The effect of the menopause on prolactin levels in patients with hyperprolactinaemia. Author(s): Karunakaran S, Page RC, Wass JA. Source: Clinical Endocrinology. 2001 March; 54(3): 295-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11298080&dopt=Abstract

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The effects of body mass index on age at menopause. Author(s): Akahoshi M, Soda M, Nakashima E, Tominaga T, Ichimaru S, Seto S, Yano K. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2002 July; 26(7): 961-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12080450&dopt=Abstract

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The efficacy of hormone assays in the differential diagnosis of amenorrhea and menopause. Author(s): Chiecchio A, Malvano R, Vignati G. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2000 October; 38(10): 971-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11140631&dopt=Abstract

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The emergence of the metabolic syndrome with menopause. Author(s): Carr MC. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2404-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788835&dopt=Abstract

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The endocrine transition around menopause--a five years prospective study with profiles of gonadotropines, estrogens, androgens and SHBG among healthy women. Author(s): Overlie I, Moen MH, Morkrid L, Skjaeraasen JS, Holte A. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1999 August; 78(7): 642-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10422913&dopt=Abstract

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The endocrinology of gonadal involution: menopause and andropause. Author(s): Lamberts SW. Source: Annales D'endocrinologie. 2003 April; 64(2): 77-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773935&dopt=Abstract

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The endocrinology of the menopause. Author(s): Burger HG. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1999 April-June; 69(1-6): 31-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10418978&dopt=Abstract

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The evolution of menopause and human life span. Author(s): Perls TT, Fretts RC. Source: Annals of Human Biology. 2001 May-June; 28(3): 237-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393331&dopt=Abstract

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The female menopause--now and in the millennium: new treatment options for a better quality of life. Author(s): Cefalu CA, Fontenot C. Source: Compr Ther. 2001 Summer; 27(2): 95-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430265&dopt=Abstract

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The greater impact of menopause on ER- than ER+ breast cancer incidence: a possible explanation (United States). Author(s): Tarone RE, Chu KC. Source: Cancer Causes & Control : Ccc. 2002 February; 13(1): 7-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11899120&dopt=Abstract

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The health-promoting behaviors and attitude towards menopause and hormone replacement therapy among women on dialysis. Author(s): Winkler J, Yogev Y, Nahum R, Blumberg G, Fisher M, Kaplan B. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 October; 16(5): 349-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587527&dopt=Abstract

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The hormone conundrum. A major study concludes that menopause drugs are perilous. Now what? Author(s): Spake A. Source: U.S. News & World Report. 2002 July 22; 133(3): 36-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149861&dopt=Abstract

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The idiopathic forms of premature menopause and early menopause show the same genetic pattern. Author(s): Tibiletti MG, Testa G, Vegetti W, Alagna F, Taborelli M, Dalpra L, Bolis PF, Crosignani PG. Source: Human Reproduction (Oxford, England). 1999 November; 14(11): 2731-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10548611&dopt=Abstract

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The impact of chronic estrogen deprivation on immunologic parameters in the ovariectomized rhesus monkey (Macaca mulatta) model of menopause. Author(s): Keller ET, Zhang J, Yao Z, Qi Y. Source: Journal of Reproductive Immunology. 2001 April; 50(1): 41-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254940&dopt=Abstract

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The impact of hormonal therapy for infertility on the age at menopause. Author(s): Pines A, Shapira I, Mijatovic V, Margalioth EJ, Frenkel Y. Source: Maturitas. 2002 April 25; 41(4): 283-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034515&dopt=Abstract

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The impact of pregnancy and menopause on CD4 lymphocyte counts in HIV-infected women. Author(s): van Benthem BH, Vernazza P, Coutinho RA, Prins M; European Study on the Natural History of HIV Infection in Women and the Swiss HIV Cohort Study. Source: Aids (London, England). 2002 April 12; 16(6): 919-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11919494&dopt=Abstract

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The impact of years since menopause on the development of impaired glucose tolerance. Author(s): Wu SI, Chou P, Tsai ST. Source: Journal of Clinical Epidemiology. 2001 February; 54(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166525&dopt=Abstract

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The impact on sexual functioning of chemotherapy-induced menopause in women with breast cancer. Author(s): Rogers M, Kristjanson LJ. Source: Cancer Nursing. 2002 February; 25(1): 57-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838721&dopt=Abstract

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The influence of age on gender differences in depression: further population-based evidence on the relationship between menopause and the sex difference in depression. Author(s): Cairney J, Wade TJ. Source: Social Psychiatry and Psychiatric Epidemiology. 2002 September; 37(9): 401-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242615&dopt=Abstract

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The influence of apo E phenotypes on the plasma triglycerides response to hormonal replacement therapy during the menopause. Author(s): Tolosa M, Peiro S, Real JT, Cano A, Ascaso JF, Carmena R. Source: Maturitas. 2001 November 30; 40(2): 173-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716996&dopt=Abstract

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The influence of menopause and body mass index on serum leptin concentrations. Author(s): Hadji P, Hars O, Bock K, Sturm G, Bauer T, Emons G, Schulz KD. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2000 July; 143(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870031&dopt=Abstract

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The International Menopause Society menopause-related terminology definitions. Author(s): Utian WH. Source: Climacteric : the Journal of the International Menopause Society. 1999 December; 2(4): 284-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11915855&dopt=Abstract

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The male menopause and mood: testosterone decline and depression in the aging male--is there a link? Author(s): Margolese HC. Source: Journal of Geriatric Psychiatry and Neurology. 2000 Summer; 13(2): 93-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10912731&dopt=Abstract

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The male menopause: possible causes, symptoms and treatment. Author(s): Peate I. Source: British Journal of Nursing (Mark Allen Publishing). 2003 January 23-February 12; 12(2): 80-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574711&dopt=Abstract

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The medicalization of female fertility--points of significance for the study of menopause. Author(s): Sievert LL. Source: Coll Antropol. 2003 June; 27(1): 67-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974134&dopt=Abstract

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The medicalization of menopause: critique and consequences. Author(s): Meyer VF. Source: International Journal of Health Services : Planning, Administration, Evaluation. 2001; 31(4): 769-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809008&dopt=Abstract

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The medicalization of menopause: implications for recruitment of study participants. Author(s): Leidy LE, Canali C, Callahan WE. Source: Menopause (New York, N.Y.). 2000 May-June; 7(3): 193-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10810965&dopt=Abstract

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The menopause and bladder weight. Author(s): Aygen EM, Ekmekcioglu O, Basbug M. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 1999; 10(5): 316-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10543340&dopt=Abstract

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The menopause and HRT. Hormone replacement therapy, cardiovascular and cerebrovascular disease. Author(s): Teede HJ. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 73-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763513&dopt=Abstract

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The menopause and HRT. HRT and cognitive decline. Author(s): Maki P, Hogervorst E. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 105-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763515&dopt=Abstract

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The menopause and HRT. Prevention and management of osteoporosis. Author(s): McClung MR. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 53-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763512&dopt=Abstract

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The menopause and HRT. Urogenital effects of hormone therapy. Author(s): Robinson D, Cardozo L. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 91-104. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763514&dopt=Abstract

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The menopause and its treatment in perspective. Author(s): Al-Azzawi F. Source: Postgraduate Medical Journal. 2001 May; 77(907): 292-304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320271&dopt=Abstract

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The 'menopause' and the aging brain: causes and repercussions of hypoestrogenicity. Author(s): Wise PM. Source: Biogerontology. 2001; 2(2): 113-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708377&dopt=Abstract

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The menopause experience: a woman's perspective. Author(s): George SA. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 2002 January-February; 31(1): 77-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843022&dopt=Abstract

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The menopause in Europe. Author(s): Rozenberg S, Fellemans C, Kroll M, Vandromme J. Source: Int J Fertil Womens Med. 2000 March-April; 45(2): 182-9. Review. Erratum In: Int J Fertil Womens Med 2000 July-August; 45(4): 296. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10831188&dopt=Abstract

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The Menopause Rating Scale (MRS): comparison with Kupperman index and qualityof-life scale SF-36. Author(s): Schneider HP, Heinemann LA, Rosemeier HP, Potthoff P, Behre HM. Source: Climacteric : the Journal of the International Menopause Society. 2000 March; 3(1): 50-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910610&dopt=Abstract

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The Menopause Rating Scale (MRS): reliability of scores of menopausal complaints. Author(s): Schneider HP, Heinemann LA, Rosemeier HP, Potthoff P, Behre HM. Source: Climacteric : the Journal of the International Menopause Society. 2000 March; 3(1): 59-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910611&dopt=Abstract

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The menopause transition and the aging process: a population perspective. Author(s): Sowers MF. Source: Aging (Milano). 2000 April; 12(2): 85-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10902050&dopt=Abstract

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The menopause transition: an update. Author(s): Santoro N. Source: Human Reproduction Update. 2002 March-April; 8(2): 155-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099630&dopt=Abstract

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The menopause, hormone replacement therapy and breast cancer. Author(s): Marsden J. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 December; 83(1-5): 123-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650709&dopt=Abstract

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The Middle Years Group: a holistic approach to the management of the menopause in primary care. Author(s): Jones RC, Keene M, Greene F. Source: Maturitas. 1999 October 24; 33(2): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10597872&dopt=Abstract

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The mysteries of menopause. Author(s): Healy B. Source: U.S. News & World Report. 2002 November 18; 133(19): 38-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501473&dopt=Abstract

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The North American Menopause Society 1998 menopause survey: Part II. Counseling about hormone replacement therapy: association with socioeconomic status and access to medical care. Author(s): Ettinger B, Woods NF, Barrett-Connor E, Pressman A. Source: Menopause (New York, N.Y.). 2000 May-June; 7(3): 143-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10810958&dopt=Abstract

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The perception of menopause among women in Taiwan. Author(s): Pan HA, Wu MH, Hsu CC, Yao BL, Huang KE. Source: Maturitas. 2002 April 25; 41(4): 269-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034513&dopt=Abstract

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The perceptions of menopause of African-American and white women and affect on willingness to participate in a HRT clinical trial. Author(s): Strickland OL, Dunbar SB. Source: J Natl Black Nurses Assoc. 2000 January; 11(1): 43-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854952&dopt=Abstract

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The physiology, medical management and oral implications of menopause. Author(s): Friedlander AH. Source: The Journal of the American Dental Association. 2002 January; 133(1): 73-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11811747&dopt=Abstract

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The psychosocial meaning of menopause: women's experiences. Author(s): Walter CA. Source: J Women Aging. 2000; 12(3-4): 117-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11151348&dopt=Abstract

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The relationship between the duration of menopause and lower urinary tract symptoms in women aged 40 to 59. Author(s): Aygen E, Ekmekcioglu O, Serin S. Source: Int J Fertil Womens Med. 2001 January-February; 46(1): 16-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11294616&dopt=Abstract

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The relationships between the degree of beta-isomerization of type I collagen degradation products in the urine and aging, menopause and osteoporosis with fractures. Author(s): Hoshino H, Takahashi M, Kushida K, Ohishi T, Inoue T. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1999; 9(5): 405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10550459&dopt=Abstract

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The rising number of underfoot accidents after the menopause causes both fractures and non-fracture injuries. Author(s): Davies JC, Manning DP, Kemp GJ, Frostick SP. Source: Qjm : Monthly Journal of the Association of Physicians. 2001 December; 94(12): 699-707. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744791&dopt=Abstract

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The risk of premature menopause induced by chemotherapy for early breast cancer. Author(s): Lower EE, Blau R, Gazder P, Tummala R. Source: Journal of Women's Health & Gender-Based Medicine. 1999 September; 8(7): 949-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10534297&dopt=Abstract

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The role of calcium in peri- and postmenopausal women: consensus opinion of The North American Menopause Society. Author(s): North American Menopause Society. Source: Menopause (New York, N.Y.). 2001 Summer; 8(2): 84-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256879&dopt=Abstract

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The role of genetic factors in age at natural menopause. Author(s): de Bruin JP, Bovenhuis H, van Noord PA, Pearson PL, van Arendonk JA, te Velde ER, Kuurman WW, Dorland M. Source: Human Reproduction (Oxford, England). 2001 September; 16(9): 2014-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527915&dopt=Abstract

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The roles of gender, the menopause and hormone replacement on cardiovascular function. Author(s): Hayward CS, Kelly RP, Collins P. Source: Cardiovascular Research. 2000 April; 46(1): 28-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10727651&dopt=Abstract

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The use of androgens in menopause. Author(s): Hoeger KM, Guzick DS. Source: Clinical Obstetrics and Gynecology. 1999 December; 42(4): 883-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10572701&dopt=Abstract

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The Utian Quality of Life (UQOL) Scale: development and validation of an instrument to quantify quality of life through and beyond menopause. Author(s): Utian WH, Janata JW, Kingsberg SA, Schluchter M, Hamilton JC. Source: Menopause (New York, N.Y.). 2002 November-December; 9(6): 402-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439099&dopt=Abstract

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The view of The International Menopause Society on the Women's Health Initiative. Author(s): Schneider HP; Executive Committee of the IMS. Source: Climacteric : the Journal of the International Menopause Society. 2002 September; 5(3): 211-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419078&dopt=Abstract

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There's more to midlife than menopause. Author(s): Montgomery P, Murkies A, Lew S. Source: Aust Fam Physician. 2001 July; 30(7): 632. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558191&dopt=Abstract

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Treatment of CIN after menopause. Author(s): Boulanger JC, Gondry J, Verhoest P, Capsie C, Najas S. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2001 April; 95(2): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301164&dopt=Abstract

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Treatment of menopause: recommendations for hormonal and non-hormonal therapy. Author(s): Johnson K. Source: J Okla State Med Assoc. 2003 March; 96(3): 140-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688227&dopt=Abstract

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Trimegestone: expanding therapeutic choices for the treatment of the menopause. Author(s): Wahab M, Al-Azzawi F. Source: Expert Opinion on Investigational Drugs. 2001 September; 10(9): 1737-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772282&dopt=Abstract

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Trisomic pregnancy and earlier age at menopause. Author(s): Kline J, Kinney A, Levin B, Warburton D. Source: American Journal of Human Genetics. 2000 August; 67(2): 395-404. Epub 2000 June 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10873791&dopt=Abstract

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Understanding risk: women's perceived risk of menopause-related disease and the value they place on preventive hormone replacement therapy. Author(s): Ballard K. Source: Family Practice. 2002 December; 19(6): 591-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429660&dopt=Abstract

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Understanding the physiological and functional consequences of menopause: the PROSALMEN study. PROgetto SALute MENopausa. Author(s): Bandinelli S, Lauretani F, Benvenuti E, Corsi A, De Marco MF, Bartali B, Ruotolo G, Miniati B, Macchi C, Russo CR, Guralnik JM, Ferrucci L. Source: Aging Clin Exp Res. 2002 June; 14(3): 170-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387523&dopt=Abstract

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Urinary incontinence and menopause: an evidence-based treatment approach. Author(s): Hendrix SL. Source: Disease-A-Month : Dm. 2002 October; 48(10): 622-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562050&dopt=Abstract

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Urinary problems around the menopause; emotional and psychological consequences; can we help our patients to cope with them? Author(s): Lachowsky M. Source: Maturitas. 2000 January; 34 Suppl 1: S25-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10759061&dopt=Abstract

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Urogenital and vasomotor symptoms in relation to menopausal status and the use of hormone replacement therapy (HRT) in healthy women during transition to menopause. Author(s): Larson B, Collins A, Landgren BM. Source: Maturitas. 1997 December 15; 28(2): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9522318&dopt=Abstract

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Urogenital prolapse and atrophy at menopause: a prevalence study. Author(s): Versi E, Harvey MA, Cardozo L, Brincat M, Studd JW. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 2001; 12(2): 107-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11374507&dopt=Abstract

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Use of hormonal therapy for menopause in nine European countries. Author(s): Banks E, Barnes I, Baker K, Key TJ; EPIC Working Group on Reproductive and Hormonal Factors. Source: Iarc Sci Publ. 2002; 156: 301-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484192&dopt=Abstract

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Use of hormone replacement therapy: women's representations of menopause and beauty care practices. Author(s): Fauconnier A, Ringa V, Delanoe D, Falissard B, Breart G. Source: Maturitas. 2000 June 30; 35(3): 215-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936738&dopt=Abstract

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Usefulness of HMG-CoA reductase inhibitor in Japanese hyperlipidemic women within seven years of menopause. Author(s): Ohta H, Masuda A, Fuyuki T, Sugimoto I, Suda Y, Makita K, Takamatsu K, Horiguchi F, Nozawa S. Source: Hormone Research. 2000; 53(3): 120-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11044791&dopt=Abstract

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Uterine amyloidosis in menopause. Author(s): Jongen VH, Grond AJ, van Veelen H, Santema JG. Source: British Journal of Obstetrics and Gynaecology. 1998 March; 105(3): 362-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9533002&dopt=Abstract

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Vaginal progesterone in menopause: Crinone 4% in cyclical and constant combined regimens. Author(s): de Ziegler D, Ferriani R, Moraes LA, Bulletti C. Source: Human Reproduction (Oxford, England). 2000 June; 15 Suppl 1: 149-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10928426&dopt=Abstract

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Vaginal ring hormone delivery systems in contraception and menopause. Author(s): Ballagh SA. Source: Clinical Obstetrics and Gynecology. 2001 March; 44(1): 106-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219238&dopt=Abstract

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Vaginal-cervical epithelial permeability decreases after menopause. Author(s): Gorodeski GI. Source: Fertility and Sterility. 2001 October; 76(4): 753-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591410&dopt=Abstract

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Validation of Italian version of the Women's Health Questionnaire: assessment of quality of life of women from the general population and those attending menopause centers. Author(s): Genazzani AR, Nicolucci A, Campagnoli C, Crosignani P, Nappi C, Serra GB, Bottiglioni E, Cianci A, De Aloysio D, Sarti CD, Gambacciani M, Monteleone P, Ciaponi M, Genazzani AD, Guaschino S, Palumbo G, Petraglia F, Schonauer S, Volpe A, Coronel GA, Di Paolantonio T, Nagni M, Tempesta A; Progetto Donna Qualita della Vita Working Group Novo Nordisk Italia. Source: Climacteric : the Journal of the International Menopause Society. 2002 March; 5(1): 70-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11974561&dopt=Abstract

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Validity and reproducibility of self-reported age at menopause in women participating in the DOM-project. Author(s): den Tonkelaar I. Source: Maturitas. 1997 June; 27(2): 117-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9255746&dopt=Abstract

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Vascular endothelial growth factor A (VEGF-A) mRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions. Author(s): Greb RR, Maier I, Wallwiener D, Kiesel L. Source: British Journal of Cancer. 1999 September; 81(2): 225-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10496346&dopt=Abstract

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Visual function in menopause: the role of hormone replacement therapy. Author(s): Guaschino S, Grimaldi E, Sartore A, Mugittu R, Mangino F, Bortoli P, Pensiero S, Vinciguerra A, Perissutti P. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544677&dopt=Abstract

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Vulvar problems in elderly women. Don't assume that menopause is the culprit. Author(s): Barhan S, Ezenagu L. Source: Postgraduate Medicine. 1997 September; 102(3): 121-5, 131-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9300022&dopt=Abstract

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Weight change in relation to natural menopause and other reproductive and behavioral factors in Japanese women. Author(s): Nagata C, Takatsuka N, Kawakami N, Shimizu H. Source: Annals of Epidemiology. 2002 May; 12(4): 237-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11988411&dopt=Abstract

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Weight control and the management of obesity after menopause: the role of physical activity. Author(s): Dubnov G, Brzezinski A, Berry EM. Source: Maturitas. 2003 February 25; 44(2): 89-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590004&dopt=Abstract

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Weight gain and menopause. Author(s): Tchernof A, Poehlman ET. Source: Menopause (New York, N.Y.). 2000 November-December; 7(6): 419-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127766&dopt=Abstract

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Weight gain and the menopause: a 5-year prospective study. Author(s): Guthrie JR, Dennerstein L, Dudley EC. Source: Climacteric : the Journal of the International Menopause Society. 1999 September; 2(3): 205-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910598&dopt=Abstract

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Weight gain at the time of menopause. Author(s): Panotopoulos G, Raison J, Ruiz JC, Guy-Grand B, Basdevant A. Source: Human Reproduction (Oxford, England). 1997 October; 12 Suppl 1: 126-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9403329&dopt=Abstract

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Weight gain during menopause. Is it inevitable or can it be prevented? Author(s): Simkin-Silverman LR, Wing RR. Source: Postgraduate Medicine. 2000 September 1; 108(3): 47-50, 53-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11004935&dopt=Abstract

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What affects bladder function more: menopause or age? Author(s): Wakamatsu MM. Source: Menopause (New York, N.Y.). 2003 May-June; 10(3): 191-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792287&dopt=Abstract

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What do women think about menopause? A qualitative study of women's expectations, apprehensions and knowledge about the climacteric period. Author(s): Bertero C. Source: International Nursing Review. 2003 June; 50(2): 109-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752910&dopt=Abstract

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What is the evidence, reasons for and impact of weight gain during menopause? Author(s): Campbell LV, Samaras K. Source: The Medical Journal of Australia. 2000 November 6; 173 Suppl: S100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149368&dopt=Abstract

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What perimenopausal women think about using hormones during menopause. Author(s): Kittell LA, Mansfield PK. Source: Women Health. 2000; 30(4): 77-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10983611&dopt=Abstract

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When to suspect androgen deficiency other than at menopause. Author(s): Davis SR. Source: Fertility and Sterility. 2002 April; 77 Suppl 4: S68-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12007906&dopt=Abstract

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Where is the evidence for effectiveness of treatments for the menopause? Introducing the Cochrane Collaboration. Author(s): Farquhar CM, MacLennan AH. Source: Climacteric : the Journal of the International Menopause Society. 1998 March; 1(1): 5-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907926&dopt=Abstract

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Who understands the menopause? Author(s): Barlow DH. Source: British Journal of Obstetrics and Gynaecology. 1997 August; 104(8): 879-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9255076&dopt=Abstract

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Will boomer women defy menopause? The drug industry is betting they will try. Author(s): Sherrid P. Source: U.S. News & World Report. 2000 September 11; 129(10): 70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11184581&dopt=Abstract

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Woman-centered information on menopause for health care providers: findings from the Midlife Women's Health Survey. Author(s): Mansfield PK, Voda AM. Source: Health Care for Women International. 1997 January-February; 18(1): 55-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9119783&dopt=Abstract

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Women & diabetes. Menopause. The latest on hormone replacement therapy. Author(s): Ross HL. Source: Diabetes Self Manag. 2002 July-August; 19(4): 90, 92, 95-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533854&dopt=Abstract

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Women and menopause: beliefs, attitudes, and behaviors. The North American Menopause Society 1997 Menopause Survey. Author(s): Kaufert P, Boggs PP, Ettinger B, Woods NF, Utian WH. Source: Menopause (New York, N.Y.). 1998 Winter; 5(4): 197-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9872483&dopt=Abstract

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Women of the thirteenth moon. The menopause experience. Part I. Author(s): Leonard C. Source: The Birth Gazette. 1999 Spring; 15(2): 39-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474333&dopt=Abstract

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Women of the thirteenth moon: the menopause experience. Part II. Author(s): Leonard C. Source: The Birth Gazette. 1999 Summer; 15(3): 12-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474337&dopt=Abstract

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Women with past history of bone fracture have low spinal bone density before menopause. Author(s): Goulding A, Gold E, Walker R, Lewis-Barned N. Source: N Z Med J. 1997 June 27; 110(1046): 232-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9236807&dopt=Abstract

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Women, menopause, and (Ms.)information: communication about the climacteric. Author(s): Buchanan MC, Villagran MM, Ragan SL. Source: Health Communication. 2002; 14(1): 99-119. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11853211&dopt=Abstract

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Women's health in midlife: the influence of the menopause, social factors and health in earlier life. Author(s): Kuh DL, Hardy R, Wadsworth M. Source: British Journal of Obstetrics and Gynaecology. 1997 December; 104(12): 1419. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9422025&dopt=Abstract

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Women's health in midlife: the influence of the menopause, social factors and health in earlier life. Author(s): Kuh DL, Wadsworth M, Hardy R. Source: British Journal of Obstetrics and Gynaecology. 1997 August; 104(8): 923-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9255084&dopt=Abstract

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Women's knowledge about menopause, hormone replacement therapy (HRT), and interactions with healthcare providers: an exploratory study. Author(s): Clinkingbeard C, Minton BA, Davis J, McDermott K. Source: Journal of Women's Health & Gender-Based Medicine. 1999 October; 8(8): 1097102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10565668&dopt=Abstract

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Women's knowledge about the physical and emotional changes associated with menopause. Author(s): Fox-Young S, Sheehan M, O'Connor V, Cragg C, Del Mar C. Source: Women Health. 1999; 29(2): 37-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10427647&dopt=Abstract

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Women's midlife health. Reframing menopause. Author(s): Rousseau ME. Source: Journal of Nurse-Midwifery. 1998 May-June; 43(3): 208-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9674351&dopt=Abstract

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Women's perceptions and concerns about menopause. Author(s): Aber CS, Arathuzik D, Righter AR. Source: Clin Excell Nurse Pract. 1998 July; 2(4): 232-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10455567&dopt=Abstract

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Women's stories: ethnic variations in women's attitudes and experiences of menopause, hysterectomy, and hormone replacement therapy. Author(s): Mingo C, Herman CJ, Jasperse M. Source: Journal of Women's Health & Gender-Based Medicine. 2000; 9 Suppl 2: S27-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714743&dopt=Abstract

·

Workshops: recommendations and plans of action for meeting the HEDIS 2000 management of menopause measure. Author(s): Berenbeim DM. Source: Am J Manag Care. 2000 September; 6(14 Suppl): S761-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11184073&dopt=Abstract

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Worsening of Parkinsonism after the use of veralipride for treatment of menopause: case report. Author(s): Teive HA, Sa DS. Source: Arquivos De Neuro-Psiquiatria. 2001 March; 59(1): 123-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299446&dopt=Abstract

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CHAPTER 2. NUTRITION AND MENOPAUSE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and menopause.

Finding Nutrition Studies on Menopause The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “menopause” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on menopause: ·

Finding natural ways to minimize the side effects of menopause. Source: Hudnall, M. Environmental-nutrition (USA). (August 1998). volume 21(8) page 1, 6. supplements hormones women soybean products foods diet drug plants heart diseases neoplasms risk 0893-4452 Summary: complement alimentaire hormone femme produit a base de soja produit alimentaire regime alimentaire plante medicinale cardiopathie neoplasme risque

Additional consumer oriented references include: ·

Age-related increase in visceral adipose tissue and body fat and the metabolic risk profile of premenopausal women. Author(s): Lipid Research Center, Laval University Medical Research Center, Ste-Foy, Quebec, Canada. Source: Pascot, A Lemieux, S Lemieux, I Prud'homme, D Tremblay, A Bouchard, C Nadeau, A Couillard, C Tchernof, A Bergeron, J Despres, J P Diabetes-Care. 1999 September; 22(9): 1471-8 0149-5992

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Alternative medicine. Natural approaches to menopause. Source: Harv-Womens-Health-Watch. 2001 October; 9(2): 6-7 1070-910X

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By the way, doctor. I'm one year into menopause and really bothered by hot flashes and vaginal dryness. I'd like to take hormone replacement therapy, but I'm worried about increasing my risk of getting breast cancer. My doctor said I can take HRT at a dose longer than what's usually prescribed. What do you think? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 2001 September; 9(1): 7 1070910X

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By the way, doctor.. I'm 70. I took hormone therapy for a while after menopause, but stopped taking it long ago. My memory definitely isn't as good as it used to be. If I started taking estrogen again, would my memory improve? Source: Lee, T H Harv-Health-Lett. 2000 December; 26(2): 8 1052-1577

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Easing through menopause without HRT. Source: Anonymous Johns-Hopkins-Med-Lett-Health-After-50. 2002 November; 14(9): 45, 7 1042-1882

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Effect of menopausal status on insulin-stimulated glucose disposal: comparison of middle-aged premenopausal and early postmenopausal women. Author(s): Division of Clinical Pharmacology and Metabolic Research, University of Vermont, Burlington 05405, USA. Source: Toth, M J Sites, C K Eltabbakh, G H Poehlman, E T Diabetes-Care. 2000 June; 23(6): 801-6 0149-5992

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I am a 54-year-old woman who has gone through menopause. Six months after starting HRT, I discovered I had gallstones, after suffering four attacks. I am not interested in having my gallbladder out, and I have drastically reduced the amount of fat in my diet, which has eliminated further attacks. However, I have also read that there is a link between estrogen and gallstone formation. Should I stop taking the estrogen? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1998 October; 6(2): 8 1070910X

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Is there a “male menopause” - and will hormones help? Source: Anonymous Harv-Mens-Health-Watch. 2001 June; 5(11): 1-5 1089-1102

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Managing menopause: an update. Source: Anonymous Harv-Womens-Health-Watch. 1998 January; 5(5): 2-4 1070-910X

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Menopause management. Estrogen update. Source: Anonymous Harv-Womens-Health-Watch. 1999 June; 6(10): 6 1070-910X

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On call. My wife and I are both 62 and healthy. She started taking Prempro during her menopause eight years ago but has now decided to stop the hormones. I began taking DHEA five years ago, but I switched to AndroGel when my doctor gave me a prescription last year. Should I stay on AndroGel, go back to DHEA, or stop hormones? Source: Simon, H B Harv-Mens-Health-Watch. 2003 January; 7(6): 8 1089-1102

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Phytoestrogens for menopause. Source: Schardt, D. Nutr-action-health-lett. [Washington, D.C. : Center for Science in the Public Interest,. Jan/February 2000. volume 27 (1) page 8-10. 0885-7792

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St. John's wort relieves menopause symptoms. Source: Hoegler, N. HerbalGram. Austin, TX : American Botanical Council and the Herb Research Foundation. 2000. (50) page 27-28. 0899-5648

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Taking charge of menopause. Source: Hall, L L FDA-Consum. 1999 Nov-December; 33(6): 17-21 0362-1332

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Taking control of menopause. Source: Anonymous Health-News. 2001 March; 7(3): 8 1081-5880

The following information is typical of that found when using the “Full IBIDS Database” to search for “menopause” (or a synonym): ·

Amenorrhea frequency with continuous combined hormone replacement therapy: a retrospective analysis. Menopause Study Group. Author(s): Wyeth-Ayerst Research, PO Box 8299, Philadelphia, PA 19101, USA. Source: Pickar, J H Bottiglioni, F Archer, D F Climacteric. 1998 June; 1(2): 130-6 1369-7137

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An open trial of mirtazapine in menopausal women with depression unresponsive to estrogen replacement therapy. Author(s): Perinatal and Reproductive Psychiatry Clinical Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. Source: Joffe, H Groninger, H Soares, C Nonacs, R Cohen, L S J-Womens-Health-GendBased-Med. 2001 December; 10(10): 999-1004 1524-6094

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Approach to menopausal symptoms in women with breast cancer. Author(s): The Breast Cancer Program, University of Michigan Comprehensive Cancer Center, 6303 Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0942, USA. [email protected] Source: Stearns, Vered Hayes, Daniel F Curr-Treat-Options-Oncol. 2002 April; 3(2): 17990 1527-2729

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Associations of calcium intake and physical activity with bone density and size in premenopausal and postmenopausal women: a peripheral quantitative computed tomography study. Author(s): The UKK Institute for Health Promotion Research, Tampere, Finland.

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Source: Uusi Rasi, Kirsti Sievanen, Harri Pasanen, Matti Oja, Pekka Vuori, Ilkka J-BoneMiner-Res. 2002 March; 17(3): 544-52 0884-0431 ·

Comparison of Alora estradiol matrix transdermal delivery system with oral conjugated equine estrogen therapy in relieving menopausal symptoms. Alora Study Group. Author(s): TheraTech, Inc., 417 Wakara Way, Suite 100, Salt Lake City, UT 84108, USA. Source: Good, W R John, V A Ramirez, M Higgins, J E Climacteric. 1999 March; 2(1): 2936 1369-7137

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Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women. Author(s): School of Medicine, University of California, San Francisco, California 94143, USA. Source: Cummings, J A Brizendine, L Menopause. 2002 Jul-August; 9(4): 253-63 10723714

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Comparison of the antioxidant effects of equine estrogens, red wine components, vitamin E, and probucol on low-density lipoprotein oxidation in postmenopausal women. Author(s): Department of Obstetrics and Gynecology, Institute of Medical Sciences, University of Toronto, Ontario, Canada. [email protected] Source: Bhavnani, B R Cecutti, A Gerulath, A Woolever, A C Berco, M Menopause. 2001 Nov-December; 8(6): 408-19 1072-3714

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Comparison of the effects of transdermal estrogen, oral estrogen, and oral estrogenprogestogen therapy on bone mineral density in postmenopausal women. Author(s): Department of Obstetrics and Gynecology, University of Ondokuz Mayis School of Medicine, Kurupelit, Samsun, Turkey. Source: Cetinkaya, Mehmet B Kokcu, Arif Yanik, Filiz F Basoglu, Tarik Malatyalioglu, Erdal Alper, Tayfun J-Bone-Miner-Metab. 2002; 20(1): 44-8 0914-8779

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Controversial issues in climacteric medicine I. Cardiovascular disease and hormone replacement therapy. International Menopause Society Expert Workshop. 13-16 October 2000, royal society of medicine, London, UK. Author(s): Department of Gynecology and Obstetrics, University of Pisa, Via Roma 35, 56126 Pisa, Italy. Source: Genazzani, A R Gambacciani, M Climacteric. 2000 December; 3(4): 233-40 13697137

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Dehydroepiandrosterone status in postmenopausal women is determined by the gene for the vitamin D receptor. Author(s): Institute of Endocrinology, Prague, Czech Republic. Source: Zofkova, I Hill, M Zajickova, K Horm-Metab-Res. 2002 March; 34(3): 127-31 0018-5043

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Do combinations of 1 mg estradiol and low doses of NETA effectively control menopausal symptoms? Source: Baerug, U Winge, T Nordland, G Faber Swensson, E Heldaas, K Norling, B Larsen, S Arce, J C Climacteric. 1998 September; 1(3): 219-28 1369-7137

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Effects of different hormone replacement regimens on postmenopausal women with abnormal lipid levels. Menopause Study Group. Author(s): Wyeth-Ayerst Research, PO Box 8299, Philadelphia, PA 19101, USA. Source: Pickar, J H Wild, R A Walsh, B Hirvonen, E Lobo, R A Climacteric. 1998 March; 1(1): 26-32 1369-7137

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Effects of dose and timing of calcium supplementation on bone resorption in early menopausal women. Author(s): Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Royal Adelaide Hospital, Adelaide 5000, South Australia, Australia. [email protected] Source: Scopacasa, Franca Need, A G Horowitz, M Wishart, J M Morris, H A Nordin, B E C Horm-Metab-Res. 2002 January; 34(1): 44-7 0018-5043

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Effects of tibolone and conventional hormone replacement therapies on arterial and hepatic cholesterol accumulation and on circulating endothelin-1, vascular cell adhesion molecule-1, and E-selectin in surgically menopausal monkeys. Author(s): Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. [email protected] Source: Register, T C Wagner, J D Zhang, L Hall, J Clarkson, T B Menopause. 2002 NovDecember; 9(6): 411-21 1072-3714

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Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Author(s): Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA. [email protected] Source: Amato, Paula Christophe, Sylvie Mellon, Pamela L Menopause. 2002 Mar-April; 9(2): 145-50 1072-3714

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Fractures before menopause: a red flag for physicians. Author(s): General Internal Medicine Section, Veterans Affairs Medical Center, San Francisco & Department of Medicine, University of California, USA. Source: Hosmer, W D Genant, H K Browner, W S Osteoporos-Int. 2002; 13(4): 337-41 0937-941X

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Goserelin (Zoladex)--its role in early breast cancer in pre- and perimenopausal women. Author(s): Gynaecology and Obstetrics Clinic, University of Kiel, Germany. Source: Jonat, W Br-J-Cancer. 2001 November; 85 Suppl 2: 1-5 0007-0920

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Gynecologists' trends and attitudes toward prescribing hormone replacement therapy during menopause. Author(s): Department of Obstetrics and Gynecology, Rabin Medical Center, Petah Tikva, Israel. [email protected] Source: Kaplan, B Aschkenazi Steinberg, S Yogev, Y Nahum, R Sulkes, J Phisher, M Menopause. 2002 Sep-October; 9(5): 354-9 1072-3714

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Hepatic dysfunction in development of menopausal hot flushes? Author(s): Department of Pathophysiology, Medical School of the University of Pecs. [email protected] Source: Garai, J Med-Hypotheses. 2002 June; 58(6): 535-9 0306-9877

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Herbs, menopause, and dialysis. Author(s): Department of Family Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA. [email protected] Source: Roemheld Hamm, B Dahl, N V Semin-Dial. 2002 Jan-February; 15(1): 53-9 08940959

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Hormonal treatment and psychological function during the menopausal transition: an evaluation of the effects of conjugated estrogens/cyclic medroxyprogesterone acetate. Author(s): University of Queensland, Department of Obstetrics and Gynaecology, Australia.

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Source: Khoo, S K Coglan, M Battistutta, D Tippett, V Raphael, B Climacteric. 1998 March; 1(1): 55-62 1369-7137 ·

Hormone replacement in postmenopausal women: impact of progestogens on autonomic tone and blood pressure regulation. Author(s): Department of Internal Medicine-Cardiology, University of Marburg, Germany. [email protected] Source: Christ, Michael Seyffart, Karen Tillmann, Hanns Christian Wehling, Martin Menopause. 2002 Mar-April; 9(2): 127-36 1072-3714

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Hot flushes and other menopausal symptoms in relation to soy product intake in Japanese women. Author(s): Department of Public Health, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan. Source: Nagata, C Shimizu, H Takami, R Hayashi, M Takeda, N Yasuda, K Climacteric. 1999 March; 2(1): 6-12 1369-7137

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How to treat a menopausal woman: a history, 1900 to 2000. Author(s): University of Wisconsin-Madison Medical School, Center of Excellence in Women's Health, Meriter Hospital, 202 S. Park Street, Madison, WI 53715, USA. [email protected] Source: Houck, J A Curr-Womens-Health-Repage 2002 October; 2(5): 349-55 1534-5874

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Informed choices. Your most valuable role in menopause care is education. Author(s): Health Resources Ltd., Bangor, Maine, USA. Source: Wardwell, S Adv-Nurse-Pract. 2002 January; 10(1): 65-8 1096-6293

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Iron deficiency and smoking. Comparative criteria for buccal mucosa keratinization in menstruating and postmenopausal women. Author(s): Department of Oral Diagnosis and Radiology, Hacettepe University Faculty of Dentistry, 06100 Ankara, Turkey. Source: Artvinli, Leyla Berna Acta-Cytol. 2002 Jul-August; 46(4): 664-6 0001-5547

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Is there a proven place for phytoestrogens in the menopause? Source: Ginsburg, J Prelevic, G M Climacteric. 1999 June; 2(2): 75-8 1369-7137

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Loss of libido in menopausal women. Management issues. Author(s): Jean Hailes Medical Centre for Women, Jean Hailes Foundation, Melbourne, Victoria. Source: Reddish, Sue Aust-Fam-Physician. 2002 May; 31(5): 427-32 0300-8495

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Low dose transdermal estradiol/norethisterone acetate treatment over 2 years does not cause endometrial proliferation in postmenopausal women. Author(s): Division of Obstetrics & Gynaecology, Department of Health and Environment, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden. [email protected] Source: Brynhildsen, January HamMarch, Mats Menopause. 2002 Mar-April; 9(2): 137-44 1072-3714

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Management of postmenopausal osteoporosis: position statement of the North American Menopause Society. Source: Menopause. 2002 Mar-April; 9(2): 84-101 1072-3714

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Menopausal changes in the myometrium: an investigation using a GnRH agonist model. Author(s): Department of Obstetrics and Gynecology, St James's University Hospital, Leeds, United Kingdom.

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Source: Weeks, A D Wilkinson, N Arora, D S Duffy, S R Wells, M Walker, J J Int-JGynecol-Pathol. 1999 July; 18(3): 226-32 0277-1691 ·

Menopausal obesity--myth or fact? Author(s): Department of Endocrinology and Diabetology, Wroclaw Medical University, Wroclaw, Poland. Source: Milewicz, A Tworowska, U Demissie, M Climacteric. 2001 December; 4(4): 27383 1369-7137

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Menopausal symptom control and side-effects on continuous estrone sulfate and three doses of medroxyprogesterone acetate. Ogen/Provera Study Group. Author(s): School of Obstetrics and Gynaecology, Royal Hospital for Women, Barker Street, Randwick, NSW, 2031, Australia. Source: Nand, S L Webster, M A Baber, R Heller, G Z Climacteric. 1998 September; 1(3): 211-8 1369-7137

·

On call. My wife and I are both 62 and healthy. She started taking Prempro during her menopause eight years ago but has now decided to stop the hormones. I began taking DHEA five years ago, but I switched to AndroGel when my doctor gave me a prescription last year. Should I stay on AndroGel, go back to DHEA, or stop hormones? Source: Simon, H B Harv-Mens-Health-Watch. 2003 January; 7(6): 8 1089-1102

·

Oral 17beta-estradiol (1 mg) continuously combined with dydrogesterone improves the serum lipid profile of postmenopausal women. Author(s): Brussels Menopause Center, Brussels, Belgium. [email protected] Source: Pornel, Bruno Chevallier, Olivier Netelenbos, J Coen Menopause. 2002 MayJune; 9(3): 171-8 1072-3714

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Perceptions about menopause and health practises among women in northeast Thailand. Author(s): Department of Psychiatric Nursing, Faculty of Nursing, Khon Kaen University, Khon Kaen 40002, Thailand. [email protected] Source: Chirawatkul, S Patanasri, K Koochaiyasit, C Nurs-Health-Sci. 2002 September; 4(3): 113-21 1441-0745

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Perceptions of alternative therapies available for women facing hysterectomy or menopause. Author(s): Department of Health Promotion and Education, The Norman J. Arnold School of Public Health, University of South Carolina, Columbia 29208, USA. [email protected] Source: Richter D, L Corwin S, J Rheaume C, E McKeown R, E J-Women-Aging. 2001; 13(4): 21-37 0895-2841

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Phytoestrogens for menopause. Source: Schardt, D. Nutr-action-health-lett. [Washington, D.C. : Center for Science in the Public Interest,. Jan/February 2000. volume 27 (1) page 8-10. 0885-7792

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Phytoestrogens in the management of the menopause: up-to-date. Author(s): Clinical Research Fellow in Gynecology, Leicester University, Leicestershire, UK. [email protected] Source: Ewies, A A Obstet-Gynecol-Survolume 2002 May; 57(5): 306-13 0029-7828

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Postmenopausal women taking HRT at risk for high triglycerides. Source: Tufts-Univ-health-nutr-lett. New York, NY : Tufts University Health & Nutrition Letter, c1997-. October 2000. volume 18 (8) page 1.

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Prevalence of and satisfaction with complementary therapies and hormone replacement therapy in a specialist menopause clinic. Author(s): Chelsea and Westminster Hospital, London, UK. Source: Vashisht, A Domoney, C L Cronje, W Studd, J W Climacteric. 2001 September; 4(3): 250-6 1369-7137

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Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Author(s): Department of Obstetrics and Gynaecology, University of Sydney, Royal North Shore Hospital, St Leonards 2056, Australia. Source: Baber, R J Templeman, C Morton, T Kelly, G E West, L Climacteric. 1999 June; 2(2): 85-92 1369-7137

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Relation between vitamin D insufficiency, bone density, and bone metabolism in healthy postmenopausal women. Author(s): Endocrinology Division, University Hospital San Cecilio, Granada, Spain. Source: Mezquita Raya, P Munoz Torres, M Luna, J D Luna, V Lopez Rodriguez, F Torres Vela, E Escobar Jimenez, F J-Bone-Miner-Res. 2001 August; 16(8): 1408-15 08840431

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Safety and efficacy of a continuous once-a-week 17beta-estradiol/levonorgestrel transdermal system and its effects on vasomotor symptoms and endometrial safety in postmenopausal women: the results of two multicenter, double-blind, randomized, controlled trials. Author(s): Department of Obstetrics and Gynecology, University of Illinois at Chicago, 60613-7313, USA. [email protected] Source: Shulman, Lee P Yankov, Vladimir Uhl, Kerstin Menopause. 2002 May-June; 9(3): 195-207 1072-3714

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Serum leptin levels of menopausal women before and after hormone replacement therapy. Author(s): Department of Gynecology and Obstetrics, General Hospital of Guangzhou Command, Guangzhou 510010, China. Source: Li, W L Guo, X Y Zhang, J Y Peng, P Zhang, Y L Di-Yi-Jun-Yi-Da-Xue-Xue-Bao. 2002 July; 22(7): 635-6 1000-2588

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The effect of hormone replacement therapy on appendicular lean tissue mass in early postmenopausal women. Author(s): Center for Clinical and Basic Research, Ballerup, Denmark. [email protected] Source: Tanko, Laszlo B Movsesyan, Lusine Svendsen, Ole L Christiansen, Claus Menopause. 2002 Mar-April; 9(2): 117-21 1072-3714

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The effect of Promensil, an isoflavone extract, on menopausal symptoms. Author(s): Caroline Chisholm Centre for Women and Children, Liverpool Hospital, Liverpool. Source: Knight, D C Howes, J B Eden, J A Climacteric. 1999 June; 2(2): 79-84 1369-7137

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The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. Author(s): Cardiovascular Research Group, Department of Medicine, Monash University, Monash Medical Centre, Clayton, Australia. Source: Kotsopoulos, D Dalais, F S Liang, Y L McGrath, B P Teede, H J Climacteric. 2000 September; 3(3): 161-7 1369-7137

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Use of alternative therapies in menopause. Author(s): Department of Obstetrics and Gynecology, Columbia University, New York, NY 10032, USA. Source: Warren, M P Shortle, B Dominguez, J E Best-Pract-Res-Clin-Obstet-Gynaecol. 2002 June; 16(3): 411-48 1521-6934

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Use of alternatives to estrogen for treatment of menopause. Author(s): Department of Obstetrics/Gynecology and the Women's Place, and The Department of Medicine, Division of Endocrinology, University of Virginia Health System, Charlottesville, Virginia, USA. Source: Pinkerton, J V Santen, R Minerva-Endocrinol. 2002 March; 27(1): 21-41 0391-1977

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Vitexagnus-castus essential oil and menopausal balance: a self-care survey. Source: Lucks, B C Sorensen, J Veal, L Complement-Ther-Nurs-Midwifery. 2002 August; 8(3): 148-54 1353-6117

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Women in transition--menopause and body composition in different populations. Author(s): National Autonomous University of Mexico, Institute of Anthropological Investigations, Mexico City, DF. Source: Arechiga, J Prado, C Canto, M Carmenate, M Coll-Antropol. 2001 December; 25(2): 443-8 0350-6134

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: ·

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDÒHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to menopause; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: ·

Vitamins Pantothenic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin B Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html Vitamin B12 Source: Healthnotes, Inc. www.healthnotes.com Vitamin B5 (Pantothenic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: Healthnotes, Inc. www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin D Source: Healthnotes, Inc. www.healthnotes.com Vitamin D Alternative names: Calciferol, Calcitrol, Cholecalciferol, Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com

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Vitamin D Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin D Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,905,00.html Vitamin E Source: Healthnotes, Inc. www.healthnotes.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin E Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,906,00.html Vitamin K Alternative names: Menadione, Menaphthone, Menaquinone, Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Vitamin K Source: Prima Communications, Inc.www.personalhealthzone.com ·

Minerals Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Beta-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Boron Source: Healthnotes, Inc. www.healthnotes.com Boron Source: Prima Communications, Inc.www.personalhealthzone.com Calcium Source: Healthnotes, Inc. www.healthnotes.com Calcium Source: Integrative Medicine Communications; www.drkoop.com

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Calcium Source: Prima Communications, Inc.www.personalhealthzone.com Calcium/magnesium Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,937,00.html Calcium: Which Form is Best? Source: Healthnotes, Inc. www.healthnotes.com Chromium Source: Integrative Medicine Communications; www.drkoop.com Cisplatin Source: Healthnotes, Inc. www.healthnotes.com Copper Source: Prima Communications, Inc.www.personalhealthzone.com D-Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Fluoxetine Source: Healthnotes, Inc. www.healthnotes.com Folate Source: Prima Communications, Inc.www.personalhealthzone.com Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Iron Source: Healthnotes, Inc. www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Manganese Source: Integrative Medicine Communications; www.drkoop.com Manganese Source: Prima Communications, Inc.www.personalhealthzone.com Sulfur Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com

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Food and Diet Bruising Source: Healthnotes, Inc. www.healthnotes.com Burdock Alternative names: Arctium lappa Source: Healthnotes, Inc. www.healthnotes.com Cancer Prevention and Diet Source: Healthnotes, Inc. www.healthnotes.com Flaxseeds Source: Healthnotes, Inc. www.healthnotes.com Hypertension Source: Healthnotes, Inc. www.healthnotes.com Low-Salt Diet Source: Healthnotes, Inc. www.healthnotes.com Soy Source: Healthnotes, Inc. www.healthnotes.com Soy Source: Prima Communications, Inc.www.personalhealthzone.com Soy products Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,135,00.html Vegetarian Diet Source: Healthnotes, Inc. www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND MENOPAUSE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to menopause. At the conclusion of this chapter, we will provide additional sources.

The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “menopause” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: ·

Soybeans: Good for Your Heart. Patient Education Source: Advance for Nurse Practitioners. 10(5): 85. May 2002. Summary: This article provides information on the health benefits of soybeans and foods made from soybeans. The possible benefits that soy proteins may have on certain diseases, such as coronary heart disease, menopause, osteoporosis, cancer, allergies, diabetes, and kidney disease, are briefly noted. The article also describes the soy products currently available, including edamame, miso, tofu, soy nuts, tempeh, soy milk, soy sauce, and natto. It lists two Web sites for additional information on soybeans.

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Imagine This!: Infinite Uses of Guided Imagery in Women's Health Source: Journal of Holistic Nursing. 17(4): 317-330. December 1999. Summary: This journal article examines the range of applications for guided imagery in women's health. First, it presents background information about the history of imagery,

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definitions, theoretical foundations, and guided imagery techniques. Then, it reviews research supporting the effectiveness of imagery in various applications such as reducing labor pain, promoting successful lactation, decreasing postpartum depression, and decreasing stress during cancer treatment. Next, it describes an approach to introducing the techniques of guided imagery during routine office procedures such as the pelvic examination, so women will be prepared for crisis situations such as the birth of a child or the diagnosis and treatment of cancer. Finally, it suggests additional applications for guided imagery in women's health care, including other stressful office procedures, endometriosis, premenstrual syndrome, chemotherapy, high risk pregnancy, labor, menopause, urinary incontinence, and chronic illness. The article has 2 tables and 34 references. ·

Women's Use of Complementary and Alternative Therapies in Reproductive Health Care Source: Journal of Nurse-Midwifery. 43(3): 224-234. May-June 1998. Summary: This journal article discusses the use of complementary and alternative therapies in women's reproductive health care. The first part reviews the literature on usage and attitudes toward complementary and alternative medicine in the United States and other selected countries. It also summarizes the classification of complementary and alternative treatments developed by the Office of Alternative Medicine. The second part discusses the complementary and alternative therapies used by women for a variety of reproductive health problems. One section discusses commonly used herbal therapies, particularly those used to treat morning sickness, induce labor, and relieve the symptoms of menopause. It includes information about potential side effects and those herbs that should be avoided during pregnancy. Another section reviews the history and principles of homeopathy and its applications to women's health, with special reference to the use of arnica and caulophyllum. A third section addresses the use of acupuncture, acupressure, and moxibustion for various women's reproductive health concerns, including the treatment of morning sickness and breech presentation. The article has 57 references.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to menopause and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “menopause” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to menopause: ·

A comprehensive approach to the menopause: so far, one size should fit all. Author(s): Ewies AA. Source: Obstetrical & Gynecological Survey. 2001 October; 56(10): 642-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11590315&dopt=Abstract

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A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients.

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Author(s): Nikander E, Kilkkinen A, Metsa-Heikkila M, Adlercreutz H, Pietinen P, Tiitinen A, Ylikorkala O. Source: Obstetrics and Gynecology. 2003 June; 101(6): 1213-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798527&dopt=Abstract ·

Acupuncture in the treatment of menopause-related symptoms in women taking tamoxifen. Author(s): Porzio G, Trapasso T, Martelli S, Sallusti E, Piccone C, Mattei A, Di Stanislao C, Ficorella C, Marchetti P. Source: Tumori. 2002 March-April; 88(2): 128-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088252&dopt=Abstract

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Alternative therapies for menopause. Author(s): Kass-Annese B. Source: Clinical Obstetrics and Gynecology. 2000 March; 43(1): 162-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694998&dopt=Abstract

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Alternative therapies for traditional disease states: menopause. Author(s): Morelli V, Naquin C. Source: American Family Physician. 2002 July 1; 66(1): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126027&dopt=Abstract

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Alternatives for women through menopause. Author(s): Gass ML, Taylor MB. Source: American Journal of Obstetrics and Gynecology. 2001 August; 185(2 Suppl): S4756. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521122&dopt=Abstract

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An integrative approach to menopause. Author(s): Dog TL, Riley D, Carter T. Source: Alternative Therapies in Health and Medicine. 2001 July-August; 7(4): 45-55; Quiz 56-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452567&dopt=Abstract

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Application of Roy's adaptation model when caring for a group of women coping with menopause. Author(s): Cunningham DA. Source: Journal of Community Health Nursing. 2002 Spring; 19(1): 49-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985211&dopt=Abstract

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Black cohosh: an alternative therapy for menopause? Author(s): Mahady GB, Fabricant D, Chadwick LR, Dietz B.

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Source: Nutrition in Clinical Care : an Official Publication of Tufts University. 2002 November-December; 5(6): 283-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557811&dopt=Abstract ·

Bone metabolism and the perimenopause overview, risk factors, screening, and osteoporosis preventive measures. Author(s): Sayegh RA, Stubblefield PG. Source: Obstetrics and Gynecology Clinics of North America. 2002 September; 29(3): 495-510. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353670&dopt=Abstract

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Botanicals: medicines and menopause. Author(s): Taylor M. Source: Clinical Obstetrics and Gynecology. 2001 December; 44(4): 853-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600866&dopt=Abstract

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Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Author(s): Woo J, Lau E, Ho SC, Cheng F, Chan C, Chan AS, Haines CJ, Chan TY, Li M, Sham A. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 352-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851519&dopt=Abstract

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Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief. Author(s): Dog TL, Powell KL, Weisman SM. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 299-313. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851513&dopt=Abstract

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Early menopause & self-care. Author(s): Baldwin C. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2002 August-September; 6(4): 376, 373-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239794&dopt=Abstract

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Effect of reproductive hormones and selective estrogen receptor modulators on mood during menopause. Author(s): Soares CN, Poitras JR, Prouty J. Source: Drugs & Aging. 2003; 20(2): 85-100. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534310&dopt=Abstract

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Effects of hormone replacement therapy on sexual psychophysiology and behavior in postmenopause. Author(s): Sarrel PM. Source: Journal of Women's Health & Gender-Based Medicine. 2000; 9 Suppl 1: S25-32. Review. Erratum In: J Womens Health Gend Based Med 2001 January-February; 10(1): 91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695871&dopt=Abstract

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Effects of ipriflavone on bone loss following a bilateral ovariectomy and menopause: a randomized placebo-controlled study. Author(s): Katase K, Kato T, Hirai Y, Hasumi K, Chen JT. Source: Calcified Tissue International. 2001 August; 69(2): 73-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683426&dopt=Abstract

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Estrogens and lipids. Can HRT designer estrogens, and phytoestrogens reduce cardiovascular risk markers after menopause? Author(s): Ariyo AA, Villablanca AC. Source: Postgraduate Medicine. 2002 January; 111(1): 23-30; Quiz 3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11810749&dopt=Abstract

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Evaluation and management of insomnia in menopause. Author(s): Jones CR, Czajkowski L. Source: Clinical Obstetrics and Gynecology. 2000 March; 43(1): 184-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694999&dopt=Abstract

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Exploring the role of progestins and phytoestrogens in menopause. Author(s): Hale G, Bievre M, Hughes C. Source: Integr. Med. 2000 March 21; 2(2): 133-141. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882887&dopt=Abstract

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Gynecologists' trends and attitudes toward prescribing hormone replacement therapy during menopause. Author(s): Kaplan B, Aschkenazi-Steinberg S, Yogev Y, Nahum R, Sulkes J, Phisher M. Source: Menopause (New York, N.Y.). 2002 September-October; 9(5): 354-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218724&dopt=Abstract

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Harmonizing herbs. Managing menopause with help from Mother Earth. Author(s): Learn CD, Higgins PG. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 1999 October-November; 3(5): 39-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10827582&dopt=Abstract

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Helping women help themselves: developing a menopause discussion group. Author(s): Boggs PP, Rosenthal MB. Source: Clinical Obstetrics and Gynecology. 2000 March; 43(1): 207. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695001&dopt=Abstract

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Herbal medicines for menopause: do they work and are they safe? Author(s): Eden JA. Source: The Medical Journal of Australia. 2001 January 15; 174(2): 63-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245502&dopt=Abstract

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Herbal treatments for menopause. Black cohosh, soy and micronized progesterone. Author(s): Pick M. Source: Adv Nurse Pract. 2000 May; 8(5): 29-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235332&dopt=Abstract

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Herbs, menopause, and dialysis. Author(s): Roemheld-Hamm B, Dahl NV. Source: Seminars in Dialysis. 2002 January-February; 15(1): 53-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874595&dopt=Abstract

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Homeopathy and the menopause. Author(s): Thompson EA. Source: The Journal of the British Menopause Society. 2002 December; 8(4): 151-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804324&dopt=Abstract

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Hormonal decline in elderly men and male menopause. Author(s): Kessenich CR, Cichon MJ. Source: Geriatric Nursing (New York, N.Y.). 2001 January-February; 22(1): 24-7; Quiz 28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11223793&dopt=Abstract

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Hormones for menopause: what might the east teach the west? Author(s): Plotnikoff GA. Source: Minn Med. 2003 February; 86(2): 6-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611101&dopt=Abstract

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Informed choices. Your most valuable role in menopause care is education. Author(s): Wardwell S. Source: Adv Nurse Pract. 2002 January; 10(1): 65-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420514&dopt=Abstract

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Is there a proven place for phytoestrogens in the menopause? Author(s): Ginsburg J, Prelevic GM. Source: Climacteric : the Journal of the International Menopause Society. 1999 June; 2(2): 75-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910670&dopt=Abstract

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Laser acupuncture and low-calorie diet during visceral obesity therapy after menopause. Author(s): Wozniak P, Stachowiak G, Pieta-Dolinska A, Oszukowski P. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2003 January; 82(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580844&dopt=Abstract

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Life event timing and the emotional consequences of surgical menopause for AsianPacific women in Guam. Author(s): Pinhey TK, Pinhey DL. Source: Women Health. 2002; 36(4): 43-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555801&dopt=Abstract

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Managing menopause. Author(s): Cutson TM, Meuleman E. Source: American Family Physician. 2000 March 1; 61(5): 1391-400, 1405-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10735345&dopt=Abstract

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Managing the menopause: phyto-oestrogens or hormone replacement therapy? Author(s): Eden JA. Source: Annals of Medicine. 2001 February; 33(1): 4-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11310938&dopt=Abstract

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Maori women and menopause. Author(s): Lawton B, Reid P, Cormack D, Dowell T, Stone P. Source: Pac Health Dialog. 2001 March; 8(1): 163-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017818&dopt=Abstract

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Medical choices available for management of menopause. Author(s): Farrell E. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 1-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763509&dopt=Abstract

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Menopause and cognitive function: estrogens and alternative therapies. Author(s): Jones KP.

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Source: Clinical Obstetrics and Gynecology. 2000 March; 43(1): 198-206. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695000&dopt=Abstract ·

Menopause and colorectal cancer. Author(s): Franceschi S, Gallus S, Talamini R, Tavani A, Negri E, La Vecchia C. Source: British Journal of Cancer. 2000 June; 82(11): 1860-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10839302&dopt=Abstract

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Menopause and mood. Is depression linked with hormone changes? Author(s): Dell DL, Stewart DE. Source: Postgraduate Medicine. 2000 September 1; 108(3): 34-6, 39-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11004934&dopt=Abstract

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Menopause in highland Guatemala Mayan women. Author(s): Stewart DE. Source: Maturitas. 2003 April 25; 44(4): 293-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697370&dopt=Abstract

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Menopause, naturally. Exploring alternatives to traditional hormone replacement therapy. Author(s): Lindsay SH. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 1999 October-November; 3(5): 32-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10827581&dopt=Abstract

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Menopause: choices for women. Author(s): Kroon V, Boyd L. Source: Australian Nursing Journal (July 1993). 2001 February; 8(7): Suppl 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11894570&dopt=Abstract

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Mind control of menopause. Author(s): Younus J, Simpson I, Collins A, Wang X. Source: Women's Health Issues : Official Publication of the Jacobs Institute of Women's Health. 2003 March-April; 13(2): 74-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732444&dopt=Abstract

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Options and issues in managing menopause. Author(s): Murray JL. Source: American Family Physician. 2000 March 1; 61(5): 1285, 1288. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10735339&dopt=Abstract

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Oversights detract from CME article on menopause. Author(s): Frey G. Source: Alternative Therapies in Health and Medicine. 2001 November-December; 7(6): 20-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712465&dopt=Abstract

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Perceptions about menopause and health practises among women in northeast Thailand. Author(s): Chirawatkul S, Patanasri K, Koochaiyasit C. Source: Nursing & Health Sciences. 2002 September; 4(3): 113-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153409&dopt=Abstract

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Perceptions of alternative therapies available for women facing hysterectomy or menopause. Author(s): Richter DL, Corwin SJ, Rheaume CE, McKeown RE. Source: J Women Aging. 2001; 13(4): 21-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876431&dopt=Abstract

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Phytoestrogens and menopause. Pharmacological attributes of plant based drugs should be discussed widely. Author(s): de Lemos M. Source: Bmj (Clinical Research Ed.). 2002 January 5; 324(7328): 52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11797646&dopt=Abstract

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Phytoestrogens and menopause. Published evidence supports a role for phytoestrogens in menopause. Author(s): Husband AJ. Source: Bmj (Clinical Research Ed.). 2002 January 5; 324(7328): 52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11777814&dopt=Abstract

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Phytoestrogens and the menopause. Author(s): Mackey R, Eden J. Source: Climacteric : the Journal of the International Menopause Society. 1998 December; 1(4): 302-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907938&dopt=Abstract

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Phytoestrogens in the management of the menopause: up-to-date. Author(s): Ewies AA. Source: Obstetrical & Gynecological Survey. 2002 May; 57(5): 306-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997677&dopt=Abstract

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Pregnancy in the postmenopause: how far can assisted reproductive technology be trusted? Author(s): al-Inany HG. Source: Obstetrical & Gynecological Survey. 2000 February; 55(2): 67-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10674252&dopt=Abstract

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Prevalence of and satisfaction with complementary therapies and hormone replacement therapy in a specialist menopause clinic. Author(s): Vashisht A, Domoney CL, Cronje W, Studd JW. Source: Climacteric : the Journal of the International Menopause Society. 2001 September; 4(3): 250-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588949&dopt=Abstract

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Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. Author(s): Stomati M, Monteleone P, Casarosa E, Quirici B, Puccetti S, Bernardi F, Genazzani AD, Rovati L, Luisi M, Genazzani AR. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 October; 14(5): 342-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11109974&dopt=Abstract

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Soy isoflavones: are they useful in menopause? Author(s): Vincent A, Fitzpatrick LA. Source: Mayo Clinic Proceedings. 2000 November; 75(11): 1174-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11075748&dopt=Abstract

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Take the medical model out of the menopause. Author(s): MacWhannell D. Source: Nurs Times. 1999 October 13-19; 95(41): 45-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10786602&dopt=Abstract

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TCM/Kampo therapy also efficacious for menopause. Author(s): Lerner JH. Source: Alternative Therapies in Health and Medicine. 2001 November-December; 7(6): 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712466&dopt=Abstract

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The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Author(s): Wuttke W, Seidlova-Wuttke D, Gorkow C. Source: Maturitas. 2003 March 14; 44 Suppl 1: S67-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609561&dopt=Abstract

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The emergence of the menopause in India. Author(s): Sengupta A. Source: Climacteric : the Journal of the International Menopause Society. 2003 June; 6(2): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841878&dopt=Abstract

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The estrogen question: more than one answer for women at menopause. Author(s): Brink S. Source: U.S. News & World Report. 2000 July 3; 129(1): 51-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10977517&dopt=Abstract

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The furor over alternative therapy for menopause. Author(s): Parkman C. Source: The Case Manager. 2003 May-June; 14(3): 32-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750685&dopt=Abstract

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The impact of premature menopause on women's experience of self. Author(s): Pasquali EA. Source: Journal of Holistic Nursing : Official Journal of the American Holistic Nurses' Association. 1999 December; 17(4): 346-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10818847&dopt=Abstract

·

The menopause in Japan--Konenki Jigoku. Author(s): Albery N. Source: Climacteric : the Journal of the International Menopause Society. 1999 September; 2(3): 160-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910591&dopt=Abstract

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The use of food supplements among women attending menopause clinics in the West Midlands. Author(s): Gokhale L, Sturdee DW, Parsons AD. Source: The Journal of the British Menopause Society. 2003 March; 9(1): 32-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804311&dopt=Abstract

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Use of alternative and complementary medicine in menopause. Author(s): Kang HJ, Ansbacher R, Hammoud MM. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 December; 79(3): 195-207. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445983&dopt=Abstract

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Use of alternative therapies for menopause symptoms: results of a population-based survey. Author(s): Newton KM, Buist DS, Keenan NL, Anderson LA, LaCroix AZ. Source: Obstetrics and Gynecology. 2002 July; 100(1): 18-25. Erratum In: Obstet Gynecol 2003 January; 101(1): 205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100799&dopt=Abstract

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Use of alternative therapies in menopause. Author(s): Warren MP, Shortle B, Dominguez JE. Source: Best Practice & Research. Clinical Obstetrics & Gynaecology. 2002 June; 16(3): 411-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099671&dopt=Abstract

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Use of alternatives to estrogen for treatment of menopause. Author(s): Pinkerton JV, Santen R. Source: Minerva Endocrinol. 2002 March; 27(1): 21-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11845111&dopt=Abstract

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Use of phytoestrogens in menopause. Author(s): Scambia G, Gallo D, Foti E. Source: J Endocrinol Invest. 2002 September; 25(8): 668-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12240896&dopt=Abstract

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Women in transition--menopause and body composition in different populations. Author(s): Arechiga J, Prado C, Canto M, Carmenate M. Source: Coll Antropol. 2001 December; 25(2): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11811273&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to menopause; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: ·

General Overview Acne Source: Prima Communications, Inc.www.personalhealthzone.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Amenorrhea Source: Healthnotes, Inc. www.healthnotes.com Amenorrhea Source: Integrative Medicine Communications; www.drkoop.com Angina Source: Healthnotes, Inc. www.healthnotes.com Angina Source: Integrative Medicine Communications; www.drkoop.com Anxiety Source: Healthnotes, Inc. www.healthnotes.com Anxiety and Panic Attacks Source: Prima Communications, Inc.www.personalhealthzone.com Arteriosclerosis Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com

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Breast Cancer Source: Healthnotes, Inc. www.healthnotes.com Breast Cancer Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Cardiovascular Disease Overview Source: Healthnotes, Inc. www.healthnotes.com Carpal Tunnel Syndrome Source: Integrative Medicine Communications; www.drkoop.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Coronary Artery Disease Source: Integrative Medicine Communications; www.drkoop.com Dementia Source: Integrative Medicine Communications; www.drkoop.com Depression Source: Healthnotes, Inc. www.healthnotes.com Depression Source: Integrative Medicine Communications; www.drkoop.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Dysmenorrhea Source: Healthnotes, Inc. www.healthnotes.com Erectile Dysfunction Source: Healthnotes, Inc. www.healthnotes.com Female Infertility Source: Healthnotes, Inc. www.healthnotes.com Fibrocystic Breast Disease Source: Healthnotes, Inc. www.healthnotes.com Gout Source: Integrative Medicine Communications; www.drkoop.com

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Heart Attack Source: Healthnotes, Inc. www.healthnotes.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Healthnotes, Inc. www.healthnotes.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com High Homocysteine Source: Healthnotes, Inc. www.healthnotes.com Hirsuitism Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Immune Function Source: Healthnotes, Inc. www.healthnotes.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Iron-Deficiency Anemia Source: Healthnotes, Inc. www.healthnotes.com Lupus Source: Integrative Medicine Communications; www.drkoop.com Menopausal Symptoms (Other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Healthnotes, Inc. www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com

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Migraine Headache Source: Integrative Medicine Communications; www.drkoop.com Migraine Headaches Source: Healthnotes, Inc. www.healthnotes.com Myocardial Infarction Source: Integrative Medicine Communications; www.drkoop.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Healthnotes, Inc. www.healthnotes.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com PMS Source: Integrative Medicine Communications; www.drkoop.com PMS Alternative names: Premenstrual Stress Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Premenstrual Syndrome Source: Healthnotes, Inc. www.healthnotes.com Premenstrual Syndrome Source: Integrative Medicine Communications; www.drkoop.com Senile Dementia Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Healthnotes, Inc. www.healthnotes.com Systemic Lupus Erythematosus Source: Healthnotes, Inc. www.healthnotes.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com Vaginitis Source: Healthnotes, Inc. www.healthnotes.com

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Varicose Veins Source: Integrative Medicine Communications; www.drkoop.com Weight Loss and Obesity Source: Healthnotes, Inc. www.healthnotes.com Wilson's Disease Source: Healthnotes, Inc. www.healthnotes.com ·

Alternative Therapy Acupuncture Source: Healthnotes, Inc. www.healthnotes.com Acupuncture Source: Integrative Medicine Communications; www.drkoop.com Bach flower remedies Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,673,00.html Herbal Medicine Source: Integrative Medicine Communications; www.drkoop.com Meditation Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,717,00.html Shamanic herbalism Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/s.html

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Chinese Medicine Gengnian'an Pian Alternative names: Gengnian'an Tablets Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Gengnian%27an%20Pian&mh =10&sb=---&view_records=View+Records

·

Homeopathy Calcarea carbonica Source: Healthnotes, Inc. www.healthnotes.com

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Glonoinum Source: Healthnotes, Inc. www.healthnotes.com Graphites Source: Healthnotes, Inc. www.healthnotes.com Ignatia Source: Healthnotes, Inc. www.healthnotes.com Lachesis Source: Healthnotes, Inc. www.healthnotes.com Lilium tigrinum Source: Healthnotes, Inc. www.healthnotes.com Natrum muriaticum Source: Healthnotes, Inc. www.healthnotes.com Pulsatilla Source: Healthnotes, Inc. www.healthnotes.com Sepia Source: Healthnotes, Inc. www.healthnotes.com Staphysagria Source: Healthnotes, Inc. www.healthnotes.com Sulphur Source: Healthnotes, Inc. www.healthnotes.com ·

Herbs and Supplements Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org ALA Source: Integrative Medicine Communications; www.drkoop.com Alfalfa Alternative names: Medicago sativa Source: Healthnotes, Inc. www.healthnotes.com Alpha-Linolenic Acid (ALA) Source: Integrative Medicine Communications; www.drkoop.com Anastrozole Source: Healthnotes, Inc. www.healthnotes.com Androstenedione Source: Healthnotes, Inc. www.healthnotes.com

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Angelica sinensis Source: Integrative Medicine Communications; www.drkoop.com Antacids Source: Prima Communications, Inc.www.personalhealthzone.com Asian Ginseng Source: Healthnotes, Inc. www.healthnotes.com Beta-Carotene Source: Prima Communications, Inc.www.personalhealthzone.com Black Cohosh Alternative names: Cimicifuga racemosa Source: Healthnotes, Inc. www.healthnotes.com Black Cohosh Alternative names: Cimicifuga racemosa (actea), Black Snakeroot Source: Integrative Medicine Communications; www.drkoop.com Black Cohosh Source: Prima Communications, Inc.www.personalhealthzone.com Black cohosh Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10009,00.html Black Snakeroot Source: Integrative Medicine Communications; www.drkoop.com Bone-building formula Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,838,00.html Caffeine Source: Healthnotes, Inc. www.healthnotes.com Calciferol Source: Integrative Medicine Communications; www.drkoop.com Calcitrol Source: Integrative Medicine Communications; www.drkoop.com Camellia sinensis Source: Integrative Medicine Communications; www.drkoop.com Carotenoids Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,763,00.html

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Chaste Tree Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Chasteberry Source: Prima Communications, Inc.www.personalhealthzone.com Chasteberry Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,767,00.html Chemotherapy Source: Healthnotes, Inc. www.healthnotes.com Chinese Angelica Source: Integrative Medicine Communications; www.drkoop.com Cholecalciferol Source: Integrative Medicine Communications; www.drkoop.com Cimicifuga Alternative names: Black Cohosh; Cimicifuga racemosa (NUTT.) Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Cimicifuga racemosa (actea) Source: Integrative Medicine Communications; www.drkoop.com Clonidine Source: Healthnotes, Inc. www.healthnotes.com Cramp Bark Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Cyclophosphamide Source: Healthnotes, Inc. www.healthnotes.com Dandelion Source: Prima Communications, Inc.www.personalhealthzone.com Danggui Alternative names: Angelica sinensis, Chinese Angelica, Dang Gui, Danngui, Dong Qua, Tang Kuei, Tan Kue Bai zhi(Note: Dong quai should not be confused with Angelica root or Angelica seed.) Source: Integrative Medicine Communications; www.drkoop.com Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc. www.healthnotes.com Dehydroepiandrosterone (DHEA) Source: Integrative Medicine Communications; www.drkoop.com

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DHEA Source: Integrative Medicine Communications; www.drkoop.com DHEA (Dehydroepiandrosterone) Source: Prima Communications, Inc.www.personalhealthzone.com Diclofenac Source: Healthnotes, Inc. www.healthnotes.com Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com Docetaxel Source: Healthnotes, Inc. www.healthnotes.com Docosahexaenoic Acid Source: Healthnotes, Inc. www.healthnotes.com Dong Quai Alternative names: Angelica sinensis Source: Healthnotes, Inc. www.healthnotes.com Dong Quai Alternative names: Angelica sinensis, Chinese Angelica, Dang Gui, Danngui, Dong Qua, Tang Kuei, Tan Kue Bai zhi(Note: Dong quai should not be confused with Angelica root or Angelica seed.) Source: Integrative Medicine Communications; www.drkoop.com Dong Quai Source: Prima Communications, Inc.www.personalhealthzone.com Dong quai (angelica) Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,774,00.html Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Estradiol Source: Healthnotes, Inc. www.healthnotes.com Estrogen Source: Prima Communications, Inc.www.personalhealthzone.com Estrogens Source: Healthnotes, Inc. www.healthnotes.com Estrogens (Combined) Source: Healthnotes, Inc. www.healthnotes.com

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Estropipate Source: Healthnotes, Inc. www.healthnotes.com False unicorn root Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10075,00.html Fiber Source: Healthnotes, Inc. www.healthnotes.com Flavonoids Source: Healthnotes, Inc. www.healthnotes.com Flavonoids Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,782,00.html Flaxseed Alternative names: Linum usitatissimum, Linseed Source: Integrative Medicine Communications; www.drkoop.com Fluorouracil Source: Healthnotes, Inc. www.healthnotes.com Gamma Oryzanol Source: Prima Communications, Inc.www.personalhealthzone.com Gamma-oryzanol Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10028,00.html Ginkgo biloba Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,788,00.html GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Green Tea Alternative names: Camellia sinensis Source: Integrative Medicine Communications; www.drkoop.com Inhalant, Systemic, and Topical Corticosteroids Source: Integrative Medicine Communications; www.drkoop.com Inhaled Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com

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Ipriflavone Source: Healthnotes, Inc. www.healthnotes.com Ipriflavone Source: Prima Communications, Inc.www.personalhealthzone.com Ipriflavone Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10039,00.html Isoflavones Source: Prima Communications, Inc.www.personalhealthzone.com Kava Alternative names: Piper methysticum Source: Healthnotes, Inc. www.healthnotes.com Kava Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,798,00.html Lepidium meyenii1 Alternative names: Maca; Lepidium meyenii Walp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc. www.healthnotes.com Licorice Source: Prima Communications, Inc.www.personalhealthzone.com Licorice Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Linseed Source: Integrative Medicine Communications; www.drkoop.com Linum usitatissimum Source: Integrative Medicine Communications; www.drkoop.com Medroxyprogesterone Source: Healthnotes, Inc. www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com

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Melatonin Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html Menadione Source: Integrative Medicine Communications; www.drkoop.com Menaphthone Source: Integrative Medicine Communications; www.drkoop.com Menaquinone Source: Integrative Medicine Communications; www.drkoop.com Menopause herbal combination Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10096,00.html Methotrexate Source: Healthnotes, Inc. www.healthnotes.com Methyltestosterone Source: Healthnotes, Inc. www.healthnotes.com Monophasic, Biphasic, and Triphasic Preparations Source: Integrative Medicine Communications; www.drkoop.com Motherwort Alternative names: Leonurus cardiaca Source: Healthnotes, Inc. www.healthnotes.com Motherwort Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Natural progesterone cream Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10099,00.html Oral Contraceptives Source: Healthnotes, Inc. www.healthnotes.com Paclitaxel Source: Healthnotes, Inc. www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc. www.amfoundation.org

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Phosphorus Source: Integrative Medicine Communications; www.drkoop.com Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Pollen Source: Healthnotes, Inc. www.healthnotes.com Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com Progesterone Source: Healthnotes, Inc. www.healthnotes.com Raloxifene Source: Healthnotes, Inc. www.healthnotes.com Red Clover Alternative names: Trifolium pratense Source: Healthnotes, Inc. www.healthnotes.com Red Clover Alternative names: Trifolium pratense , beebread, cow clover, cow grass, meadow clover, purple clover Source: Integrative Medicine Communications; www.drkoop.com Red Clover Source: Prima Communications, Inc.www.personalhealthzone.com Royal Jelly Source: Healthnotes, Inc. www.healthnotes.com Sage Alternative names: Salvia officinalis Source: Healthnotes, Inc. www.healthnotes.com SAMe Source: Healthnotes, Inc. www.healthnotes.com SAMe (S-Adenosylmethionine) Source: Prima Communications, Inc.www.personalhealthzone.com Siberian ginseng Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,821,00.html Soy isoflavones Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10057,00.html

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St. John’s Wort Alternative names: Hypericum perforatum Source: Healthnotes, Inc. www.healthnotes.com St. John's Wort Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca St. John's Wort Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html Suma Alternative names: Pfaffia paniculata , Hebanthe paniculata Source: Healthnotes, Inc. www.healthnotes.com Suma Source: Prima Communications, Inc.www.personalhealthzone.com Tang Kuei Source: Integrative Medicine Communications; www.drkoop.com Thiazide Diuretics Source: Healthnotes, Inc. www.healthnotes.com Thiazide Diuretics Source: Prima Communications, Inc.www.personalhealthzone.com Thyroid Hormones Source: Healthnotes, Inc. www.healthnotes.com Tribulus Puncture Alternative names: Puncture Vine, Goathead; Tribulus terrestris L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Vitex Alternative names: Chaste; Vitex agnus-castus Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Warfarin Source: Healthnotes, Inc. www.healthnotes.com Wild Yam Alternative names: Dioscorea villosa Source: Healthnotes, Inc. www.healthnotes.com Wild yam Alternative names: Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com

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Wild yam Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10070,00.html Women's herbal combination Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10100,00.html

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON MENOPAUSE Overview In this chapter, we will give you a bibliography on recent dissertations relating to menopause. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “menopause” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on menopause, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Menopause ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to menopause. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: ·

A Study of Awareness and Knowledge of Menopause for the General Health Concern of Menopausal Women by Healy, Ranae, Phd from Walden University, 1995, 121 pages http://wwwlib.umi.com/dissertations/fullcit/9602151

·

A Study of the Relationship between Attitude toward Menopause, Reported Symptoms and Role Involvements of Middle Aged Women by Wilheim, Beatrice Verdes, Phd from Temple University, 1988, 112 pages http://wwwlib.umi.com/dissertations/fullcit/8902996

·

An Ethnography of Menopause: Menopausal Experiences of Mayan Women in a Yucatan Village (mexico) by Beyene, Yewoubdar, Phd from Case Western Reserve University, 1985, 201 pages http://wwwlib.umi.com/dissertations/fullcit/8510111

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An Investigation of the Health Concerns of the Menopause Discussion Group on Internet by Giordano, Nancy A., Edd from Columbia University Teachers College, 1995, 230 pages http://wwwlib.umi.com/dissertations/fullcit/9606654

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Are Perimenopausal and Postmenopausal Women More Apt to Choose Hormone Replacement Therapy If They Are More Knowledgeable about the Effects of Said Therapy? by Pineda, Cleo C. Ms from California State University, Long Beach, 2002, 58 pages http://wwwlib.umi.com/dissertations/fullcit/1410331

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Attitudes toward Menopause among Midlife Women in the United States: a Phenomenological Study by Pingree, Dianne P., Phd from Texas Woman's University, 1994, 197 pages http://wwwlib.umi.com/dissertations/fullcit/9522022

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Attitudes toward Menopause in Midlife Women (sexuality) by Seymour, Sandra Elizabeth Fields, Phd from The Florida State University, 1986, 122 pages http://wwwlib.umi.com/dissertations/fullcit/8702247

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Attitudes toward Menopause of College-educated Women: a Factor Analytic Study by Battistoni, Susan Boyer; Phd from University of Maryland College Park, 2000, 155 pages http://wwwlib.umi.com/dissertations/fullcit/9982785

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Biological and Cultural Effects of Obesity on Women during Menopause by Smith, Linda Kay, Phd from Wayne State University, 1987, 160 pages http://wwwlib.umi.com/dissertations/fullcit/8714563

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Blood, Sweat, and Tears: Social Concealment of Menopause by Kittell, Linda Ann Madden, Phd from The Pennsylvania State University, 1996, 158 pages http://wwwlib.umi.com/dissertations/fullcit/9702320

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Changing Women: Stories and Journeys of Menopause by Colletti, Francesca Mary, Edd from Syracuse University, 1996, 169 pages http://wwwlib.umi.com/dissertations/fullcit/9737806

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Climacteric among the 'new' Women of Mochudi, Botswana (gender Roles, Menopause, South Africa) by Suggs, David N., Phd from University of Florida, 1986, 244 pages http://wwwlib.umi.com/dissertations/fullcit/8716049

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Common Experiences and Changing Meanings: Women, Medicine, and Menopause in the United States, 1897-1980 by Houck, Judith Anne, Phd from The University of Wisconsin - Madison, 1998, 472 pages http://wwwlib.umi.com/dissertations/fullcit/9910440

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Cultural Variability in the Experience of Menopause: a Comparison of Navajo and Western Data by Wright, Anne Lucille, Phd from The University of Arizona, 1980, 234 pages http://wwwlib.umi.com/dissertations/fullcit/8011128

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Depression and Anxiety in Postmenopausal Women: a Study of Black, White, and Hispanic Women by Groessl, Patricia Ann, Edd from Western Michigan University, 1987, 87 pages http://wwwlib.umi.com/dissertations/fullcit/8714651

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Differential Diagnosis of Women in Drug Treatment: Methadone or Menopause by Tuchman, Ellen Lee; Phd from New York University, 2003, 198 pages http://wwwlib.umi.com/dissertations/fullcit/3073504

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Effect of Exercise Mode on Bone Mineral Mass in Recently Postmenopausal Women by Little, Kathleen Dudley, Phd from Kent State University, 1992, 150 pages http://wwwlib.umi.com/dissertations/fullcit/9317550

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Effects of N-3 Supplementation in Postmenopausal Women Receiving and Not Receiving Hormone Replacement Therapy by Stark, Kenneth Douglas; Phd from University of Guelph (canada), 2002, 163 pages http://wwwlib.umi.com/dissertations/fullcit/NQ67237

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Embodied Knowing: Women's Menopausal and Mid-life Stories (women's Body Experiences) by Jones, Jill B., Phd from Bryn Mawr College, the Grad. Sch. of Social Work and Social Research, 1993, 268 pages http://wwwlib.umi.com/dissertations/fullcit/9328314

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Exploring the Relationship of Attitude, Knowledge, Support, and Self-efficacy on Intent to Adhere to Hormonal Replacement Therapy for Menopause by Wilhelm, Susan Lynn; Phd from University of Wyoming, 2001, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3010736

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Factors Associated with the Utilization of Hormone Replacement Therapy among Postmenopausal Women: a Case Study of a Suburban Philadelphia Retirement Community (pennsylvania) by Powers, Barbara L., Phd from Temple University, 1996, 94 pages http://wwwlib.umi.com/dissertations/fullcit/9623796

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Feminist Praxis in the Making: the Menopause Collective (medicalization, Women's Health Movement, Self-help, Conflict) by Macpherson, Kathleen Isabelle, Phd from Brandeis University, 1986, 449 pages http://wwwlib.umi.com/dissertations/fullcit/8617017

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From 'goodwives' to Menoboomers: Reinventing Menopause in American History (aging, Womanhood) by Barbre, Joy Webster, Phd from University of Minnesota, 1994, 251 pages http://wwwlib.umi.com/dissertations/fullcit/9428910

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Heritability in the Age of Menopause and the Genetic Correlation between the Ages of Menarche and Menopause by Peccei, Jocelyn Scott, Phd from University of California, Los Angeles, 1998, 154 pages http://wwwlib.umi.com/dissertations/fullcit/9905509

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Human Ovarian Function in Late Reproductive Life (reproductive Senescence, Menopause) by O'rourke, Mary T., Phd from Harvard University, 1992, 162 pages http://wwwlib.umi.com/dissertations/fullcit/9228346

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Influence of Motherhood and Other Psychosocial Variables in How Women Experience Menopause (spanish Text) by Cavalcanti Cabral, Maria Das Merces; Dr from Universidad De Deusto (spain), 2003, 348 pages http://wwwlib.umi.com/dissertations/fullcit/3076826

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Language of Menopause: the Change in Japan by Zeserson, Jan Morgan, Phd from Cornell University, 1996, 307 pages http://wwwlib.umi.com/dissertations/fullcit/9639565

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Measure of Attitude toward Menopause Using the Semantic Differential Model by Bowles, Cheryl Lee, Edd from Northern Illinois University, 1984, 213 pages http://wwwlib.umi.com/dissertations/fullcit/8426692

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Medusa at Menopause: Writing from the Crone's Body by Kirkpatrick, Kim; Phd from Saint Louis University, 2002, 261 pages http://wwwlib.umi.com/dissertations/fullcit/3059677

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Menopausal Experiences: a Comparison of White and Black Women Utilizing Theory of Planned Behavior and Other Predictor Variables by Spatz, Barbara A. Phd from Kent State University, 2001, 151 pages http://wwwlib.umi.com/dissertations/fullcit/3026116

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Menopause in Social Context: Women's Experiences of Reproductive Aging in the United States by Dillaway, Heather Elise; Phd from Michigan State University, 2002, 475 pages http://wwwlib.umi.com/dissertations/fullcit/3074998

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Menopause: a Symbolic Interactionist Perspective by Estok, Patricia Jenaway, Phd from Kent State University, 1981, 165 pages http://wwwlib.umi.com/dissertations/fullcit/8121088

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Menopause: Perceptions and Meanings of Lived Experiences of the Agikuyu Postmenopausal Women of Kenya by Kamau, Wanjiru Josephine, Edd from The Pennsylvania State University, 1998, 276 pages http://wwwlib.umi.com/dissertations/fullcit/9915869

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Midlife African American Women's Attitudes toward Menopause and the Relationship between Attitudes and Menopausal Symptom Reporting by Huffman, Shirley Baker; Phd from The University of North Carolina at Greensboro, 1999, 217 pages http://wwwlib.umi.com/dissertations/fullcit/9958907

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Midlife Women Making Decisions about Menopausal Symptoms by Axley, Lawrette Bright; Phd from The University of Tennessee Center for the Health Sciences, 2003, 135 pages http://wwwlib.umi.com/dissertations/fullcit/3085393

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Migration and Menopause: Women's Experience of Maturation in Three Immigrant Communities by Spitzer, Denise Lee, Phd from University of Alberta (canada), 1998, 196 pages http://wwwlib.umi.com/dissertations/fullcit/NQ29112

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Patterns and Predictors of Bone Mineral Density and Its Change among Pre-, and Early Postmenopausal Women: toward the Identification of At-risk Women by Bainbridge, Kathleen Elise; Phd from University of Michigan, 2003, 128 pages http://wwwlib.umi.com/dissertations/fullcit/3079406

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Perceptions of Menopause: Importance of Role Satisfaction in a Peruvian Town (bart Model) by Barnett, Elyse Ann, Phd from Stanford University, 1986, 215 pages http://wwwlib.umi.com/dissertations/fullcit/8612712

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Psychological Reactions to Menopause: a Sociological Study by Lennon, Mary Clare, Phd from Columbia University, 1980, 244 pages http://wwwlib.umi.com/dissertations/fullcit/8104946

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Quality of Life Enhancement for Women Approaching Menopause Based on Participatory Research by Theisen, Susan Carol, Phd from The Pennsylvania State University, 1992, 382 pages http://wwwlib.umi.com/dissertations/fullcit/9311735

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Race, Class and the Change: a Cultural Analysis of American Women's and Biomedical Care Providers' Conceptualizations of Menopause by Agee, Eve, Phd from University of Virginia, 1999, 248 pages http://wwwlib.umi.com/dissertations/fullcit/9930091

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Raising Voices: an Analysis of the Narratives of Post-menopausal Women on the Experience of Menopause by Miller, Kelly Marie, Phd from The Pennsylvania State University, 1994, 114 pages http://wwwlib.umi.com/dissertations/fullcit/9518819

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Reading Elizabeth: Menopause and the Cult of the Virgin Queen by Bennett, Stephen Smith, Phd from New York University, 1997, 356 pages http://wwwlib.umi.com/dissertations/fullcit/9731374

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Responses to Aerobic Training of Pre- and Post-menopausal Women by Cowan, Mary Albrecht, Phd from The University of New Mexico, 1983, 130 pages http://wwwlib.umi.com/dissertations/fullcit/8404431

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Revolutionary Women at Middle Age: an Ethnographic Survey of Menopause and Midlife Aging in Beijing, China by Shea, Jeanne Laraine, Phd from Harvard University, 1998, 353 pages http://wwwlib.umi.com/dissertations/fullcit/9832306

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Self-care Responses in Breast Cancer Survivors Who Are Menopausal by Carsonmccollum, Candace Lynn; Ms from University of Alaska Anchorage, 2002, 100 pages http://wwwlib.umi.com/dissertations/fullcit/1409945

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Self-care Responses of Rural Thai Perimenopausal Women by Chaiphibalsarisdi, Puangtip, Phd from University of Illinois at Chicago, Health Sciences Center, 1990, 211 pages http://wwwlib.umi.com/dissertations/fullcit/9104543

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Social and Personality Correlates of Psychological Adjustment in Perimenopausal Women (menopause) by Martin, Anne Hamilton, Phd from New York University, 1996, 169 pages http://wwwlib.umi.com/dissertations/fullcit/9622194

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Suffering, Modernity and Morality: Menopause in Urban Oaxaca, Mexico by Ramirez, Michelle Lynette; Phd from The University of Iowa, 2002, 195 pages http://wwwlib.umi.com/dissertations/fullcit/3073394

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The Central Role of Objectification in the Experience of Menopause by Herberger, Jeanne Lind; Phd from Arizona State University, 2000, 104 pages http://wwwlib.umi.com/dissertations/fullcit/9962920

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The Changing Woman: Reflections at Menopause on the Meaning and Experience of Sexuality by Trapedo-dworsky, Madeleine, Phd from University of Toronto (canada), 1997, 285 pages http://wwwlib.umi.com/dissertations/fullcit/NQ28070

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The Consequences of Serum Calcium Homeostasis, Reproductive Life History and Bone Mineral Content in Postmenopausal Women with Implications to Theories of Aging by Huxley, Angie Kay; Phd from The University of Arizona, 1999, 767 pages http://wwwlib.umi.com/dissertations/fullcit/9946785

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The Effects of Resistance Training on Fracture Risk and Psychological Variables in Postmenopausal Women (menopause) by Shaw, Janet Marie, Phd from Oregon State University, 1995, 147 pages http://wwwlib.umi.com/dissertations/fullcit/9535976

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The Experience and Knowledge of Menopause among Low-income Cleveland Women (ohio) by Cooney, Margaret Cecilia; Phd from Case Western Reserve University, 2002, 272 pages http://wwwlib.umi.com/dissertations/fullcit/3066029

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The Experience of Menopause: a Phenomenological Investigation by Lundgren, Joan D., Phd from California Institute of Integral Studies, 1992, 442 pages http://wwwlib.umi.com/dissertations/fullcit/9315426

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The Incidence of Panic Disorder Presentation Related to Perimenopausal Women by Balentine, Pamela Virginia; Phd from Capella University, 2002, 95 pages http://wwwlib.umi.com/dissertations/fullcit/3068399

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The Lived Experience of Menopause in Immigrant Haitian Women: a Phenomenological Analysis by Bellefleur, Carmelle Marie, Phd from Adelphi University, 1996, 294 pages http://wwwlib.umi.com/dissertations/fullcit/9717836

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The New Menopause: Growing the Wise Woman by Walden, Jacqueline, Phd from University of California, Riverside, 1995, 266 pages http://wwwlib.umi.com/dissertations/fullcit/9527806

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The Social Definition of Bodily State Changes: the Menopause. by Mitteness, Linda S., Phd from The Pennsylvania State University, 1979, 348 pages http://wwwlib.umi.com/dissertations/fullcit/7915726

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The Timing of Menopause in Biological and Sociocultural Context: a Lifespan Approach (age Scales) by Leidy, Lynnette E., Phd from State University of New York at Albany, 1991, 268 pages http://wwwlib.umi.com/dissertations/fullcit/9123801

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Unravelling the Account of Menopause As Hormone Deficiency: Working Practices of the Menopause Clinic by Guillemin, Marilys Noelle, Phd from University of Melbourne (australia), 1997, 258 pages http://wwwlib.umi.com/dissertations/fullcit/9732583

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Women in Transition: Discourses of Menopause by Mcpherson, Sue; Ma from University of Windsor (canada), 2002, 163 pages http://wwwlib.umi.com/dissertations/fullcit/MQ75798

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Women's Expectations about Menopause: How Expectations Are Affected by Demographic Characteristics, Sex Role, Life Satisfaction, Career Salience, the Mother's Menopausal Experience and Other Factors by Blanco, Michelle, Phd from New York University, 1994, 224 pages http://wwwlib.umi.com/dissertations/fullcit/9502369

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Women's Experience of Menopause in a Newfoundland Fishing Village by Davis, Dona Lee, Phd from The University of North Carolina at Chapel Hill, 1980, 303 pages http://wwwlib.umi.com/dissertations/fullcit/8022443

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Women's Perceptions of Menopause: an Examination of the Use of Personal Models Theory by Schnebly, Mary L., Phd from University of Oregon, 1993, 137 pages http://wwwlib.umi.com/dissertations/fullcit/9405224

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Women's Ways of Speaking about Menopause and Hormone Replacement Therapy: an American Discourse on Personhood by Suopis, Cynthia Anne; Phd from University of Massachusetts Amherst, 2002, 274 pages http://wwwlib.umi.com/dissertations/fullcit/3056283

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND MENOPAUSE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning menopause.

Recent Trials on Menopause The following is a list of recent trials dedicated to menopause.8 Further information on a trial is available at the Web site indicated. ·

Black cohosh and red clover efficacy for the relief of menopausal symptoms Condition(s): Hot Flashes; Menopause Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM); National Institute of General Medical Sciences (NIGMS); Office of Dietary Supplements (ODS); Office of Research on Women's Health (ORWH) Purpose - Excerpt: This Phase II study, a follow-up to a Phase I trial in normal volunteers, will determine the efficacy of black cohosh and red clover for the relief of menopausal symptoms. It will also assess the safety of chronic dosing (1 year) by evaluating uterine (endometrial biopsies), breast (mammography), and hematology parameters (CBC and chemistry lab values) at baseline and 1 year. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066144

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Black Cohosh Extract in Postmenopausal Breast Health Condition(s): Menopause; Hot Flashes Study Status: This study is currently recruiting patients.

8

These are listed at www.ClinicalTrials.gov.

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Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of the study is to determine if black cohosh extract (BCE) administration in symptomatic postmenopausal women results in estrogenic stimulation of the breast, as determined by estradiol, pS2, FSH, LH, and PSA levels in nipple aspirate fluid. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064831 ·

Bone Loss in Premenopausal Women with Depression Condition(s): Depression; Healthy; Osteopenia; Osteoporosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to determine whether women with major depression lose bone mass at a faster rate than women without depression. This study will also determine if the drug alendronate can maintain or increase bone mass in premenopausal women with major depression and osteoporosis. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006180

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Buccal estrogen in toothpaste study: Systemic absorption of estradiol when administered mixed with toothpaste in postmenopausal or surgically menopausal women Condition(s): Menopause; Postmenopause Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Background: The use of estrogen in postmenopausal (or surgically menopausal) women is a common practice. Compliance is problematic in that estimates show only 1/3 of women use hormone replacement therapy (HRT) and only 30% are compliant. Estrogen has many documented benefits including symptomatic relief of hot flashes, improvement of the dry vagina and dysparunia. Estrogen has been found to improve bone mineral density and increase the high- density lipoprotein portion of a cholesterol panel. To improve compliance and to provide an alternate method of delivery, we propose the use of estrogen which is admixed in toothpaste and propose to study the absorption, rate of build-up and rate of decline. Hypothesis: Estrogen can potentially be absorbed systemically when toothpaste is admixed with estradiol and is applied in a timed, consistent fashion to postmenopausal or surgically postmenopausal women, not on HRT. Absorption takes place across the buccal mucosa. Specific Aims:1) To estimate the systemic absorption of estrogen from daily use of estrogen containing toothpaste. 2) To estimate the rate of build-up of serum estrogen levels based upon daily use of toothpaste containing estrogen for eight days. 3) To estimate the rate of decline in

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serum estrogen levels when the use of estrogen containing toothpaste is discontinued for a week. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029757 ·

Celecoxib in Preventing Breast Cancer in At-Risk Premenopausal Women Condition(s): Breast Cancer Study Status: This study is currently recruiting patients. Sponsor(s): University of Kansas; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Chemoprevention therapy uses certain drugs to try to prevent the development or recurrence of cancer. Celecoxib may be effective in preventing breast cancer in at-risk women. PURPOSE: Phase II trial to study the effectiveness of celecoxib in preventing breast cancer in premenopausal women who are at risk of developing cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056082

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Development and Evaluation of a Hormone Replacement Therapy Decision-Aid Condition(s): Menopause Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: The decision regarding the use of post-menopausal estrogen hormone replacement therapy (HRT) is complex because patients must balance the short- and long-term risks and benefits. Information from new and important clinical trials must also be considered. The purpose of this research is to develop and evaluate the efficacy of a HRT CD-ROM decision-aid in improving the decision-making process for women considering the use of estrogen HRT. The objectives of the study are to: 1) develop a model of the decision-making process for women considering estrogen hormone replacement therapy (HRT), based on Multi-Attribute Utility Theory (MAUT); 2) produce an interactive CD-ROM decision-aid for HRT; 3) evaluate the effect of the interactive CD-ROM decision-aid on patient satisfaction with decision (SWD) and knowledge about menopause and HRT; and 4) test the effect of the interactive CD-ROM decision-aid on women's decisions regarding initiation of HRT. Phase I (completed) used structured interviews and surveys in the development of a decision model for HRT. In phase II, an interactive CD-ROM decision-aid was developed and a randomized controlled trial (RCT) of its effect on decision processes was initiated. Postmenopausal women, aged 45-74, are being recruited from the primary care clinics of the four participating Veterans Affairs hospitals: Milwaukee, Madison, Chicago-Hines, and Chicago-Westside. The primary hypothesis is that women who use the CD-ROM decision-aid will demonstrate increased satisfaction with their decision regarding hormone replacement therapy use compared to women receiving the control intervention.

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012909 ·

Effects of Black Cohosh on Menopausal Hot Flashes Condition(s): Postmenopause; Hot Flashes; Osteoporosis, Postmenopausal Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: This study will assess whether treatment with black cohosh is effective in reducing the frequency and intensity of menopausal hot flashes. In addition, it will determine whether or not black cohosh reduces the frequency of other menopausal symptoms and improves quality of life. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010712

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Effects of Estrogen on Memory in Post-Menopausal Women and Patients With Alzheimer's Disease Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Alzheimer's Association; Pfizer; Eisai Medical Research Inc Purpose - Excerpt: The goal of this study is to examine whether the administration of estrogen to post-menopausal women and women with mild to moderate Alzheimer's disease will enhance their memory and their capacity for learning. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006399

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Effects of Raloxifene on the Uterus and Ovaries of Premenopausal Patients Condition(s): Breast Cancer; Breast Neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This research study is designed to work in cooperation with another study being conducted by the National Cancer Institute. The National Cancer Institute (NCI) is studying the effects of a drug called raloxifene on premenopausal women believed to have a high risk of developing breast cancer (98-C-0123). In this study, researchers are interested in learning about the effects of raloxifene on the uterus and ovaries of the women participating in the NCI study. To do this researchers plan to conduct ultrasounds on the patients enrolled in the NCI study. In addition researchers plan to take samples of the lining of the uterus in these patients (endometrial biopsy) if

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found to be necessary. The purpose of this study is to determine the reproductive effects of raloxifene on women who have normal functioning ovaries by taking ultrasounds of the ovaries and lining of the uterus (endometrium). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001837 ·

Estrogen Modulation of Mood and Cognition Following Monoaminergic Depletion in Post-Menopausal Women Condition(s): Menopause Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: This study will examine whether estrogen administration in postmenopausal women can alter the response to changes in brain chemistry brought about by dietary manipulation. Women who are recently menopausal (50-60 yrs. of age) and over 20 years postmenopausal (>70 yrs. of age) will take estrogen or placebo for three months. At the end of that time they will participate in three challenges using dietary techniques to briefly change the relative amounts of neurotransmitters in the brain that are believed to be related to mood regulation (serotonin, dopamine, and norepinephrine). Previous research has shown that these dietary manipulations can briefly produce negative changes in mood. The investigator hypothesizes that estrogen administration will blunt or buffer these negative effects in a quantifiable way. The investigator believes that this will provide a direct test of the ability of estrogen to meaningfully change the brain chemistry of mood in a clinically measurable and positive way. The proposed procedure will also allow assessment of the effects of estrogen on brain neurotransmitter systems after many years of very low estrogen levels. Phase(s): Phase II; MEDLINEplus consumer health information Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005768

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Feasibility Study for Development of an Early Test for Ovarian Failure Condition(s): Healthy; Premature Ovarian Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: This purpose of this study is to gain information about normal ovarian function that will be useful in developing a test for early detection of ovarian failure. The ovaries produce female hormones, such as estrogen, that are important in maintaining a woman's health. When the ovaries do not work properly, problems can develop. Unfortunately, there is no test that can detect ovarian failure early in its course. By the time premature ovarian failure is diagnosed in young women, two-thirds have already developed osteopenia (loss of some bone mass) and nearly one in ten have osteoporosis, a greater loss of bone mineral density that weakens bones and increases the risk of fractures. Women with normal ovarian function ages 18 to 55 and postmenopausal women 60 years of age or older may be eligible for this study.

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Candidates will be screened with a medical history, physical examination, blood tests and vaginal ultrasound examination. For the ultrasound study, a probe that emits sound waves is inserted into the vagina, and the sound waves are converted to form images of the ovaries. The procedure is done with an empty bladder and takes about 10 minutes. After this screening visit (Visit 1), those enrolled in the study will return to the NIH Clinical Center for the following additional procedures: Visit 2-Will be scheduled between days 3 and 5 of the menstrual cycle (for women who are still menstruating). Participants will have blood tests to measure hormone levels and to check for pregnancy, and will have another transvaginal ultrasound examination. They will then receive an injection of a synthetic form of follicle stimulating hormone (FSH), a hormone the body makes normally. Visits 3 and 4-Will be scheduled 24 and 36 hours after the FSH injection given during Visit 2 for collection of blood samples. Visit 5-Will be scheduled 48 hours after the FSH injection for additional blood sampling and a final transvaginal ultrasound examination. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006156 ·

Hormone Replacement in Young Women with Premature Ovarian Failure Condition(s): Healthy; Osteoporosis; Premature Ovarian Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: The human ovary produces male sex hormones (androgen) and female sex hormones (estrogen). Currently, androgen is not included in hormone replacement therapy for women with premature ovarian failure. Present hormone replacement therapy (HRT) was designed to treat women who experience ovarian failure at menopause (around the age of 50). However, 1% of women will experience premature failure of the ovaries before the age of 40. There have been no studies conducted to determine proper hormone replacement therapies for these younger women. Some research suggests that the usual menopausal hormone replacement therapy is not adequate to protect young women with premature ovarian failure from developing osteoporosis. Women with premature ovarian failure have abnormally low levels of androgens circulating in their blood. This may contribute to the increase risk for osteoporosis. This study will compare two treatment plans for women with premature ovarian failure. Treatment plan one will be physiological estrogen hormone replacement. Treatment plan two will be physiological estrogen hormone replacement plus androgen. The study will attempt to determine which plan is more beneficial to women in relation to osteoporosis and heart disease. The hormones will be contained in patches and given by placing the patches against the patient's skin. The patches were designed to deliver the same amount of hormone as would be normally produced by the ovary in young women. The success of the treatment will be measured by periodically checking the density of patient's bone in the leg (femoral neck bone). Researchers will take an initial (baseline) measurement of bone density before beginning treatment and then once a year, for 3 additional years, during treatment. The study will also consider bone density of the spine, bone turnover, heart disease risk factors, and psychological state. Phase(s): Phase II

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001951 ·

Hormone Replacement Therapy and the Risk of Breast Cancer Recurrence in Women With Previous Early Stage Breast Cancer Condition(s): menopausal symptoms; stage I breast cancer; stage II breast cancer; breast cancer in situ Study Status: This study is currently recruiting patients. Sponsor(s): Regional Oncologic Center; Scandinavian Breast Group; International Breast Cancer Study Group; EORTC Breast Cancer Cooperative Group Purpose - Excerpt: RATIONALE: Hormone replacement therapy is effective for relieving symptoms of menopause. It is not yet known if hormone replacement therapy increases the risk of breast cancer recurrence in women previously treated for early stage breast cancer. PURPOSE: Randomized phase III trial to determine the risk of breast cancer recurrence in women with previous early stage breast cancer who are receiving hormone replacement therapy for menopause symptoms. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003771

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Ovarian Follicle Function in Patients with Premature Ovarian Failure Condition(s): Amenorrhea; Hypoaldosteronism; Hypogonadism; Infertility; Premature Ovarian Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Premature ovarian failure may be the result of the destruction of eggs in the ovaries. Some patients experience complete destruction of all eggs within the ovaries. In these cases, no treatment will restore egg development. However, some patients experience a condition known as premature autoimmune ovarian failure. In these cases eggs still remain in the ovaries, but they are prevented from working normally by the body's own immune system. This study was designed to evaluate patients with premature ovarian failure. It will provide researchers with information that may be used later in other studies related to this condition. In addition, patients participating in this study may be selected for other studies that may benefit them directly. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001275

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Perimenopause-Related Mood and Behavioral Disorders Condition(s): Depressive Disorder; Healthy Study Status: This study is currently recruiting patients.

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Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to investigate mood and behavior changes in the time period surrounding and including menopause. This is an observational study; volunteers who participate will not receive any new or experimental therapies. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001231 ·

Phytoestrogens and Memory Decline in Menopause Condition(s): Memory Loss; Postmenopausal Period Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this study is to investigate whether soy-derived phytoestrogens taken as dietary supplements improve memory function in postmenopausal women who have experienced early memory decline. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051402

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Raloxifene and Rimostil for Perimenopause-Related Depression Condition(s): Climacteric Depression Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate the effectiveness of the drugs raloxifene and rimostil in treating perimenopause-related depression. Phase(s): Phase IV; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030147

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Risedronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy for Primary Breast Cancer Condition(s): Osteoporosis; stage I breast cancer; stage II breast cancer; stage IIIA breast cancer Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Preventing bone loss in patients who are receiving chemotherapy for breast cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without risedronate in preventing bone loss. PURPOSE: Randomized phase III trial to

Clinical Trials 315

compare the effectiveness of two forms of calcium with or without risedronate in preventing bone loss in premenopausal women who are receiving chemotherapy for primary stage I, stage II, or stage IIIA breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054418 ·

Standard Follow-up Compared With Extended Follow-up in Treating Patients Who Have Undergone Stem Cell Transplantation for Cancer Condition(s): Cancer; Depression; Fatigue; menopausal symptoms; psychosocial effects and treatment; transitional care planning Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Telephone counseling by trained counselors may enhance the well-being and quality of life of patients who have undergone stem cell transplantation for cancer. PURPOSE: Randomized clinical trial to compare the effectiveness of standard follow-up care with extended follow-up care in treating patients who have undergone stem cell transplantation for cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049465

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Steroid Therapy in Autoimmune Premature Ovarian Failure Condition(s): Autoimmune Disease; Infertility; Premature Ovarian Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: No therapy for infertile patients with premature ovarian failure has been proven effective. Some anecdotal reports have suggested that high dose, long term prednisone (steroid) therapy may be useful in treating autoimmune ovarian failure. However, prednisone, when used in high-doses for long periods of time has substantial side effects, including aseptic necrosis of bone where portions of bone die without the presence of infection and are surrounded by healthy tissue. Aseptic necrosis of bone often requires major surgical treatment. Even with this known level of risk, patients with premature ovarian failure are being treated based on this anecdotal evidence. This study will test the hypothesis that a lower risk therapy (alternate-day, lower dose, shorter-term prednisone) will cause a remission of autoimmune ovarian failure. There is no reliable blood test to identify patients who have premature ovarian failure. Therefore, all patients must undergo a laparoscopic ovarian biopsy to confirm the presence of an auto immune reaction in the ovaries (autoimmune oophoritis). Laparoscopy is a surgical procedure that allows doctors to explore the abdomen using a camera-like device called a laparoscope. The procedure has been used clinically by some reproductive endocrinologists to identify patients with premature ovarian failure who have an autoimmune mechanism for the disorder. The treatment will be deemed successful based on the return of ovulation as determined by weekly serum progesterone levels.

316 Menopause

Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001306 ·

Study of Low Bone Mass in Premenopausal or Perimenopausal Women Condition(s): Osteoporosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Columbia University Purpose - Excerpt: Objectives: I. Determine the possible causes of bone loss in premenopausal or perimenopausal women. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005101

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Suppression of Ovarian Function and Either Tamoxifen or Exemestane With or Without Chemotherapy in Treating Premenopausal Women With Resected Breast Cancer Condition(s): stage IIIA breast cancer; stage I breast cancer; stage II breast cancer Study Status: This study is currently recruiting patients. Sponsor(s): International Breast Cancer Study Group; National Cancer Institute (NCI); Breast International Group Purpose - Excerpt: RATIONALE: Estrogen can stimulate the growth of breast tumor cells. Suppression of ovarian function combined with hormone therapy may fight breast cancer by reducing the production of estrogen. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether suppression of ovarian function and hormone therapy are more effective with or without chemotherapy in treating breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of ovarian-function suppression and hormone therapy with or without chemotherapy in treating premenopausal women who have resected breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066807

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Suppression of Ovarian Function Plus Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With HormoneResponsive Breast Cancer Condition(s): stage I breast cancer; stage II breast cancer; stage IIIA breast cancer Study Status: This study is currently recruiting patients. Sponsor(s): International Breast Cancer Study Group; National Cancer Institute (NCI); Breast International Group

Clinical Trials 317

Purpose - Excerpt: RATIONALE: Estrogen can stimulate the growth of breast tumor cells. Ovarian function suppression combined with hormone therapy using tamoxifen or exemestane may fight breast cancer by reducing the production of estrogen. It is not yet known whether suppression of ovarian function plus either tamoxifen or exemestane is more effective than tamoxifen alone in preventing the recurrence of hormone-responsive breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of ovarian suppression plus either tamoxifen or exemestane with that of tamoxifen alone in treating premenopausal women who have undergone surgery for hormone-responsive breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066690 ·

Tamoxifen to Prevent Bone Loss and Heart Disease in Premenopausal Women Receiving Chemotherapy for Stage I or Stage II Breast Cancer Condition(s): Osteoporosis; stage I breast cancer; stage II breast cancer Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Tamoxifen may be able to increase bone density and decrease cholesterol in women who are undergoing chemotherapy for breast cancer. PURPOSE: Clinical trial to study the effectiveness of tamoxifen in preventing bone loss and heart disease caused by chemotherapy treatment in premenopausal women who have stage I or stage II breast cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005605

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The Effects of Hormone Withdrawal on Mood Symptoms in Women with Perimenopausal Depression Condition(s): Perimenopause; Depression Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to investigate the effects of estrogen levels on perimenopausal depression. This study will examine short-term withdrawal of estrogen in women whose mood had improved with estrogen therapy. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00060736

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The Role of Cytokines on Growth Hormone Suppression in Premenopausal Women with Rheumatoid Arthritis and the Effect of Treatment with Etanercept Condition(s): Rheumatoid Arthritis; Healthy Study Status: This study is currently recruiting patients.

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Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study has two phases. Phase 1 will examine the role of inflammatory mediators called cytokines on growth hormone levels in women with rheumatoid arthritis (RA). Phase 2 will evaluate the effect of etanercept on these growth hormone levels. Etanercept is approved for the treatment of RA. It lowers the levels of a key inflammatory mediator called tumor necrosis factor-alpha and is very effective in reducing arthritis symptoms. Growth hormone promotes bone and muscle growth. With aging, people lose muscle mass and bone strength, possibly because of decreased levels of growth hormone. People with RA have bone and muscle changes similar to those in older people, perhaps also due to decreased levels of growth hormone. The first part of this study will see if the inflammatory mediators responsible for joint inflammation (warmth, redness, pain, and swelling) in RA are related to the lowered growth hormone levels in this disease. The second part will evaluate the effect of etanercept treatment on muscle mass and bone density, in addition to growth hormone levels. Premenopausal women between 18 and 55 years of age with a recent diagnosis of rheumatoid arthritis (less than 3 years) are eligible for this study. Healthy volunteers will also be enrolled in the first phase of the study as control subjects. This study is conducted at two sites, the NIH and the Johns Hopkins Medical Center in Baltimore. Healthy volunteers enrolled in this study will be interviewed about their health status and will fill out questionnaires on diet and general physical function, including fatigue, energy and well being. In addition, they will be hospitalized once at the NIH Clinical Center for 24-hour blood sampling and will visit to Johns Hopkins Medical Center in Baltimore for a brachial artery reactivity study, as follows: - 24-hour blood sampling for growth hormone levels. Blood samples (1/2 teaspoon each) will be collected every 20 minutes from 8 AM one day until 8 AM the following day through a plastic tube in an arm vein. - Dual energy X-ray absorptiometry (DEXA) scan on a small area of the spine, hip and wrist to assess bone density and a total body DEXA scan to assess the amount and distribution of muscle and body fat. - Blood vessel (brachial artery reactivity) study to measure the ability of the brachial artery to dilate and increase its blood flow. For this procedure, the subject lies on a table with electrocardiogram leads attached to the chest. A blood pressure cuff is inflated for several minutes and a drop of nasal spray of nitroglycerin is given that may cause a headache. Blood pressure and headache are monitored and treated as needed. Patients with rheumatoid arthritis will be seen at the NIH clinic on six separate visits (weeks 0, 1, 6, 12, 18, and 26) over 26 weeks. Week 0 is a screening visit. At weeks 1 and 26, patients will be admitted to the hospital for 24-hour blood sampling, DEXA scans, and brachial artery reactivity tests, as described above, plus X-rays of the hand and feet. After the first visit, they will start taking etanercept, given by self-injection under the skin (like insulin shots) twice a week. Follow-up visits at weeks 6, 12, and 18 will involve evaluations of disease activity and drug side effects through joint examination, blood tests, and questionnaires. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034060 ·

Triptorelin Compared With Either Exemestane or Tamoxifen Premenopausal Women With Hormone-Responsive Breast Cancer

in

Treating

Condition(s): stage I breast cancer; stage II breast cancer; stage IIIA breast cancer

Clinical Trials 319

Study Status: This study is currently recruiting patients. Sponsor(s): International Breast Cancer Study Group; National Cancer Institute (NCI); Breast International Group Purpose - Excerpt: RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using triptorelin, exemestane, and tamoxifen may fight breast cancer by blocking the uptake of estrogen. It is not yet known whether triptorelin is more effective when combined with exemestane or tamoxifen in treating hormoneresponsive breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combining triptorelin with either exemestane or tamoxifen in treating premenopausal women who have hormone-responsive breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066703 ·

Zoledronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy After Surgery For Early Stage Breast Cancer Condition(s): Osteoporosis; stage I breast cancer; stage II breast cancer Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: It is not yet known whether zoledronate is effective in preventing bone loss in premenopausal women who are receiving adjuvant chemotherapy after undergoing surgery for early stage breast cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of zoledronate in preventing bone loss in premenopausal women who are receiving chemotherapy after surgery for early stage breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049452

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A Phase II Trial of Raloxifene in Pre-Menopausal Women at High Risk for Developing Invasive Breast Cancer Condition(s): Breast Cancer; Breast Neoplasm Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This is an open-label phase II trial designed to study the safety and tolerability of raloxifene, a selective estrogen receptor modulating agent, in premenopausal women at high risk of developing invasive breast cancer. Two doses of raloxifene will be studied in sequential cohorts: a 60 mg dose (standard dose) and a 300 mg dose administered daily for 2 years. The primary objective of this trial will be to determine the safety of raloxifene in a pre-menopausal population using bone mineral density as the primary endpoint. Secondary objectives include assessment of endogenous hormones and lipid levels, menstrual cycle effects, effects on endometrium

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and ovaries, health related quality of life, and breast density. Tissue samples will be obtained for future studies of potential surrogate endpoint biomarkers. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001700 ·

Alternative Therapies for Menopause: A Randomized Trial Condition(s): Menopause; Hot Flashes Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute on Aging (NIA) Purpose - Excerpt: This randomized, controlled trial will evaluate the efficacy and safety of three alternative approaches utilizing phytoestrogens to treat hot flashes and night sweats in peri- and post-menopausal women. The treatments were chosen because of the scientific evidence supporting a possible benefit, the availability of products with adequate quality control, and their frequency of use in naturopathic medicine. RECRUITMENT FOR THIS STUDY SHOULD END BY AUGUST 1, 2003. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061711

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Epidemiology of Cardiovascular Risk Factors in Women (Healthy Women Study) Condition(s): Cardiovascular Diseases; Heart Diseases; Depression; Carotid Artery Diseases; Menopausal Complaints; Menopause Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine cardiovascular risk factors and the change in risk factors during and following the menopause. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005160

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Hormone Replacement in Menopausal Women with Epilepsy Condition(s): Menopause; Epilepsy Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The goal of this study is to evaluate the effect of synthetic hormone replacement therapy on anti-seizure medication levels, menopausal symptom relief, and seizure frequency and safety in menopausal women with epilepsy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00027209 ·

Hormone Replacement Therapy and Insulin Action: A Double-Blind, Parallel, Placebo-Controlled Hormone Intervention Study in Postmenopausal Women Condition(s): Menopause Study Status: This study is no longer recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Considerable controversy exists regarding the effect of estrogen and progesterone on insulin sensitivity in postmenopausal women. Thus, the goal is to examine the effect of estradiol and progestin on in vivo insulin sensitivity and pathways of intracellular glucose metabolism in postmenopausal women. This will be accomplished by examining the effects of unopposed estrogen (CEE) or combination estrogen and progestin (CEE/MPA) versus placebo therapy in 30 early menopausal women (defined from 6 months to 3 years post-cessation of menses). Women will be treated for 16 weeks and the outcome measures will be: 1) insulin sensitivity and glucose oxidation as determined by euglycemic clamp, 2) assessments of insulin sensitivity on muscle biopsy cultures with the primary endpoints being glucose uptake and glycogen accumulation/synthesis, 3) protein levels of insulin action cascade steps based on muscle biopsy Western blots. Phase(s): Phase II; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005769

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Hormone Replacement Therapy for Hot Flashes and/or Vaginal Symptoms in Postmenopausal Women Receiving Tamoxifen for Breast Cancer Condition(s): stage I breast cancer; ductal breast carcinoma; menopausal symptoms; Hot Flashes; stage II breast cancer; breast cancer in situ Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group Purpose - Excerpt: RATIONALE: Hormone replacement therapy may be effective in managing the hot flashes and/or vaginal symptoms in postmenopausal women who are receiving tamoxifen for breast cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of hormone replacement therapy in managing hot flashes and/or vaginal symptoms in postmenopausal women who are receiving tamoxifen for breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026286

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Longitudinal Study of the Menopause and Fat Patterning Condition(s): Cardiovascular Diseases; Menopause; Heart Diseases Study Status: This study is no longer recruiting patients.

322 Menopause

Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To study the natural history of the accumulation of intra-abdominal fat as women progress through the menopause. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035659 ·

Nurses' Health Study Condition(s): Cardiovascular Diseases; Diabetes Mellitus; Coronary Disease; Heart Diseases; Cerebrovascular Accident; Pulmonary Embolism; Angina Pectoris; Myocardial Infarction; Menopause; Postmenopause Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the relationships of hormonal factors, a variety of nutrients, diabetes, exercise, and brand of cigarettes smoked with the subsequent risk of coronary heart disease, pulmonary embolism, and stroke in a cohort of female registered nurses. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005152

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Obesity Prevention after Smoking Cessation in Menopause Condition(s): Obesity; Menopause Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute on Aging (NIA) Purpose - Excerpt: This study addresses the high risk of weight gain associated with smoking cessation in women. The obesity prevention pilot study is designed for the primary prevention of weight gain that can lead to overweight in normal-weight women, that can progress to obesity in women who are already overweight, and for the prevention of additional weight gain in obese women with BMI greater than or equal to 30.0. Fat and other macronutrient intake, specifically, sugar, complex carbohydrates, and protein, are analyzed as a target for individually tailored, weight control intervention following smoking cessation in Caucasian and African American women. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064961

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Prevalence & Progression of Subclinical Atherosclerosis Condition(s): Atherosclerosis; Cardiovascular Diseases; Coronary Arteriosclerosis; Carotid Artery Diseases; Menopause Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)

Clinical Trials 323

Purpose - Excerpt: To evaluate subclinical atherosclerotic disease in menopausal women. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006503 ·

Raloxifene With or Without Exercise Compared With Exercise Alone in Women Who Have Been Previously Treated for Breast Cancer Condition(s): Osteoporosis; stage I breast cancer; stage IIIB breast cancer; menopausal symptoms; stage IIIA breast cancer; stage II breast cancer; Quality of Life Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Oregon Health and Science University Purpose - Excerpt: RATIONALE: Raloxifene and exercise may improve bone health and quality of life in breast cancer survivors. Assessing bone health and quality of life may improve the ability to plan treatment. PURPOSE: Randomized clinical trial to study the effectiveness of raloxifene with or without exercise compared with exercise alone in women who have been previously treated for breast cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031811

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Single-Dose Study of Black Cohosh and Red Clover Condition(s): Menopause Study Status: This study is no longer recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM); National Institute of General Medical Sciences (NIGMS); Office of Dietary Supplements (ODS); Office of Research on Women's Health (ORWH) Purpose - Excerpt: This Phase I study will assess the pharmacokinetics of two botanicals, Trifolium pratense (red clover) and Cimicifuga racemosa (black cohosh). Participants will receive a single dose of one botanical preparation. The observation period will be one week. Drug toxicity, absorption, distribution, metabolism and elimination data will be collected, and dosages to be utilized in a Phase II clinical trial will be determined. The Phase II trial will examine the efficacies of red clover and black cohosh for the reduction of menopausal symptoms in healthy menopausal women. The study will be randomized, double-blinded, and placebo-controlled. Study duration will be one year. Phase(s): Phase I; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010959

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CHD Risk, Behavioral Stress and Reproductive Hormones Condition(s): Cardiovascular Diseases; Coronary Disease; Heart Diseases; Menopause Study Status: This study is completed.

324 Menopause

Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the effects of behavioral stress and reproductive hormones on coronary heart disease (CHD) risk. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005538 ·

Estrogen, Cytokines and Heart Failure in Women Condition(s): Cardiovascular Diseases; Heart Failure, Congestive; Heart Diseases; Menopause Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the effects of estrogen therapy on postmenopausal women with congestive heart failure. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041431

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Goserelin in Preventing Early Menopause in Women Receiving Adjuvant Chemotherapy for Breast Cancer Condition(s): Breast Cancer; Hot Flashes; menopausal symptoms; Osteoporosis; sexual dysfunction and infertility Study Status: This study is not yet open for patient recruitment. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Goserelin blocks hormone production in the ovaries. It is not yet known whether ovarian suppression using goserelin will prevent early menopause in women receiving chemotherapy for breast cancer. PURPOSE: Randomized phase III trial to study the effectiveness of ovarian suppression using goserelin in preventing early menopause in women who are receiving adjuvant chemotherapy for stage I, stage II, or stage IIIA breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068601

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Myocardial Infarction and Non-contraceptive Estrogen Use Condition(s): Cardiovascular Menopause; Postmenopause

Diseases;

Heart

Diseases;

Myocardial

Infarction;

Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate whether the use of noncontraceptive estrogen influenced the incidence of first myocardial infarction in women.

Clinical Trials 325

Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005185 ·

Myocardial Infarction and Past Oral Contraceptive Use Condition(s): Cardiovascular Diseases; Coronary Disease; Myocardial Infarction; Heart Diseases; Menopause; Postmenopause Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate whether the long-term use of oral contraceptives, after discontinuation, was associated with an increased incidence of first nonfatal myocardial infarction among women above the age of 50. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005173

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Soy Estrogen Alternative Study (SEA) Condition(s): Cardiovascular Diseases; Endometrial Hyperplasia; Heart Diseases; Menopausal Complaints; Uterine Diseases; Menopause Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To conduct a three-armed trial assessing the effect of soy phytoestrogens on menopausal complaints, plasma lipids and lipoproteins, vaginal bleeding and endometrial proliferation, and health related quality of life. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000612

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Timing of Menstrual Cycle and Surgery in Treating Premenopausal Women With Stage I, Stage II, or Stage III Breast Cancer Condition(s): stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer Study Status: This study is completed. Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: The timing of breast cancer surgery within the menstrual cycle may affect outcome. It is not yet known if treatment is more effective during the initial or final phase of the menstrual cycle. PURPOSE: Phase III trial to determine the effect of menstrual cycle phase at surgery in treating premenopausal women who have stage I, stage II, or stage III breast cancer. Phase(s): Phase III Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005079 ·

Use of the Synthetic Hormone CDB-2914 in Treating Symptoms of Menopause Condition(s): Postmenopause Study Status: This study is completed. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: This study will examine the safety and effectiveness of a synthetic hormone, CDB-2914, for treating symptoms of menopause. It will compare the effects of estrogen and CDB-2914 with those of estrogen and progesterone in postmenopausal women. The study will also evaluate whether CDB-2914 affects adrenal gland function. CDB-2914 is chemically similar to cortisol, a hormone that is produced by the adrenal glands and regulates the body's response to stresses, such as infection or injury. Healthy women volunteers between the ages of 45 and 70 who have not had a menstrual period for over a year, are not currently taking hormone replacement therapy, do not smoke and have not had a hysterectomy may be eligible for this study. Candidates will provide a medical history and have a physical examination, including a breast and pelvic exam. They will also provide a blood sample, have a mammogram and pap smear, and be instructed in dietary sources and/or supplements required to be sure they consume at least 1,000 mg. of calcium each day. Participants will be randomly assigned to take: a) estrogen plus CDB-2914, b) estrogen plus progesterone, or c) estrogen plus a placebo (look-alike tablet with no active ingredient) daily by mouth for 6 weeks. During the study period, they will keep a record of any symptoms, vaginal bleeding, and other medicines they take. They will return to the NIH Clinical Center weekly for blood tests and to fill out a questionnaire on mood, appetite, sleep patterns, menopausal symptoms, and other quality of life issues. At the 6-week visit, participants will: -Bring a 24-hour urine collection -Have a vaginal ultrasound to evaluate the effects of the medication on the thickness of the endometrium (lining of the uterus) -Bring all bottles of study medication for a pill count -Discuss any unusual or troubling symptoms with the study nurse or physician A final visit will be scheduled 1 to 3 weeks after the 6-week visit, when participants will turn in their calendar of daily symptoms and return unused progesterone pills. Phase(s): Phase II; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009659

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Women's Healthy Lifestyle Project: Cardiovascular Risk Factors and Menopause Condition(s): Cardiovascular Diseases; Diabetes Mellitus; Heart Hypercholesterolemia; Hypertension; Obesity; Menopause; Postmenopause

Diseases;

Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine if the increase in low density lipoprotein (LDL) cholesterol at the time of menopause could be ameliorated or prevented by an intensive dietary intervention. Also, to prevent the increase in body weight and associated

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changes in insulin, glucose, blood pressure, triglycerides, and high density lipoprotein cholesterol during the peri- to postmenopausal period. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000532

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “menopause” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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·

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON MENOPAUSE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “menopause” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on menopause, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Menopause By performing a patent search focusing on menopause, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on menopause: ·

Composition for the prevention and/or treatment of osteoporosis and alterations due to menopause syndrome Inventor(s): Cavazza; Claudio (Rome, IT) Assignee(s): Sigma-Tau Healthscience S.p.A. (Pomezia, IT) Patent Number: 6,335,038 Date filed: December 22, 2000 Abstract: A composition that may take the form of a dietary supplement or of a medicament is disclosed which comprises as active ingredients propionyl L-carnitine and the isoflavone genistein for the therapeutic treatment of osteoporosis and menopause syndrome. Excerpt(s): The present invention relates to a composition for the prevention and/or treatment of osteoporosis and alterations due to menopause syndrome.. Accordingly the composition may take the form and exert the action of a dietary supplement or of an actual medicine, depending upon the support or preventive action, or the strictly therapeutic action, which the composition is intended to exert in relation to the particular individuals it is to be used in.. (b) 4',5,7-trihydroxyisoflavone (genistein) optionally in combination with at least another isoflavone selected from the group comprising 4',7-dihidroxyisoflavone (daidzein), its 7-glucoside (daidzin) and its 4,7diglucoside. Web site: http://www.delphion.com/details?pn=US06335038__

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Compositions and treatment for alleviation of symptoms associated with menopause Inventor(s): Borneman; John P. (Bryn Mawr, PA), Phillips; Mark S. (Huntington Beach, CA) Assignee(s): Standard Homeopathic Company (Los Angeles, CA) Patent Number: 6,248,307 Date filed: March 7, 2000 Abstract: A composition having at least one herbal compound and at least one homeopathic drug is useful for treating symptoms associated with menopause. Methods of preparing the composition and methods of treating, alleviating or otherwise mitigating the menopausal symptoms are also described. Excerpt(s): The present invention relates to a composition having at least one herbal compound and at least one homeopathic drug that is useful for treating symptoms associated with menopause. Methods of preparing the composition and methods of treating, alleviating or otherwise mitigating the menopausal symptoms are the subject of the present invention.. Menopause is the termination of the menstrual cycle in woman, and is caused by the changes in hormone levels that occur naturally over time. Estrogen and progesterone are the key hormones involved in these changes, but other factors may be involved as well.. The onset of menopause is associated with many symptoms will vary between women, but will generally include one or more of the following symptoms: hot flashes, numbness, tingling, insomnia, nervousness, depression, vertigo,

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fatigue, arthralgia, myalgia, headaches, palpitations, and formication. Osteoporosis is another condition associated with the onset of menopause, and leads to decreased bone density and an increase in fractures and breaks. Web site: http://www.delphion.com/details?pn=US06248307__ ·

Formulation for menopausal women Inventor(s): Hermelin; Marc S. (Glendale, MO), Kirschner; Mitchell I. (St. Louis, MO), Levinson; R. Saul (Chesterfield, MO) Assignee(s): Drugtech Corporation (Wilmington, DE) Patent Number: 6,479,545 Date filed: September 30, 1999 Abstract: The present disclosure relates to novel compositions which provide improved nutritional support for premenopausal and menopausal women and/or relief from symptoms associated with menopause, as well as prophylactic effects, and methods for using same. Excerpt(s): The present invention is directed to novel compositions for use by premenopausal women and menopausal women for the purpose of providing improved nutritional support and/or relief from the symptoms of menopause, as well as to methods for using same.. Menopause, the transition from the reproductive stage to the non-reproductive stage of a woman's life, is characterized primarily by the cessation of menstruation. However, menopause has come to signify much more than simply the loss of reproductive capability, as it is also associated with a number of acute and chronic conditions. Menopausal syndrome consists of a number of varying and often highly distressing symptoms resulting from hormonal imbalance and nutritional deficiency in the female body.. Hot flashes and sweating secondary to vasomotor instability affect 75% of women. Psychologic and emotional symptoms of fatigue, insomnia, irritability and nervousness are common. Lack of sleep due to disturbance by recurring hot flashes contributes to fatigue and irritability. Dizziness, parenthesis and cardiac symptoms of palpitations and tachycardia may also occur; the incidence of heart disease increases. Other common symptoms include nausea, constipation, diarrhea, arthralgia and myalgia. The Merck Manual, 1793 (16.sup.th Ed. 1992). Web site: http://www.delphion.com/details?pn=US06479545__

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Method for increasing intestinal absorption of fat soluble vitamins in postmenopausal women and lower animals Inventor(s): Koo; Sung I. (Manhattan, KS), Owen; Kevin (Manhattan, KS), Gross; Kathy Lynn (Topeka, KS) Assignee(s): Kansas State Research Foundation (Manhattan, KS), Lonza Ltd. (Basel, CH), Hill's Pet Nutrition (Topeka, KS) Patent Number: 6,476,010 Date filed: March 1, 2001 Abstract: The present invention provides a method for increasing the intestinal (lymphatic) absorption, cellular concentration, biliary secretion, hepatic storage, and/or liver concentration of a fat soluble vitamin in a post-menopausal woman. The method

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comprises orally administering to a post-menopausal woman in need thereof, a fat soluble vitamin and a fat soluble vitamin absorption increasing effective amount of Lcarnitine. The L-carnitine enhances the antioxidant defense mechanism and lowers the risk of certain degenerative diseases, such as coronary heart disease, age-related macular degeneration, osteoporosis, cancer, and Alzheimer's, in post-menopausal women. The invention also provides a method for increasing the intestinal absorption of a fat soluble vitamin in an animal. The method comprises orally administering to the animal in need thereof, a fat soluble vitamin and a fat soluble vitamin absorption increasing effective amount of L-carnitine. Excerpt(s): This invention relates to a method for increasing the intestinal absorption, cellular concentration, biliary secretion, hepatic storage, and/or liver concentration of a fat soluble vitamin in a post-menopausal woman or a lower animal by orally administering L-carnitine and a fat soluble vitamin.. L-carnitine plays a crucial role in the energy supply of tissues by modulating the entry of long-chain fatty acids into the mitochondrial matrix and their subsequent oxidation. Consistent with such a metabolic role, L-carnitine has been shown to be effective in lowering the serum levels of cholesterol, triglyceride, and free fatty acids, while increasing high density lipoprotein (HDL) cholesterol which is antiatherogenic. See Pola, P. et al., "Carnitine in the theraphy of dyslipemic patients", Curr Ther Res 27:208-16 (1980); Lacour, B. et al., "Carnitine improves lipid abnormalies in haemodialysis patients", Lancet 12:763-4 (1980); Avogaro, P., "Acute effect of L-carnitine on FFA and beta-hydroxy-butyrate in man", Pharmacol Res Commun 13:433-50 (1981); and Vacha, G. M. et al. "Favourable effects of L-carnitine treatment on hypertriglyceridemia in hemodialysis patients: Decisive role of low levels of high density lipoprotein cholesterol", Am J Clin Nutr 38:532-40 (1983). Existing evidence indicates that L-carnitine and its esters enhance the stability and integrity of erythrocyte membranes by participating in the reacylation (repair) of membrane phospholipids subjected to oxidative damage. See Arduini, A. et al., "Effect of propionyl-L-carnitine treatment on membrane phospholipid fatty acid turnover in diabetic rat erythrocytes", Mol Cell Biochem 152:31-7 (1995); Arduini, A. et al., "Carnitine palmitoyltransferase and acyl-CoA binding protein: two more players in the membrane phospholipid fatty acid turnover of human red cells?", Biochem J 325:811-4 (1997); and Arduini, A. et al., "Addition of L-carnitine to additive solution-suspended red cells stored at 4.degree. C. reduces in vitro hemolysis and improves in vivo viability", Trandfusion 37:166-74 (1997). It is of interest to note that such an action of L-carnitine and its esters is shown in the erythrocyte devoid of mitochondrial. L-carnitine supplementation to old rats has been shown to reverse the age-related decline in mitochondrial function, which may be linked to the membrane-stabilizing effect of Lcarnitine. See Hagen, T. M. et al., "Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity", Proc Natl Acad Sci USA 95:9562-6 (1998). This finding is of particular significance in that oxidative damage to mitochondrial DNA increases markedly with age, leading to impaired cellular metabolism and function. See Hagen, T. M. et al., "Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase", Proc Natl Acad Sci USA 94:3064-9 (1997).. Postmenopausal women make up over 15% of the total population in industrialized countries. By 2030, the proportion of postmenopausal women is predicted to increase to 23% of the total population. See Hill, K., "The demography of menopause", Maturitas 23:113-127 (1996). In addition, numerous epidemiological studies have shown that depletion of estrogen at the menopause influences cause-specific morbidity and mortality in later life. From the nutritional standpoint, the menopause is the time when the body's ability to absorb, assimilate, and metabolize nutrients begins to deteriorate. Consequently, the body status of nutrients is

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compromised at and after menopause, with the manifestations of specific nutrient deficiency symptoms with time. Web site: http://www.delphion.com/details?pn=US06476010__ ·

Method for the treatment of vaginal dryness and sexual dysfunction in women during or after the menopause Inventor(s): DeGregorio; Michael W. (Granite Bay, CA), Kangas; Lauri (Raisio, FI), Halonen; Kaija (Rusko, FI) Assignee(s): Hormos Medical Oy, Ltd. (FI), Tess Diagnostics and Pharmaceuticals, Inc. (Granite Bay, CA) Patent Number: 6,245,819 Date filed: July 21, 2000 Abstract: This invention concerns a method for the treatment of vaginal dryness or sexual dysfunction in women during or after the menopause, said method comprising administering to the woman an effective amount of the compound (deaminohydroxy)toremifene or a pharmaceutically acceptable salt or ester thereof, or a metabolite thereof. Excerpt(s): This invention relates to a method for the treatment of vaginal dryness or sexual dysfunction in women during or after menopause.. The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference.. During and after menopause, elderly women commonly develop symptoms which are due to estrogen deficiency. These symptoms include hot flashes, sweating, insomnia, depression, vaginal dryness, urinary incontinence, nausea, pain, osteoporosis, coronary heart disease, breast tenderness, oedema, fatigue, decreased sexual activity, as well as subsequent psychosocial problems (Payer, 1990; Rekers, 1990). In addition, estrogens are suggested to have neuroprotective effects. Thus, declining estrogen concentrations may negatively affect the mental activities of aging women (Schneider & Finch, 1997; Wickelgren, 1997). Estradiol is known to be excellent in the treatment of climacteric symptoms, and its use in the treatment of these symptoms is rapidly increasing. However, estrogens cause an increased risk of endometrial and breast cancers. It is possible to decrease the carcinogenicity of endometrial cancer by sequential progestin administration, but the risk of breast cancer is not diminished by progestins. The carcinogenicity risk limits the length of estrogen replacement therapy, although it would be very useful to continue the therapy long term, due to the protective effects of estrogens in the bone, in the cardiovascular system, in the central nervous system, and for urinary symptoms. Web site: http://www.delphion.com/details?pn=US06245819__

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Method for treating flushing associated with menopause Inventor(s): Gollobin; Charlotte (6710 Bradley Blvd., Bethesda, MD 20817) Assignee(s): none reported Patent Number: 5,789,443 Date filed: April 25, 1997

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Abstract: A method for treating flushing as a symptom of menopause is disclosed. Specifically, the method comprises administering to a patient in need thereof an effective amount of leucine, or leucine in combination with isoleucine and valine. Preferably the leucine is administered as a dietary supplement. However, treatment may be achieved via manipulation of dietary protein intake. Due to the depletion effect that leucine has on other branched chain amino acids, it is preferred that isoleucine and valine are administered in combination with leucine. Excerpt(s): This invention is directed to a method for treating symptoms of menopause, such as hot flashes (flushing) and the like. Specifically, this invention is directed to administering, to a female patient, an effective amount of branched chain amino acids, specifically leucine. Leucine may be administered by manipulation of diet or in a composition comprising an effective amount of leucine and a pharmaceutically acceptable carrier. A combination of leucine, isoleucine and valine is preferred.. Menopausal syndrome consists of a number of varying and often highly distressing symptoms resulting from hormonal imbalance in the female body, specifically a deficiency of estrogen in the body. Symptoms of menopausal syndrome sufficiently severe to require treatment occur in approximately 50 percent of women. One particular symptom experienced by women is hot flashes or flushing. This is characterized by a sudden onset of warmth in the face and neck and often progressing to the chest. Such an episode generally lasts several minutes and is evidenced by a visible red flushing of the skin. Often such episodes are accompanied by sweating, dizziness, nausea, palpitations and diaphoresis.. Estrogen replacement therapy provides relief to 90% of women who experience such menopausal symptoms and has, over the years, become increasingly popular. U.S. Pat. No. 3,608,075, to Glen et al. discloses the Use of an orally active estrogen in the treatment of menopausal syndrome. In particular, a composition containing sodium 17 beta-dihydroequilin sulfate as the sole estrogenic agent for the treatment of menopausal syndrome in women is disclosed. An example of the use of a graded sequential estrogen-progestogen regime is disclosed in U.S. Pat. No. 3,733,407 to Segre. Web site: http://www.delphion.com/details?pn=US05789443__ ·

Method of hormonal treatment for menopausal or post-menopausal disorders involving continuous administration of progestogens and estrogens Inventor(s): Wolfe; Bernard M. J. (London, CA), Plunkett; Earl R. (London, CA) Assignee(s): Pre Jay Holdings Limited (CA), WOCO Investments Ltd. (CA) Patent Number: 4,826,831 Date filed: July 24, 1984 Abstract: A method of hormonally treating menopausal (including perimenopausal and post-menopausal) disorders in women, a composition, and a multi-preparation pack therefor. The administrative regimen to which the pack is particularly adapted comprises continuously and uninterruptedly administering a progestogen to a woman while cyclically administering an estrogen by using a repetitive dosage regimen. This regimen calls for administering the estrogen continuously for a period of time between about 20 and about 120 days, followed by terminating administering the estrogen for a period of time between about 3 and about 7 days. Alternatively, both the progestogen and estrogen may be administered for the full treatment period without interruption. The regimen avoids many of the problems associated with the administration of estrogen alone or with progestogen administered according to conventional regimens,

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and also avoids problems associated with such conventional regimens by maintaining the estrogen and progestogen at low daily dosage levels of between 0.005 mg and 2.5 mg estrogen and 0.25 mg and 30 mg progestogen. Excerpt(s): An experimental study of thirty women was instituted under a randomized double blind protocol with crossover and involved the administration of placebos, progestogen only, estrogen only and the combination of the continuous, uninterrupted progestogen/cyclic estrogen treatment. Treatment comprised administering each hormone and the combination as follows: (1) estrogen alone for two months; (2) progestogen alone for two months; (3) combination therapy using (1) and (2) for six months. Each period of administering a hormone of the combination was followed by a one month period of placebo (substance with no endocrine activity) administration. The estrogen was micronized 17.beta.-estradiol administered at a daily dosage level of 1 milligram, while the progestogen was dl-norgestrel administered at a dosage level of 75 micrograms.. Of 30 women who have completed this study, 22, on the basis of their responses throughout the fourteen months of observation, selected the combination treatment and requested to continue it. This represents a high level of acceptability.. In a follow-up phase of observation, 17 subjects (with intact uterus) have completed a total of 125 lunar months of the combination therapy (continuous, uninterrupted administration of dl-norgestrel, cyclic administration of 17.beta.-estradiol). None of the patients experienced "bleeding" which required protection. 1.6 percent of the cycles involved spotting requiring no protection. 98.4 percent of the cycles were completely clear. Web site: http://www.delphion.com/details?pn=US04826831__ ·

Method of treating menopausal symptoms Inventor(s): Lawrason; F. Douglas (53 Spring Valley Rd., Convent Station, NJ 07960) Assignee(s): none reported Patent Number: 4,315,033 Date filed: January 22, 1981 Abstract: This invention relates to a method of treating vasomotor instability, particularly in relation to the menopausal syndrome, by the administration of methyldopa. Excerpt(s): The term "menopausal syndrome" and its various symptoms have been well described in the literature (e.g. see Essentials of Gynecology, E. S. Taylor, Chapt. 33, 4th Ed., Publ. by Lea & Febiger, Phila., Pa. 1969). The usual symptoms consist of a variety of unpleasant and often highly distressing disturbances involving any or all of the systems of the body and result from hormonal imbalance, essentially from a deficiency of estrogens. Many different estrogens have thus been used in medicine for the treatment of menopausal syndrome.. Some symptoms mostly associated with the menopause are disturbances of the autonomic nervous system classified as vasomotor instability. Such symptoms of vasomotor instability in many patients are usually manifested in the form of excessive or inappropriate perspiration often accompanied by hot flashes (or hot flushes), tachycardia, nervousness, fatigue and insomnia and occasionally by irritability and other distressing secondary symptoms.. At present estrogen replacement therapy provides the most specific and effective method of treating the disturbing symptoms of menopause, including the aforementioned vasomotor symptoms. However, the many adverse and potentially dangerous side effects associated with the administration of estrogenic products are becoming increasingly apparent. For example, diethystilbestrol,

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a once widely used and well established estrogen, has been implicated as possibly being responsible for vaginal cancer and adenosis of the female offspring of pregnant women treated with the compound (Lancet 1975, 1960). Also ethinyl estradiol and mestranol, which represent estrogenic components in current oral contraceptives are now known to be involved in certain serious side effects associated with oral contraceptives including depression, (Nature 243,58 (1973)), hypertension (Am. J. Obstet. Gynecol. 112, 912 (1972), carbohydrate and lipid abnormalities (Lancet 1969, Oct. 11, 783), interference with blood clotting mechanism resulting in thrombosis and stroke (Ann. Intern Med. 72, 111 (1970)), and jaundice (Am. J. Obstet. Gynecol. 119, 165 (1974)). Also, the administration of estrogens to postmenopausal women has been implicated as a cause of endometrial cancer (Science 191, 838 (1976)). Consequently, there is a need for an improved nonestrogenic method of treating those symptoms ascribed to vasomotor instability, particularly in relation to the menopausal syndrome. Web site: http://www.delphion.com/details?pn=US04315033__ ·

Method of treating post menopausal osteoporosis with hexafluro-vitamin D Inventor(s): Deluca; Hector F. (Deerfield, WI), Ogura; Yosuke (Tokyo, JP) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 5,571,802 Date filed: February 18, 1994 Abstract: A method of treating post menopausal osteoporosis which comprises administering to a subject having the disease an effective daily dose of 26,26,26,27,27,27hexafluoro-1.alpha.,25-dihydroxycholecalciferol compound in an amount from about 0.05.mu.g to about 2.0.mu.g. Excerpt(s): The present invention relates to a novel method of treating diseases resulting from calcium metabolism disorders. More specifically, this invention relates to a method comprising the use of 26,26,26,27,27,27-hexafluoro-1.alpha.,25-dihydroxycholecalciferol, a derivative of vitamin D.sub.3.. Vitamin D.sub.3 is a well-known agent for the control calcium and phosphorous homeostasis. It is also now well known that to be effective, vitamin Da must be converted to its hydroxylated forms. For example, the vitamin is first hydroxylated in the liver to form 25-hydroxyvitamin D.sub.3 and is further hydroxylated in the kidney to produce 1.alpha.,25-dihydroxyvitamin D.sub.3 or 24,25dihydroxy vitamin D.sub.3. The 1.alpha.-hydroxylated form of the vitamin is generally considered to be the physiologically active or hormonal form of the vitamin and to be responsible for what are termed the vitamin D-like activities, such as increasing intestinal absorption of calcium phosphate, mobilizing bone mineral, and reabsorbing calcium in the kidneys.. Since the discovery of biologically active metabolites of vitamin D.sub.3 there has been much interest in the preparation of structural analogs of these metabolites, because such compounds may represent useful therapeutic agents for the treatment of diseases resulting from calcium metabolism disorders. A variety of vitamin D-like compounds have been synthesized. See, for example, U.S. Pat. Nos. 3,741,996 directed to 1.alpha.-hydroxycholecalciferol; 3,907,843 directed to 1.alpha.hydroxyergocalciferol; 3,786,062 directed to 22-dehydro-25-hydroxycholecalciferol; 3,906,014 directed to 3-deoxy-1.alpha.-hydroxycholecalciferol; and 4,069,321 directed to the preparation of various side chain-fluorinated vitamin D.sub.3 derivatives and side chain-fluorinated dihydrotachysterol analogs. Web site: http://www.delphion.com/details?pn=US05571802__

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Methods for treating or reducing prediposition to breast cancer, pre-menstrual syndrome or symptoms associated with menopause by administration of phytoestrogen Inventor(s): Kelly; Graham Edmund (Northbridge, AU) Assignee(s): Novogen Research Pty Limited (New South Wales, AU) Patent Number: 6,562,380 Date filed: August 13, 1997 Abstract: Phyto-estrogen-containing health supplement compositions containing any two or more of Genistein, Daidzein, Formononetin and Biochanin A, or the natural glycosides thereof are administered for treating or reducing predisposition to breast cancer, pre-menstrual syndrome or symptoms of menopause. Excerpt(s): This invention relates to natural products containing phyto-oestrogens, or phyto-oestrogen metabolites, which have various beneficial physiological effects in man, and which have a variety of uses, such as to promote good health and as a dietary additive, for example.. The particular product in accordance with the invention is an extract of certain plants with the particular purpose of enrichment for phyto-oestrogens, both in their natural state and their closely related derivatives and metabolites.. Plants which are used as foodstuffs or medicinal herbs contain a wide variety of chemicals which are assimilated into the body following ingestion. Some of these chemicals are important nutrients for man and animals (e.g. fats, carbohydrates, proteins, vitamins, minerals) while others have none, or little or no known nutritional value. The phytooestrogens hitherto have fallen into this latter category of no known nutritional value. Web site: http://www.delphion.com/details?pn=US06562380__

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Methods of treating hot flashes, estrogen deficiencies and deferring menopause by the administration of a luteinizing hormone antagonist Inventor(s): Groendahl; Christian (Vaerloese, DK) Assignee(s): Novo Nordisk A/S (Bagsvaerd, DK) Patent Number: 6,297,243 Date filed: October 29, 1998 Abstract: A pharmaceutical composition comprising a LH antagonist or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier is useful for deferring the onset of menopause. Excerpt(s): The present invention relates to a pharmaceutical composition, to use of luteinizing hormone (LH) antagonists for preparing a medicament for treatment of hot flushes or hot flashes (i.e., menopausal vaso-motor symptoms), to use of LH antagonists for preparing a medicament for treatment of estrogen deficiencies, to use of LH antagonists for preparing a medicament for decreasing the loss of follicles during the pre- and per-menopausal period, thereby deferring the onset of menopause and consequently the symptoms related to lack of estrogen. Furthermore the invention relates to use of LH antagonists for preparing a contraceptive.. The mammalian female is born with a fixed and subsequently decreasing number of meiotically arrested oocytes in the ovaries. Oocytes encompassed by a single layer of flattened epithelial cells form

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primordial follicles and constitute the fixed resting pool of oocytes in the ovaries from which oocytes are recruited throughout the reproductive life. An unknown signal triggers a cohort of the primordial follicles to develop into primary, secondary and ultimately Graafian follicles.. Approximately one million primordial follicles is present in a human ovary in a newborn. The functional activity of the human ovary depends on the size of the follicle store. It has been speculated that a threshold exist of approximately 1000-2000 oocytes that mediates the onset of menopause or cessation of cyclic activity in the ovary (Gosden, 1996, Serono Symposium, Leeds). Web site: http://www.delphion.com/details?pn=US06297243__ ·

N-(1-allyl-2-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide and derivatives thereof and method for treating hot flushes associated with natural or surgical menopause Inventor(s): Thominet; Michel L. (Paris, FR), Perrot; Jacques J. (Paris, FR) Assignee(s): Societe D'Etudes Scientifiques et Industrielles de l'Ile de France (Paris, FR) Patent Number: 4,499,019 Date filed: October 13, 1983 Abstract: N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide and dvatives thereof and method for treating the psycho neuro-vegetative syndrome of the natural or surgical menopause by administering an effective amount of said compound to a patient. Excerpt(s): This invention relates to a new compound N-(1'-allyl-2'-pyrrolidylmethyl)2,3-dimethoxy-5-sulfamoylbenzamide and a method for treating the psycho neurovegetative syndrome of the natural or surgical menopause by administering to a patient suffering from the psycho neuro-vegetative syndrome a therapeutically effective amount of said compound sufficient to relieve the symptoms of the syndrome including hot flashes, vulvar irritation, headaches, anxiety, irritability, etc.. In the past the symptoms of the psycho neuro-vegetative syndrome caused by the natural or surgical menopause have normally been treated by administering to a patient hormonal compounds such as estrogen steroids and synthesized estrogens. Estrogens and other compounds having estrogenic action, however, have recently been suspected of causing cancer in patients resulting in considerable concern with respect to the use of these compounds.. Applicants have found that patients suffering from the psycho neurovegetative syndrome of the natural or surgical menopause may be successfully treated with N-(1'-allyl-2'-pyrrolidylmethyl)-2,3-dimethoxy-5-sulfamoylbenzamide to relieve the symptoms. The structure of the compound is fundamentally different from estrogen steroids or synthesized estrogens and consequently can be used without concern for side effects such as cancer. The pharmaceutical compound can be administered orally or subcutaneously. A marked decrease in the symptoms of the psycho neuro-vegetative syndrome of the natural or surgical menopause have been observed after treatment for only two days. The symptoms have been observed to disappear completely after treatment for as short a time as eight days. Web site: http://www.delphion.com/details?pn=US04499019__

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Ovariectomized mouse model for human menopause Inventor(s): Haslam; Sandra Z. (Laingsburg, MI) Assignee(s): Board of Trustees operating Michigan State University (East Lansing, MI) Patent Number: 6,583,334 Date filed: May 23, 2000 Abstract: A method for determining a response to a biologically active agent in ovariectomized lower test mammals is described. The mammals are divided into those which have an early time post ovariectomy and those which have a late time post ovariectomy and then each group is tested simultaneously with the agent. The method is used to simulate menopause in humans for the purpose of determining a positive or negative response and a possible treatment. Excerpt(s): The present invention relates to an mouse model for human menopause which provides a simulated comparison between early and late menopause. In particular the present invention uses time after an ovariectomy of the mouse to simulate early and late human menopause.. Hormone replacement therapy (HRT) with estrogen in postmenopausal women is used to alleviate menopausal symptoms such as vasomotor and urogenital dysfunction, as well as to reduce the risk of bone fractures and cardiovascular disease, and it may also decrease the debilitating symptoms of Alzheimer's disease (Stampfer, M. J., et al., N Engl J Med 325:756-762 (1991); Riggs, B. L., et al., N Engl J Med 327:620-627 (1992); Compston, J. E., Br Med Bull 48:309-344 (1992); Col, F. N., et al., JAMA 277:1140-1147 (1997); The writing group of PEPI trial, JAMA 276:1389-1396 (1996); Henderson, V. W., et al., Arch Neurol 51:896-900 (1994); and MingXin, T., et al., The Lancet 348:429-432 (1996)). While most breast cancers occur in postmenopausal women, the role of menopause per se in the etiology of breast cancer is not known. However, there is solid epidemiological evidence for an important role of ovarian hormones in mammary cancer development (MacMahon, B., et al., J. Natl Cancer Inst 50:21-42 (1973)). Lifetime total exposure of the mammary gland to the mitogenic effects of ovarian hormones has been proposed to be a major risk factor for the development of breast cancer (MacMahon, B., et al., J. Natl Cancer Inst 50:21-42 (1973)). However, very little is known about the mitogenic effects of estrogen in the postmenopausal human breast.. The mouse has been widely studied in vivo for elucidating roles of hormones in mammary gland development and function, and the mouse mammary gland is similar to the human breast in many aspects of hormonal regulation of cell proliferation (Neville, M. C., et al., The mammary gland development, regulation and function. Plenum Press New York and London 625 (1987)). Most mammals, including mice, maintain their reproductive capacity throughout their entire life and do not experience natural menopause (Kirkwood, T. B. L., Comparative and evolutionary aspects of longevity In: Adelman R., et al. (eds) Handbook of the biology of aging. Van Nostrand Reinhold Co. New York 27-42 (1985)). However, a menopausal state in animals can be induced surgically, by ovariectomy. This is comparable to the situation in women who undergo bilateral ovariectomy prior to menopause, and prematurely experience the symptoms and side effects of menopause soon after surgery. In many instances women start hormone replacement therapy in the early postmenopausal period in order to alleviate menopausal symptoms. However, older postmenopausal women who have never previously received HRT are also given estrogen for its ability to reduce osteoporosis and decrease risk of cardiovascular disease (Michaelsson, K., et al., Br Med J 316:1858-1863 (1997); Prelevic, G. M., et al., Bailliere's Clinical Endocrinology and Metabolism 11:311-340 (1997); Leveille, S. G., et al., J. Am

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Geriatr Soc 45:1496-1500 (1997); and Miller, K. L., Clin Obst Gynec 39:912-932 (1996)). Thus it was of interest to study the effects of estrogen in early vs. late postmenopause. Web site: http://www.delphion.com/details?pn=US06583334__ ·

Treatment of menopausal symptoms Inventor(s): Pitchford; Alan G. (Berkshire, GB2) Assignee(s): Syntex (U.S.A.) Inc. (Palo Alto, CA) Patent Number: 4,425,339 Date filed: April 9, 1981 Abstract: A method for treating menopausal symptoms and a pharmaceutical package for effecting the method are disclosed. The method comprises a three phase sequence of estrogen and progestogen administration and an additional drug-free fourth phase during at least one menstrual cycle as follows:(a) as phase one, 0.2 mg to 1.5 mg of estrone, (or of other natural estrogen in an amount sufficient to result in an effect equivalent to the selected amount of estrone within the aforegiven range) for 4-9 days, followed by(b) as phase two, 0.2 mg to 1.5 mg of estrone, (or of other natural estrogen in an amount sufficient to result in an effect equivalent to the selected amount of estrone within the aforegiven range), plus 0.2 to 1.5 mg of norethisterone (or of other styptic progestogen, in an amount sufficient to result in an effect equivalent to the selected amount of norethisterone within the aforegiven range); with the proviso that the dosage levels of estrogen and progestogen be approximately equal (as defined in terms of estrone and nonethisterone above); for 6-11 days, followed by(c) as phase three, twice the dosage of estrogen and twice the dosage of progestogen used in phase two, for at least 6 days, or for an arbitrarily selected greater number of days to a maximum of 90 days; followed by(d) as phase four, no therapeutically active dosage, i.e., either no treatment or a placebo, for 6-8 days. Excerpt(s): The present invention relates to novel methods and articles of manufacture which are packages containing compositions useful for treating symptoms associated with the menopause. More particularly, the present invention is directed to relieving or preventing menopausal or perimenopausal symptoms in the female human by use of a stepwise, graded, sequential, natural estrogen-progestogen regimen.. Treatment of the menopause has been focused largely on the distressing symptoms associated therewith, e.g., hot flushes (or flashes), headache, insomnia, fatigue, nervousness, depression, joint pains, and so forth.. More serious symptoms are recurrent cysto-urethritis; dysparunia and vaginal atrophy; and menorrhagia. Perhaps the most serious associated biological change is osteoporosis, a process which begins during menopause and continues in the post-menopausal years. This bone-degeneration is gradual, but irreversible; hip fractures, which are associated with substantial mortality risk, are common among postmenopausal women. Web site: http://www.delphion.com/details?pn=US04425339__

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Treatment of premenstrual syndrome and menopause Inventor(s): Ellenberger; William P. (Woodward, OK), Andrus; G. Merrill (Orem, UT), Ellenberger; Suzanne R. (Woodward, OK) Assignee(s): Designed Nutritional Products, Inc. (Vineyard, UT) Patent Number: 6,613,792 Date filed: August 2, 1999 Abstract: A method of treating premenstrual syndrome and menopausal symptoms in a patient, the method comprising: administering to the patient an 1H-indole-3-methanol compound (e.g., 1H-indole-3-methanol; ascorbigen) in a medically acceptable manner in a pharmaceutically effective amount. It has been found that the administration of such indoles, particularly, 1H-indole-3-methanol, greatly relieves the symptoms of PMS. Patients with PMS have reported decreased menstrual cramping, decreased menstrual flow, shorter duration of menses, decreased fatigue, less frequent headaches, improved mood, and decreased bloating resulting from the oral administration each day or during specific portions of the menstrual cycle of pharmaceutically effective amounts of dietary indoles derived from 1H-indole-3-methanol. It has also been found that the administration of such indoles, particularly, 1H-indole-3-methanol, greatly relieves the symptoms of menopause. Excerpt(s): This invention relates to the use of various naturally occurring compounds to treat the symptoms of diseases, and, more particularly, to the use of the natural product indole-3-methanol and related compounds to alleviate the symptoms associated with premenstrual syndrome and menopause.. Premenstrual syndrome ("PMS"), a chronic complaint of a substantial percentage of women between the ages of 12 and 50, manifests in symptoms before and during menses. The symptoms include pain, marked general tension, marked irritability, anxiety, depression, abdominal bloating, swelling of subcutaneous tissues, nausea, fatigue, painful swelling of the breasts, headaches, dizziness, and palpitations. J. T. E. Richardson, "The Menstrual Cycle, Cognition, and Paramenstrual Symptomatology", Cognition and the Menstrual Cycle(Springer-Verlag 1992). While virtually all women experience pain at the onset of menstruation, many women also experience some of the listed symptoms several days before the onset of menses. The symptoms vary from one menstrual cycle to another, and vary considerably among individual women. These symptoms are generally conceded to be related to the release of various hormones, including estrogens.. For women who experience severe PMS, there is considerable desire for their pain and suffering to be relieved. Some women find that their cognitive abilities are impaired and hope for ways to improve their cognitive performance during the days when affected by PMS. Id. Web site: http://www.delphion.com/details?pn=US06613792__

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Use of CGRP antagonists and CGRP release inhibitors for combating menopausal hot flushes Inventor(s): Engel; Wolfhard (Biberach, DE), Rudolf; Klaus (Warthausen, DE), Doods; Henri (Warthausen, DE), Eberlein; Wolfgang (Biberach, DE) Assignee(s): Boehringer Ingelheim Pharma KG (Ingelheim, DE) Patent Number: 6,521,609 Date filed: July 12, 2000

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Abstract: A method for treating menopausal hot flushes using CGRP antagonists and/or CGRP release inhibitors and the corresponding pharmaceutical compositions containing as active substance one or more CGRP antagonists and/or CGRP release inhibitors, and the preparation thereof. Excerpt(s): Hot flushes are a common symptom of peri/post-menopausal syndrome the physiology of which is still not fully understood. Apart from hormone replacement therapy, which is a complex intervention and frequently cannot be used long-term owing to its side effects, there has up until now been no simple therapy largely free from side effects for this generally troublesome condition.. Hot flushes are caused by vasodilatation and increased blood flow. A number of publications have mentioned the possibility that CGRP (calcitonin gene-related peptide) plays a part in the occurrence of menopausal hot flushes in oestrogen-deficient women owing to the vasodilatory properties of this neuropeptide ([1]: J. Endocrinol. (1995), 146(3), 431-437; [2]: Acta Physiol. Scand. (1998), 162(4), 517-522; [3]: Am. J. Obstet. Gynecol. (1996), 175(3, Pt. 1), 638-642). The therapeutic use of CGRP antagonists for treating menopausal syndrome has not previously been proposed in the literature.. It has now been found that the symptoms of menopausal hot flushes can be effectively prevented or their distressing effects substantially alleviated by substances which antagonize the effects of CGRP (CGRP antagonists) or inhibit or reduce the release of CGRP from sensory nerve endings (CGRP release inhibitors), this therapeutic approach being superior to hormone replacement therapy in particular because of its lack of side effects. Web site: http://www.delphion.com/details?pn=US06521609__

Patent Applications on Menopause As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to menopause: ·

Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women Inventor(s): Strony, John T. (Lebanon, NJ) Correspondence: SCHERING-PLOUGH CORPORATION; PATENT DEPARTMENT (K6-1, 1990); 2000 GALLOPING HILL ROAD; KENILWORTH; NJ; 07033-0530; US Patent Application Number: 20030119796 Date filed: September 19, 2002 Abstract: The present invention provides compositions, therapeutic combinations and methods including: (a) at least one hormone replacement therapy composition; and (b) at least one sterol absorption inhibitor which can be useful for treating vascular conditions in post-menopausal women and lowering plasma levels of sterols or 5.alpha.stanols. Excerpt(s): This application claims the benefit of priority from U.S. Provisional Patent Application Serial No. 60/324,118, filed Sep. 21, 2001, and is a continuation-in-part of U.S. patent application Ser. No.10/166,942, filed Jun. 11, 2002, each incorporated herein

10

This has been a common practice outside the United States prior to December 2000.

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by reference.. The present invention relates to compositions, therapeutic combinations and methods for treating vascular conditions in post-menopausal women comprising at least one hormone replacement therapy composition and at least one sterol and/or 5.alpha.-stanol absorption inhibitor.. Cardiovascular diseases, such as coronary artery disease, arteriosclerosis, atherosclerosis, hypertension, hypercholesterolemia, hyperlipidemia, congestive heart failure and other cerebro- or peripheral vascular diseases are a leading risk factor and a major cause of death worldwide. Recently, trends have shown post-menopausal women to be at a greater risk than previously thought. It is now generally acknowledged that after menopause, protection from vascular disease slowly dwindles over time and by the seventh and eighth decade of life even approaches the frequency found in men. A number of ongoing studies have and are in the process of evaluating this aspect of women's health and determining recommended courses of therapy which may be effective in preventing or treating post-menopausal women who suffer from vascular diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Formulation for menopausal women Inventor(s): Levinson, R. Saul; (Chesterfield, MO), Kirschner, Mitchell I. (St. Louis, MO), Hermelin, Marc S. (Glendale, MO) Correspondence: Gary M. Nath; NATH & ASSOCIATES PLLC; 6th Floor; 1030 15th Street, N.W. Washington; DC; 20005; US Patent Application Number: 20020173510 Date filed: April 25, 2002 Abstract: The present disclosure relates to novel compositions which provide improved nutritional support for premenopausal and menopausal women and/or relief from symptoms associated with menopause, as well as prophylactic effects, and methods for using same. Excerpt(s): The present invention is directed to novel compositions for use by premenopausal women and menopausal women for the purpose of providing improved nutritional support and/or relief from the symptoms of menopause, as well as to methods for using same.. Menopause, the transition from the reproductive stage to the non-reproductive stage of a woman's life, is characterized primarily by the cessation of menstruation. However, menopause has come to signify much more than simply the loss of reproductive capability, as it is also associated with a number of acute and chronic conditions. Menopausal syndrome consists of a number of varying and often highly distressing symptoms resulting from hormonal imbalance and nutritional deficiency in the female body.. Hot flashes and sweating secondary to vasomotor instability affect 75% of women. Psychologic and emotional symptoms of fatigue, insomnia, irritability and nervousness are common. Lack of sleep due to disturbance by recurring hot flashes contributes to fatigue and irritability. Dizziness, parenthesis and cardiac symptoms of palpitations and tachycardia may also occur; the incidence of heart disease increases. Other common symptoms include nausea, constipation, diarrhea, arthralgia and myalgia. The Merck Manual, 1793 (16.sup.th Ed. 1992). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and composition for preventing or reducing the symptoms of menopause Inventor(s): Troxel, Gary; (Lafayette, CA), Bagchi, Debasis; (Concord, CA) Correspondence: Oral Caglar, Esquire; Sheppard, Mullin, Richter & Hampton LLP; 48th Floor; 333 South Hope Street; Los Angeles; CA; 90071; US Patent Application Number: 20010039296 Date filed: March 23, 2001 Abstract: A method for preventing and or reducing the symptoms of menopause in women comprises identifying women having or at risk for having such symptoms, and administering to them an effective amount of a composition comprising transresveratrol and other compounds that prevent or reduce the symptoms. Excerpt(s): This application claims priority from U.S. Provisional Application Ser. No. 60/191,634. The invention relates generally to a method and composition for preventing or reducing the symptoms of menopause in women.. Menopause and its symptoms occur due to reduced production of estrogen in women. Estrogen is largely responsible for the changes that take place at puberty in girls, and it accounts for the secondary sexual characteristics of females. By direct action, estrogen causes growth and development of the vagina, uterus, and fallopian tubes. Estrogen acts in concert with other hormones to cause enlargement of the breasts through promotion of ductal growth, stromal development, and molding and shaping of body contours. With aging, and particularly beginning in the fifties for most women, the production of estrogen in the body begins to decline. This is a slow and gradual process that can continue for some years after menstruation has ceased. The menopausal symptoms are characterized by bone loss, osteoporosis, hot flashes, inappropriate sweating, vaginal dryness and/or itching, anemia and cardiovascular dysfunctions.. To reduce or prevent these symptoms, hormone replacement therapy or estrogen therapy is a common practice in women during menopause. Estrogenic activity is shared by many steroidal and nonsteroidal compounds. The most potent naturally-occurring estrogen in human beings is estradiol, followed by estrone and estriol. Women suffering from or at risk for suffering from these symptoms are administered estrogen in sufficient quantity to reduce or prevent them. However, administration of estrogens and synthetic therapeutic agents presents several problems, including increased incidence of breast and uterine cancers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for increasing intestinal absorption of fat soluble vitamins in postmenopausal women and lower animals Inventor(s): Gross, Kathy Lynn; (Topeka, KS), Koo, Sung I. (Manhattan, KS), Owen, Kevin; (Manhattan, KS) Correspondence: COLGATE-PALMOLIVE COMPANY; 909 River Road; P.O. Box 1343; Piscataway; NJ; 08855-1343; US Patent Application Number: 20010041695 Date filed: March 1, 2001 Abstract: Applicants have discovered that L-carnitine increases the intestinal (lymphatic) absorption of fat soluble vitamins, such as vitamins A, D, and E, in postmenopausal women. As a result, L-carnitine enhances the antioxidant defense

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mechanism and lowers the risk of certain degenerative diseases, such as coronary heart disease, age-related macular degeneration, osteoporosis, cancer, and Alzheimer's, in post-menopausal women. The present invention provides a method for increasing the intestinal absorption, cellular concentration, biliary secretion, hepatic storage, and/or liver concentration of a fat soluble vitamin in a post-menopausal woman. The method comprises orally administering to a post-menopausal woman in need thereof, a fat soluble vitamin and a fat soluble vitamin absorption increasing effective amount of Lcarnitine. The invention also provides a method for increasing the intestinal absorption of a fat soluble vitamin in an animal. The method comprises orally administering to the animal in need thereof, a fat soluble vitamin and a fat soluble vitamin absorption increasing effective amount of L-carnitine. Excerpt(s): This application claims the benefit of U.S. Provisional application No. 60/188,419 filed Mar. 10, 2000.. This invention relates to a method for increasing the intestinal absorption, cellular concentration, biliary secretion, hepatic storage, and/or liver concentration of a fat soluble vitamin in a post-menopausal woman or a lower animal by oraly administering L-carnitine and a fat soluble vitamin.. L-carnitine plays a crucial role in the energy supply of tissues by modulating the entry of long-chain fatty acids into the mitochondrial matrix and their subsequent oxidation. Consistent with such a metabolic role, L-carnitine has been shown to be effective in lowering the serum levels of cholesterol, triglyceride, and free fatty acids, while increasing high density lipoprotein (HDL) cholesterol which is anti atherogenic. See Pola, P. et al., "Carnitine in the theraphy of dyslipemic patients", Curr Ther Res 27:208-16 (1980); Lacour, B. et al., "Carnitine improves lipid abnormalies in haemodialysis patients", Lancet 12:763-4 (1980); Avogaro, P., "Acute effect of L-carnitine on FFA and beta-hydroxy-butyrate in man", Pharmacol Res Commun 13:433-50 (1981); and Vacha, G. M. et al. "Favourable effects of L-carnitine treatment on hypertriglyceridemia in hemodialysis patients: Decisive role of low levels of high density lipoprotein cholesterol", Am J Clin Nutr 38:532-40 (1983). Existing evidence indicates that L-carnitine and its esters enhance the stability and integrity of erythrocyte membranes by participating in the reacylation (repair) of membrane phospholipids subjected to oxidative damage. See Arduini, A. et al., "Effect of propionyl-L-carnitine treatment on membrane phospholipid fatty acid turnover in diabetic rat erythrocytes", Mol Cell Biochem 152:31-7 (1995); Arduini, A. et al., "Carnitine palmitoyltransferase and acyl-CoA binding protein: two more players in the membrane phospholipid fatty acid turnover of human red cells?", Biochem J 325:8114 (1997); and Arduini, A. et al., "Addition of L-carnitine to additive solution-suspended red cells stored at 4.degree. C. reduces in vitro hemolysis and improves in vivo viability", Trandfusion 37:166-74 (1997). It is of interest to note that such an action of Lcarnitine and its esters is shown in the erythrocyte devoid of mitochondria. L-carnitine supplementation to old rats has been shown to reverse the age-related decline in mitochondrial function, which may be linked to the membrane-stabilizing effect of Lcarnitine. See Hagen, T. M. et al., "Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity", Proc Natl Acad Sci USA 95:9562-6 (1998). This finding is of particular significance in that oxidative damage to mitochondrial DNA increases markedly with age, leading to impaired cellular metabolism and function. See Hagen, T. M. et al., "Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase", Proc Natl Acad Sci USA 94:3064-9 (1997). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Once-a-month injection as a depot contraceptive and for hormone replacement therapy for perimenopausal and premenopausal women Inventor(s): Aydinlik, Semiramis; (Berlin, DE), Lachnit-Fixson, Ursula; (Berlin, DE) Correspondence: MILLEN, WHITE, ZELANO & BRANIGAN, P.C. 2200 CLARENDON BLVD. SUITE 1400; ARLINGTON; VA; 22201; US Patent Application Number: 20020193358 Date filed: February 5, 2002 Abstract: This invention describes the use of a once-a-month injection (once-a-month injectable) that contains an estrogenic and gestagenic component as an active ingredient for the production of a pharmaceutical agent for contraception and simultaneous hormone replacement therapy for perimenopausal and premenopausal women.With this pharmaceutical agent, a more reliable contraceptive effect with a "natural" estrogen (without ethinylestradiol) with accompanying active therapy of the beginning estrogenloss symptoms, as well as prevention of osteoporosis, is achieved. Excerpt(s): This invention relates to the use of a once-a-month injection (once-a-month injectable composition) that contains an estrogenic and gestagenic component as an active ingredient for the production of a pharmaceutical agent for contraception and simultaneous hormone replacement therapy for perimenopausal and premenopausal women.. A once-a-month injection as defined by this invention means a hormone preparation that is injected in women of child-bearing age once a month for contraception. In this hormone preparation, a gestagenic as well as an estrogenic component are contained as active substances, each with a sufficiently long action to achieve a contraceptive effect for a one-month period.. So-called progestogen-only injectables are also available, which ensure longer-lasting contraceptive protection, but with poor cycle control. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment or prevention of menopausal symptoms and osteoporosis Inventor(s): Kelly, Graham E. (Northbridge, AU) Correspondence: FINNEGAN, HENDERSON, FARABOW, GARRETT &; DUNNER LLP; 1300 I STREET, NW; WASHINGTON; DC; 20005; US Patent Application Number: 20020035074 Date filed: November 9, 2001 Abstract: There is described a method for the treatment or prevention of menopausal symptoms or osteoporosis wherein there is administered to a subject in need of such treatment a therapeutically effective amount of the isoflavone formononetin, or a method for the treatment or prevention of menopausal symptoms wherein there is administered to a subject in need of such treatment a therapeutically effective amount of the isoflavone daidzein, the isoflavone being optionally administered with one or more pharmaceutically acceptable adjuvants, carriers and/or excipients. Therapeutic uses and compositions/foods are also described, comprising daidzein or formononetin optionally in association with one or more pharmaceutically acceptable adjuvants, carriers, food components and/or excipients. Excerpt(s): This invention relates to compositions, therapeutic uses and methods of treatment or prevention of menopausal symptoms and osteoporosis.. Menopausal

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symptoms and osteoporosis are significant scourges in the female population, generally affecting many women in later life.. Menopausal symptoms are very well known and are described, for example, by Greene, J. G. and Cooke, D. J. (1980) British Journal of Psychiatry Volume 136, 486-491 (incorporated herein by reference). Hot flushes are one of the principal menopausal symptoms which are uncomfortable and irritating. Greene and Cooke have developed a score in order to measure menopausal symptoms in women. This score is approved by the US Department of Health and widely used in the medical community. The indicators of menopausal symptoms according to Greene and Cooke comprise hot flushes, sweating at night, heart beating quickly or strongly, feelings of tension or nervousness, difficulty in sleeping, excitability, attacks of panic, difficulties in concentrating, feelings of tiredness or lack of energy, unhappiness or depression, crying spells, irritability, feelings of dizziness or faintness, pressure or tightness in head or body, parts of the body feeling numb or tingling, dry vagina and/or dry mouth, headaches, muscle and joint pains, loss of feeling in hands or feet, breathing difficulties, and loss of interest in sex. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with menopause, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “menopause” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on menopause. You can also use this procedure to view pending patent applications concerning menopause. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON MENOPAUSE Overview This chapter provides bibliographic book references relating to menopause. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on menopause include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “menopause” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on menopause: ·

The baby boomers' menopause handbook: Making your own choices through the other end of puberty Source: Gualala, CA: CA Publishing, Ink. 2000. 80 pp. Contact: Available from CA Publishing, Ink, 35501 South Highway One, Unit 103, Gualala, CA 95445-5103 / Web site: http://www.menopausebook.org/. $12.95. Summary: The purpose of this book is to present women with information on menopause and to provide resources for access further information on the subject. The book presents a definition of menopause, a chapter on other women's experiences with menopause, and a discussion of hormonal replacement and alternatives to hormonal replacement. A list of resources and an annotated bibliography are presented. A glossary of common terms used in the discussion of female anatomy is included in the book.

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Today and tomorrow's woman: Menopause: Before and after (Girls of 16 to women of 99) Source: Potomac, MD: Health Leadership Associates. 1996. 279 pp. Contact: Available from Health Leadership Associates, Inc, P.O. Box 59153, Potomac, MD 20854. Telephone: (800) 435-4775 / fax: (301) 983-2693. $10.00. Summary: This book is written for women 16 and older, and discusses ways menopause can be managed and controlled with proper planning and healthy activities. Topics include understanding the myths and realities of menopause, osteoporosis, cardiovascular disease in women, management through hormone replacement therapy, and starting and maintaining a healthy lifestyle. The final chapter centers on research in the area of women's health and menopause. Appendices include a glossary, a resource directory, references, and an index.

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Management of the perimenopausal and postmenopausal woman: A total wellness program Source: Philadelphia, MD: Lippencott. 1999. 302 pp. Contact: Available from Lippencott Williams and Wilkins, 12105 Insurance Way, Hagerstown, MD 21740-5176. Telephone: (800) 638-3030 / fax: (301) 824-7390. $37.95. Summary: This book primarily discusses health issues generally affecting women from pre-menopause through climacteric, incorporating traditional medical and alternative health care practices. Topics include reproductive physiology and symptomology during pre- and postmenopausal phases; cardiovascular disease; osteoporosis; psychologic, sociologic, sexual and contraceptive issues; a total wellness program, hormonal and drug therapies; and complementary therapies and holistic medicine. Appendices, resources, guidelines for the care of women over 30, a list of sample questions for the health professional to ask the woman, and an index are also included.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “menopause” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “menopause” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “menopause” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·

"No, It's Not Hot In Here" , A Husbands Guide to Menopause by Dick Roth; ISBN: 0965506738; http://www.amazon.com/exec/obidos/ASIN/0965506738/icongroupinterna

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"No, It's Not Hot in Here": A Partner's Guide to Understanding Menopause by Dick Roth; ISBN: 0717132277; http://www.amazon.com/exec/obidos/ASIN/0717132277/icongroupinterna

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150 Most-Asked Questions About Menopause : What Women Really Want to Know by Ruth S. Jacobowitz (Author) (1996); ISBN: 0688147682; http://www.amazon.com/exec/obidos/ASIN/0688147682/icongroupinterna

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2004 Menopause Calendar by Gina Wei, et al; ISBN: 1588084604; http://www.amazon.com/exec/obidos/ASIN/1588084604/icongroupinterna

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50 Ways to Cope With Menopause by International Publications, Linda Hughey Holt (1994); ISBN: 0785308032; http://www.amazon.com/exec/obidos/ASIN/0785308032/icongroupinterna

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60 Second Menopause Management: The Quickest Ways to Handle Problems and Discomfort by Carol R. Schulz, Mary Jenkins (Contributor) (1995); ISBN: 0882821377; http://www.amazon.com/exec/obidos/ASIN/0882821377/icongroupinterna

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A Certain Age: Reflecting on the Menopause by Joanna Goldsworthy (1994); ISBN: 185381606X; http://www.amazon.com/exec/obidos/ASIN/185381606X/icongroupinterna

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A Change for the Better: A Women's Guide Through the Menopause by Patricia Davis, Patricia Davies (1994); ISBN: 0852072651; http://www.amazon.com/exec/obidos/ASIN/0852072651/icongroupinterna

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A Change for the Better: How to Survive - and Thrive - During the Menopause by Hilary Jones; ISBN: 034076810X; http://www.amazon.com/exec/obidos/ASIN/034076810X/icongroupinterna

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A Clinician's Guide to Menopause by Donna E. Stewart (Editor), Gail Erlick Robinson (Editor); ISBN: 0880487542; http://www.amazon.com/exec/obidos/ASIN/0880487542/icongroupinterna

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A Funny Thing Happened on the Way to Menopause by Jean Green (2002); ISBN: 1403320217; http://www.amazon.com/exec/obidos/ASIN/1403320217/icongroupinterna

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A Meditation for Mastering Menopause by Belleruth Naparstek (2002); ISBN: 1881405559; http://www.amazon.com/exec/obidos/ASIN/1881405559/icongroupinterna

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A Menopausal Memoir: Letters from Another Climate by Ann Herrmann, Anne Herrmann (1998); ISBN: 1560239190; http://www.amazon.com/exec/obidos/ASIN/1560239190/icongroupinterna

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A Portrait of the Menopause: Expert Reports on Medical and Therapeutic Strategies for the 1990's by M. Boulet (Editor), H. G. Burger; ISBN: 1850703574; http://www.amazon.com/exec/obidos/ASIN/1850703574/icongroupinterna

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A Seven-Step Program for Getting Through Menopause and Enjoying a Longer, Healthier Life Without Drugs by Catherine D. Lowes, Catherine D. Lowes (1998); ISBN: 0968149219; http://www.amazon.com/exec/obidos/ASIN/0968149219/icongroupinterna

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A Woman Doctor's Guide to Menopause: Essential Facts and Up-To-The-Minute Information for a Woman's Change of Life (Books for Women by Women) by Lois Jovanovic-Peterson, et al; ISBN: 156282855X; http://www.amazon.com/exec/obidos/ASIN/156282855X/icongroupinterna

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A Woman's Best Medicine for Menopause: Your Personal Guide to Radiant Good Health Using Maharishi Ayurveda by Nancy K., M.D. Lonsdorf, Rama Kant Mishra;

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ISBN: 0809293358; http://www.amazon.com/exec/obidos/ASIN/0809293358/icongroupinterna ·

A Woman's Guide to Male Menopause: Real Solutions for Helping Him Maintain Vitality and Virility by Marc R., Md Rose, et al; ISBN: 0658001434; http://www.amazon.com/exec/obidos/ASIN/0658001434/icongroupinterna

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A Woman's Guide to Menopause and Hormone Replacement Therapy by Lorraine Dennerstein (Editor), et al; ISBN: 0880487828; http://www.amazon.com/exec/obidos/ASIN/0880487828/icongroupinterna

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Adventures in Menopause: A Lighthearted Guide to Surviving the Menomonsters by Jayne L. Garrett; ISBN: 0972917802; http://www.amazon.com/exec/obidos/ASIN/0972917802/icongroupinterna

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Aging and Menopause Among Indian South African Women (Suny Series in Medical Anthropology) by Brian M. Du Toit (1990); ISBN: 0791403890; http://www.amazon.com/exec/obidos/ASIN/0791403890/icongroupinterna

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All About the Menopause and Its Treatment Without Drugs by David Potterton; ISBN: 0572021542; http://www.amazon.com/exec/obidos/ASIN/0572021542/icongroupinterna

·

All You Wanted to Know About Menopause by Savitri Ramaiah; ISBN: 8120723007; http://www.amazon.com/exec/obidos/ASIN/8120723007/icongroupinterna

·

Ama Essential Guide to Menopause by American Medical Association (Editor); ISBN: 0743403584; http://www.amazon.com/exec/obidos/ASIN/0743403584/icongroupinterna

·

An Atlas of Menopausal Aging by Pietro M., Md. Motta, et al; ISBN: 1842141228; http://www.amazon.com/exec/obidos/ASIN/1842141228/icongroupinterna

·

An Atlas of the Menopause by S.I.J. Whitcroft, et al; ISBN: 1850703884; http://www.amazon.com/exec/obidos/ASIN/1850703884/icongroupinterna

·

Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis (Who Technical Report, No 843) by Who Study Group on Assessment of Fracture Risk and Its Application to, et al (1994); ISBN: 9241208430; http://www.amazon.com/exec/obidos/ASIN/9241208430/icongroupinterna

·

Beating Menopause and Early Ovarian Failure With the Help of One Natural Ingredient by Julia Elliott (1995); ISBN: 096586460X; http://www.amazon.com/exec/obidos/ASIN/096586460X/icongroupinterna

·

Before the Change : Taking Charge of Your Perimenopause by Ann Louise Gittleman (Author) (1999); ISBN: 0062515373; http://www.amazon.com/exec/obidos/ASIN/0062515373/icongroupinterna

·

Biology of Menopause by Francis L. Bellino (Editor); ISBN: 0387989870; http://www.amazon.com/exec/obidos/ASIN/0387989870/icongroupinterna

·

Black Woman's Guide to Menopause: Doing Menopause With Heart and Soul by Carolyn Scott Brown, et al (2003); ISBN: 1570719330; http://www.amazon.com/exec/obidos/ASIN/1570719330/icongroupinterna

·

Breezing Through the Change: Managing Menopause Naturally by Lynne P. Walker, et al; ISBN: 1883319129; http://www.amazon.com/exec/obidos/ASIN/1883319129/icongroupinterna

Books 353

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Change of Life a Psychological Study of Dreams and the Menopause: A Psychological Study of Dreams and the Menopause (Studies in Jungian Psychology by Jungian Analysts, 16) by Ann Mankowitz (1993); ISBN: 0919123155; http://www.amazon.com/exec/obidos/ASIN/0919123155/icongroupinterna

·

Changing Perspectives on Menopause by Ann M. Voda (1982); ISBN: 0292710690; http://www.amazon.com/exec/obidos/ASIN/0292710690/icongroupinterna

·

Changing Woman's Workbook : Menopause as Path of Empowerment by Dalen Daniels; ISBN: 1883230101; http://www.amazon.com/exec/obidos/ASIN/1883230101/icongroupinterna

·

Changing Woman's Workbook: Approaching Menopause As Journey of Spiritual Transformation by Magdalen Daniels; ISBN: 188323008X; http://www.amazon.com/exec/obidos/ASIN/188323008X/icongroupinterna

·

Choice Years: Health, Happiness, and Beauty Through Menopause and Beyond by Judith Paige, Pamela Gordon (Contributor); ISBN: 0394583973; http://www.amazon.com/exec/obidos/ASIN/0394583973/icongroupinterna

·

Clinical Management of Perimenopause by Shawky Z. A. Badawy (Editor) (1999); ISBN: 0412128519; http://www.amazon.com/exec/obidos/ASIN/0412128519/icongroupinterna

·

Clinical Management of the Menopause by Barry G. Wren, Lila Nachtigall (Contributor); ISBN: 0074529145; http://www.amazon.com/exec/obidos/ASIN/0074529145/icongroupinterna

·

Clinical Management of the Perimenopause by Shawky Za Badawy (Editor); ISBN: 0340741503; http://www.amazon.com/exec/obidos/ASIN/0340741503/icongroupinterna

·

Complete Idiot's Guide to Menopause by Dr. Maureen Pelletier, Deborah S. Romaine; ISBN: 0028639375; http://www.amazon.com/exec/obidos/ASIN/0028639375/icongroupinterna

·

Comprehensive management of menopause; ISBN: 3540979727; http://www.amazon.com/exec/obidos/ASIN/3540979727/icongroupinterna

·

Comprehensive Management of Menopause (Clinical Perspectives in Obstetrics and Gynecology) by Jacques Lorrain (Editor), et al (1994); ISBN: 0387979727; http://www.amazon.com/exec/obidos/ASIN/0387979727/icongroupinterna

·

Consensus on menopause research : a summary of international opinion : the proceedings of the first International Congress on the Menopause, held at La Grande Motte, France, in June 1976; ISBN: 0839109849; http://www.amazon.com/exec/obidos/ASIN/0839109849/icongroupinterna

·

Consensus on Menopause Research: A Summary of International Opinion by P.A. van Keep (Editor); ISBN: 0852001665; http://www.amazon.com/exec/obidos/ASIN/0852001665/icongroupinterna

·

Contemporary Issues in Perimenopause and Menopause by Frances R. Batzer; ISBN: 1884065163; http://www.amazon.com/exec/obidos/ASIN/1884065163/icongroupinterna

·

Controlling Hormones Naturally: My Journey for Solutions to Pms, Menopause & Osteoporsis With Wild Yam by Melinda Bonk, et al (1996); ISBN: 0965082709; http://www.amazon.com/exec/obidos/ASIN/0965082709/icongroupinterna

354 Menopause

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Coping With Menopause by Janet Horwood (2001); ISBN: 0859698343; http://www.amazon.com/exec/obidos/ASIN/0859698343/icongroupinterna

·

Could it Be Perimenopause? by M.D. Steven R. Goldstein (Author) (2000); ISBN: 0316319457; http://www.amazon.com/exec/obidos/ASIN/0316319457/icongroupinterna

·

Could It Be..Perimenopause? by L. S./Ashner Goldstein (Author) (1998); ISBN: 0316318981; http://www.amazon.com/exec/obidos/ASIN/0316318981/icongroupinterna

·

Creative Menopause (Illuminating Women's Health & Spirituality) by Farida Sharan; ISBN: 1570930023; http://www.amazon.com/exec/obidos/ASIN/1570930023/icongroupinterna

·

Discover Your Menopause Type by Joseph Collins (2002); ISBN: 076153749X; http://www.amazon.com/exec/obidos/ASIN/076153749X/icongroupinterna

·

Diseases Explained: Menopause Wall Chart by Lexi-Comp; ISBN: 1930598165; http://www.amazon.com/exec/obidos/ASIN/1930598165/icongroupinterna

·

DK Healthcare: Natural Menopause (Dorling Kindersley Health Care) by Miriam Stoppard; ISBN: 0751305502; http://www.amazon.com/exec/obidos/ASIN/0751305502/icongroupinterna

·

Doctor Discusses Menopause and Estrogens by M. Edward and Dona Meilach Davis (1980); ISBN: 0910304262; http://www.amazon.com/exec/obidos/ASIN/0910304262/icongroupinterna

·

Double Menopause: What to Do When Both You and Your Mate Have Hormonal Changes Together by Nancy Cetel (Author); ISBN: 0471402621; http://www.amazon.com/exec/obidos/ASIN/0471402621/icongroupinterna

·

Dr. Linda Page's Healthy Healing Guide to Menopause & Osteoporosis by Linda Rector-Page, Linda R. Page; ISBN: 1884334903; http://www.amazon.com/exec/obidos/ASIN/1884334903/icongroupinterna

·

Dr. Susan Lark's the Estrogen Decision Self Help Book: A Complete Guide for Relief of Menopausal Symptoms Through Hormonal Replacement and Alternative Therapies by Susan M. Lark (1996); ISBN: 0890877769; http://www.amazon.com/exec/obidos/ASIN/0890877769/icongroupinterna

·

Dr. Susan Love's Hormone Book: Making Informed Choices About Menopause by Susan M. Love, Karen Lindsey (Contributor) (1997); ISBN: 0679449701; http://www.amazon.com/exec/obidos/ASIN/0679449701/icongroupinterna

·

Dr. Susan Love's Menopause and Hormone Book: Making Informed Choices by Susan M., Md. Love, et al (2003); ISBN: 0609809962; http://www.amazon.com/exec/obidos/ASIN/0609809962/icongroupinterna

·

Drawing from the Women's Well: Reflections on the Life Passage of Menopause by Joan C. Borton (1992); ISBN: 0931055873; http://www.amazon.com/exec/obidos/ASIN/0931055873/icongroupinterna

·

Eat to Beat Menopause: Over 100 Recipes to Help You Overcome Symptoms Naturally by Linda Kearns; ISBN: 0007110421; http://www.amazon.com/exec/obidos/ASIN/0007110421/icongroupinterna

Books 355

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Eat Well for a Healthy Menopause : The Low-Fat, High Nutrition Guide by Elaine Magee (Author); ISBN: 0471193607; http://www.amazon.com/exec/obidos/ASIN/0471193607/icongroupinterna

·

Eat Your Way Through the Menopause by Marilyn Glenville; ISBN: 1856264688; http://www.amazon.com/exec/obidos/ASIN/1856264688/icongroupinterna

·

Encounters With Aging: Mythologies of Menopause in Japan and North America by Margaret M. Lock (1995); ISBN: 0520201620; http://www.amazon.com/exec/obidos/ASIN/0520201620/icongroupinterna

·

Estrogen, Memory and Menopause : 136 Questions and Answers on the Symptoms and Treatment of Hormone Related Memory and Mood Disorders by Gayatri Devi M.D. (2000); ISBN: 0970468105; http://www.amazon.com/exec/obidos/ASIN/0970468105/icongroupinterna

·

Estrogen: The Natural Way: Over 250 Easy and Delicious Recipes for Menopause by Nina Shandler (1998); ISBN: 0375751416; http://www.amazon.com/exec/obidos/ASIN/0375751416/icongroupinterna

·

Faqs All About Menopause, Phytoestrogens, and Red Clover (Avery's Faqs Series) by Frank Murray, Jack Challem (Editor); ISBN: 0895299097; http://www.amazon.com/exec/obidos/ASIN/0895299097/icongroupinterna

·

Feelin' Hot? A Humorous, Informative and Truthful Look at Menopause by Rebecca J. Hulem (2003); ISBN: 0974161802; http://www.amazon.com/exec/obidos/ASIN/0974161802/icongroupinterna

·

Flash : a pause for the menopause by MaryEllen Bell Ray; ISBN: 0917047001; http://www.amazon.com/exec/obidos/ASIN/0917047001/icongroupinterna

·

From Menarche to Menopause: Reproductive Lives of Peasant Women in Two Cultures (Suny Series in Medical Anthropology) by Yewoubdar Beyene (1989); ISBN: 0887068677; http://www.amazon.com/exec/obidos/ASIN/0887068677/icongroupinterna

·

From Menarche to Menopause: The Female Body in Feminist Therapy by Joan C. Chrisler (Editor) (2004); ISBN: 0789023490; http://www.amazon.com/exec/obidos/ASIN/0789023490/icongroupinterna

·

Get Off the Menopause Roller Coaster: Natural Solutions for Mood Swings, Hot Flashes, Fatigue, Anxiety, Depression, and Other Symptons by Shari, Phd Lieberman; ISBN: 1583330003; http://www.amazon.com/exec/obidos/ASIN/1583330003/icongroupinterna

·

Gods Pathway to Healing: Menopause by Reginald B. Cherry, Linda D. Cherry (1999); ISBN: 157778118X; http://www.amazon.com/exec/obidos/ASIN/157778118X/icongroupinterna

·

Guidelines for the Management of the Menopause by Martin Birkhauser; ISBN: 1842141384; http://www.amazon.com/exec/obidos/ASIN/1842141384/icongroupinterna

·

Healthy Menopause ('Zi xin mei li geng nian qi', in traditional Chinese, NOT in English) by Meihui Lin (Author); ISBN: 9574694380; http://www.amazon.com/exec/obidos/ASIN/9574694380/icongroupinterna

·

Help Yourself Dynamic Menopause by Beth MacEoin; ISBN: 0071396624; http://www.amazon.com/exec/obidos/ASIN/0071396624/icongroupinterna

356 Menopause

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Herbal Medicine for the Menopause by Andrew Chevallier (2001); ISBN: 1899308261; http://www.amazon.com/exec/obidos/ASIN/1899308261/icongroupinterna

·

Holistic Menopause: A New Approach to Midlife Change by Judy Hall, Robert Jacobs (1998); ISBN: 1899171320; http://www.amazon.com/exec/obidos/ASIN/1899171320/icongroupinterna

·

Homeopathy for Menopause by Beth MacEoin (1997); ISBN: 0892816481; http://www.amazon.com/exec/obidos/ASIN/0892816481/icongroupinterna

·

Homeopathy for the Menopause: A Woman's Guide to the Menopause and Health for the Middle Years (New Popular Family Health Series) by Trevor Smith; ISBN: 0946670188; http://www.amazon.com/exec/obidos/ASIN/0946670188/icongroupinterna

·

Hormone Replacement Therapy : an Option for Women at Menopause by Spellacy, Sturdee; ISBN: 1885274181; http://www.amazon.com/exec/obidos/ASIN/1885274181/icongroupinterna

·

Hormone Replacement Therapy for Menopausal Women: A Clinical Appraisal by J. P. Thomas; ISBN: 9057024772; http://www.amazon.com/exec/obidos/ASIN/9057024772/icongroupinterna

·

Hormone Replacement Therapy Yes or No?: How to Make an Informed Decision About Estrogen, Progesterone, & Other Strategies for Dealing With Pms, Menopause, & Osteoporosis by Betty Kamen (1996); ISBN: 0944501109; http://www.amazon.com/exec/obidos/ASIN/0944501109/icongroupinterna

·

Hormone Replacement Therapy: Conventional Medicine and Natural Alternates, Your Guide to Menopausal Health Care Choices by Linda Laucella; ISBN: 1565651545; http://www.amazon.com/exec/obidos/ASIN/1565651545/icongroupinterna

·

Hormone Replacement Therapy: Conventional Medicines and Natural Alternatives, Your Guide to Menopausal Health Care Choices by Linda Laucella; ISBN: 1565658051; http://www.amazon.com/exec/obidos/ASIN/1565658051/icongroupinterna

·

Hormone therapy of the menopause and aging by Helen Z. Jern; ISBN: 0398027447; http://www.amazon.com/exec/obidos/ASIN/0398027447/icongroupinterna

·

Hormones or Natural Alternatives? Exploring All Your Options at Menopause by Jan Clark; ISBN: 1589231066; http://www.amazon.com/exec/obidos/ASIN/1589231066/icongroupinterna

·

Hormones, Hot Flashes and Mood Swings: Living Through the Ups and Downs of Menopause by Clark, Md. Gillespie; ISBN: 0060551623; http://www.amazon.com/exec/obidos/ASIN/0060551623/icongroupinterna

·

How to Cope Successfully with Menopause (How to Cope Successfully With..) by Joan McClelland; ISBN: 1903784050; http://www.amazon.com/exec/obidos/ASIN/1903784050/icongroupinterna

·

How to Survive Menopause Without Going Crazy by Leona Lipari Lee (2001); ISBN: 0595192416; http://www.amazon.com/exec/obidos/ASIN/0595192416/icongroupinterna

·

How to Survive the Male Menopause by Geoffrey Aquilana Ross; ISBN: 024111442X; http://www.amazon.com/exec/obidos/ASIN/024111442X/icongroupinterna

Books 357

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Hrt and the Menopause: Current Issues by Michael, Md. Marsh, et al (2002); ISBN: 1853176915; http://www.amazon.com/exec/obidos/ASIN/1853176915/icongroupinterna

·

Hypertension in Postmenopausal Women by Franz H. Messerli (Editor), Franz C. Aepfelbacher (Editor) (1996); ISBN: 0824796527; http://www.amazon.com/exec/obidos/ASIN/0824796527/icongroupinterna

·

I Love Menopause Because by Joyce Silverman Ben-Kiki, et al; ISBN: 0836267664; http://www.amazon.com/exec/obidos/ASIN/0836267664/icongroupinterna

·

Intermission: Women, Menopause and Mildlife by Lyn Richards, et al; ISBN: 0195539478; http://www.amazon.com/exec/obidos/ASIN/0195539478/icongroupinterna

·

Internal Cleansing : Rid Your Body of Toxins to Naturally and Effectively Fight Heart Disease, Chronic Pain, Fatigue, PMS and Menopause Symptoms, and More (Revised 2nd Edition) by Linda Berry, Jan Fawcett; ISBN: 0761529322; http://www.amazon.com/exec/obidos/ASIN/0761529322/icongroupinterna

·

Is it Hot in Here or is it Me? (Mastering the Maze of Menopause) by Lorraine D'Abate, Nancy Kenyon (2000); ISBN: 1890838039; http://www.amazon.com/exec/obidos/ASIN/1890838039/icongroupinterna

·

Is It Hot in Here or Is It Me?: A Personal Look at the Facts, Fallacies, and Feelings of Menopause by Gayle Sand; ISBN: 0061093572; http://www.amazon.com/exec/obidos/ASIN/0061093572/icongroupinterna

·

Is It Hot in Here or Is It Me?: Facts, Fallacies and Feelings About Menopause by Gayle Sand; ISBN: 0747516235; http://www.amazon.com/exec/obidos/ASIN/0747516235/icongroupinterna

·

Journey Through Menopause: A Personal Rite of Passage by Christine Downing; ISBN: 082450836X; http://www.amazon.com/exec/obidos/ASIN/082450836X/icongroupinterna

·

Kathy Smith's Moving Through Menopause: The Complete Program for Exercise, Nutrition, and Total Wellness by Kathy Smith (Author), Robert Miller (2002); ISBN: 0446678716; http://www.amazon.com/exec/obidos/ASIN/0446678716/icongroupinterna

·

Las 25 Preguntas Mas Importantes Acerca De LA Menopausia/the 25 Most Important Questions About Menopause by Ruth S. Jacobowitz (1997); ISBN: 9683805965; http://www.amazon.com/exec/obidos/ASIN/9683805965/icongroupinterna

·

Life Change: A Guide to the Menopause, Its Effects and Treatment by Barbara Evans; ISBN: 0330301705; http://www.amazon.com/exec/obidos/ASIN/0330301705/icongroupinterna

·

Making Sense of Menopause: Over 150 Women and Experts Share Their Wisdom, Experience, and Commonsense Advice by Faye Kitchener Cone (1993); ISBN: 0671786385; http://www.amazon.com/exec/obidos/ASIN/0671786385/icongroupinterna

·

Male Menopause by Jed Diamond (1998); ISBN: 1570713979; http://www.amazon.com/exec/obidos/ASIN/1570713979/icongroupinterna

·

Management of the Menopause by Margaret Rees (Editor), David W. Purdie (Editor) (2002); ISBN: 0953622819; http://www.amazon.com/exec/obidos/ASIN/0953622819/icongroupinterna

358 Menopause

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Management of the Perimenopausal and Postmenopausal Woman: A Total Wellness Program by Barbara Kass-Annese, Kass; ISBN: 0781716543; http://www.amazon.com/exec/obidos/ASIN/0781716543/icongroupinterna

·

Managing Menopause Naturally with Chinese Medicine by Honora Lee Wolfe, Bob S. Flaws; ISBN: 0936185988; http://www.amazon.com/exec/obidos/ASIN/0936185988/icongroupinterna

·

Managing Your Menopause by Wulf H. Utian, Ruth S. Jacobwitz (Contributor) (1991); ISBN: 0135462681; http://www.amazon.com/exec/obidos/ASIN/0135462681/icongroupinterna

·

Men Surviving Menopause: You and the Woman You Love at Mid-Life by Paul Selinger (2000); ISBN: 0595098983; http://www.amazon.com/exec/obidos/ASIN/0595098983/icongroupinterna

·

Menopause by Margot Frommer; ISBN: 0523424477; http://www.amazon.com/exec/obidos/ASIN/0523424477/icongroupinterna

·

Menopause by Sarah Brewer; ISBN: 0722533896; http://www.amazon.com/exec/obidos/ASIN/0722533896/icongroupinterna

·

Menopause by Miriam, Dr. Stoppard, Miriam Stoppard; ISBN: 0789483572; http://www.amazon.com/exec/obidos/ASIN/0789483572/icongroupinterna

·

Menopause by Raewyn Mackenzia (1985); ISBN: 0859694747; http://www.amazon.com/exec/obidos/ASIN/0859694747/icongroupinterna

·

Menopause by Steve London, H. Jane Chihal (1995); ISBN: 0929240049; http://www.amazon.com/exec/obidos/ASIN/0929240049/icongroupinterna

·

Menopause - the Best Years of Your Life? by Ada P. Kahn, Linda Hughey Holt; ISBN: 0747500703; http://www.amazon.com/exec/obidos/ASIN/0747500703/icongroupinterna

·

Menopause & Emotions: Making Sense of Your Feelings When Your Feelings Make No Sense by Lafern Page; ISBN: 0969787405; http://www.amazon.com/exec/obidos/ASIN/0969787405/icongroupinterna

·

Menopause & Homeopathy: A Guide for Women in Midlife by Ifeoma Ikenze, Afeoma Akenze; ISBN: 1556432917; http://www.amazon.com/exec/obidos/ASIN/1556432917/icongroupinterna

·

Menopause & osteoporosis : A-Z guide to natural healing by Brenda Beeley; ISBN: 0966224000; http://www.amazon.com/exec/obidos/ASIN/0966224000/icongroupinterna

·

Menopause (Fast Facts) by David H. Barlow, Barry G. Wren (2000); ISBN: 189954108X; http://www.amazon.com/exec/obidos/ASIN/189954108X/icongroupinterna

·

Menopause (Food Solutions):: Recipes and Advice to Relieve Symptoms by Sally Lewis (2001); ISBN: 0600602982; http://www.amazon.com/exec/obidos/ASIN/0600602982/icongroupinterna

·

Menopause (Herbal Health) by Jill Wright (2002); ISBN: 1857037243; http://www.amazon.com/exec/obidos/ASIN/1857037243/icongroupinterna

·

Menopause (Pocket Doc Library Patient Guide) by Randy J. Shields (1997); ISBN: 1888886048; http://www.amazon.com/exec/obidos/ASIN/1888886048/icongroupinterna

Books 359

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Menopause (The Well Woman) by Jan de Vries, Gloria Hunniford; ISBN: 1851584498; http://www.amazon.com/exec/obidos/ASIN/1851584498/icongroupinterna

·

Menopause : questions and answers by Suzanne Mollie Beedell; ISBN: 0894370022; http://www.amazon.com/exec/obidos/ASIN/0894370022/icongroupinterna

·

Menopause 2003 Weekly Planner by Marie Borum, et al; ISBN: 1588082059; http://www.amazon.com/exec/obidos/ASIN/1588082059/icongroupinterna

·

Menopause a Second Spring; ISBN: 093618518X; http://www.amazon.com/exec/obidos/ASIN/093618518X/icongroupinterna

·

Menopause a Second Spring: Making a Smooth Transition With Traditional Chinese Medicine by Honora Lee Wolfe; ISBN: 0936185473; http://www.amazon.com/exec/obidos/ASIN/0936185473/icongroupinterna

·

Menopause and Culture by Gabriella Elfriede Berger; ISBN: 0745314880; http://www.amazon.com/exec/obidos/ASIN/0745314880/icongroupinterna

·

Menopause and Estrogen: Natural Alternatives to Harmone Replacement Therapy by Ellen Hodgson Breezing Through the Change Brown, et al (1996); ISBN: 1883319536; http://www.amazon.com/exec/obidos/ASIN/1883319536/icongroupinterna

·

Menopause and Its Effects on the Family; ISBN: 0819124990; http://www.amazon.com/exec/obidos/ASIN/0819124990/icongroupinterna

·

Menopause and Madness: The Truth About Estrogen and the Mind by Marcia Lawrence (2002); ISBN: 0735104085; http://www.amazon.com/exec/obidos/ASIN/0735104085/icongroupinterna

·

Menopause and Mid-Life by Robert G. Wells, Mary C. Wells (Contributor); ISBN: 0842339752; http://www.amazon.com/exec/obidos/ASIN/0842339752/icongroupinterna

·

Menopause and Midlife Health by Morris Notelovitz, Diana Tonnessen (Contributor) (1994); ISBN: 0312113145; http://www.amazon.com/exec/obidos/ASIN/0312113145/icongroupinterna

·

Menopause and Natural Hormones: Charting Your Course Through Your Change of Life by Daved Rosensweet (2002); ISBN: 0972667113; http://www.amazon.com/exec/obidos/ASIN/0972667113/icongroupinterna

·

Menopause and Osteoporosis: Taking Charge of Your Life Change and Preventing Bone Loss (Healthy Healing Library Series) by Linda Garland Page (1994); ISBN: 1884334261; http://www.amazon.com/exec/obidos/ASIN/1884334261/icongroupinterna

·

Menopause and Postmenopause: The Proceedings of an International Symposium Held in Rome, June, 1979. Ed by N. Pasetto (322P) by Rome, 1979 International Symposium on Estrogens and the Menopause; ISBN: 0852003439; http://www.amazon.com/exec/obidos/ASIN/0852003439/icongroupinterna

·

Menopause and the Brain : A Scientific American article [DOWNLOAD: PDF] by Phyllis M. Wise (Author); ISBN: B00006BNP7; http://www.amazon.com/exec/obidos/ASIN/B00006BNP7/icongroupinterna

·

Menopause and the Heart by Manual Neves-E-Castro (Editor), et al; ISBN: 1850700710; http://www.amazon.com/exec/obidos/ASIN/1850700710/icongroupinterna

·

Menopause and the Mind : The Complete Guide to Coping with the Cognitive Effects of Perimenopause and Menopause Including: +Memory Loss + Foggy Thinking +

360 Menopause

Verbal Slips by Claire L. Warga Ph.D. (Author) (2000); ISBN: 0684854791; http://www.amazon.com/exec/obidos/ASIN/0684854791/icongroupinterna ·

Menopause and the Years Ahead by Mary K. Beard, et al; ISBN: 1555610439; http://www.amazon.com/exec/obidos/ASIN/1555610439/icongroupinterna

·

Menopause Book by Louisa Rose; ISBN: 0801549957; http://www.amazon.com/exec/obidos/ASIN/0801549957/icongroupinterna

·

Menopause Book: A Guide to Health and Well-Being for Women by Sheldon H., Md Cherry, Carolyn D., MD Runowicz (1994); ISBN: 0788190121; http://www.amazon.com/exec/obidos/ASIN/0788190121/icongroupinterna

·

Menopause Care Guide by Mary Anne Arnold (2001); ISBN: 1585510092; http://www.amazon.com/exec/obidos/ASIN/1585510092/icongroupinterna

·

Menopause Core Curriculum Study Guide (2nd Edition) by The North American Menopause Society; ISBN: 0970125127; http://www.amazon.com/exec/obidos/ASIN/0970125127/icongroupinterna

·

Menopause Diet by Dr. Allan N. Spreen (Editor), et al (1999); ISBN: 1580540481; http://www.amazon.com/exec/obidos/ASIN/1580540481/icongroupinterna

·

Menopause For Dummies by Marcia Jones (Author), Marcia Jones (Author) (2002); ISBN: 0764554581; http://www.amazon.com/exec/obidos/ASIN/0764554581/icongroupinterna

·

Menopause for the MRCOG and Beyond by Margaret Rees (Editor); ISBN: 190036445X; http://www.amazon.com/exec/obidos/ASIN/190036445X/icongroupinterna

·

Menopause Guidebook by The North American Menopause Society (2003); ISBN: 0970125143; http://www.amazon.com/exec/obidos/ASIN/0970125143/icongroupinterna

·

Menopause in Modern Perspective: A Guide to Clinical Practice by Wulf H., Utian; ISBN: 0838562973; http://www.amazon.com/exec/obidos/ASIN/0838562973/icongroupinterna

·

Menopause Made Easy: How to Make the Right Decisions for the Rest of Your Life by Carolle Jean-Murat (1999); ISBN: 156170606X; http://www.amazon.com/exec/obidos/ASIN/156170606X/icongroupinterna

·

Menopause Madness: An Empathetic Little Book by Pat Ross (1998); ISBN: 0684842270; http://www.amazon.com/exec/obidos/ASIN/0684842270/icongroupinterna

·

Menopause Matters by J. Hall, J Hall (2002); ISBN: 1843331284; http://www.amazon.com/exec/obidos/ASIN/1843331284/icongroupinterna

·

Menopause Myths & Facts : What Every Woman Should Know about Hormone Replacement Therapy by Lorraine Rothman, Marcia Wexler; ISBN: 0962994561; http://www.amazon.com/exec/obidos/ASIN/0962994561/icongroupinterna

·

Menopause Naturally by Carolyn Dean, Phyllis Herman (Editor); ISBN: 0879836814; http://www.amazon.com/exec/obidos/ASIN/0879836814/icongroupinterna

·

Menopause Naturally by Kathleen Fry, Claudia Wingo; ISBN: 1890694320; http://www.amazon.com/exec/obidos/ASIN/1890694320/icongroupinterna

·

Menopause Pink, Midlife Reflections of Wisdom and Humor by Terri Malucci; ISBN: 0967374448; http://www.amazon.com/exec/obidos/ASIN/0967374448/icongroupinterna

Books 361

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Menopause Planner 2002 by Marie Borum, et al; ISBN: 1588080641; http://www.amazon.com/exec/obidos/ASIN/1588080641/icongroupinterna

·

Menopause the Natural Way: The Women's Natural Health Series by Molly Siple (Author), Deborah Gordon (Author); ISBN: 0471379573; http://www.amazon.com/exec/obidos/ASIN/0471379573/icongroupinterna

·

Menopause Vitamins and You by Muriel C. Clausen (1980); ISBN: 0960366415; http://www.amazon.com/exec/obidos/ASIN/0960366415/icongroupinterna

·

Menopause With Healing Yoga [ABRIDGED] by Kelly Piper (Reader); ISBN: 0787116785; http://www.amazon.com/exec/obidos/ASIN/0787116785/icongroupinterna

·

Menopause Without Medicine by Linda, Ph.D. Ojeda, Jeffrey S., Ph.D. Bland (2003); ISBN: 0897934059; http://www.amazon.com/exec/obidos/ASIN/0897934059/icongroupinterna

·

Menopause, Exercise & Your Fairy Godmother by Janan Clark; ISBN: 0929593022; http://www.amazon.com/exec/obidos/ASIN/0929593022/icongroupinterna

·

Menopause, Me and You: The Sound of Women Pausing (Haworth Innovations in Feminist Studies) by Ann M., Ph.D. Voda (1997); ISBN: 1560239220; http://www.amazon.com/exec/obidos/ASIN/1560239220/icongroupinterna

·

Menopause, Naturally by Sadja Greenwood; ISBN: 0941683060; http://www.amazon.com/exec/obidos/ASIN/0941683060/icongroupinterna

·

Menopause, Naturally: Preparing for the Second Half of Life by Sadja Greenwood; ISBN: 091207874X; http://www.amazon.com/exec/obidos/ASIN/091207874X/icongroupinterna

·

Menopause, Sisterhood, and Tennis: A Miraculous Journey Through "the Change" by Alice Wilson-Fried (2003); ISBN: 1591200768; http://www.amazon.com/exec/obidos/ASIN/1591200768/icongroupinterna

·

Menopause: A Basic Guide for Women by Alan J. Silverstein, Cynthia S. Cotten (1996); ISBN: 0875730663; http://www.amazon.com/exec/obidos/ASIN/0875730663/icongroupinterna

·

Menopause: A Comprehensive Guide by Mariposa Bernstein; ISBN: 0965794423; http://www.amazon.com/exec/obidos/ASIN/0965794423/icongroupinterna

·

Menopause: A Gentle, Natural Approach by Edna Copeland Ryneveld (1998); ISBN: 1567185959; http://www.amazon.com/exec/obidos/ASIN/1567185959/icongroupinterna

·

Menopause: A Guide for Women and the Men Who Love Them by Winnifred Berg Cutler, et al; ISBN: 0393017095; http://www.amazon.com/exec/obidos/ASIN/0393017095/icongroupinterna

·

Menopause: A Guide for Women and Those Who Love Them by Winnifred B., Ph.D. Cutler, et al (1993); ISBN: 0393309959; http://www.amazon.com/exec/obidos/ASIN/0393309959/icongroupinterna

·

Menopause: A Guide to Health and Happiness by James E. Huston (1998); ISBN: 0816036756; http://www.amazon.com/exec/obidos/ASIN/0816036756/icongroupinterna

·

Menopause: A Midlife Passage by Joan C. Callahan (Editor) (1993); ISBN: 0253208173; http://www.amazon.com/exec/obidos/ASIN/0253208173/icongroupinterna

362 Menopause

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Menopause: A Positive Approach by Rosetta Reitz; ISBN: 0140051201; http://www.amazon.com/exec/obidos/ASIN/0140051201/icongroupinterna

·

Menopause: A Spiritual Renaissance--What You Can Do to Empower Your Life from Someone Who's Been There and Done It by Helene B. Leonetti; ISBN: 1893157083; http://www.amazon.com/exec/obidos/ASIN/1893157083/icongroupinterna

·

Menopause: A Time for Positive Change by Judi Fairlie, et al; ISBN: 0713720557; http://www.amazon.com/exec/obidos/ASIN/0713720557/icongroupinterna

·

Menopause: A Well Woman Book by The Montreal Health Press (1993); ISBN: 0929005104; http://www.amazon.com/exec/obidos/ASIN/0929005104/icongroupinterna

·

Menopause: A Woman Doctor's Guide by Lois, MD Jovanovic, et al (2000); ISBN: 1575666014; http://www.amazon.com/exec/obidos/ASIN/1575666014/icongroupinterna

·

Menopause: An Intergrative Approach (The Intergrative Health Series) by Milton, Dr Hammerly, Milton Hammerly; ISBN: 158062328X; http://www.amazon.com/exec/obidos/ASIN/158062328X/icongroupinterna

·

Menopause: Biology and Pathobiology by Rogerio A. Lobo (Editor), et al (2000); ISBN: 0124537901; http://www.amazon.com/exec/obidos/ASIN/0124537901/icongroupinterna

·

Menopause: Bridging the Gap Between Natural and Conventional Medicine by Lorilee Schoenbeck, et al; ISBN: 1575668157; http://www.amazon.com/exec/obidos/ASIN/1575668157/icongroupinterna

·

Menopause: Clinical Concepts by H. Jane Chihal, et al; ISBN: 0917634039; http://www.amazon.com/exec/obidos/ASIN/0917634039/icongroupinterna

·

Menopause: Endocrinology and Management (Contemporary Endocrinology, Vol 18) by David B. Seifer (Editor), Elizabeth A. Kennard (Editor) (1999); ISBN: 0896036774; http://www.amazon.com/exec/obidos/ASIN/0896036774/icongroupinterna

·

Menopause: Evaluation, Treatment, and Health Concerns: Proceedings of a National Institutes of Health Symposium Held in Bethesda, Maryland, April 21 by Charles B. Hammond, et al; ISBN: 0471562238; http://www.amazon.com/exec/obidos/ASIN/0471562238/icongroupinterna

·

Menopause: Help and Hope for This Passage by Sally Conway; ISBN: 0310522714; http://www.amazon.com/exec/obidos/ASIN/0310522714/icongroupinterna

·

Menopause: Hormones and Cancer by Sociedade Portuguesa De Menopausa International Symposium, et al; ISBN: 185070628X; http://www.amazon.com/exec/obidos/ASIN/185070628X/icongroupinterna

·

Menopause: How You Can Benefit from Diet, Vitamins, Minerals, Herbs, Exercise, and Other Natural Methods (Getting Well Naturally) by Michael T., N.D. Murray (1994); ISBN: 1559584270; http://www.amazon.com/exec/obidos/ASIN/1559584270/icongroupinterna

·

Menopause: Natural and Medical Solutions by Kaz Cooke (Illustrator), Ruth Trickey; ISBN: 1865087637; http://www.amazon.com/exec/obidos/ASIN/1865087637/icongroupinterna

Books 363

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Menopause: Nomally and Naturally (Natural Health Guide) by Zoltan P. Rona (2002); ISBN: 155312023X; http://www.amazon.com/exec/obidos/ASIN/155312023X/icongroupinterna

·

Menopause: Physiology and Pharmacology by Daniel R. Mishell; ISBN: 0815159145; http://www.amazon.com/exec/obidos/ASIN/0815159145/icongroupinterna

·

Menopause: Questions You Have..Answers You Need (Questions You Have..Answers You Need Series) by Annette Thevenin Doran, Lisa Bonnell Samalonis (1999); ISBN: 1882606450; http://www.amazon.com/exec/obidos/ASIN/1882606450/icongroupinterna

·

Menopause: The Age of Choice by MacFarland; ISBN: 0962860409; http://www.amazon.com/exec/obidos/ASIN/0962860409/icongroupinterna

·

Menopause: The Alternative Way Facts and Fallacies on the 'Menopause Industry' by Chris Black; ISBN: 0730008290; http://www.amazon.com/exec/obidos/ASIN/0730008290/icongroupinterna

·

Menopause: The Common Sense Approach (The Common Sense Approach) by Ruth Appleby (1998); ISBN: 0717127087; http://www.amazon.com/exec/obidos/ASIN/0717127087/icongroupinterna

·

Menopause: The Complete Guide to Maintaining Health and Well-being and Managing Your Life by Miriam Stoppard; ISBN: 075133426X; http://www.amazon.com/exec/obidos/ASIN/075133426X/icongroupinterna

·

Menopause: The Inner Journey by Susanne F. Fincher (1995); ISBN: 1570621527; http://www.amazon.com/exec/obidos/ASIN/1570621527/icongroupinterna

·

Menopause: The New Integrative Approach: How to Combine the Best of Traditional and Alternative Therapies (Integrative Health Series) by Milton, Md. Hammerly (2001); ISBN: 1580624804; http://www.amazon.com/exec/obidos/ASIN/1580624804/icongroupinterna

·

Menopause: The State of the Art- Research and Practice by Hermann P. G. Schneider (Editor), Herman P. G. Schneider; ISBN: 1842141600; http://www.amazon.com/exec/obidos/ASIN/1842141600/icongroupinterna

·

Menopause: The Storm Before the Calm by Mary Martin; ISBN: 1560022361; http://www.amazon.com/exec/obidos/ASIN/1560022361/icongroupinterna

·

Menopause: Time for a Change by Merri Lu Park (1997); ISBN: 0920470335; http://www.amazon.com/exec/obidos/ASIN/0920470335/icongroupinterna

·

Menopause: Treating the Symptoms (The BMA Family Doctor Guides) by Peter Bromwich MRCOG; ISBN: 1853360511; http://www.amazon.com/exec/obidos/ASIN/1853360511/icongroupinterna

·

MenOpop (A Menopause Pop-Up and Activity Book) by Kathy Kelly, et al; ISBN: 0971909504; http://www.amazon.com/exec/obidos/ASIN/0971909504/icongroupinterna

·

Menstrual Disorders and Menopause: Biological, Psychological, and Cultural Research by Linda Gannon (1985); ISBN: 0030038782; http://www.amazon.com/exec/obidos/ASIN/0030038782/icongroupinterna

·

Menstruation and Menopause: The Physiology and Psychology, the Myth and the Reality by Paula Weideger; ISBN: 0394496477; http://www.amazon.com/exec/obidos/ASIN/0394496477/icongroupinterna

364 Menopause

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Midlife, Madness, or Menopause : Does Anyone Know What's Normal? by Patricia J. Richter (Author), Roger Duvivier (Author); ISBN: 0471346853; http://www.amazon.com/exec/obidos/ASIN/0471346853/icongroupinterna

·

Mind Over Menopause : The Complete Mind/Body Approach to Coping with Menopause by Herbert Benson (Author), et al (2004); ISBN: 0743236971; http://www.amazon.com/exec/obidos/ASIN/0743236971/icongroupinterna

·

Motorcycling Through Menopause by Dianne Grabowski, Jean Cheeley; ISBN: 0964448408; http://www.amazon.com/exec/obidos/ASIN/0964448408/icongroupinterna

·

Multidisciplinary perspectives on menopause; ISBN: 0897665961; http://www.amazon.com/exec/obidos/ASIN/0897665961/icongroupinterna

·

Multidisciplinary Perspectives on Menopause (Annals of the New York Academy of Sciences, Vol 592) by Marcha Flint, et al (1990); ISBN: 0897665953; http://www.amazon.com/exec/obidos/ASIN/0897665953/icongroupinterna

·

Natural Choices for Menopause by Marilyn Glenville; ISBN: 0312970137; http://www.amazon.com/exec/obidos/ASIN/0312970137/icongroupinterna

·

Natural Hormone Solutions: Secrets to Conquering Stress, Weight, Aging, Menopause, and More (Women's Edge Health Enhancement Guide) by Elizabeth Shimer, et al (2001); ISBN: 1579543502; http://www.amazon.com/exec/obidos/ASIN/1579543502/icongroupinterna

·

Natural Menopause Remedies by Nadine Taylor (2004); ISBN: 0451210573; http://www.amazon.com/exec/obidos/ASIN/0451210573/icongroupinterna

·

Natural Menopause: The Complete Guide by Susan Perry, et al (1996); ISBN: 0201479877; http://www.amazon.com/exec/obidos/ASIN/0201479877/icongroupinterna

·

Natural Menopause: The Complete Guide to a Woman's Most Misunderstood Passage by Susan Perry, et al; ISBN: 0201581426; http://www.amazon.com/exec/obidos/ASIN/0201581426/icongroupinterna

·

Natural Menopause: The Complete Guide to a Women's Most Misunderstood Passage by Susan Perry, Katherine O'Hanlan (Contributor); ISBN: 020162477X; http://www.amazon.com/exec/obidos/ASIN/020162477X/icongroupinterna

·

Natural Progesterone: The Natural Way to Alleviate Symptoms of Menopause, Pms, Endometriosis and Other Hormone-Related Problems by Anna Rushton, Shirley A. Bond (2003); ISBN: 000715609X; http://www.amazon.com/exec/obidos/ASIN/000715609X/icongroupinterna

·

Natural Therapies for Menopause by Nancy Beckham; ISBN: 0658012215; http://www.amazon.com/exec/obidos/ASIN/0658012215/icongroupinterna

·

Natural Treatments for Menopause by Joanne Marie Snow, et al; ISBN: 0761524711; http://www.amazon.com/exec/obidos/ASIN/0761524711/icongroupinterna

·

Natural Woman, Natural Menopause by Marcus Laux, Christine Conrad (1998); ISBN: 0060928948; http://www.amazon.com/exec/obidos/ASIN/0060928948/icongroupinterna

·

New Menopausal Years, The Wise Woman Way: Alternative Approaches for Women 30-90 (Wise Woman Herbal Series, Book 5) by Susun S. Weed; ISBN: 1888123036; http://www.amazon.com/exec/obidos/ASIN/1888123036/icongroupinterna

Books 365

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No Hormones, No Fear: A Natural Journey Through Menopause by Trisha Posner; ISBN: 0812967550; http://www.amazon.com/exec/obidos/ASIN/0812967550/icongroupinterna

·

No More Horse Estrogen: A Safe, Natural and Effective Means of Helping Women With Pms, Menstrual Dysfunctin, Menopause and Aging by Roger Mason (2002); ISBN: 1884820654; http://www.amazon.com/exec/obidos/ASIN/1884820654/icongroupinterna

·

No More Hrt: Menopause Treat the Cause by Karen, Dr Jenson, et al (2003); ISBN: 1550413244; http://www.amazon.com/exec/obidos/ASIN/1550413244/icongroupinterna

·

Off the Rag: Lesbians Writing on Menopause by Lee Lynch (Editor), Akia Woods (Editor) (1996); ISBN: 0934678774; http://www.amazon.com/exec/obidos/ASIN/0934678774/icongroupinterna

·

Our own harms : the startling facts behind menopause and estrogen therapy by Jo Hynes Newman; ISBN: 089307005X; http://www.amazon.com/exec/obidos/ASIN/089307005X/icongroupinterna

·

Overcoming Chronic Fatigue: Effective Self-Help Options to Relieve the Fatigue Associated With Cfs, Candida, Allergies, Pms, Menopause, Anemia, Low Thyroid and Depression ((Good Health Guide Ser.: Women's Self Care Library)) by Susan M. Lark; ISBN: 0879837160; http://www.amazon.com/exec/obidos/ASIN/0879837160/icongroupinterna

·

Passage to Power: Natural Menopause Revolution by Leslie Kenton; ISBN: 1561704873; http://www.amazon.com/exec/obidos/ASIN/1561704873/icongroupinterna

·

Perimenopause by Rogerio A. Lobo (Editor), et al (1997); ISBN: 0387949674; http://www.amazon.com/exec/obidos/ASIN/0387949674/icongroupinterna

·

Perimenopause 2 Ed: Changes in Women's Health After 35 by L. Darlene, M.D. Lanka, et al (2001); ISBN: 1572242345; http://www.amazon.com/exec/obidos/ASIN/1572242345/icongroupinterna

·

Perimenopause--Preparing for the Change, Revised 2nd Edition: A Guide to the Early Stages of Menopause and Beyond by Nancy Lee Teaff, et al; ISBN: 0761519289; http://www.amazon.com/exec/obidos/ASIN/0761519289/icongroupinterna

·

Periods: From Menarche to Menopause by Sharon Golub; ISBN: 0803942060; http://www.amazon.com/exec/obidos/ASIN/0803942060/icongroupinterna

·

PMS and Menopause and Hysterectomy (Dr. Donsbach Tells You) by Kurt W. Donsbach (1993); ISBN: 1569595712; http://www.amazon.com/exec/obidos/ASIN/1569595712/icongroupinterna

·

PMS, Perimenopause, and You : A Guide to the Physical, Mental, and Emotional Patterns of a Woman's Life by Lori, Ph.D. Futterman, et al; ISBN: 0737305118; http://www.amazon.com/exec/obidos/ASIN/0737305118/icongroupinterna

·

Pocket Guide to Menopause (Pocket Guide Series) by Ruth Appleby (2000); ISBN: 1580910122; http://www.amazon.com/exec/obidos/ASIN/1580910122/icongroupinterna

·

Postcards from Menopause: Wishing I Weren't Here with Postcard by Lois Mowday Rabey (2003); ISBN: 1572295015; http://www.amazon.com/exec/obidos/ASIN/1572295015/icongroupinterna

366 Menopause

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Power of Perimenopause: A Woman's Guide to Physical and Emotional Health During the Transitional Decade by Stephanie Degraff Bender, Treacy Colbert (1999); ISBN: 0609804162; http://www.amazon.com/exec/obidos/ASIN/0609804162/icongroupinterna

·

Practical Guide to Menopause by Stoppard (1994); ISBN: 0394223977; http://www.amazon.com/exec/obidos/ASIN/0394223977/icongroupinterna

·

Premature Menopause: A Multidsciplinary Approach by Dani Singer (Editor), Myra, Phd Hunter (Editor); ISBN: 1861561520; http://www.amazon.com/exec/obidos/ASIN/1861561520/icongroupinterna

·

Premenstrual, Postpartum, and Menopausal Mood Disorders by Laurence M Demers, et al; ISBN: 0806704217; http://www.amazon.com/exec/obidos/ASIN/0806704217/icongroupinterna

·

Progress in the Management of the Menopause: Proceedings of the 8th International Congress on the Menopause, Sydney, Aus by N.S.W.)/ Wren, B. International Congress on the Menopause 1996 Sydney (Editor), Barry G. Wren (Editor); ISBN: 1850707995; http://www.amazon.com/exec/obidos/ASIN/1850707995/icongroupinterna

·

Rapid Reference to Menopause (Rapid Reference Series) by Goran Samsioe, et al (2003); ISBN: 0723433127; http://www.amazon.com/exec/obidos/ASIN/0723433127/icongroupinterna

·

Recipes for Change: Gourmet Wholefood Cooking for Health and Vitality at Menopause by Lissa Deangelis, Molly Siple; ISBN: 0452272939; http://www.amazon.com/exec/obidos/ASIN/0452272939/icongroupinterna

·

Red Hot Mamas Do Menopause With Style by Marie Evans, Ann Shakeshaft (1999); ISBN: 1887166491; http://www.amazon.com/exec/obidos/ASIN/1887166491/icongroupinterna

·

Red Moon Passage: The Power and Wisdom of Menopause by Bonnie J. Horrigan (1997); ISBN: 0517888300; http://www.amazon.com/exec/obidos/ASIN/0517888300/icongroupinterna

·

Reinterpreting Menopause: Cultural and Philosophical Issues by Paul A. Komesaroff (Editor), et al (1997); ISBN: 0415915651; http://www.amazon.com/exec/obidos/ASIN/0415915651/icongroupinterna

·

Research on the Menopause in the 1990s: Report of a Who Scientific Group (Who Technical Report Series , No 866) (1997); ISBN: 924120866X; http://www.amazon.com/exec/obidos/ASIN/924120866X/icongroupinterna

·

Sailing Thru Menopause by Gail E. Mewes (Illustrator), Melissa G. McEwen (Editor); ISBN: 0966578902; http://www.amazon.com/exec/obidos/ASIN/0966578902/icongroupinterna

·

Secrets of a Natural Menopause: A Positive Drug-Free Approach (Llewellyn's Health and Healing) by Edna Copeland Ryneveld; ISBN: 1567185967; http://www.amazon.com/exec/obidos/ASIN/1567185967/icongroupinterna

·

Sex, Lies, and Menopause : The Shocking Truth About Hormone Replacement Therapy by T. S. Wiley (Author), et al (2003); ISBN: 0060542330; http://www.amazon.com/exec/obidos/ASIN/0060542330/icongroupinterna

Books 367

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Smart Medicine for Menopause: Hormone Replacement Therapy and Its Natural Alternatives by Sandra Cabot M.D. (1998); ISBN: 0895296284; http://www.amazon.com/exec/obidos/ASIN/0895296284/icongroupinterna

·

Soyfoods Cooking for a Positive Menopause by Bryanna Clark Grogan (Introduction) (1999); ISBN: 1570670765; http://www.amazon.com/exec/obidos/ASIN/1570670765/icongroupinterna

·

Sports Car Menopause: A Novel by Page Stegner; ISBN: 0316812242; http://www.amazon.com/exec/obidos/ASIN/0316812242/icongroupinterna

·

Stay Cool Through Menopause by Melvin Frisch; ISBN: 0399517162; http://www.amazon.com/exec/obidos/ASIN/0399517162/icongroupinterna

·

Stay Cool Through Menopause: Answers to Your Most-Asked Questions by Melvin M.D. Frisch; ISBN: 0399518185; http://www.amazon.com/exec/obidos/ASIN/0399518185/icongroupinterna

·

Strategies for Managing the Menopause by Jean Coope (2000); ISBN: 1873839375; http://www.amazon.com/exec/obidos/ASIN/1873839375/icongroupinterna

·

Sudden Menopause: Restoring Health and Emotional Well-Being by Debbie Deangelo; ISBN: 0897933257; http://www.amazon.com/exec/obidos/ASIN/0897933257/icongroupinterna

·

Sudden Menopause: What Do You Do When "the Change" Happens Before You're Ready for It? by Debbie Deangela; ISBN: 0717134369; http://www.amazon.com/exec/obidos/ASIN/0717134369/icongroupinterna

·

Super Nutrition for Menopause by Ann Louise Gittleman; ISBN: 0895298775; http://www.amazon.com/exec/obidos/ASIN/0895298775/icongroupinterna

·

Suzanne Beedell's Menopause Questions and Answers by Suzanne Beedell; ISBN: 0851402038; http://www.amazon.com/exec/obidos/ASIN/0851402038/icongroupinterna

·

Taking Charge of the Change: A Holistic Approach to the Three Phases of Menopause by Lennie Martin, Pam Jung; ISBN: 0766832767; http://www.amazon.com/exec/obidos/ASIN/0766832767/icongroupinterna

·

TCM: A Woman's Guide to a Trouble-Free Menopause by Nan Lu (Author), Ellen Schaplowsky (Author) (2000); ISBN: 0380809044; http://www.amazon.com/exec/obidos/ASIN/0380809044/icongroupinterna

·

Tell Me What to Eat As I Approach Menopause (Tell Me What to Eat) by Elaine Magee (1999); ISBN: 1564144259; http://www.amazon.com/exec/obidos/ASIN/1564144259/icongroupinterna

·

Textbook of Perimenopausal Gynecology by Nanette, Md. Santoro (Editor), et al; ISBN: 1842141708; http://www.amazon.com/exec/obidos/ASIN/1842141708/icongroupinterna

·

Textbook of the Menopause by Christian Lauritzen, et al (2003); ISBN: 184184232X; http://www.amazon.com/exec/obidos/ASIN/184184232X/icongroupinterna

·

The Andropause Mystery: Unraveling Truths About the Male Menopause by Robert S. Tan, Robert Tan (2001); ISBN: 0970706103; http://www.amazon.com/exec/obidos/ASIN/0970706103/icongroupinterna

·

The Baby Boomers Guide to Menopause by Sally Franz; ISBN: 0738822221; http://www.amazon.com/exec/obidos/ASIN/0738822221/icongroupinterna

368 Menopause

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The Bible Cure for Menopause: Ancient Truths, Natural Remedies and the Latest Findings for Your Health Today by Don Colbert (2000); ISBN: 0884196836; http://www.amazon.com/exec/obidos/ASIN/0884196836/icongroupinterna

·

The Boomer Menopause Manual Natural Choices by Jim McEnany (2001); ISBN: 0759614296; http://www.amazon.com/exec/obidos/ASIN/0759614296/icongroupinterna

·

The Change Before the Change: Everything You Need to Know to Stay Healthy in the Decade Before Menopause by Laura E. Corio, Linda G. Kahn (2002); ISBN: 0553380311; http://www.amazon.com/exec/obidos/ASIN/0553380311/icongroupinterna

·

The Change: Women, Aging and the Menopause by Germaine Greer (1993); ISBN: 0449908534; http://www.amazon.com/exec/obidos/ASIN/0449908534/icongroupinterna

·

The Change'll Do You Good: The Baby Boomers Guide to Menopause by Carol Psy D Schulen, Vance Howard (Illustrator) (2000); ISBN: 0967235200; http://www.amazon.com/exec/obidos/ASIN/0967235200/icongroupinterna

·

The Changing Years: The Menopause Without Fear by Madeline Gray; ISBN: 0385126352; http://www.amazon.com/exec/obidos/ASIN/0385126352/icongroupinterna

·

The Complete Book of Menopause: Every Woman's Guide to Good Health by Carol Landau, et al (1995); ISBN: 0399519068; http://www.amazon.com/exec/obidos/ASIN/0399519068/icongroupinterna

·

The Complete Nutrition Counter for Menopause by Lynn Sonberg; ISBN: 0312956053; http://www.amazon.com/exec/obidos/ASIN/0312956053/icongroupinterna

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The Doctors Book of Home Remedies for Managing Menopause: More Than 100 Solutions for Conquering Symptons and Facing the Future With Confidence by Mary S. Kittel (Editor), et al; ISBN: 1579542344; http://www.amazon.com/exec/obidos/ASIN/1579542344/icongroupinterna

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The Everything Menopause Booke: Reassuring Advice and the Latest Information to Keep You Healthy and Sane (Everything Series) by Lorna Gentry (Contributor), Ramona, M.D. Slupik (2003); ISBN: 1580627412; http://www.amazon.com/exec/obidos/ASIN/1580627412/icongroupinterna

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The Geripause: Medical Management During the Late Menopause by Bernard A. Eskin, Bruce R. Troen; ISBN: 184214037X; http://www.amazon.com/exec/obidos/ASIN/184214037X/icongroupinterna

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The Healing Journey Through Menopause: Your Journal for Reflection and Renewal by Phil Rich (Author), Fran Mervyn (Author); ISBN: 0471326917; http://www.amazon.com/exec/obidos/ASIN/0471326917/icongroupinterna

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The Healthy Woman: Menopause and Other Things We Don't Talk About by Susan Davis, H. G. Burger (1996); ISBN: 087630806X; http://www.amazon.com/exec/obidos/ASIN/087630806X/icongroupinterna

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The Herbal Menopause Book by Amanda McQuade Crawford (1996); ISBN: 0895947994; http://www.amazon.com/exec/obidos/ASIN/0895947994/icongroupinterna

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The Hormone of Desire : The Truth About Testosterone, Sexuality, and Menopause by Susan Rako (1999); ISBN: 0609803867; http://www.amazon.com/exec/obidos/ASIN/0609803867/icongroupinterna

Books 369

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The Hormone Solution: Naturally Alleviate Symptoms of Hormone Imbalance from Adolescence Through Menopause by Erika Schwartz (2002); ISBN: 0446678287; http://www.amazon.com/exec/obidos/ASIN/0446678287/icongroupinterna

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The Hrt-Free Menopause Breakthrough: The New Natural Alternatives by Marilyn, Ph.D. Glenville (2003); ISBN: 1569753571; http://www.amazon.com/exec/obidos/ASIN/1569753571/icongroupinterna

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The Infinite Mind: Menopause and the Mind by Lichtenstein Creative Media Inc. ISBN: 1932479147; http://www.amazon.com/exec/obidos/ASIN/1932479147/icongroupinterna

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The male menopause by Derek Bowskill; ISBN: 0912588152; http://www.amazon.com/exec/obidos/ASIN/0912588152/icongroupinterna

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The Management of the menopause & post-menopausal years : the proceedings of the International Symposium held in London 24-26 November 1975; arranged by the Institute of Obstetrics and Gynaecology, the University of London; ISBN: 0852001479; http://www.amazon.com/exec/obidos/ASIN/0852001479/icongroupinterna

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The Management of the Menopause, Third Edition by John Studd (Editor); ISBN: 1842141376; http://www.amazon.com/exec/obidos/ASIN/1842141376/icongroupinterna

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The Management of the Menopause: The Millennium Review 2000 by John Studd (Editor); ISBN: 1850700796; http://www.amazon.com/exec/obidos/ASIN/1850700796/icongroupinterna

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The Many Faces of Menopause with Humor by Gladys Gobely (2003); ISBN: 1410732479; http://www.amazon.com/exec/obidos/ASIN/1410732479/icongroupinterna

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The Meanings of Menopause: Historical, Medical, and Clinical Perspectives by Ruth Formanek (Editor) (1990); ISBN: 0881630802; http://www.amazon.com/exec/obidos/ASIN/0881630802/icongroupinterna

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The Medical Management of Menopause and Premenopause: Their Endocrinologic Basis by Winnifred Berg Cutler, Celso-Ramon Garcia; ISBN: 0397506317; http://www.amazon.com/exec/obidos/ASIN/0397506317/icongroupinterna

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The Menopause by D. Mango (Editor), S. Mancuso (Editor); ISBN: 1842140159; http://www.amazon.com/exec/obidos/ASIN/1842140159/icongroupinterna

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The Menopause by Herbert J. Buchsbaum (Editor); ISBN: 0387908250; http://www.amazon.com/exec/obidos/ASIN/0387908250/icongroupinterna

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The Menopause by Mary Anderson; ISBN: 0571130712; http://www.amazon.com/exec/obidos/ASIN/0571130712/icongroupinterna

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The Menopause - Key Issues: Balliere's Clinical Obstetrics and Gynaecology (Balliere's International Practice and Research) by David H. Barlow; ISBN: 0702021776; http://www.amazon.com/exec/obidos/ASIN/0702021776/icongroupinterna

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The Menopause and Hormonal Replacement Therapy: Facts and Controversies by Regine Sitruk-Ware, Wulf H. Utian (Editor); ISBN: 0824785649; http://www.amazon.com/exec/obidos/ASIN/0824785649/icongroupinterna

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The Menopause and Hormone Replacement Therapy by Roger Smith, John Studd (1998); ISBN: 1853176192; http://www.amazon.com/exec/obidos/ASIN/1853176192/icongroupinterna

370 Menopause

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The Menopause and HRT by Kathy Abernethy (1997); ISBN: 0702020230; http://www.amazon.com/exec/obidos/ASIN/0702020230/icongroupinterna

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The Menopause at the Millennium: The Proceedings of the 9th World Congress on the Menopause by Japan)/ Yanaihara, Takumi World Congress on the Menopause 1999 Yokohama-Shi (Editor), et al; ISBN: 185070709X; http://www.amazon.com/exec/obidos/ASIN/185070709X/icongroupinterna

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The Menopause Book: A Guide to Health and Well-Being for Women After Forty by Sheldon H. Cherry, Carolyn D. Runowicz; ISBN: 0025247581; http://www.amazon.com/exec/obidos/ASIN/0025247581/icongroupinterna

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The Menopause Cookbook: How to Eat Now and for the Rest of Your Life by Hope Ricciotti, et al (2000); ISBN: 0393319830; http://www.amazon.com/exec/obidos/ASIN/0393319830/icongroupinterna

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The Menopause Diet by Larrian Gillespie (2003); ISBN: 0967131774; http://www.amazon.com/exec/obidos/ASIN/0967131774/icongroupinterna

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The Menopause Diet Daily Journal by Larrian Gillespie (1999); ISBN: 0967131723; http://www.amazon.com/exec/obidos/ASIN/0967131723/icongroupinterna

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The Menopause Diet Mini Meal Cookbook by Larrian Gillespie (Introduction) (1999); ISBN: 0967131715; http://www.amazon.com/exec/obidos/ASIN/0967131715/icongroupinterna

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The Menopause Handbook by Susan Flamholtz Trien; ISBN: 0345373898; http://www.amazon.com/exec/obidos/ASIN/0345373898/icongroupinterna

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The Menopause Handbook: A General Health Book; ISBN: 1575441233; http://www.amazon.com/exec/obidos/ASIN/1575441233/icongroupinterna

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The Menopause in Practice by Catrina Bain, et al (2003); ISBN: 1853155160; http://www.amazon.com/exec/obidos/ASIN/1853155160/icongroupinterna

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The Menopause Industry: A Guide to Medicine's "Discovery" of the Mid-life Woman by Sandra Coney; ISBN: 0704343983; http://www.amazon.com/exec/obidos/ASIN/0704343983/icongroupinterna

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The Menopause Industry: How the Medical Establishment Exploits Women by Sandra Coney, Barbara Seaman (1994); ISBN: 0897931602; http://www.amazon.com/exec/obidos/ASIN/0897931602/icongroupinterna

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The Menopause Made Simple Program: Maximise Your Lifestyle by Minimising Your Symptoms by Debra Anderson, Vicky Graham (2002); ISBN: 186508767X; http://www.amazon.com/exec/obidos/ASIN/186508767X/icongroupinterna

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The Menopause Manager: A Safe Path for a Natural Change by Joseph L. Mayo, Mary Ann, M.A. Mayo (2000); ISBN: 0800757335; http://www.amazon.com/exec/obidos/ASIN/0800757335/icongroupinterna

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The Menopause Map by Barbara Dehn; ISBN: 0972658017; http://www.amazon.com/exec/obidos/ASIN/0972658017/icongroupinterna

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The Menopause Myth by Sheldon H. Cherry; ISBN: 0345253558; http://www.amazon.com/exec/obidos/ASIN/0345253558/icongroupinterna

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The Menopause Self Help Book: A Woman's Guide to Feeling Wonderful for the Second Half of Her Life by Susan M. Lark M.D. ISBN: 0788160745; http://www.amazon.com/exec/obidos/ASIN/0788160745/icongroupinterna

Books 371

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The Menopause Sourcebook, Third Edition by Gretchen Henkel, et al; ISBN: 0737303786; http://www.amazon.com/exec/obidos/ASIN/0737303786/icongroupinterna

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The Menopause Survival Guide: Surviving the Change of Life by Donna Rogers; ISBN: 0972534806; http://www.amazon.com/exec/obidos/ASIN/0972534806/icongroupinterna

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The Menopause, Hormone Therapy, & Women's Health (1992); ISBN: 1568060424; http://www.amazon.com/exec/obidos/ASIN/1568060424/icongroupinterna

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The Menopause, Hormone Therapy, and Women's Health (Background Paper) by 52003012847 (1992); ISBN: 0160379121; http://www.amazon.com/exec/obidos/ASIN/0160379121/icongroupinterna

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The Menopause: Comprehensive Management by Bernard A. Eskin (Editor); ISBN: 0070196192; http://www.amazon.com/exec/obidos/ASIN/0070196192/icongroupinterna

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The Menopause: Coping With the Change by Jean Coope; ISBN: 0668058196; http://www.amazon.com/exec/obidos/ASIN/0668058196/icongroupinterna

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The Modern Management of the Menopause: A Perspective for the 21st Century by M. Hammar (Editor), Goran Berg; ISBN: 1850705445; http://www.amazon.com/exec/obidos/ASIN/1850705445/icongroupinterna

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The Modern Management of the Menopause: Annual Review 1998 by J. W. W. Studd (Editor), J.W.W. Studd; ISBN: 1850700222; http://www.amazon.com/exec/obidos/ASIN/1850700222/icongroupinterna

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The Natural Estrogen Diet: Healthy Recipes for Perimenopause and Menopause by Lana Liew, et al; ISBN: 0897932463; http://www.amazon.com/exec/obidos/ASIN/0897932463/icongroupinterna

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The Natural Pharmacist: Your Complete Guide to Menopause by Joanne Marie Snow, et al (1999); ISBN: 0761515607; http://www.amazon.com/exec/obidos/ASIN/0761515607/icongroupinterna

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The New Truth About Menopause : Straight Talk About Treatments and Choices from Two Leading Women Doctors by Carol Landau (Author), Michele G. Cyr (Author) (2003); ISBN: 0312317980; http://www.amazon.com/exec/obidos/ASIN/0312317980/icongroupinterna

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The Not-So-Silent Passage: How to Manage Your Man's Menopause by Cheryl Solimini (1998); ISBN: 0879057513; http://www.amazon.com/exec/obidos/ASIN/0879057513/icongroupinterna

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The Old Girls' Book of Spells: the real meaning of menopause, sex, car keys, and other important stuff about magic by Cal Garrison (2002); ISBN: 1590030184; http://www.amazon.com/exec/obidos/ASIN/1590030184/icongroupinterna

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The Only Menopause Guide You'll Need by Michele Moore MD; ISBN: 0801864089; http://www.amazon.com/exec/obidos/ASIN/0801864089/icongroupinterna

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The Passage Through Menopause: Women's Lives in Transition by Brenda McNamara Millette; ISBN: 0835954617; http://www.amazon.com/exec/obidos/ASIN/0835954617/icongroupinterna

372 Menopause

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The Pause: Positive Approaches to Menopause by Lonnie Garfield Barbach (1994); ISBN: 0451180356; http://www.amazon.com/exec/obidos/ASIN/0451180356/icongroupinterna

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The Pause: Positive Approaches to Perimenopause and Menopause by Lonnie Garfield Barbach (2000); ISBN: 0452281105; http://www.amazon.com/exec/obidos/ASIN/0452281105/icongroupinterna

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The Perimenopause Handbook : What Every Woman Needs to Know About the Years Before Menopause by Carol Turkington, Susan Johnson; ISBN: 0809229358; http://www.amazon.com/exec/obidos/ASIN/0809229358/icongroupinterna

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The Premature Menopause Book: : When The "change Of Life" Comes Too Early by Kathryn Petras (Author) (1999); ISBN: 0380805413; http://www.amazon.com/exec/obidos/ASIN/0380805413/icongroupinterna

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The Role of estrogen/progestogen in the management of the menopause : proceedings of a symposium held at the University of Sheffield on March 16th, 1978; ISBN: 0839113706; http://www.amazon.com/exec/obidos/ASIN/0839113706/icongroupinterna

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The Seven Sacred Rites of Menopause by Kristi Meisenbach Boylan, Kristi Meisenbach Boylan (2000); ISBN: 1891661132; http://www.amazon.com/exec/obidos/ASIN/1891661132/icongroupinterna

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The Silent Passage: Menopause by Gail Sheehy; ISBN: 0671567772; http://www.amazon.com/exec/obidos/ASIN/0671567772/icongroupinterna

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The Soy Solution for Menopause: The Estrogen Alternative by Machelle M. Seibel, Mark Blumenthal (2002); ISBN: 0743421523; http://www.amazon.com/exec/obidos/ASIN/0743421523/icongroupinterna

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The Taking Charge of Menopause Workbook by Robert M. Dosh (Editor), et al (1997); ISBN: 1572240601; http://www.amazon.com/exec/obidos/ASIN/1572240601/icongroupinterna

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The Testosterone Revolution: Rediscover Your Energy and Overcome the Symptoms of Male Menopause by Malcolm Carruthers (2001); ISBN: 0007122756; http://www.amazon.com/exec/obidos/ASIN/0007122756/icongroupinterna

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The Testosterone Syndrome: The Critical Factor for Energy, Health, & Sexuality-Reversing the Male Menopause by Eugene Shippen, William Fryer; ISBN: 0871318296; http://www.amazon.com/exec/obidos/ASIN/0871318296/icongroupinterna

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The Truth About Hormone Replacement Therapy: How to Break Free from the Medical Myths of Menopause by National Women's Health Network (Editor) (2002); ISBN: 0761534784; http://www.amazon.com/exec/obidos/ASIN/0761534784/icongroupinterna

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The Ultimate Nutrition Guide for Menopause : Natural Strategies to Stay Healthy, Control Weight, and Feel Great by Leslie Beck (Author) (2003); ISBN: 0471274259; http://www.amazon.com/exec/obidos/ASIN/0471274259/icongroupinterna

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The Unofficial Guide to Coping With Menopause (The Unofficial Guide Series) by Donna Howell, et al; ISBN: 002862694X; http://www.amazon.com/exec/obidos/ASIN/002862694X/icongroupinterna

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The Wisdom of Menopause by Christiane Northrup; ISBN: 055338080X; http://www.amazon.com/exec/obidos/ASIN/055338080X/icongroupinterna

Books 373

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The Wisdom of Menopause: The Complete Guide to Creating Physical and Emotional Health and Healing by Christiane Northrup; ISBN: 0749922222; http://www.amazon.com/exec/obidos/ASIN/0749922222/icongroupinterna

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The Wise Woman: A Natural Approach to the Menopause by Judy Hall, Robert Jacobs (Contributor) (1992); ISBN: 1852303441; http://www.amazon.com/exec/obidos/ASIN/1852303441/icongroupinterna

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The Yale Guide to Women's Reproductive Health: From Menarche to Menopause by Mary Jane Minkin, Carol V. Wright (2003); ISBN: 0300098200; http://www.amazon.com/exec/obidos/ASIN/0300098200/icongroupinterna

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Time of Her Life: Menopause, Health and Well-Being by Myra Hunter, Jean Coope (1994); ISBN: 0563367598; http://www.amazon.com/exec/obidos/ASIN/0563367598/icongroupinterna

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Today and Tomorrow's Woman: Menopause: Before and After (Girls of 16 to Women of 99) by Virginia Layng Millonig; ISBN: 1878028235; http://www.amazon.com/exec/obidos/ASIN/1878028235/icongroupinterna

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Transformation Through Menopause by Marian Van Eyk McCain (Author) (1991); ISBN: 0897892690; http://www.amazon.com/exec/obidos/ASIN/0897892690/icongroupinterna

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Treatment of the Postmenopausal Woman: Basic and Clinical Aspects by Rogerio A., MD Lobo (Editor); ISBN: 0781715598; http://www.amazon.com/exec/obidos/ASIN/0781715598/icongroupinterna

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Trouble-Free Menopause by Judy E. Marshel, Linda Konner (Contributor); ISBN: 0380777320; http://www.amazon.com/exec/obidos/ASIN/0380777320/icongroupinterna

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Trouble-Free Menopause: Manage Your Symptoms and Your Weight by Judy E. Marshel, Judy E. Marshel (Introduction); ISBN: 0380731703; http://www.amazon.com/exec/obidos/ASIN/0380731703/icongroupinterna

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Turning Point: The Myths and Realities of Menopause by C. Sue Furman, et al; ISBN: 0195087739; http://www.amazon.com/exec/obidos/ASIN/0195087739/icongroupinterna

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Understanding Menopause by Karen Ballard (Author); ISBN: 047084471X; http://www.amazon.com/exec/obidos/ASIN/047084471X/icongroupinterna

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Understanding the Menopause and HRT by Anne MacGregor; ISBN: 1898205833; http://www.amazon.com/exec/obidos/ASIN/1898205833/icongroupinterna

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Update on Hormonal Treatment in the Menopause (Progress in Reproductive Biology and Medicine, Vol 13) by M. L'Hermite (Editor) (1989); ISBN: 3805549040; http://www.amazon.com/exec/obidos/ASIN/3805549040/icongroupinterna

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Users Guide to Easing Menopause Symptoms Naturally: Learn How to Prevent Hot Flashes and Other Symptoms Safely and Naturally by Cynthia M. Watson (2003); ISBN: 1591200954; http://www.amazon.com/exec/obidos/ASIN/1591200954/icongroupinterna

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Viropause/Andropause: The Male Menopause by Aubry M. Dr. Hill (2000); ISBN: 0882821792; http://www.amazon.com/exec/obidos/ASIN/0882821792/icongroupinterna

374 Menopause

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Ways to Help Your Mate Through Menopause by Anne Cannon-Wilson; ISBN: 0967842700; http://www.amazon.com/exec/obidos/ASIN/0967842700/icongroupinterna

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Wellness in Menopause: A Guide to Holistic Healing by Marylyn Meek (2001); ISBN: 1858600642; http://www.amazon.com/exec/obidos/ASIN/1858600642/icongroupinterna

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What Every Woman Needs to Know About Menopause: The Years Before, During, and After by Mary Jane, Md. Minkin, et al (1997); ISBN: 0300072619; http://www.amazon.com/exec/obidos/ASIN/0300072619/icongroupinterna

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What Women Should Know About Menopause (The Dell Medical Library) by Judith Sachs, Dennis Smith; ISBN: 044020643X; http://www.amazon.com/exec/obidos/ASIN/044020643X/icongroupinterna

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What You Need to Know About Menopause: Answers to the Questions Women Ask Most by Paul C. Reisser, Teri Reisser (Contributor); ISBN: 0892838809; http://www.amazon.com/exec/obidos/ASIN/0892838809/icongroupinterna

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What You Need to Know About Perimenopause (Vital Information Series) by Bernard J. Cortese (1998); ISBN: 0895949148; http://www.amazon.com/exec/obidos/ASIN/0895949148/icongroupinterna

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What Your Doctor May Not Tell You About Menopause:Break- Through Bk Natural Progestero by M.D./Hopkins John R. Lee V (1996); ISBN: 0446671444; http://www.amazon.com/exec/obidos/ASIN/0446671444/icongroupinterna

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What Your Doctor May Not Tell You About Premenopause by V. John R./Hopkins Lee (Author) (1999); ISBN: 0446673803; http://www.amazon.com/exec/obidos/ASIN/0446673803/icongroupinterna

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Where's the Toast? A Woman's Guide to Managing Menopause Naturally by Yvonne Lewis; ISBN: 0966431448; http://www.amazon.com/exec/obidos/ASIN/0966431448/icongroupinterna

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Whole Woman Homeopathy: The Comprehensive Guide to Treating PMS, Menopause, Cystitis, and Other Problems - Naturally and Effectively by Judyth Reichenberg-Ullman; ISBN: 0761524118; http://www.amazon.com/exec/obidos/ASIN/0761524118/icongroupinterna

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Wild Yam: Nature's Progesterone: The Safe and Little Known Answer to Hormonal Imbalance, Pms, Menopause and Osteoporosis (Woodland Health Ser) by Rita Elkins, Woodland Publishing (1999); ISBN: 1885670257; http://www.amazon.com/exec/obidos/ASIN/1885670257/icongroupinterna

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Wise-Woman Archetype: Menopause As Initiation/Cassette by Jean Shinoda, M.D. Bolen; ISBN: 1564550052; http://www.amazon.com/exec/obidos/ASIN/1564550052/icongroupinterna

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Without Estrogen: Natural Remedies for Menopause and Beyond by Dee Ito, Amy Gross (1994); ISBN: 0517588250; http://www.amazon.com/exec/obidos/ASIN/0517588250/icongroupinterna

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Woman at the Edge of Two Worlds: The Spiritual Journey Through Menopause by Lynn V. Andrews, Ginny Joyner (Illustrator); ISBN: 0060925507; http://www.amazon.com/exec/obidos/ASIN/0060925507/icongroupinterna

Books 375

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Woman's Choice: A Guide to Contraception, Fertility, Abortion, and Menopause, by Robert H. Glass, Nathan G. Kase; ISBN: 0465092012; http://www.amazon.com/exec/obidos/ASIN/0465092012/icongroupinterna

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Women and the Menopause: A Book for and About Women and the Climacteric by Brenda McNamara and Hawkins, Joellen Beck Watson Millette; ISBN: 0835987728; http://www.amazon.com/exec/obidos/ASIN/0835987728/icongroupinterna

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Women at the Well : The Many Voices of Menopause by Marielena Zuniga, Frances Schwabenland; ISBN: 0738857963; http://www.amazon.com/exec/obidos/ASIN/0738857963/icongroupinterna

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Women Menopause and Middle Age by Vidals Clay; ISBN: 091278637X; http://www.amazon.com/exec/obidos/ASIN/091278637X/icongroupinterna

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Women of the 14th Moon: Writings on Menopause by Dena Taylor (Editor), Amber Coverdale Sumrall (Editor); ISBN: 0895944774; http://www.amazon.com/exec/obidos/ASIN/0895944774/icongroupinterna

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Women on Menopause: A Practical Guide to a Positive Transition by Anne Dickson, Nikki Henriques (Contributor) (1989); ISBN: 0892812370; http://www.amazon.com/exec/obidos/ASIN/0892812370/icongroupinterna

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Women's Health and Menopause: New Strategies-Improved Quality of Life (Medical Science Symposia Series, 17) by International Symposium on Women's Health in Menopause 2001 Washingto, et al (2002); ISBN: 1402071493; http://www.amazon.com/exec/obidos/ASIN/1402071493/icongroupinterna

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Women's Health and Menopause: Risk Reduction Strategies-Improved Quality of Health (Medical Science Symposia Series, V. 13) by R. Paoletti (Editor), et al; ISBN: 0792359062; http://www.amazon.com/exec/obidos/ASIN/0792359062/icongroupinterna

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Women's Health Guide: A Natural Approach to Breast Cancer, Hearst Disease, Fibroids, Pms, Bulemia, Childbirth, Menopause, and Osteoporosis by Gale Jack (Editor), Wendy Esko (Editor); ISBN: 1882984250; http://www.amazon.com/exec/obidos/ASIN/1882984250/icongroupinterna

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Women's Health in Menopause: Behaviour, Cancer, Cardiovascular Disease, Hormone Replacement Therapy (Medical Science Symposia Series, Vol 7) by P. G. Crosignani, et al (1994); ISBN: 0792330684; http://www.amazon.com/exec/obidos/ASIN/0792330684/icongroupinterna

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Women's Health in Menopause: Risk Reduction Strategies (Medical Science Symposia Series, Vol. 11) by Rodolfo Paoletti (Editor), International Symposium on Women's Health in Menopause 1996 Florence (1997); ISBN: 0792346971; http://www.amazon.com/exec/obidos/ASIN/0792346971/icongroupinterna

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Women's Health: The Market for Menopause, Fertility and Contraceptive Drugs [DOWNLOAD: PDF] by Kalorama Information (Author); ISBN: B00005R910; http://www.amazon.com/exec/obidos/ASIN/B00005R910/icongroupinterna

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'Yeeks!' Getting Safely through Perimenopause, Menopause and Beyond by Helen Greco, Jane Rabin Stern; ISBN: 0967442206; http://www.amazon.com/exec/obidos/ASIN/0967442206/icongroupinterna

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Yoga and the Wisdom of Menopause : A Guide to Physical, Emotional and Spiritual Health at Midlife and Beyond by Suza Francina (Author); ISBN: 0757300650; http://www.amazon.com/exec/obidos/ASIN/0757300650/icongroupinterna

376 Menopause

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You Know You're in Menopause When-- by Group Ink Members, Group (1997); ISBN: 0965808777; http://www.amazon.com/exec/obidos/ASIN/0965808777/icongroupinterna

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Your Menopause, Your Menotype : Find Your Type and Free Yourself from the Symptoms of Menopause by Angela Stengler, Mark Stengler (2003); ISBN: 1583331581; http://www.amazon.com/exec/obidos/ASIN/1583331581/icongroupinterna

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Your Middle Years: A Gynecologist's Guide to the Menopause by Wulf H. Utian; ISBN: 0838599370; http://www.amazon.com/exec/obidos/ASIN/0838599370/icongroupinterna

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You've Hit Menopause: Now What? by George Gillson, Tracy Marsden; ISBN: 0973296208; http://www.amazon.com/exec/obidos/ASIN/0973296208/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “menopause” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 ·

A clinical and histologic study of clinically significant postmenopausal endometriosis. Author: Kempers, Roger D.; Year: 1967; [Minneapolis] 1959

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A clinical guide to the menopause and the postmenopause. Author: Ayerst Laboratories, inc.; Year: 1967; New York [c1968]

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A doctor discusses menopause and estrogens, by M. Edward Davis, with Dona Z. Meilach. Author: Davis, M. Edward (Morris Edward),; Year: 1964; Chicago, Budlong Press, c1969

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A rational approach to the treatment of the menopause. Author: Schering Corporation. Medical Research Division.; Year: 1967; Bloomfield, N. J. [c1946]

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Facts about the menopause. Author: Davis, Maxine.; Year: 1967; New York, McGrawHill [c1951]

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Hemorrhagic disorders in pregnancy, ed. by Fritz K. Beller. The climacteric and the postmenopause, ed. by E. Jürgen Plotz. Author: Beller, Fritz K.; Year: 1965; [New York] Harper; Row [c1964]

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Hormone therapy of the menopause and aging; a woman-doctor, with the cooperation of her patients, focuses attention on misconceptions, indications, contraindications and methods of hormone therapy. Author: Jern, Helen Z.,; Year: 1966; Springfield, Ill. Thomas [c1973]

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Management of the principal symptoms in the menopausal patient; a discussion. Author: Kupperman, Herbert S.,; Year: 1968; [New York, Ayerst Laboratories, 1969]

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Manual of menopause counseling for the perimenopausal and menopausal patient: a clinican's guide Author: Minkin, Mary Jane.; Year: 1962; Boca Raton: Parthenon Pub. Group, 2003; ISBN: 1842141813 http://www.amazon.com/exec/obidos/ASIN/1842141813/icongroupinterna

·

Medical management of the menopause. Author: Goldberg, Minnie Berelson,; Year: 2000; New York, Grune; Stratton, 1959

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Menopause and aging; summary report and selected papers from a research conference on menopause and aging, May 23-26, 1971, Hot Springs, Arkansas. Editors: Kenneth J. Ryan [and] Don C. Gibson. Author: Gibson, Don C.; Year: 1968; Bethesda, Md., National Institute of Child Health and Human Development; [for sale by the Supt. of Docs., U. S. Govt. Print. Off., Washington, 1973]

·

On the assessment of biological age. II. A factorial study of aging in postmenopausal women, by Eeva Jalavisto and T. Makkonen. Author: Jalavisto, Eeva.; Year: 2003; Helsinki, 1963

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Postmenopausal bleeding from the senile endometrium. Author: Meyer, William Campbell,; Year: 1966; [Minneapolis] 1970

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The ageless woman; menopause, hormones, and the quest for youth. Author: Kaufman, Sherwin A.; Year: 2003; Englewood Cliffs, N. J., Prentice-Hall [c1967]

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The changing years; the menopause without fear. Author: Gray, Madeline.; Year: 1967; Garden City, N. Y., Doubleday, 1967

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The Menopausal syndrome, edited by Robert B. Greenblatt, Virendra B. Mahesh [and] Paul G. McDonough. Author: Greenblatt, Robert B. (Robert Benjamin),; Year: 1969; [New York] Medcom Press [c1974]; ISBN: 0846301369 http://www.amazon.com/exec/obidos/ASIN/0846301369/icongroupinterna

·

The menopause and the role of estrogens; transcript of a round table conference on the menopausal syndrome, discussed in terms of symptomatology and treatment with particular emphasis on the specificity of estrogens in the management of certain postmenopausal states or sequelae. Author: Excerpta Medica Foundation.; Year: 1959; Amsterdam [1962]

·

Treatment of gallbladder disease; guest editor: James B. Carey, Jr. Treatment of menopausal problems: guest editor: Eugene J. Cohen. Author: Carey, James B.,; Year: 2003; [New York] Hoeber [c1968]

·

Your menopause. Author: Carson, Ruth.; Year: 1963; New York, Public Affairs Committee, 1970]

Chapters on Menopause In order to find chapters that specifically relate to menopause, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and menopause using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “menopause” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on menopause:

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Menopause and Hormone Replacement Therapy Source: in Carlin, B.I. and Leong, F.C., eds. Female Pelvic Health and Reconstructive Surgery. New York, NY: Marcel Dekker, Inc. 2003. p. 417-474. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $185.00 plus shipping and handling. ISBN: 0824708229. Summary: This chapter on menopause and hormone replacement therapy (HRT) is from a textbook that provides comprehensive, authoritative coverage of female pelvic health and reconstructive surgery. The authors introduce menopause and discuss the factors that influence the age of menopause onset. They also discuss the transition to menopause; symptoms of menopause, including those of the central nervous system, skin, and genitourinary tract, osteoporosis, and cardiovascular disease; the use of estrogen in menopausal women for both primary and secondary prevention of cardiovascular disease; the risks of HRT, including endometrial cancer, breast cancer, venous thromboembolic events, and alternative benefits of HRT; regimens for HRT, including the supplementation with calcium and vitamin D; and alternative therapies for symptoms of menopause. The authors conclude that the menopause is a normal life event that carries with it an increased risk of morbidity and mortality. The use of HRT can be beneficial in obtaining preventive health benefits. Whether a woman chooses HRT or an alternative, the decision should be based on factual information about the risks and benefits of a given treatment. 5 figures. 11 tables. 266 references.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to menopause have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 ·

Women's health on the Internet Source: New York, NY: Haworth Press. 2000. 153 pp. Contact: Available from Haworth Press, 10 Alice Street, Binghamton, NY 13904-1580. Telephone: (800) 342-9678 / fax: (607) 722-1424. $34.95 cloth, $24.95 paper, plus shipping and handling. Summary: This book shows searchers how the Internet can be used to locate information about the diagnosis, treatment, and prognosis of women's health problems. Topics included are Web resources and how to evaluate and search Web sites, a case study of NOAH (New York Online Access to Health), a women's health site, and women as health care consumers. Additionally provided are sections on specific women's health issues such as physical fitness, pregnancy, childbirth and early pregnancy resources, caregiving, menopause, and diabetes. Each section begins with an abstract and keywords, and an index concludes the book.

12

You will need to limit your search to “Directory” and “menopause” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “menopause” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

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Who? What? Where?: Resources for women's health and aging Source: Bethesda, MD: National Institute on Aging, U.S. Department of Health and Human Services. 1992. 82 pp. Contact: Available from National Institute on Aging Information Center, P.O. Box 8057, Gaithersburg, MD 20898-8057. Telephone: (301) 587-2528 or (800) 222-2225 or (800) 2224225 TDD / fax: (301) 589-3014 / e-mail: [email protected] / Web site: http://www.nih.gov/nia. Available at no charge. Summary: This directory lists resources available to women which can help them cope with the processes of aging. The first section provides resources for health promotion and prevention. Topics included here are skin care, nutrition and exercise, and menopause. The second section concentrates on common disorders associated with age such as osteoporosis, urinary incontinence, cancer, and heart disease. The third section focuses on other aspects of women's lives such as widowhood, finances, and caregiving. The final sections provided information on women's health research and other organizations and readings.

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CHAPTER 8. MULTIMEDIA ON MENOPAUSE Overview In this chapter, we show you how to keep current on multimedia sources of information on menopause. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on menopause is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “menopause” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “menopause” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on menopause: ·

Menopause and Nutrition Source: Los Angeles, CA: National Health Video, 15 min., n.d. Contact: National Health Video. 12021 Wilshire Blvd., Suite 550, Los Angeles, CA 90025. 1-800-543-6803. Summary: This video provides information on the role of nutrition during menopause. Topics include the role of supplements such as magnesium and calcium, iron needs, weight gain, heart disease risks, and the importance of a healthy diet. The video is accompanied by an instruction resource package that includes learning objectives and activities, a before-after knowledge quiz, and handout masters.

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Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “menopause” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on menopause: ·

Adolescent Health Initiative: New Partnership For HIV/AIDS, STD Prevention In Teens; the 16th National Lesbian & Gay Health Conference & 12th Annual AIDS/HIV Forum, New York, NY, June 24 - 26, Contact: Encore Cassettes, PO Box 231340, San Diego, CA, 92194, (619) 596-8402. Summary: This audio tape records a workshop on adolescent reproductive health presented by the Association of Reproductive Health Professionals (ARHP), a medical specialty organization based in Washington, DC. The speaker reviews the logistics of the workshop, followed by a formal presentation on adolescent reproductive health. The presentation includes a discussion of how the organization's Adolescent Health Initiative can be improved to ensure that there is more involvement of the gay and lesbian community, and specifically gay and lesbian youth. The principal objective of the workshop leaders is to receive input from the audience on this objective. The ARHP's focus is on sexually transmitted diseases, HIV, contraception, and menopause.

Bibliography: Multimedia on Menopause The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in menopause (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on menopause: ·

Appropriate use of postmenopausal estrogens [videorecording] Source: a Hahnemann University and Videotech Associates Inc. production; Year: 1983; Format: Videorecording; [S.l.]: The Associates, c1983

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Cardiovascular health in postmenopausal women [videorecording] Source: presented by the Department of Gynecology & Obstetrics, Emory University School of Medicine; Year: 1987; Format: Videorecording; Atlanta, Ga.: The University, 1987

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Hormonal needs of the perimenopausal woman [videorecording] Source: the University of Texas Medical School at Houston; produced by UT-TV, Houston; Year: 1992; Format: Videorecording; [Houston, Tex.: UT-TV], c1992

·

Is there life after menopause [videorecording] Source: a production of the Office of Learning Resources-Television, University of California, School of Medicine, San Diego; Year: 1990; Format: Videorecording; [Berkeley, Calif.]: UC Regents, c1990

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Menopause [videorecording] Source: presented by the Department of Gynecology/Obstetrics, Emory University, School of Medicine; Year: 1983; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1983

Multimedia 383

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Menopause [videorecording]: a natural passage Source: produced by the University of Wisconsin Hospital and Clinics; Year: 1993; Format: Videorecording; Madison, Wis.: Board of Regents, University of Wisconsin System, c1993

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Menopause [videorecording]: and before menopause Source: Time Life Medical; produced in association with Sonalysts Studios; Year: 1996; Format: Videorecording; New York, NY: Patient Education Media, c1996

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Menopause [videorecording]: living the change Source: [produced by KCTS/TV]; Year: 1993; Format: Videorecording; [Seattle, Wash.]: KCTS Television, c1993

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Menopause [videorecording]: new views, old taboos Source: produced by UT/TV; Year: 1993; Format: Videorecording; [Houston, Tex.]: UT/TV, c1993

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Menopause and estrogen replacement therapy [videorecording] Source: presented by the Department of Gynecology & Obstetrics, Emory University School of Medicine; Year: 1987; Format: Videorecording; Atlanta, Ga.: The University, 1987

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Menopause and estrogen therapy [videorecording] Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic & St. Joseph's Hospital; Year: 1983; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1983

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Perimenopause and menopause [sound recording]: diagnosis and treatment Source: American College of Surgeons; Year: 1978; Format: Sound recording; [Chicago]: The College, [1978]

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Primary care [videorecording]: the menopause a co-production of the Regional Audio Visual Center and Physician Education & Development. Year: 1995; Format: Videorecording; [Oakland, Calif.]: Kaiser Foundation Health Plan, c1995

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The long-range problems of the postmenopausal woman [motion picture] Source: Ayerst Laboratories; produced by Medical Dynamics; Year: 1969; Format: Motion picture; [New York: Ayerst Laboratories] 1969

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The menopausal woman [videorecording] Source: [presented by] Journal of women's health; Year: 1993; Format: Videorecording; Bethesda, MD: BioConferences International, c1993

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The menopausal woman [videorecording] Source: [presented by] the Medical University of South Carolina, College of Medicine and the Health Communications Network; Year: 1993; Format: Videorecording; Charleston, S.C.: The University, c1993

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The Menopause: a self-instructional program [slide] Source: Luther M. Talbert; Year: 1977; Format: Slide; Chapel Hill, N. C.: Health Sciences Consortium, c1977

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The psychohormonal aspects of the menopause [motion picture] Source: Ayerst Laboratories; produced by Aegis Productions; Year: 1972; Format: Motion picture; [New York]: Ayerst Laboratories, 1972

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What you should know about menopause [videorecording] Source: [HSTN]; Year: 2003; Format: Videorecording; Carrollton, TX: PRIMEDIA Workplace Learning, c2003

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What's new about menopause [videorecording] Source: a NOVA production by the WGBH/Boston Science Unit, in association with New England Research Institutes and NDR International/Hamburg; Year: 1994; Format: Videorecording; [Boston, Mass.]: WGBH Educational Foundation, c1994

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CHAPTER 9. PERIODICALS AND NEWS ON MENOPAUSE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover menopause.

News Services and Press Releases One of the simplest ways of tracking press releases on menopause is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing.

PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “menopause” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance.

Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to menopause. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “menopause” (or synonyms). The following was recently listed in this archive for menopause: ·

IV ibandronate may prevent bone loss in postmenopausal women Source: Reuters Industry Breifing Date: October 08, 2003 http://www.reutershealth.com/archive/2003/10/08/business/links/20031008drgd001 .html

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Four shots a year may curb menopausal bone loss Source: Reuters Health eLine Date: October 08, 2003

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Menopause not linked with memory loss Source: Reuters Health eLine Date: September 23, 2003

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Menopause not linked to decline in cognitive functioning Source: Reuters Medical News Date: September 23, 2003

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Premature menopause linked to epileptic seizures Source: Reuters Medical News Date: September 05, 2003

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Estrogen may help depression at menopause Source: Reuters Health eLine Date: August 25, 2003

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HRT does not slow progression of heart disease in postmenopausal women Source: Reuters Industry Breifing Date: August 06, 2003

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Researchers: Popular menopause herb may worsen cancer Source: Reuters Health eLine Date: July 14, 2003

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Black cohosh used for menopausal symptoms may promote metastasis Source: Reuters Medical News Date: July 14, 2003

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Phytoestrogen supplements not useful for menopause symptoms Source: Reuters Industry Breifing Date: July 09, 2003

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FDA approves lower-dose Prempro for menopausal symptoms Source: Reuters Medical News Date: June 09, 2003

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Age at menopause seems to have a moderate effect on mortality rate Source: Reuters Medical News Date: June 09, 2003

Periodicals and News 387

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Paroxetine CR reduces menopausal hot flashes Source: Reuters Industry Breifing Date: June 03, 2003

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Phytoestrogens ineffective for menopausal symptoms in breast cancer patients Source: Reuters Industry Breifing Date: June 02, 2003

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Mutations in human DACH2 gene a risk factor for premature menopause Source: Reuters Medical News Date: May 29, 2003

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HRT may increase risk of dementia in postmenopausal women Source: Reuters Medical News Date: May 27, 2003

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Menopause tied to increased risk of sleep-disordered breathing Source: Reuters Medical News Date: May 26, 2003

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Paroxetine reduces number and severity of menopausal hot flashes Source: Reuters Industry Breifing Date: May 02, 2003

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After menopause, sugar doesn't taste as sweet Source: Reuters Health eLine Date: April 17, 2003

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Menopause can alter taste perception Source: Reuters Medical News Date: April 16, 2003

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Women approaching menopause urged to modify cardiovascular risk factors Source: Reuters Industry Breifing Date: March 10, 2003

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Pre-eclampsia may be a risk factor for postmenopausal cardiovascular disease Source: Reuters Medical News Date: February 06, 2003

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Strength training can build postmenopausal bone Source: Reuters Health eLine Date: January 23, 2003

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Early menopause not always 'unnatural': study Source: Reuters Health eLine Date: January 22, 2003

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Depression linked to early onset of perimenopause Source: Reuters Health eLine Date: January 13, 2003

The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine.

Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “menopause” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests.

Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “menopause” (or synonyms). If you know the name of a company that is relevant to menopause, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

Periodicals and News 389

BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “menopause” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “menopause” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on menopause: ·

Menopausal Weight Gain Source: Mayo Clinic Women's HealthSource. December 1998. Contact: Mayo Clinic Women's HealthSource, P.O. Box 56931, Boulder, CO 80322-6931. Summary: This article discusses the changes a woman can expect to go through during perimenopause and menopause. The author points out the changes of puberty and pregnancy as models for the change of menopause. According to the author, lowered estrogen production contributes to the mood swings, sleep disturbances, and hot flashes of menopause. For most women, their metabolism also slows down, and their lean muscle mass diminishes. This can lead to weight gain. A starvation diet is not the answer, according to the author, who says that exercise is a better choice. Exercise boosts the metabolism, burns fat, and can strengthen bones. All forms of exercise are potentially beneficial, including aerobic exercise to burn fat, stretching to increase flexibility, and strength training to improve muscle mass and strengthen bones. Other topics discussed include hormone replacement therapy and a healthy diet.

Academic Periodicals covering Menopause Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to menopause. In addition to these sources, you can search for articles covering menopause that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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APPENDICES

393

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

13

These publications are typically written by one or more of the various NIH Institutes.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

·

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources 395

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 ·

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

·

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

14

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.

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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

·

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “menopause” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “menopause” (or synonyms) into the “For these words:” box. The following is a sample result: ·

Towards a women's health research agenda: Women's health research and the menopause: A dialogue among public policy, community and health leaders Source: Washington, DC: Society for the Advancement of Women's Health Research. ca. 1993. 16 pp. Contact: Available from Society for the Advancement of Women's Health Research, 1828 L Street, N.W., Suite 625, Washington, DC 20036. Telephone: (202) 223-8224 / fax: (202) 833-3472 / e-mail: [email protected] / Web site: http://www.womenshealth.org. Price unknown. Also available from Soroptimist International, P.O. Box 1052, La Jolla, CA 92038. Telephone: (619) 459-6652. Summary: This report summarizes a two-day conference held in February 1993 which focused on women's health research, menopause, and related public policy issues. The conference was convened by the Society for the Advancement of Women's Health Research, the School of Medicine at the University of California, San Diego, and Soroptimist International of La Jolla, California. The report includes an overview; provides a discussion of the health and policy implications of menopause; and includes an action plan for future research efforts, for the dissemination of information, and for improving the public's understanding of the condition. Attachments include the agenda, a list of the speakers, and description of the sponsoring organizations.

The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. 16 17

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

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Type “menopause” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 23173 1098 510 38 16 24835

HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.20 Simply search by “menopause” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.22 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/. 18

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

19

The HSTAT URL is http://hstat.nlm.nih.gov/.

20

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 21 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 22

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story.

23 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: ·

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

·

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Menopause In the following section, we will discuss databases and references which relate to the Genome Project and menopause.

Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “menopause” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for menopause: ·

Premature Ovarian Failure, X-linked Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?311360

Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: 24

Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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·

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

·

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

·

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

·

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html

Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “menopause” (or synonyms) into the search box and click “Go.”

Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html.

25

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.

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The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “menopause” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

26

Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on menopause can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to menopause. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.

The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below.

Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to menopause. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “menopause”:

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·

Guides on menopause Menopause http://www.nlm.nih.gov/medlineplus/tutorials/menopauseloader.html

·

Other guides Breast Cancer http://www.nlm.nih.gov/medlineplus/breastcancer.html Hormone Replacement Therapy http://www.nlm.nih.gov/medlineplus/hormonereplacementtherapy.html Hormones http://www.nlm.nih.gov/medlineplus/hormones.html Infertility http://www.nlm.nih.gov/medlineplus/infertility.html Menopause http://www.nlm.nih.gov/medlineplus/menopause.html Menstruation and Premenstrual Syndrome http://www.nlm.nih.gov/medlineplus/menstruationandpremenstrualsyndrome.h ml Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Pituitary Disorders http://www.nlm.nih.gov/medlineplus/pituitarydisorders.html Uterine Cancer http://www.nlm.nih.gov/medlineplus/uterinecancer.html Uterine Diseases http://www.nlm.nih.gov/medlineplus/uterinediseases.html

Within the health topic page dedicated to menopause, the following was listed: ·

General/Overviews Menopause Years Source: American College of Obstetricians and Gynecologists http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZ6CGQV77C& sub_cat=327

·

Diagnosis/Symptoms Estrogen Tests Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/estrogen/test.html

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·

Treatment FDA Approves Estrasorb for Treatment of Menopausal Hot Flashes Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01255.html MEDLINEplus: Hormone Replacement Therapy Source: National Library of Medicine http://www.nlm.nih.gov/medlineplus/hormonereplacementtherapy.html Menopausal Hormone Use: Questions and Answers Source: National Cancer Institute http://www.cancer.gov/newscenter/estrogenplus

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Alternative Therapy Herbal Products for Menopause Source: American College of Obstetricians and Gynecologists http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZSPYZT5FD& sub_cat=2002 Hot Flashes: Treatments Are Available Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01409 Questions and Answers About Black Cohosh and the Symptoms of Menopause Source: National Center for Complementary and Alternative Medicine, National Institutes of Health, Office of Dietary Supplements http://ods.od.nih.gov/factsheets/blackcohosh.html

·

Specific Conditions/Aspects JAMA Patient Page: Perimenopause: Beginning of Menopause Source: American Medical Association http://www.ama-assn.org/public/journals/patient/archive/jpg021903.htm Menopause and Bladder Control http://kidney.niddk.nih.gov/kudiseases/pubs/menopause_ez/index.htm Menopause and Diabetes Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DA00038 Menopause and the Risk of Heart Disease and Stroke Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4658 Perimenopause Source: National Women's Health Information Center http://www.4woman.gov/Menopause/menopause.cfm?page=336&mtitle=perime nopause Perimenopause: A Period Before Your Period Ends Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01199

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Talking to Your Health Care Provider about Menopause Source: National Women's Health Information Center http://www.4woman.gov/Menopause/menopause.cfm?page=337&mtitle=postme nopause Very-Low-Dose Birth Control Pills for Perimenopausal Women Source: American Academy of Family Physicians http://familydoctor.org/handouts/326.html Weight Gain As You Age Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01076 ·

Latest News Estrogen Patch May Be Safer Than Pill Form Source: 09/26/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14112 .html FDA Approves Estrasorb for Treatment of Menopausal Hot Flashes Source: 10/10/2003, Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01255.html Four Shots a Year May Curb Menopausal Bone Loss Source: 10/08/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14223 .html Menopause Not Linked with Memory Loss Source: 09/23/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14057 .html

·

Organizations Hormone Foundation http://www.hormone.org/ National Institute on Aging http://www.nia.nih.gov/ National Women's Health Information Center Source: Dept. of Health and Human Services http://www.4woman.org/ North American Menopause Society http://www.menopause.org/

·

Research FDA Revises Finding on Estrogen/Androgen Combination Products in the Treatment of Hot Flashes Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01210.html Hormone Therapy Can Relieve Menopause-Type Symptoms Common in Elderly

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Women: HERS Study Report Source: American College of Obstetricians and Gynecologists http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZRMBOL19D &sub_cat=2 NHLBI Stops Trial of Estrogen Plus Progestin Due to Increased Breast Cancer Risk, Lack of Overall Benefit Source: National Heart, Lung, and Blood Institute http://www.nih.gov/news/pr/jul2002/nhlbi-09.htm Relationship between Use of Cholesterol-Lowering Drugs (Statins) and Osteoporosis in Women after Menopause Source: American College of Physicians http://www.annals.org/cgi/content/full/139/2/I-27 Women Urged to Reduce Heart Disease Risk Before Menopause Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3009770 Women with Premature Menopause at Increased Risk for Potentially Fatal Adrenal Condition: Early Diagnosis Can Lead to Effective Treatment Source: National Institute of Child Health and Human Development http://www.nih.gov/news/pr/aug2002/nichd-30.htm You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on menopause. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·

Menopause and Osteoporosis: Choices for a Healthy Future Source: Washington, DC: National Osteoporosis Foundation (NOF). 199x. 23 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This booklet provides women with information about the impact of menopause on osteoporosis, a disease characterized by a loss of bone mass and by poor bone quality, which lead to reduced bone strength and increased risk of fractures. Following menopause, production of estrogen, which has an important role in the bone renewal process, ceases. In many women, the loss of estrogen after menopause leads to

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rapid bone removal. The booklet lists the risk factors for osteoporosis, explains how a bone mineral density test can determine the strength of a woman's bones, and outlines steps women can take to prevent osteoporosis, among them the use of estrogen replacement therapy or hormone replacement therapy, which slows or stops bone loss in postmenopausal women. Additional medications that may be used to treat osteoporosis include calcitonin and alendronate. Other approaches include consuming enough calcium and vitamin D and exercising. The booklet also lists some questions women should ask their doctor about osteoporosis, offers suggestions for improving health and well-being, presents a list of resources, and concludes with information on the National Osteoporosis Foundation. 3 figures and 1 table. ·

Menopause and Bladder Control. [La Menopausia y el Control de la Vejiga] Source: Bethesda, MD: National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 1997. 8 p. Contact: Available from National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 3 Information Way, Bethesda, MD 20892-3580. (800) 891-5390 or (301) 654-4415. Fax (301)634-0716. E-mail: [email protected]. Website: http://www.niddk.nih.gov/health/kidney/nkudic.htm. PRICE: Full-text available online at no charge; single copy free; bulk orders available. Order number: KU-111. Summary: This brochure, part of a public health awareness campaign on bladder control for women, describes the interplay between menopause and bladder control. Topics include the role of estrogen in keeping the lining of the bladder and the urethra healthy; the anatomy of the female bladder control system; stress incontinence, in which pressure from coughing, sneezing, or lifting can cause urine leakage; the other causes of bladder control problems in older women, including infections, nerve damage from diabetes or stroke, heart problems, medicines, depression, and mobility problems; treatment options for bladder control, including dietary modifications, pelvic muscle exercises, bladder training, biofeedback, drug therapy, and surgery; and professionals who can help with bladder control issues. The brochure includes illustrations depicting the muscles and organs described. The brochure is written in nontechnical, clear language, with medical terms defined for the reader.

·

Questions and Answers About Black Cohosh and the Symptoms of Menopause Source: Bethesda, MD: Office of Dietary Supplements, National Institutes of Health. 2001. 7 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL: [email protected]. PRICE: Free. Publication Number: D176. Summary: This fact sheet from the National Institutes of Health Office of Dietary Supplements and the National Center for Complementary and Alternative Medicine provides an overview of the use of black cohosh for menopausal symptoms. It lists key points about black cohosh and menopause, followed by a series of questions and answers on the topic. The information provided in the fact sheet includes an explanation of what black cohosh is, a description of its preparations, the history of its use, details about clinical studies on black cohosh and its effect on menopausal symptoms, how black cohosh works, and the possible side effects of, and drug interactions with, black cohosh. The fact sheet offers additional sources of information on black cohosh. 24 references.

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The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “menopause” (or synonyms). The following was recently posted: ·

AACE medical guidelines for clinical practice for management of menopause Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1999 Nov-December; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2138&nbr=1364&a mp;string=menopause

·

Amended report from the NAMS Advisory Panel on postmenopausal hormone therapy Source: The North American Menopause Society - Private Nonprofit Organization; 2002 October 6; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3464&nbr=2690&a mp;string=menopause

·

Clinical challenges of perimenopause: consensus opinion of The North American Menopause Society Source: The North American Menopause Society - Private Nonprofit Organization; 2000 January; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2564&nbr=1790&a mp;string=menopause

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Investigation of post-menopausal bleeding. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2002 September; 25 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3456&nbr=2682&a mp;string=menopause

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Management of postmenopausal osteoporosis: position statement of The North American Menopause Society Source: The North American Menopause Society - Private Nonprofit Organization; 2002 March; 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3179&nbr=2405&a mp;string=menopause

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·

Perimenopausal and postmenopausal hormone replacement therapy Source: American College of Preventive Medicine - Medical Specialty Society; 1999 October; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2120&nbr=1346&a mp;string=menopause

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Postmenopausal hormone replacement therapy for the primary prevention of chronic conditions: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2002); 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3455&nbr=2681&a mp;string=menopause

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Role of progestogen in hormone therapy for postmenopausal women: position statement of The North American Menopause Society Source: The North American Menopause Society - Private Nonprofit Organization; 2003 Mar-April; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3736&nbr=2962&a mp;string=menopause

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Screening for osteoporosis in postmenopausal women: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2002 September 17); 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3417&nbr=2643&a mp;string=menopause

·

The role of aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 2002 September 3; 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3608&nbr=2834&a mp;string=menopausal

·

The role of calcium in peri- and postmenopausal women: consensus opinion of The North American Menopause Society Source: The North American Menopause Society - Private Nonprofit Organization; 2001 March; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2740&nbr=1966&a mp;string=menopause

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·

The role of isoflavones in menopausal health: consensus opinion of The North American Menopause Society Source: The North American Menopause Society - Private Nonprofit Organization; 2000 July; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2567&nbr=1793&a mp;string=menopause

Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·

Estrogen in a Woman's Life Summary: This education animation describes the role that estrogen plays in four stages of a woman's life: adolescence, reproductive, perimenopause, and menopause. Source: Hormone Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7153

·

Menopause Summary: This document is designed to provide women with basic information about menopause -- body changes, symptoms, relief from symptoms, and how to manage menopause. Source: National Institute on Aging, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3765

·

Menopause: Treatment Options for Women Surviving Breast Cancer or Concerned About Estrogen Replacement Therapy Summary: This document represents a summary of a report from a meeting of experts to discuss various ways to identify and treat symptoms of postmenopausal hormone deficiency in patients surviving breast Source: Hormone Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4591

·

Menopause: What To Expect When Your Body Is Changing Summary: This brochure describes menopause and its signs, symptoms, and treatment. Source: American Academy of Family Physicians http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7662

412 Menopause

·

Questions and Answers: Use of Hormones After Menopause Summary: Postmenopausal hormone use usually involves hormone replacement therapy (HRT) with either estrogen alone or in combination with progestin to compensate for the decrease in natural hormones that occurs Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6794

·

Women's Health and Menopause: A Comprehensive Approach Summary: This international and multidisciplinary monograph is based on extensive international review and evaluation of the scientific evidence for current clinical practices as presented in the published Source: National Heart, Lung, and Blood Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7465 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to menopause. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources

A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

·

Family Village: http://www.familyvillage.wisc.edu/specific.htm

·

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

·

Med Help International: http://www.medhelp.org/HealthTopics/A.html

·

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

·

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

·

WebMDÒHealth: http://my.webmd.com/health_topics

Patient Resources 413

Associations and Menopause The following is a list of associations that provide information on and resources relating to menopause: ·

Hormone Foundation Telephone: Toll-free: (800) 467-6663 Fax: (310) 941-0259 Email: [email protected] Web Site: www.hormone.org Background: The Hormone Foundation is dedicated to serving as a resource for the public by promoting the prevention, treatment and cure of hormone-related diseases. It provides information on diseases including congenital adrenal hyperplasia, diabetes insipidus, hypoparathyroidism, hypothyroidism, polycystic ovary syndrome, and pseudohypoparathyroidism. Relevant area(s) of interest: Menopause

·

The Daisy Network, Premature Menopause Support Group Web Site: http://www.daisynetwork.org.uk Background: The Daisy Network, Premature Menopause Support Group, is for women who have suffered a premature menopause. It provides advice and support for affected women, and their families, through what can be a devastating, life-changing diagnosis. Premature menopause, also called premature ovarian failure, is defined as the onset of menopause before the age of 40. It can occur for several reasons, including a malfunctioning of the body's immune system, damage to the ovaries, and, in a few cases, an inherited genetic cause. The Daisy Network provides opportunities to share feelings, experiences, and information with others. It also provides information about treatments and research in the fields of hormone replacement therapy and assisted conception. In addition, it seeks to raise awareness of the condition among the medical community and policy-makers. Relevant area(s) of interest: Menopause

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to menopause. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with menopause.

The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about menopause. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

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Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “menopause” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information.

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “menopause”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “menopause” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “menopause” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.27

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

27

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)28: ·

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

·

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

·

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

·

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

·

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

·

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

·

California: Gateway Health Library (Sutter Gould Medical Foundation)

·

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

·

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

·

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

·

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

·

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

·

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

·

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

·

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

·

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

·

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

·

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

28

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries 417

·

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

·

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

·

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

·

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

·

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

·

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

·

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

·

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

·

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

·

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

·

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

·

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

·

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

·

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

·

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

·

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

·

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

·

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

·

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

·

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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·

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

·

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

·

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

·

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

·

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

·

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

·

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

·

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

·

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

·

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

·

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

·

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

·

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

·

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

·

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

·

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

·

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

·

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

·

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries 419

·

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

·

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

·

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

·

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

·

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

·

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

·

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

·

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

·

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

·

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

·

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

·

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

·

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

·

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

·

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

·

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

·

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

·

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

·

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

·

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

420 Menopause

·

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

·

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

·

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

·

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

421

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: ·

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

·

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

·

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

·

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

·

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

·

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

·

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on menopause: ·

Basic Guidelines for Menopause Climacteric Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000894.htm Menopause Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000894.htm

·

Signs & Symptoms for Menopause Abdominal bloating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003123.htm Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Breast tenderness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003152.htm

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Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Dyspareunia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003157.htm Flushing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003241.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Incontinence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003142.htm Insomnia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Irregular menstrual periods Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003263.htm Irritability Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003214.htm Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Lethargy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Mood changes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Nausea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Tiredness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Vaginal bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003156.htm Vaginitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003158.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm

Online Glossaries 423

Wrinkles Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003252.htm ·

Diagnostics and Tests for Menopause 17-hydroxycorticosteroids Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003459.htm 17-OH progesterone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003713.htm ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Endometrial biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003917.htm Estradiol - test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003711.htm FSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003710.htm Mammogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003380.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Pap smear Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003911.htm Prolactin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003718.htm Serum progesterone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003714.htm Testosterone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003707.htm

424 Menopause

TSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003684.htm ·

Nutrition for Menopause Vitamin D Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002405.htm

·

Surgery and Procedures for Menopause Hysterectomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002915.htm

·

Background Topics for Menopause Adrenal glands Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002219.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Bone fracture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Cardiovascular Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002310.htm Epithelial Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002363.htm Hypothalamic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002380.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Kegel exercises Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003975.htm Mucosa Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002264.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm

Online Glossaries 425

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: ·

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

·

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

·

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

·

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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MENOPAUSE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 17-Hydroxycorticosteroids: A group of hydroxycorticosteroids bearing a hydroxy group at the 17-position. Urinary excretion of these compounds is used as an index of adrenal function. They are used systemically in the free alcohol form, but with esterification of the hydroxy groups, topical effectiveness is increased. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Ablate: In surgery, is to remove. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Absolute risk: The observed or calculated probability of an event in a population under study, as contrasted with the relative risk. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinomycosis: Infections with bacteria of the genus Actinomyces. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the

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intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the

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tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical

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steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylate: To treat with an alkylating agent. [EU] Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveolar Bone Loss: The resorption of bone in the supporting structures of the maxilla or mandible as a result of periodontal disease. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH]

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Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Androstenedione: A steroid with androgenic properties that is produced in the testis, ovary, and adrenal cortex. It is a precursor to testosterone and other androgenic hormones. [NIH]

Anecdotal report: An incomplete description of the medical and treatment history of one or more patients. Anecdotal reports may be published in places other than peer-reviewed, scientific journals. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthetics:

Agents that are capable of inducing a total or partial loss of sensation,

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especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Hypothalamic Nucleus: Loose heterogeneous collection of cells in the anterior hypothalamus, continuous rostrally with the medial and lateral preoptic areas and caudally with the tuber cinereum. [NIH] Anthropometry: The technique that deals with the measurement of the size, weight, and proportions of the human or other primate body. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier

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for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH]

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Appendicular skeleton: The framework around and within which the soft parts of the body are situated. [NIH] Approximate: Approximal [EU] Aptitude: The ability to acquire general or special types of knowledge or skill. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arnica: Genus of composite-flowered plants in the family Asteraceae. The dried flower heads of Arnica montana are used externally as a counterirritant and tincture for sprains and bruises. Arnica contains volatile oils, arnicin, arnisterol, flavonoids, tannins, and resin. [NIH]

Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthralgia: Pain in the joint. [NIH]

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Articular: Of or pertaining to a joint. [EU] Aseptic: Free from infection or septic material; sterile. [EU] Aspirate: Fluid withdrawn from a lump, often a cyst, or a nipple. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH]

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Autopsy: Postmortem examination of the body. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH]

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Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived

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constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blepharospasm: Excessive winking; tonic or clonic spasm of the orbicularis oculi muscle. [NIH]

Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Burden: The total amount of a chemical, metal or radioactive substance present at any time after absorption in the body of man or animal. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Image: Individuals' personal concept of their bodies as objects in and bound by space, independently and apart from all other objects. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Development: Gross development of bones from fetus to adult. It includes osteogenesis, which is restricted to formation and development of bone from the undifferentiated cells of the germ layers of the embryo. It does not include osseointegration. [NIH]

Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types,

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yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broad Ligament: A broad fold of peritoneum that extends from the side of the uterus to the wall of the pelvis. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU]

Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buccal mucosa: The inner lining of the cheeks and lips. [NIH] Burning Mouth Syndrome: A group of painful oral symptoms associated with a burning or similar sensation. There is usually a significant organic component with a degree of functional overlay; it is not limited to the psychophysiologic group of disorders. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical),

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electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcaneus: The largest of the tarsal bones and is situated at the lower and back part of the foot forming the heel. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [NIH] Calcitonin Gene-Related Peptide: Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Metabolism Disorders: Disorders in the processing of calcium in the body, including absorption, transport, storage, and utilization. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU]

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Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogenicity: The ability to cause cancer. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Castration: Surgical removal or artificial destruction of gonads. [NIH] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It

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can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH]

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Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cesarean Section: Extraction of the fetus by means of abdominal hysterotomy. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Antagonists: Drugs that bind to but do not activate cholinergic receptors, thereby blocking the actions of acetylcholine or cholinergic agonists. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chorioallantoic membrane: The membrane in hen's eggs that helps chicken embryos get enough oxygen and calcium for development. The calcium comes from the egg shell. [NIH]

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Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Aberrations: Deviations from the normal number or structure of chromosomes, not necessarily associated with disease. [NIH] Chromosome Painting: A technique for visualizing chromosome aberrations using fluorescently labeled DNA probes which are hybridized to chromosomal DNA. Multiple fluorochromes may be attached to the probes. Upon hybridization, this produces a multicolored, or painted, effect with a unique color at each site of hybridization. This technique may also be used to identify cross-species homology by labeling probes from one species for hybridization with chromosomes from another species. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other

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medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH]

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Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Comet Assay: A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage. [NIH] Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH]

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Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Concept Formation: A cognitive process involving the formation of ideas generalized from the knowledge of qualities, aspects, and relations of objects. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confidence Intervals: A range of values for a variable of interest, e.g., a rate, constructed so that this range has a specified probability of including the true value of the variable. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH]

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Continence: The ability to hold in a bowel movement or urine. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: group. [NIH]

An experiment or clinical trial that includes a comparison (control)

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or

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clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or

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complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, .. New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Defecation: The normal process of elimination of fecal material from the rectum. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care:

The concept concerned with all aspects of providing and

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distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demography: Statistical interpretation and description of a population with reference to distribution, composition, or structure. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Abutments: Natural teeth or teeth roots used as anchorage for a fixed or removable denture or other prosthesis (such as an implant) serving the same purpose. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dental Hygienists: Persons trained in an accredited school or dental college and licensed by the state in which they reside to provide dental prophylaxis under the direction of a licensed dentist. [NIH] Dental implant: A small metal pin placed inside the jawbone to mimic the root of a tooth. Dental implants can be used to help anchor a false tooth or teeth, or a crown or bridge. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU]

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Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic Errors: Incorrect diagnoses after clinical examination or technical diagnostic procedures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphoresis: Perspiration, especially profuse perspiration. Called also sudoresis. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diestrus: Period of sexual quiescence separating phases of the estrous cycle in polyestrous animals. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotachysterol: Vitamin D. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilate: Relax; expand. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH]

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Dilator: A device used to stretch or enlarge an opening. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diurnal: Occurring during the day. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of singlestranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH]

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Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drinking Behavior: Behaviors associated with the ingesting of water and other liquids; includes rhythmic patterns of drinking (time intervals - onset and duration), frequency and satiety. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Industry: That segment of commercial enterprise devoted to the design, development, and manufacture of chemical products for use in the diagnosis and treatment of disease, disability, or other dysfunction, or to improve function. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dydrogesterone: A synthetic progestational hormone with no androgenic or estrogenic properties. Unlike many other progestational compounds, dydrogesterone produces no increase in temperature and does not inhibit ovulation. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH]

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Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH]

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Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH]

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Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enhancers: Transcriptional element in the virus genome. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelial ovarian cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH]

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Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estriol: (16 alpha,17 beta)-Estra-1,3,5(10)-triene-3,16,17-triol. A metabolite of estradiol and usually the predominant estrogenic metabolite in urine. During pregnancy, large amounts of estriol are produced by the placenta. It has also been obtained from plant sources. The 16 beta-isomer has also been isolated from the urine of pregnant women. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen Antagonists: Compounds which inhibit or antagonize the action or biosynthesis of estrogen. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrogen receptor positive: ER+. Breast cancer cells that have a protein (receptor molecule) to which estrogen will attach. Breast cancer cells that are ER+ need the hormone estrogen to grow and will usually respond to hormone (antiestrogen) therapy that blocks these receptor sites. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Ethinyl Estradiol: A semisynthetic estrogen with high oral estrogenic potency. It is often used as the estrogenic component in oral contraceptives. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU]

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Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exemestane: An anticancer drug used to decrease estrogen production and suppress the growth of estrogen-dependent tumors. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH]

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Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fecal Incontinence: Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Flatus: Gas passed through the rectum. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluoroscopy: Production of an image when X-rays strike a fluorescent screen. [NIH] Fluorosis: Discoloration of the tooth enamel due to fluorine. [NIH] Flush: Transient, episodic redness of the face and neck caused by certain diseases, ingestion

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of certain drugs or other substances, heat, emotional factors, or physical exertion. [EU] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Foetoplacental: Pertaining to the fetus and placenta. [EU] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH] Follicular Phase: The period of the menstrual cycle that begins with menstruation and ends with ovulation. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frail Elderly: Older adults or aged individuals who are lacking in general strength and are unusually susceptible to disease or to other infirmity. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH]

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Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase

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arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH]

Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH]

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Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Goserelin: 6-(O-(1,1-Dimethylethyl)-D-serine)-10-deglycinamideluteinizing hormonereleasing factor (pig) 2-(aminocarbonyl)hydrazide. A long-acting gonadorelin agonist. It is used in the treatment of malignant neoplasms of the prostate, uterine fibromas, and metastatic breast cancer. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH]

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Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH]

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Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation.

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[NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH]

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Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

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Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypophyseal: Hypophysial. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hysterectomy: Excision of the uterus. [NIH] Hysterotomy: An incision in the uterus, performed through either the abdomen or the vagina. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: (antigens). [NIH]

The activity of the immune system against foreign substances

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH]

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Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impregnation: 1. The act of fecundation or of rendering pregnant. 2. The process or act of saturation; a saturated condition. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU]

Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized,

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subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhibin: Glyceroprotein hormone produced in the seminiferous tubules by the Sertoli cells in the male and by the granulosa cells in the female follicles. The hormone inhibits FSH and LH synthesis and secretion by the pituitary cells thereby affecting sexual maturation and fertility. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Interindividual: Occurring between two or more individuals. [EU] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH]

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Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intrahepatic: Within the liver. [NIH] Intraindividual: Being or occurring within the individual. [EU] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [EU] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH]

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Keratolytic: An agent that promotes keratolysis. [EU] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH]

Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [NIH] Levonorgestrel: A progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense

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(pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: circulation. [NIH]

Services offered to the library user. They include reference and

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Light microscope: A microscope (device to magnify small objects) in which objects are lit directly by white light. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU]

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Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]

Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other material, used for carrying an injured or disabled person. [NIH] Litter Size: The number of offspring produced at one birth by an animal. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobule: A small lobe or subdivision of a lobe. [NIH] Local therapy: Treatment that affects cells in the tumor and the area close to it. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large

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numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-calorie diet: Caloric restriction of about 800 to 1,500 calories (approximately 12 to 15 kcal/kg of body weight) per day. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lower Body Negative Pressure: External decompression applied to the lower body. It is used to study orthostatic intolerance and the effects of gravitation and acceleration, to produce simulated hemorrhage in physiologic research, to assess cardiovascular function, and to reduce abdominal stress during childbirth. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH]

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Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mammography: Radiographic examination of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mass Media: Instruments or technological means of communication that reach large numbers of people with a common message: press, radio, television, etc. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Eminence: Raised area on the infundibular hypothalamus at the floor of the third ventricle of the brain which contains the primary capillary network of the hypophyseal portal system. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical castration: Refers to the use of drugs to suppress the function of the ovaries or testicles. [NIH]

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Medical Errors: Errors or mistakes committed by health professionals which result in harm to the patient. They include errors in diagnosis (diagnostic errors), errors in the administration of drugs and other medications (medication errors), errors in the performance of surgical procedures, in the use of other types of therapy, in the use of equipment, and in the interpretation of laboratory findings. Medical errors are differentiated from malpractice in that the former are regarded as honest mistakes or accidents while the latter is the result of negligence, reprehensible ignorance, or criminal intent. [NIH] Medical Records: illnesses. [NIH]

Recording of pertinent information concerning patient's illness or

Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] Medication Errors: Errors in prescribing, dispensing, or administering medication with the result that the patient fails to receive the correct drug or the indicated proper drug dosage. [NIH]

MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH]

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Menorrhagia: Excessive menstrual flow. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesenteric Arteries: Arteries which arise from the abdominal aorta and distribute to most of the intestines. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methyldopa: An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent. Before its alphaadrenergic actions became clear, methyldopa was thought to act by inhibiting decarboxylation of DOPA leading to depletion of norepinephrine or by conversion to and release as the false transmitter alpha-methylnorepinephrine. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH]

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Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently labeled with radioisotopes or various reagents acting as tags or markers. [NIH] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

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Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multiparous: 1. Having had two or more pregnancies which resulted in viable fetuses. 2. Producing several ova or offspring at one time. [EU] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fatigue: A state arrived at through prolonged and strong contraction of a muscle. Studies in athletes during prolonged submaximal exercise have shown that muscle fatigue increases in almost direct proportion to the rate of muscle glycogen depletion. Muscle fatigue in short-term maximal exercise is associated with oxygen lack and an increased level of blood and muscle lactic acid, and an accompanying increase in hydrogen-ion concentration in the exercised muscle. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH]

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Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervousness: Excessive excitability and irritability, with mental and physical unrest. [EU] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion

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cells arise by differentiation of neural crest cells. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurofibroma: A fibrous tumor, usually benign, arising from the nerve sheath or the endoneurium. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]

Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nitrendipine: Ethyl methyl 2,4-dihydro-2,6-dimethyl-4(3-nitrophenyl)-3,5pyridinedicarboxylate. A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as

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acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norethindrone: A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. [NIH] Norgestrel: (+-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one. A progestational agent with actions similar to those of progesterone. This racemic or (+-)-form has about half the potency of the levo form (levonorgestrel). Norgestrel is used as a contraceptive and ovulation inhibitor and for the control of menstrual disorders and endometriosis. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nulliparous: Having never given birth to a viable infant. [EU] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which

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normalizes body fluids to restore water-electrolyte balance. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Oculi: Globe or ball of the eye. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Oestradiol: Growth hormone. [NIH] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncology: The study of cancer. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Oogenesis: The formation, development, and maturation of the female germ cell. [NIH]

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Oophorectomy: Surgery to remove one or both ovaries. [NIH] Oophoritis: Inflammation of an ovary. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]

Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osseointegration: The growth action of bone tissue, as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants). [NIH] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH]

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Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palpitation: A subjective sensation of an unduly rapid or irregular heart beat. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU]

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Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: regimen. [NIH]

Voluntary cooperation of the patient in following a prescribed

Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Pelvic: Pertaining to the pelvis. [EU]

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Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Perceived risk: Estimate or evaluation of risk as observed through personal experience or personal study, and personal evaluation of consequences. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: simplex. [NIH]

Inflammation of the periodontal membrane; also called periodontitis

Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH]

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Perivascular: Situated around a vessel. [EU] Perspiration: Sweating; the functional secretion of sweat. [EU] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU]

Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise.

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[NIH]

Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen:

Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of

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molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their

Dictionary 493

complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Portal System: A system of vessels in which blood, after passing through one capillary bed, is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postmenopause: The physiological period following the menopause, the permanent cessation of the menstrual life. Since in the United States the age of the menopause ranges between 48 and 55 years, generally conceived as middle age, the postmenopause often refers to women considerably older. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH]

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Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary tumor: The original tumor. [NIH] Private Sector: That distinct portion of the institutional, industrial, or economic structure of a country that is controlled or owned by non-governmental, private interests. [NIH] Privatization: Process of shifting publicly controlled services and/or facilities to the private sector. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body,

Dictionary 495

secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progestogen: A term applied to any substance possessing progestational activity. [EU] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Prolapse: The protrusion of an organ or part of an organ into a natural or artificial orifice. [NIH]

Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate-Specific Antigen: Kallikrein-like serine proteinase produced by epithelial cells of

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both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychological Tests: Standardized tests designed to measure abilities, as in intelligence, aptitude, and achievement tests, or to evaluate personality traits. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychomotor Performance: The coordination of a sensory or ideational (cognitive) process and a motor activity. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior.

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[NIH]

Psychosexual: Pertaining to the mental aspects of sex. [NIH] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier

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proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radius: The lateral bone of the forearm. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH]

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Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

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Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Reproductive History: An important aggregate factor in epidemiological studies of women's health. The concept usually includes the number and timing of pregnancies and their outcomes, the incidence of breast feeding, and may include age of menarche and menopause, regularity of menstruation, fertility, gynecological or obstetric problems, or contraceptive usage. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Research Support: Financial support of research activities. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Resting metabolic rate: RMR accounts for 65 to 75 percent of daily energy expenditure and represents the minimum energy needed to maintain all physiological cell functions in the resting state. The principal determinant of RMR is lean body mass (LBM). Obese subjects have a higher RMR in absolute terms than lean individuals, an equivalent RMR when corrected for LBM and per unit surface area, and a lower RMR when expressed per kilogram of body weight. Obese persons require more energy for any given activity because of a larger mass, but they tend to be more sedentary than lean subjects. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It

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occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Sagittal: The line of direction passing through the body from back to front, or any vertical plane parallel to the medial plane of the body and inclusive of that plane; often restricted to the medial plane, the plane of the sagittal suture. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to

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create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Sclerotic: Pertaining to the outer coat of the eye; the sclera; hard, indurated or sclerosed. [NIH]

Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Second cancer: Refers to a new primary cancer that is caused by previous cancer treatment, or a new primary cancer in a person with a history of cancer. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretin: A hormone made in the duodenum. Causes the stomach to make pepsin, the liver to make bile, and the pancreas to make a digestive juice. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH]

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Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: female or male. [NIH]

The biological characteristics which distinguish human beings as

Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the

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one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Smooth Muscle Tumor: A tumor composed of smooth muscle tissue, as opposed to leiomyoma, a tumor derived from smooth muscle. [NIH] Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Class: A stratum of people with similar position and prestige; includes social stratification. Social class is measured by criteria such as education, occupation, and income. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland,

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27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Sonogram: A computer picture of areas inside the body created by bouncing sound waves off organs and other tissues. Also called ultrasonogram or ultrasound. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soy Proteins: Proteins which are present in or isolated from soybeans. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in

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the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spotting: A slight discharge of blood via the vagina, especially as a side-effect of oral contraceptives. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress incontinence: An involuntary loss of urine that occurs at the same time that internal abdominal pressure is increased, such as with laughing, sneezing, coughing, or physical activity. [NIH]

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Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] Stress urinary: Leakage of urine caused by actions--such as coughing, laughing, sneezing, running, or lifting--that place pressure on the bladder from inside the body. Stress urinary incontinence can result from either a fallen bladder or weak sphincter muscles. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH]

Stromal: Large, veil-like cell in the bone marrow. [NIH] Styptic: Astringent. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subfornical Organ: A structure, situated close to the intraventricular foramen, which induces drinking behavior after stimulation with angiotensin II. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Subtrochanteric: Below a trochanter. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Supine: Having the front portion of the body upwards. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprachiasmatic Nucleus: An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the optic chiasm. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using

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life table methods. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tarsal Bones: The seven bones which form the tarsus - namely, calcaneus, talus, cuboid,

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navicular, and first, second and third cuneiforms. The tarsus is a skeletal part of the foot. [NIH]

Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from

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a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]

Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH]

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Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toremifene: A first generation selective estrogen receptor modulator (SERM). Like tamoxifen, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of

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ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transvaginal ultrasound: A procedure used to examine the vagina, uterus, fallopian tubes, and bladder. An instrument is inserted into the vagina, and sound waves bounce off organs inside the pelvic area. These sound waves create echoes, which a computer uses to create a picture called a sonogram. Also called TVS. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Triptorelin: A long-acting gonadorelin analog agonist. It has been used in the treatment of prostatic cancer, ovarian cancer, precocious puberty, endometriosis, and to induce ovulation for in vitro fertilization. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuber Cinereum: Layer of gray matter in the hypothalamus that also forms part of the floor of the third ventricle and merges anteriorly into the infundibulum (pituitary gland, posterior). [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs

Dictionary 513

from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]

Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Umbilical Veins: Veins which carry oxygenated, nutrient-rich blood from the placenta and which are obliterated in the first few days after birth. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urban Population: The inhabitants of a city or town, including metropolitan areas and suburban areas. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urethritis: Inflammation of the urethra. [EU] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urodynamics: The mechanical laws of fluid dynamics as they apply to urine transport. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uterine Prolapse: Downward displacement of the uterus. It is classified in various degrees: in the first degree the cervix is within the vaginal orifice; in the second degree the cervix is outside the orifice; in the third degree the entire uterus is outside the orifice. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH]

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Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virilization: The induction or development of male secondary sec characters, especially the induction of such changes in the female, including enlargement of the clitoris, growth of facial and body hair, development of a hairline typical of the male forehead, stimulation of secretion and proliferation of the sebaceous glands (often with acne), and deepening of the

Dictionary 515

voice. Called also masculinization) [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Visceral fat: One of the three compartments of abdominal fat. Retroperitoneal and subcutaneous are the other two compartments. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Void: To urinate, empty the bladder. [NIH] Waist circumference: To define the level at which the waist circumference is measured, a bony landmark is first located and marked. The subject stands, and the technician, positioned to the right of the subject, palpates the upper hip bone to locate the right ileum. Just above the uppermost lateral border of the right ileum, a horizontal mark is drawn and then crossed with a vertical mark on the midaxillary line. The measuring tape is then placed around the trunk, at the level of the mark on the right side, making sure that it is on a level horizontal plane on all sides. The tape is then tightened slightly without compressing the skin and underlying subcutaneous tissues. The measure is recorded in centimeters to the nearest millimeter. [NIH] War: Hostile conflict between organized groups of people. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb:

A hollow, thick-walled, muscular organ in which the impregnated ovum is

516 Menopause

developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]

Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoledronate: A drug that belongs to the family of drugs called bisphosphonates. It is used to prevent bone fractures and reduce bone pain in people who have cancer that has spread to the bone. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

517

INDEX 1 17-Hydroxycorticosteroids, 423, 427 A Abdomen, 315, 427, 438, 439, 469, 472, 475, 487, 489, 501, 506, 509 Abdominal fat, 12, 16, 22, 65, 75, 88, 109, 113, 322, 427, 515 Ablate, 61, 427, 455 Abortion, 375, 427, 485 Abscess, 427, 503 Absolute risk, 35, 427 Acceptor, 427, 487 ACE, 409, 427 Acetylcholine, 427, 443, 483, 484 Acidity, 427, 490 Acne, 283, 427, 501, 514 Actin, 56, 427, 481, 482 Actinomycosis, 220, 427 Acyl, 332, 345, 427, 458 Adaptability, 43, 427, 442 Adaptation, 175, 273, 427, 471, 492 Adenocarcinoma, 428, 467 Adenosine, 428, 435, 440, 490 Adenovirus, 61, 428 Adipocytes, 428, 447, 473 Adipose Tissue, 65, 91, 138, 168, 237, 258, 427, 428, 475 Adjustment, 4, 6, 11, 14, 15, 16, 99, 303, 427, 428 Adjuvant, 24, 36, 149, 207, 319, 324, 428 Adjuvant Therapy, 24, 428 Adolescence, 111, 369, 411, 428 Adrenal Cortex, 428, 429, 431, 449, 458, 485, 495, 500 Adrenal Glands, 326, 428, 431 Adrenal Medulla, 428, 442, 457, 484 Adrenergic, 428, 453, 457, 479, 508 Adverse Effect, 125, 428, 503 Aerobic, 10, 12, 57, 79, 303, 389, 428, 480 Aerobic Exercise, 10, 57, 389, 428 Aetiology, 118, 159, 428 Afferent, 99, 428, 459, 473 Affinity, 32, 428, 429, 504 Agar, 429, 491 Age Groups, 76, 104, 136, 429 Age of Onset, 3, 51, 87, 429, 513 Age-Adjusted, 14, 429 Aged, 80 and Over, 429

Ageing, 88, 150, 152, 171, 231, 429 Agonist, 42, 47, 64, 113, 133, 262, 429, 453, 464, 479, 498, 508, 511, 512 Airway, 429, 504 Albumin, 429, 491 Aldosterone, 67, 429 Alendronate, 175, 308, 408, 429 Alertness, 429, 440 Algorithms, 429, 438 Alimentary, 430, 452, 488 Alkaline, 167, 430, 440, 446, 509 Alkaline Phosphatase, 167, 430 Alkaloid, 430, 435, 445 Alkylate, 32, 430 Alkylation, 32, 430 Alleles, 74, 430, 467 Alpha Particles, 430, 497 Alternative medicine, 258, 388, 430 Alveolar Bone Loss, 9, 20, 430 Alveolar Process, 9, 430, 500 Ameliorated, 326, 430 Amenorrhea, 19, 168, 239, 259, 283, 313, 430, 484, 492 Amino acid, 334, 430, 431, 432, 434, 440, 453, 458, 464, 468, 472, 473, 483, 486, 489, 495, 496, 501, 503, 507, 510, 512, 513, 514 Amino Acid Sequence, 430, 431, 432, 503 Amlodipine, 178, 430 Amphetamines, 430, 445 Amygdala, 85, 431, 436, 474, 509 Amyloid, 25, 64, 89, 431 Amyloidosis, 250, 431 Anal, 51, 84, 108, 118, 141, 163, 174, 300, 431, 457, 460, 475 Analog, 431, 473, 512 Analogous, 97, 431, 511 Analytes, 404, 431 Anaphylatoxins, 431, 446 Anaplasia, 431 Anatomical, 431, 435, 443, 447, 452, 455, 470, 502 Androgen-Binding Protein, 431, 503 Androgenic, 110, 431, 454, 484 Androgens, 23, 130, 153, 197, 219, 227, 232, 239, 247, 312, 428, 431, 434, 449 Androstenedione, 14, 288, 431 Anecdotal report, 131, 315, 431

518 Menopause

Anemia, 285, 344, 365, 399, 431, 461 Anesthetics, 431, 457 Aneuploidy, 39, 432 Aneurysm, 432, 514 Angina, 283, 322, 430, 432, 484 Angina Pectoris, 322, 430, 432 Angiogenesis, 61, 117, 136, 432, 477 Angiotensinogen, 67, 432, 500 Animal model, 59, 61, 89, 103, 116, 135, 215, 432 Annealing, 432, 492 Anomalies, 39, 432 Anovulation, 117, 189, 432, 492 Antagonism, 432, 440 Anterior Hypothalamic Nucleus, 84, 432 Anthropometry, 83, 432 Antibacterial, 432, 485, 505 Antibiotic, 432, 439, 458, 489, 505, 509 Antibodies, 55, 145, 432, 435, 465, 466, 468, 469, 470, 476, 491 Antibody, 429, 432, 433, 446, 465, 467, 469, 470, 477, 481, 497, 498, 505 Anticoagulant, 433, 496 Anticonvulsant, 54, 433 Antidepressant, 106, 433 Antigen, 95, 134, 429, 432, 433, 446, 451, 467, 468, 469, 470, 477, 497 Antigen-Antibody Complex, 433, 446 Antigen-presenting cell, 433, 451 Antihypertensive, 58, 110, 184, 433, 479, 483 Anti-inflammatory, 433, 435, 442, 449, 463, 494 Anti-Inflammatory Agents, 433, 435, 442, 449 Antineoplastic, 433, 449, 462 Antioxidant, 164, 260, 332, 344, 433, 487 Antiseptic, 433, 441 Antithrombotic, 433, 495 Antiviral, 70, 433 Anus, 431, 433, 435, 439, 446, 499 Anxiety, 89, 154, 283, 300, 338, 341, 355, 421, 433, 487 Aorta, 111, 433, 479, 514 Apnea, 87, 433 Apolipoproteins, 190, 433, 474 Apoptosis, 61, 64, 80, 85, 99, 103, 115, 129, 134, 154, 217, 433, 441 Appendicular skeleton, 182, 434 Approximate, 26, 34, 102, 434 Aptitude, 434, 496 Aqueous, 114, 434, 436, 450, 473

Arachidonic Acid, 434, 495 Archaea, 434, 480 Arginine, 431, 434, 483 Arnica, 272, 434 Aromatase, 410, 434 Arterial, 16, 27, 132, 261, 434, 441, 443, 448, 468, 484, 496, 508 Arteries, 111, 209, 433, 434, 438, 439, 441, 443, 448, 476, 479, 482, 497 Arteriolar, 27, 434, 439, 500 Arterioles, 434, 438, 440, 514 Arteriolosclerosis, 434 Arteriosclerosis, 170, 190, 210, 226, 283, 322, 343, 434, 468 Arthralgia, 331, 343, 434 Articular, 435, 486 Aseptic, 315, 435, 486, 506 Aspirate, 133, 308, 435 Aspirin, 29, 435 Assay, 32, 58, 63, 68, 105, 130, 136, 141, 163, 435, 446, 497 Astringent, 435, 441, 507 Asymptomatic, 19, 122, 139, 142, 143, 435 Ataxia, 399, 435, 509 ATP, 435, 453, 462, 472, 476, 490, 496 Atresia, 26, 54, 103, 435, 448 Atrial, 131, 435, 448 Atrium, 435, 448, 514 Atrophy, 17, 28, 51, 249, 340, 399, 435 Atropine, 155, 435, 436 Attenuation, 26, 435 Autoantibodies, 90, 219, 435 Autoantigens, 435 Autoimmune disease, 55, 435 Autoimmunity, 219, 435 Autonomic, 131, 262, 335, 427, 435, 436, 484, 489, 505, 508 Autonomic Nervous System, 335, 435, 436, 489, 505, 508 Autopsy, 39, 436 Axillary, 436, 439, 480 Axillary Artery, 436, 439 Axonal, 103, 436 B Bacterial Physiology, 428, 436 Bacteriophage, 436, 491, 511 Bacteriostatic, 436, 458 Bacterium, 436, 446 Bacteriuria, 7, 8, 176, 436 Basal Ganglia, 435, 436, 462, 469, 474 Basal Ganglia Diseases, 435, 436, 469

Index 519

Base, 12, 93, 104, 105, 258, 436, 451, 459, 472, 509 Basement Membrane, 436, 459 Basophils, 436, 465, 473 Behavior Therapy, 113, 436 Belladonna, 435, 436 Benign, 78, 434, 437, 460, 462, 465, 473, 482, 483, 496, 498, 515 Benzene, 35, 437, 472 Beta-pleated, 431, 437 Bilateral, 51, 101, 275, 339, 437, 492 Bile, 55, 437, 461, 472, 475, 502, 506 Bile Acids, 437, 506 Bile Acids and Salts, 437 Bile duct, 55, 437, 461 Bile Pigments, 437, 472 Biliary, 55, 331, 332, 345, 437 Bilirubin, 429, 437, 461, 468 Bioassay, 34, 63, 437 Bioavailability, 34, 437 Biochemical, 34, 157, 175, 430, 437, 486, 490, 503 Biological Markers, 49, 437 Biological therapy, 437, 465 Biomarkers, 24, 134, 147, 205, 320, 437 Biopsy, 26, 97, 310, 315, 321, 423, 437 Biotechnology, 144, 146, 376, 388, 395, 398, 399, 400, 437 Bladder, 136, 243, 252, 312, 405, 408, 438, 447, 470, 495, 500, 507, 512, 513, 515 Blastocyst, 438, 447, 491 Blepharospasm, 208, 438 Bloating, 341, 421, 438 Blood Coagulation, 438, 440, 510 Blood Glucose, 5, 28, 75, 438, 466, 468, 469, 471 Blood Platelets, 438, 503 Blot, 81, 438 Body Burden, 67, 438 Body Composition, 49, 65, 75, 88, 91, 109, 198, 210, 265, 282, 438 Body Fluids, 437, 438, 454, 460, 485, 504, 512 Body Image, 7, 438 Bolus, 101, 438 Bolus infusion, 438 Bone Development, 9, 438 Bone Marrow, 65, 437, 438, 462, 469, 476, 481, 505, 506, 507 Bone Remodeling, 128, 171, 439 Bone Resorption, 9, 49, 129, 174, 261, 439 Bone scan, 439, 501

Bowel, 431, 439, 448, 452, 472, 506 Bowel Movement, 439, 448, 452, 506 Brachial, 58, 132, 318, 439 Brachial Artery, 58, 318, 439 Brachytherapy, 439, 471, 497 Bradykinin, 439, 484, 491 Branch, 419, 439, 455, 462, 488, 497, 505, 508 Breakdown, 439, 442, 452, 462 Broad Ligament, 439, 459 Broad-spectrum, 439, 485 Bronchi, 439, 457, 511 Buccal, 87, 262, 308, 439, 476 Buccal mucosa, 262, 308, 439 Burning Mouth Syndrome, 9, 439 Burns, 389, 439, 440 Burns, Electric, 440 C Caffeine, 36, 289, 440 Calcaneus, 75, 189, 237, 440, 508 Calcification, 52, 111, 170, 226, 434, 440 Calcitonin, 165, 197, 342, 408, 440 Calcitonin Gene-Related Peptide, 342, 440 Calcium channel blocker, 430, 440, 483 Calcium Channel Blockers, 440, 483 Calcium Metabolism Disorders, 336, 440 Capillary, 116, 439, 440, 463, 475, 477, 493, 514 Captopril, 27, 441 Carbohydrate, 12, 46, 69, 336, 441, 449, 463, 464, 493 Carcinogen, 74, 441, 458 Carcinogenesis, 32, 39, 79, 132, 441 Carcinogenic, 33, 132, 437, 441, 471, 495, 506, 513 Carcinogenicity, 333, 441 Carcinoma, 17, 136, 165, 321, 441 Cardiac, 31, 57, 162, 177, 331, 343, 440, 441, 448, 457, 459, 482, 487, 506 Cardiac Output, 31, 441 Cardiology, 22, 58, 164, 170, 262, 441 Cardiorespiratory, 428, 441 Cardiovascular System, 57, 119, 133, 333, 441 Carnitine, 330, 332, 344, 345, 441 Carotenoids, 83, 289, 441 Carotid Arteries, 111, 441 Carrier Proteins, 441, 491, 498 Case report, 152, 220, 222, 255, 441, 445 Caspase, 85, 441 Castration, 45, 441 Catechol, 32, 441

520 Menopause

Catecholamine, 69, 442, 453, 490 Caudal, 442, 452, 469, 493 Causal, 83, 122, 442, 457, 466, 472 Cause of Death, 28, 67, 71, 132, 343, 442 Celecoxib, 309, 442 Cell Adhesion, 261, 442 Cell Aggregation, 442, 486 Cell Death, 64, 101, 433, 442 Cell Differentiation, 442, 504 Cell Division, 399, 436, 442, 465, 478, 480, 491, 495, 502 Cell membrane, 440, 441, 442, 451, 462, 472, 490 Cell proliferation, 61, 99, 339, 434, 442, 504 Cell Respiration, 442, 480, 500 Cell Size, 116, 442 Cell Survival, 134, 442, 465 Cell Transplantation, 315, 442 Cellular metabolism, 332, 345, 442 Cellulose, 442, 491 Central Nervous System Infections, 443, 465 Cerebellar, 435, 443, 499, 512 Cerebral, 23, 27, 57, 162, 435, 436, 443, 448, 457, 459, 488, 496, 509 Cerebral Arteries, 57, 443 Cerebral Cortex, 435, 443, 459 Cerebrovascular, 23, 243, 322, 436, 440, 441, 443, 509 Cerebrum, 443, 491, 512 Cervical, 19, 38, 70, 182, 250, 443 Cervix, 95, 427, 443, 500, 513 Cesarean Section, 108, 443 Character, 432, 443, 450 Chemotactic Factors, 443, 446 Chin, 182, 229, 443, 479 Cholesterol Esters, 443, 474 Cholinergic, 25, 41, 61, 443 Cholinergic Antagonists, 62, 443 Chondrocytes, 443, 460 Chorioallantoic membrane, 102, 443 Chromaffin System, 444, 456 Chromatin, 38, 433, 444, 457, 483 Chromosomal, 39, 222, 432, 444, 509 Chromosome, 39, 432, 444, 465, 474, 481, 502, 509, 512 Chromosome Aberrations, 444 Chromosome Painting, 39, 444 Chronic Disease, 7, 47, 130, 444 Chronic renal, 444, 492 Chylomicrons, 444, 474, 475 Circadian, 66, 124, 444

Circadian Rhythm, 124, 444 Circulatory system, 444, 456 Cirrhosis, 55, 444 CIS, 60, 444 Clamp, 58, 65, 69, 95, 205, 321, 444 Clinical Medicine, 144, 444, 494 Clinical Protocols, 42, 444 Clinical study, 444, 448 Clone, 55, 445 Clonic, 438, 445 Cloning, 438, 445 Coagulation, 28, 438, 445, 466, 491 Coal, 437, 445 Coca, 445 Cocaine, 99, 445 Cofactor, 445, 496, 510 Cognition, 4, 42, 93, 113, 206, 311, 341, 445 Cognitive restructuring, 445, 507 Cohort Studies, 126, 445, 457 Collagen, 60, 73, 94, 163, 165, 167, 180, 206, 246, 430, 436, 445, 459, 460, 477, 492, 495 Collapse, 439, 446, 504 Colon, 399, 446, 473 Colorectal, 151, 278, 284, 446 Colorectal Cancer, 151, 278, 284, 446 Combination Therapy, 78, 335, 446, 458 Comet Assay, 32, 446 Competency, 44, 446 Complement, 258, 265, 431, 446, 491 Complementary and alternative medicine, 271, 272, 297, 446 Complementary medicine, 272, 281, 446 Complete remission, 447, 500 Compliance, 14, 23, 46, 58, 68, 89, 194, 308, 447 Computational Biology, 395, 398, 447 Computed tomography, 109, 175, 259, 438, 447, 501 Computerized tomography, 49, 52, 447 Concentric, 30, 434, 447 Concept Formation, 4, 447 Conception, 54, 67, 413, 427, 447, 448, 460, 506 Concomitant, 89, 95, 110, 447 Conduction, 183, 447 Confidence Intervals, 35, 447 Confounding, 16, 41, 42, 47, 78, 88, 91, 447 Congestive heart failure, 324, 343, 447 Conjugated, 11, 16, 135, 260, 261, 280, 437, 447, 450

Index 521

Connective Tissue, 94, 219, 220, 439, 445, 447, 452, 460, 461, 476, 479, 501, 508 Connective Tissue Cells, 447 Consciousness, 447, 451, 453, 496 Constipation, 331, 343, 447 Constriction, 447, 472, 514 Constriction, Pathologic, 447, 514 Consultation, 70, 447 Consumption, 13, 14, 27, 37, 81, 215, 447, 500 Continence, 118, 136, 448 Continuum, 100, 448 Contraception, 42, 169, 202, 250, 346, 375, 382, 448, 473, 484 Contraindications, ii, 6, 17, 85, 376, 448 Contrast medium, 448 Control group, 36, 40, 49, 54, 66, 100, 113, 122, 138, 448, 491, 494, 498 Controlled clinical trial, 100, 138, 448, 498 Controlled study, 57, 158, 176, 183, 275, 280, 448 Convulsions, 433, 448, 455 Coordination, 70, 448, 496 Cor, 448 Corneum, 234, 448, 457 Coronary Angiography, 202, 448 Coronary Thrombosis, 449, 479, 482 Corpus, 449, 476, 489, 491, 495, 509, 515 Corpus Luteum, 449, 476, 495 Corpuscle, 449, 458 Cortex, 27, 64, 102, 449, 457, 499 Cortical, 56, 102, 104, 175, 449, 459, 502, 509 Corticosteroid, 54, 449, 494 Cortisol, 37, 87, 121, 130, 326, 429, 449 Cortisone, 449, 494 Cranial, 449, 459, 465, 482, 489 Craniocerebral Trauma, 436, 449, 465, 509 Creatinine, 14, 449 Criterion, 96, 127, 449 Critical Care, 144, 171, 182, 204, 211, 449 Crossing-over, 449, 499 Cross-Sectional Studies, 449, 457 Crowns, 449, 451 Cutaneous, 450, 476 Cyclic, 114, 261, 335, 338, 440, 450, 465, 484 Cyclin, 24, 450 Cyst, 435, 450 Cytochrome, 70, 72, 105, 118, 434, 450 Cytokine, 49, 95, 145, 164, 450

Cytoplasm, 433, 436, 442, 450, 457, 465, 481, 483, 501, 508 Cytoskeleton, 56, 450 Cytotoxic, 99, 450, 498, 504 D Data Collection, 131, 140, 450, 461 Decarboxylation, 450, 479 Decision Making, 43, 450 Decompression, 450, 476 Defecation, 51, 450 Degenerative, 25, 84, 332, 345, 450, 467, 477, 486 Dehydroepiandrosterone, 14, 121, 148, 172, 194, 260, 280, 290, 291, 450 Deletion, 433, 450 Delivery of Health Care, 450, 465 Dementia, 4, 10, 11, 27, 53, 152, 180, 284, 286, 387, 451 Demography, 31, 332, 451 Denaturation, 451, 492 Dendrites, 451, 483 Dendritic, 59, 70, 96, 116, 127, 451, 478 Dendritic cell, 70, 96, 451 Dental Abutments, 451 Dental Caries, 8, 451, 460 Dental Hygienists, 8, 9, 172, 451 Dental implant, 8, 451, 486 Dentate Gyrus, 451, 467 Dentists, 8, 19, 451 Dentures, 20, 451 Depolarization, 451, 504 Depressive Disorder, 106, 167, 313, 451 Deprivation, 8, 57, 94, 241, 451 Dermis, 452, 511 Deuterium, 109, 452, 468 Diabetes Insipidus, 413, 452 Diabetes Mellitus, 16, 84, 229, 284, 322, 326, 452, 463, 466 Diagnostic Errors, 452, 478 Diagnostic procedure, 329, 388, 452 Dialyzer, 452, 466 Diaphoresis, 334, 452 Diarrhea, 51, 331, 343, 452 Diastolic, 452, 468 Diencephalon, 452, 469, 509 Diestrus, 63, 452 Dietary Fats, 452, 474 Dietary Fiber, 138, 452 Digestion, 430, 437, 439, 452, 472, 474, 475, 506 Digestive system, 328, 452 Digestive tract, 452, 504

522 Menopause

Dihydrotachysterol, 336, 452 Dihydrotestosterone, 452, 499, 503 Dihydroxy, 336, 429, 452 Dilatation, 58, 228, 427, 432, 452, 494, 514 Dilatation, Pathologic, 452, 514 Dilate, 318, 452 Dilation, 439, 452, 514 Dilator, 453, 484 Dilution, 109, 453 Dimerization, 56, 453 Dimethyl, 453, 483 Diploid, 432, 453, 481, 491, 512 Direct, iii, 48, 51, 61, 68, 87, 94, 106, 108, 109, 311, 344, 444, 453, 481, 499, 508 Discrete, 439, 453, 475 Discrimination, 214, 453 Disease Progression, 38, 453 Dissociation, 429, 453 Distal, 20, 66, 86, 218, 436, 453, 494, 496 Diuresis, 440, 453 Diurnal, 37, 453 Dizziness, 331, 334, 341, 343, 347, 453, 514 DNA Topoisomerase, 453, 462 Domesticated, 135, 453 Dopamine, 311, 445, 453, 483 Dorsal, 454, 482, 493 Dose-dependent, 91, 454 Double-blind, 11, 14, 29, 77, 100, 158, 176, 183, 193, 195, 264, 280, 323, 454 Double-blinded, 77, 323, 454 Drinking Behavior, 454, 507 Drive, ii, vi, 17, 257, 259, 454, 472, 473 Drug Industry, 253, 454 Drug Interactions, 408, 454 Drug Tolerance, 454, 510 Duct, 454, 501 Duodenum, 437, 454, 502, 506 Dydrogesterone, 263, 454 Dyes, 431, 436, 454, 483 Dyslipidemia, 15, 96, 109, 121, 454 Dyspareunia, 422, 454, 458 Dysphoric, 451, 454 Dysplasia, 399, 454 Dystrophy, 399, 454 E Echocardiography, 37, 58, 454 Eclampsia, 387, 455 Ectoderm, 455, 482 Ectopic, 121, 455 Edema, 455, 485 Effector, 427, 446, 455, 483 Efferent, 99, 431, 455, 459

Elastic, 104, 455, 505 Elasticity, 434, 455 Elastin, 94, 445, 455, 459 Elective, 108, 455 Electrocardiogram, 318, 455 Electrocoagulation, 445, 455 Electrolyte, 429, 449, 455, 460, 480, 485, 493, 505 Electromyography, 69, 455 Electrophoresis, 446, 455 Electrophysiological, 103, 455 Electroplating, 441, 455 Embryo, 427, 438, 442, 455, 463, 470, 485, 486 Empirical, 127, 455 Enamel, 451, 455, 460 Encapsulated, 455, 475 Endemic, 182, 455, 506 Endocrine Glands, 455, 456, 488 Endocrine System, 137, 456, 483 Endometriosis, 42, 67, 99, 272, 364, 376, 456, 473, 484, 512 Endometrium, 32, 70, 78, 99, 105, 106, 117, 195, 311, 319, 326, 377, 456, 479 Endopeptidases, 456, 496 Endorphins, 456, 483 Endothelial cell, 63, 119, 132, 456, 460, 510 Endothelium, 62, 119, 132, 456, 483, 492 Endothelium, Lymphatic, 456 Endothelium, Vascular, 456 Endothelium-derived, 456, 483 Endotoxic, 456, 474 Endotoxin, 456, 512 End-stage renal, 444, 456, 492 Energy balance, 91, 138, 456, 473 Energy Intake, 16, 21, 49, 456, 457 Enhancers, 132, 457 Enkephalins, 457, 483 Enterocytes, 37, 457 Entorhinal Cortex, 85, 457, 467 Environmental Exposure, 437, 457, 485 Environmental Health, 229, 394, 396, 457 Enzymatic, 164, 430, 440, 446, 451, 457, 458, 478, 493 Enzyme Inhibitors, 457, 491 Eosinophils, 457, 465, 473 Epidemic, 76, 457, 506 Epidemiologic Studies, 48, 437, 457 Epidemiological, 13, 32, 64, 73, 155, 208, 225, 332, 339, 457, 500 Epidermis, 448, 452, 457

Index 523

Epinephrine, 48, 428, 453, 457, 483, 484, 513 Epithelial, 33, 56, 80, 95, 151, 160, 182, 250, 337, 424, 428, 457, 464, 467, 487, 495 Epithelial Cells, 56, 80, 96, 337, 457, 467, 495 Epithelial ovarian cancer, 151, 160, 457 Epithelium, 48, 104, 436, 456, 457, 487 Erythrocyte Membrane, 332, 345, 458 Erythrocytes, 332, 345, 431, 439, 458, 466, 499 Erythromycin, 136, 458 Esophagus, 435, 452, 458, 506 Essential Tremor, 399, 458 Esterification, 221, 427, 458 Estriol, 17, 344, 458 Estrogen Antagonists, 61, 458 Estrogen receptor, 24, 32, 60, 61, 72, 73, 87, 103, 112, 113, 115, 132, 134, 185, 319, 458 Estrogen receptor positive, 112, 458 Estrone, 11, 87, 141, 263, 340, 344, 458 Ethinyl Estradiol, 97, 114, 336, 458 Eukaryotic Cells, 458, 470 Evacuation, 447, 458 Evoke, 459, 506 Excipients, 346, 459 Excitability, 102, 347, 459, 482 Excitation, 430, 459, 483 Excitatory, 25, 103, 459, 464 Exemestane, 316, 317, 318, 319, 459 Exogenous, 27, 38, 66, 69, 72, 85, 101, 109, 117, 441, 456, 459, 496, 513 External-beam radiation, 459, 497 Extracellular, 60, 94, 431, 447, 459, 460, 477, 486, 504, 509 Extracellular Matrix, 60, 94, 447, 459, 460, 477, 486 Extracellular Matrix Proteins, 459, 477 Extracellular Space, 459 Extrapyramidal, 453, 459 Eye Infections, 428, 459 F Facial, 459, 488, 505, 514 Facial Nerve, 459, 488 Fallopian tube, 95, 344, 459, 500, 512 Family Planning, 185, 395, 459 Fatigue, 36, 117, 315, 318, 331, 333, 335, 340, 341, 343, 355, 357, 365, 460, 466, 481 Fatty acids, 16, 29, 49, 212, 332, 345, 429, 460, 464, 495 Fecal Incontinence, 51, 460, 470 Feces, 447, 460, 506

Femoral, 18, 20, 60, 132, 312, 460, 467 Femoral Neck Fractures, 460, 467 Femur, 18, 20, 104, 137, 460, 467 Fetus, 26, 427, 438, 443, 460, 461, 491, 513 Fibrinogen, 15, 28, 460, 491, 492, 509 Fibroblast Growth Factor, 187, 460 Fibroblasts, 447, 460, 471 Fibroid, 77, 460, 473 Fibrosis, 144, 399, 460, 502 Flatus, 460, 462 Fluid Therapy, 460, 484 Fluorescence, 68, 460 Fluorine, 460 Fluoroscopy, 52, 460 Fluorosis, 182, 460 Flush, 107, 125, 460 Flushing, 5, 333, 334, 422, 461 Focus Groups, 89, 461 Foetoplacental, 461, 485 Folate, 83, 268, 461 Fold, 15, 439, 461, 479 Folic Acid, 461 Follicles, 26, 54, 80, 101, 102, 103, 104, 115, 337, 452, 461, 471 Follicular Phase, 64, 81, 101, 117, 461 Foramen, 443, 461, 489, 507 Forearm, 59, 112, 149, 438, 461, 498 Fractionation, 34, 461 Frail Elderly, 100, 461 Free Radicals, 152, 433, 453, 461 Functional magnetic resonance imaging, 11, 461 Fungi, 459, 461, 479, 480, 516 G Gallbladder, 197, 258, 377, 427, 437, 452, 461 Gallstones, 17, 197, 258, 437, 461 Gamma Rays, 461, 497, 498 Ganglia, 427, 436, 461, 482, 489, 508 Ganglion, 462, 482 Gap Junctions, 462 Gas, 460, 462, 468, 483, 484, 507, 514 Gasoline, 437, 462 Gastric, 441, 462 Gastrin, 462, 467 Gastrointestinal, 439, 457, 460, 462, 473, 503, 505, 507, 512 Gastrointestinal tract, 460, 462, 473, 503, 512 Gene Expression, 26, 37, 57, 63, 64, 70, 75, 101, 115, 400, 462 Gene Therapy, 428, 462

524 Menopause

General practitioner, 8, 156, 462 Generator, 80, 104, 462 Genetic Markers, 42, 72, 462 Genetic testing, 462, 493 Genetics, 22, 24, 35, 71, 74, 81, 120, 176, 189, 191, 248, 462 Genistein, 82, 106, 330, 337, 462 Genital, 17, 56, 70, 96, 463, 465, 472, 513 Genitourinary, 378, 463, 513 Genotype, 4, 36, 67, 91, 463, 490 Germ Cells, 39, 115, 463, 478, 485, 487, 505, 509 Germ Layers, 438, 455, 463 Gestational, 165, 463 Gingivitis, 8, 463 Ginseng, 289, 294, 295, 463 Glomerular, 60, 463, 483 Glomerular Filtration Rate, 463, 483 Glomeruli, 60, 463 Glomerulosclerosis, 60, 231, 463 Glomerulus, 463 Glucocorticoid, 463, 494 Gluconeogenesis, 463 Glucose Intolerance, 452, 463 Glucose tolerance, 13, 15, 91, 95, 109, 229, 241, 463 Glucose Tolerance Test, 15, 91, 109, 463, 464 Glutamate, 64, 464 Glutamic Acid, 461, 464, 483, 495 Glycerol, 464, 490 Glycerophospholipids, 464, 490 Glycine, 430, 437, 464, 483, 503 Glycogen, 321, 464, 481 Glycoprotein, 70, 105, 460, 464, 503, 510, 512 Glycoside, 464, 501 Goblet Cells, 457, 464 Gonad, 464 Gonadal, 62, 70, 240, 464, 506 Gonadorelin, 464, 473, 512 Gonadotropic, 40, 464 Gonadotropin, 25, 42, 47, 63, 80, 89, 101, 464, 473 Goserelin, 261, 324, 464 Governing Board, 464, 493 Government Agencies, 76, 464, 493 Graft, 464, 467 Grafting, 102, 464, 470 Gram-negative, 456, 465, 485 Gram-positive, 465, 485 Granulocytes, 465, 482, 504, 515

Granulosa Cells, 101, 115, 465, 471, 476 Gravidity, 465, 488 Growth factors, 46, 95, 136, 465 Guanylate Cyclase, 465, 484 H Haemodialysis, 332, 345, 465 Haploid, 465, 491 Haptens, 429, 465, 497 Headache, 105, 191, 214, 286, 318, 340, 422, 440, 465, 494 Headache Disorders, 465 Health Behavior, 28, 45, 93, 465 Health Care Costs, 36, 87, 465, 466 Health Education, 152, 224, 466 Health Expenditures, 465, 466 Health Policy, 29, 76, 466 Health Promotion, 77, 140, 259, 263, 379, 466 Health Services, 46, 98, 126, 243, 309, 451, 466 Health Status, 31, 44, 49, 75, 126, 165, 318, 465, 466 Heart attack, 155, 441, 466 Heart failure, 466, 485 Hematology, 307, 466 Heme, 437, 450, 466 Hemodialysis, 332, 345, 452, 466 Hemodynamics, 60, 164, 210, 466 Hemoglobin, 15, 16, 75, 119, 431, 458, 466, 472, 473 Hemoglobin A, 75, 119, 466 Hemoglobinuria, 399, 466 Hemolysis, 332, 345, 458, 466 Hemorrhage, 449, 455, 465, 466, 476, 507 Hemostasis, 181, 466, 503 Hepatic, 74, 93, 109, 261, 331, 332, 345, 429, 463, 467, 493 Hepatitis, 38, 99, 467 Hepatocellular, 150, 467 Hepatocellular carcinoma, 150, 467 Hepatocytes, 332, 345, 467 Hereditary, 467, 501 Heredity, 462, 467 Heterogeneity, 71, 111, 132, 332, 345, 429, 467 Heterozygotes, 91, 467 Hip Fractures, 15, 137, 340, 460, 467 Hippocampus, 25, 58, 64, 85, 127, 451, 467, 474, 507 Homeostasis, 72, 304, 336, 439, 467, 505 Homodimer, 467, 511

Index 525

Homogeneous, 91, 139, 142, 143, 434, 448, 467 Homologous, 430, 449, 462, 467, 502, 508 Hormonal therapy, 17, 193, 241, 248, 249, 467 Host, 25, 38, 70, 122, 123, 436, 467, 469, 515 Human papillomavirus, 38, 468 Hybrid, 113, 445, 468 Hybridization, 444, 468 Hybridomas, 468, 471 Hydrogen, 427, 436, 441, 451, 452, 459, 468, 481, 483, 487, 490, 496 Hydrolysis, 74, 468, 472, 474, 489, 490, 496 Hydrophobic, 132, 464, 468, 474 Hydroxylysine, 445, 468 Hydroxyproline, 430, 445, 468 Hyperbilirubinemia, 468, 472 Hypercholesterolemia, 117, 285, 326, 343, 454, 468 Hyperglycemia, 48, 468 Hyperlipidemia, 19, 343, 454, 468 Hyperplasia, 136, 200, 219, 325, 413, 468 Hypersensitivity, 468, 501 Hypertriglyceridemia, 332, 345, 454, 468 Hypertrophy, 27, 30, 115, 448, 468 Hypnotic, 106, 124, 468 Hypoglycemia, 5, 6, 468 Hypoglycemic, 14, 468, 469 Hypoglycemic Agents, 14, 469 Hypogonadism, 45, 313, 469 Hypokinesia, 469, 488 Hypophyseal, 469, 477 Hypothalamic, 14, 25, 57, 63, 80, 84, 110, 115, 117, 121, 124, 424, 469 Hypothalamus, 116, 432, 435, 452, 464, 469, 474, 477, 491, 507, 509, 512 Hypothyroidism, 59, 233, 413, 469 Hysterectomy, 22, 61, 75, 95, 101, 190, 197, 255, 263, 279, 326, 365, 424, 469 Hysterotomy, 443, 469 I Id, 117, 266, 282, 341, 405, 406, 409, 410, 411, 412, 418, 420, 469 Idiopathic, 51, 241, 469 Ileum, 469, 515 Illusion, 469, 514 Immune function, 95, 469, 511 Immune response, 48, 61, 71, 428, 433, 435, 449, 465, 469, 470, 507, 515 Immune Sera, 469 Immune system, 37, 55, 95, 99, 313, 413, 433, 435, 437, 469, 470, 476, 490, 513, 515

Immunity, 99, 469, 470, 485, 511 Immunization, 99, 469, 494 Immunodeficiency, 48, 399, 469 Immunofluorescence, 81, 145, 469 Immunogenic, 470, 474, 497 Immunoglobulins, 470, 491 Immunohistochemistry, 63, 470 Immunologic, 38, 241, 443, 469, 470, 498 Immunology, 29, 163, 219, 229, 241, 428, 429, 470 Impairment, 25, 27, 62, 124, 435, 459, 470, 479 Implant radiation, 470, 471, 497 Implantation, 447, 470, 485 Impregnation, 127, 470 In situ, 39, 64, 99, 112, 117, 127, 313, 321, 470 In Situ Hybridization, 39, 64, 127, 470 In vitro, 34, 39, 60, 75, 80, 101, 115, 129, 136, 189, 332, 345, 442, 462, 470, 492, 510, 512 In vivo, 25, 33, 40, 41, 48, 60, 64, 70, 80, 85, 97, 132, 321, 332, 339, 345, 462, 470, 487 Incision, 469, 470, 472 Incontinence, 7, 17, 51, 68, 94, 108, 118, 136, 200, 249, 272, 333, 379, 422, 470, 507 Incubated, 134, 470 Incubation, 52, 470 Indicative, 30, 39, 53, 350, 470, 488, 514 Induction, 431, 470, 495, 514 Infant, Newborn, 429, 470 Infarction, 286, 322, 324, 325, 470 Infertility, 26, 42, 54, 61, 67, 102, 110, 115, 126, 177, 198, 219, 241, 284, 313, 315, 324, 404, 471 Infusion, 117, 471 Ingestion, 337, 460, 463, 471, 479, 492, 509 Inhibin, 26, 50, 54, 80, 101, 117, 141, 234, 471 Initiation, 47, 130, 309, 374, 471, 511 Inotropic, 155, 453, 471 Insecticides, 471, 516 Insight, 23, 26, 32, 63, 64, 73, 80, 85, 96, 101, 115, 128, 471 Insomnia, 87, 122, 123, 124, 275, 285, 330, 331, 333, 335, 340, 343, 422, 471, 494 Institutionalization, 51, 471 Insulin-dependent diabetes mellitus, 471 Insulin-like, 109, 167, 179, 471 Interindividual, 75, 471 Interleukin-6, 135, 234, 471

526 Menopause

Internal Medicine, 42, 55, 59, 109, 110, 137, 151, 198, 222, 228, 236, 261, 262, 456, 466, 471 Internal radiation, 471, 497 Intervention Studies, 84, 107, 472 Intestinal, 37, 105, 331, 332, 336, 344, 345, 457, 463, 472, 477, 487 Intestine, 70, 105, 437, 439, 446, 472, 473 Intoxication, 472, 515 Intracellular, 63, 321, 440, 470, 472, 478, 484, 493, 499, 504 Intrahepatic, 121, 472 Intraindividual, 182, 472 Intramuscular, 12, 472, 488 Intravenous, 48, 69, 109, 471, 472, 488 Intrinsic, 79, 429, 436, 472 Invasive, 319, 469, 472, 477 Involuntary, 436, 458, 460, 472, 482, 504, 505, 506 Involution, 240, 472 Ion Transport, 63, 472, 480 Ions, 427, 436, 453, 455, 468, 472 Ischemia, 117, 432, 435, 472 Isoflavones, 14, 33, 106, 124, 125, 135, 178, 280, 293, 295, 411, 472 Isoleucine, 334, 472 J Jaundice, 336, 468, 472 Joint, 105, 318, 340, 347, 434, 435, 472, 486, 508 K Kb, 394, 472 Keratolytic, 451, 473 Kidney Disease, 60, 199, 271, 328, 394, 399, 473 Kidney stone, 208, 473 Kinetics, 65, 69, 473 L Labile, 446, 473 Lactation, 272, 473, 485, 495 Large Intestine, 446, 452, 472, 473, 499, 504 Latency, 78, 473 Latent, 473, 494 Least-Squares Analysis, 473, 499 Leiomyoma, 61, 460, 473, 504 Lens, 222, 473 Leptin, 183, 203, 230, 242, 264, 473 Lethal, 71, 473 Lethargy, 422, 469, 473 Leucine, 334, 473 Leukemia, 399, 462, 473

Leukocytes, 96, 436, 439, 443, 457, 465, 473, 481, 483, 512 Leuprolide, 47, 473 Levonorgestrel, 264, 473, 484 Libido, 262, 431, 473 Library Services, 418, 474 Life cycle, 236, 461, 474 Life Expectancy, 110, 474 Ligament, 474, 495 Ligands, 134, 474 Light microscope, 127, 474 Likelihood Functions, 474, 499 Limbic, 431, 474 Limbic System, 431, 474 Linear Models, 474, 499 Linkage, 11, 71, 75, 462, 474 Lipase, 74, 93, 474 Lipid, 15, 16, 22, 36, 58, 69, 91, 106, 107, 109, 120, 124, 132, 139, 144, 179, 181, 182, 203, 212, 230, 239, 258, 260, 263, 319, 332, 336, 345, 433, 434, 464, 471, 474, 475, 512 Lipid A, 15, 58, 91, 109, 239, 332, 336, 345, 474 Lipolysis, 48, 65, 95, 474 Lipopolysaccharides, 474 Lipoprotein Lipase, 90, 475 Lipoprotein(a), 185, 475 Liposomal, 132, 475 Liposomes, 183, 475 Litter, 68, 475 Litter Size, 68, 475 Liver scan, 475, 501 Lobe, 475 Lobule, 11, 475 Local therapy, 42, 475 Localization, 63, 81, 101, 470, 475 Localized, 40, 431, 451, 455, 470, 475, 485, 491 Locomotion, 475, 491 Logistic Models, 475, 499 Longitudinal Studies, 19, 30, 97, 237, 449, 475 Longitudinal study, 4, 49, 53, 76, 87, 122, 123, 129, 130, 147, 148, 204, 226, 475 Long-Term Potentiation, 102, 476 Loop, 234, 476 Low-calorie diet, 277, 476 Low-density lipoprotein, 58, 109, 125, 179, 236, 260, 454, 474, 475, 476 Lower Body Negative Pressure, 60, 476 Luciferase, 33, 476

Index 527

Lumbar, 18, 20, 53, 60, 100, 104, 165, 476 Lupus, 54, 72, 285, 286, 476, 508 Luteal Phase, 47, 64, 78, 83, 144, 476 Lutein Cells, 476, 495 Lymph, 436, 443, 444, 449, 456, 476 Lymph node, 436, 443, 476 Lymphatic, 331, 344, 456, 471, 476, 479, 485, 492, 505, 506, 510 Lymphocyte, 95, 241, 433, 476, 477 Lymphocyte Count, 241, 476 Lymphoid, 65, 432, 476 Lymphoma, 42, 399, 476 M Macrophage, 132, 476 Macula, 477 Macula Lutea, 477 Macular Degeneration, 332, 345, 477 Magnetic Resonance Imaging, 477, 501 Malabsorption, 399, 477 Malignant, 399, 428, 433, 434, 464, 477, 482, 496, 498 Malnutrition, 429, 435, 477, 481 Malondialdehyde, 176, 477 Mammary, 33, 79, 135, 147, 339, 475, 477, 498, 508, 511 Mammogram, 83, 326, 423, 440, 477, 480 Mammography, 84, 307, 477 Mandible, 9, 19, 430, 443, 477, 500 Manifest, 34, 67, 436, 477 Man-made, 442, 477 Mass Media, 222, 477 Matrix metalloproteinase, 60, 94, 477 Maxillary, 20, 477 Medial, 120, 432, 434, 477, 486, 501 Median Eminence, 116, 477 Mediate, 58, 128, 453, 477 Mediator, 318, 477, 503 Medical castration, 45, 477 Medical Errors, 89, 478 Medical Records, 19, 29, 478, 501 Medical Staff, 454, 478 Medicament, 330, 337, 478 Medication Errors, 478 MEDLINE, 395, 398, 399, 478 Medroxyprogesterone, 16, 207, 260, 261, 263, 293, 478 Medroxyprogesterone Acetate, 261, 263, 478 Meiosis, 39, 478, 508 Melanocytes, 478 Melanoma, 399, 478 Membrane Lipids, 478, 490

Membrane Proteins, 475, 478 Menarche, 6, 10, 11, 35, 55, 67, 72, 74, 79, 150, 195, 199, 208, 301, 355, 365, 373, 478, 500 Meninges, 442, 443, 449, 478 Menorrhagia, 61, 340, 479 Menstrual Cycle, 5, 23, 47, 53, 54, 64, 67, 78, 83, 89, 95, 99, 101, 123, 125, 144, 154, 163, 165, 175, 187, 229, 312, 319, 325, 330, 340, 341, 461, 476, 479, 485, 494, 495 Menstruation, 8, 19, 331, 341, 343, 344, 363, 404, 430, 461, 476, 478, 479, 485, 494, 500 Mental Disorders, 128, 328, 469, 479, 494, 496 Mental Health, iv, 21, 86, 92, 93, 154, 212, 220, 223, 308, 314, 317, 328, 394, 397, 479, 494, 497 Mental Retardation, 74, 400, 479 Mentors, 107, 120, 479 Mesenchymal, 65, 479 Mesenteric, 133, 479 Mesenteric Arteries, 133, 479 Mesentery, 479 Metabolic disorder, 452, 479 Metabolite, 72, 333, 453, 458, 479 Metastasis, 386, 477, 479 Metastatic, 410, 464, 479, 502 Methanol, 341, 479 Methyldopa, 335, 479 MI, 43, 45, 64, 66, 80, 121, 126, 140, 162, 259, 339, 425, 479 Microbe, 479, 511 Microbiology, 8, 64, 99, 428, 436, 480 Microcalcifications, 440, 480 Microorganism, 445, 480, 488, 515 Micro-organism, 55, 451, 480 Microscopy, 59, 436, 480 Microspheres, 132, 480 Midaxillary line, 480, 515 Milligram, 335, 480 Milliliter, 438, 480 Millimeter, 480, 515 Mineralization, 181, 480 Mineralocorticoids, 428, 449, 480 Mitochondria, 345, 480 Mitosis, 433, 480 Mitotic, 78, 480 Mobility, 79, 408, 480 Mobilization, 213, 480 Modeling, 109, 214, 480

528 Menopause

Modification, 52, 75, 77, 83, 103, 138, 430, 480, 497 Modulator, 85, 480 Monitor, 40, 70, 75, 114, 119, 123, 131, 153, 449, 481, 484 Monoclonal, 468, 481, 497 Monocytes, 471, 473, 481, 482 Mononuclear, 105, 145, 481, 512 Monosomy, 432, 481 Morphological, 103, 429, 455, 478, 481 Morphology, 101, 104, 434, 466, 481 Motility, 481, 503 Motion Sickness, 481, 482 Motor Activity, 448, 481, 496 Mucins, 457, 464, 481, 501 Mucosa, 96, 424, 457, 476, 481, 495 Multicenter study, 111, 481 Multiparous, 94, 481 Muscle Contraction, 60, 481 Muscle Fatigue, 69, 481 Muscle Fibers, 481, 482 Muscular Atrophy, 399, 481 Muscular Dystrophies, 454, 482 Myalgia, 331, 343, 482 Myeloid Cells, 65, 99, 482 Myocardial infarction, 62, 90, 208, 324, 325, 449, 479, 482 Myocardium, 432, 479, 482 Myometrium, 61, 154, 187, 262, 482 Myosin, 56, 481, 482 Myotonic Dystrophy, 399, 482 N Nausea, 331, 333, 334, 341, 343, 422, 482, 494 NCI, 1, 309, 310, 314, 315, 316, 317, 319, 321, 323, 324, 325, 327, 393, 444, 482 Neoplasia, 38, 199, 399, 482 Neoplasm, 310, 319, 482, 513 Neoplastic, 431, 468, 476, 482 Nephropathy, 473, 482 Nerve Endings, 342, 482 Nervousness, 105, 330, 331, 335, 340, 343, 347, 482 Neural, 57, 64, 81, 84, 85, 136, 428, 431, 440, 482 Neural Crest, 81, 482 Neuroeffector Junction, 482, 483 Neuroendocrine, 37, 57, 58, 110, 166, 208, 215, 483 Neurofibroma, 81, 483 Neurologic, 59, 483

Neuronal, 25, 27, 57, 60, 84, 102, 115, 127, 134, 483 Neurons, 25, 26, 57, 62, 63, 85, 102, 115, 134, 445, 451, 459, 461, 482, 483, 508 Neuropeptide, 342, 440, 483 Neuropsychological Tests, 74, 483 Neurosecretory Systems, 456, 483 Neurotransmitter, 311, 427, 428, 430, 439, 440, 453, 464, 483, 484, 504, 507 Neutrons, 430, 483, 497 Neutrophils, 465, 473, 483 Nitrendipine, 184, 483 Nitric Oxide, 60, 62, 183, 483 Nitrogen, 430, 431, 459, 484, 512 Nitroglycerin, 318, 484 Norepinephrine, 57, 84, 311, 428, 453, 479, 483, 484 Norethindrone, 97, 148, 184, 484 Norgestrel, 335, 473, 484 Normotensive, 57, 109, 484 Nosocomial, 71, 484 Nuclear, 70, 110, 182, 436, 458, 461, 462, 474, 477, 484 Nuclei, 430, 431, 462, 474, 477, 480, 483, 484, 496 Nucleic acid, 468, 470, 484 Nulliparous, 94, 484 Nurse Practitioners, 4, 184, 205, 271, 484 Nutritional Support, 331, 343, 484 O Observational study, 314, 485 Occupational Exposure, 55, 485 Oculi, 438, 485 Odds Ratio, 10, 11, 14, 35, 485, 499 Oedema, 333, 485, 494 Oestradiol, 169, 485 Oestrogen, 4, 145, 179, 188, 337, 342, 485 Ofloxacin, 145, 485 Oligomenorrhea, 485, 492 Omega-3 fatty acid, 49, 485 Oncogene, 399, 485 Oncology, 24, 85, 147, 149, 158, 198, 205, 207, 214, 232, 321, 324, 485 On-line, 34, 421, 485 Oocytes, 39, 115, 337, 485 Oogenesis, 39, 485 Oophorectomy, 6, 51, 101, 160, 486 Oophoritis, 315, 486 Opacity, 451, 486 Optic Chiasm, 469, 486, 507 Oral Health, 8, 9, 18, 486 Oral Manifestations, 8, 9, 38, 172, 486

Index 529

Orbicularis, 438, 486 Organ Culture, 70, 102, 486, 510 Orthostatic, 476, 486 Osseointegration, 438, 486 Osteoarthritis, 30, 229, 486 Osteoblasts, 65, 129, 486 Osteocalcin, 36, 73, 103, 170, 486 Osteoclasts, 65, 128, 440, 486 Osteogenesis, 438, 486 Ovarian Follicle, 26, 101, 313, 449, 465, 486 Ovariectomy, 25, 27, 28, 48, 63, 94, 119, 135, 136, 275, 339, 486 Overweight, 13, 16, 19, 21, 77, 95, 98, 113, 137, 265, 322, 487 Ovulation, 30, 68, 110, 120, 315, 432, 454, 461, 465, 476, 484, 487, 512 Ovum, 449, 474, 486, 487, 495, 515, 516 Oxidants, 332, 345, 487 Oxidation, 32, 91, 179, 260, 321, 332, 345, 427, 433, 450, 487 Oxidation-Reduction, 487 Oxygenation, 59, 487 P Pacemaker, 487 Palliative, 485, 487 Palpitation, 131, 487 Pancreas, 427, 437, 452, 471, 474, 487, 502, 512 Pancreatic, 69, 399, 441, 487 Pancreatic cancer, 399, 487 Paneth Cells, 457, 487 Panic, 283, 304, 347, 487 Papillomavirus, 487 Paradoxical, 133, 487 Parathyroid, 137, 488, 509 Parathyroid Glands, 488 Parathyroid hormone, 137, 488 Parenteral, 457, 488 Parietal, 11, 488, 492 Parietal Lobe, 488 Parity, 55, 74, 94, 108, 488 Parkinsonism, 51, 255, 488 Parotid, 203, 488 Paroxysmal, 399, 432, 465, 488 Partial remission, 488, 500 Parturition, 120, 488, 495 Patch, 132, 168, 176, 406, 488, 511 Pathogen, 470, 488 Pathogenesis, 48, 49, 70, 87, 136, 488 Pathologic, 17, 106, 433, 437, 448, 468, 488, 500 Pathologic Processes, 433, 488

Pathologies, 104, 488 Pathophysiology, 51, 56, 261, 488 Patient Compliance, 68, 488 Patient Education, 147, 152, 228, 271, 383, 407, 416, 418, 425, 488 Patient Satisfaction, 309, 488 Pelvis, 104, 427, 439, 476, 486, 488, 489, 513 Penicillin, 432, 489, 514 Penis, 489, 500 Pepsin, 489, 502 Peptide, 64, 81, 106, 181, 430, 440, 456, 460, 473, 489, 496, 510 Peptide Fragments, 64, 489 Perceived risk, 248, 489 Perception, 7, 9, 89, 92, 139, 245, 387, 489, 502 Perfusion, 489, 510 Pericardium, 489, 508 Periodontal disease, 19, 20, 430, 489 Periodontitis, 8, 19, 463, 489 Peripheral blood, 105, 489 Peripheral Nervous System, 457, 479, 483, 489, 494, 507 Peripheral Vascular Disease, 343, 489 Peritoneal, 485, 489 Peritoneal Cavity, 485, 489 Perivascular, 440, 490 Perspiration, 335, 452, 490 PH, 20, 151, 177, 217, 238, 438, 490 Phagocyte, 487, 490 Pharmacists, 92, 490 Pharmacodynamics, 105, 490 Pharmacokinetic, 34, 105, 490 Pharmacologic, 4, 14, 38, 91, 100, 106, 490, 510, 511 Pharmacotherapy, 125, 196, 490 Phenotype, 24, 25, 61, 67, 74, 437, 490 Phospholipases, 490, 504 Phospholipids, 74, 332, 345, 460, 474, 478, 490 Phosphorous, 336, 490 Phosphorus, 295, 440, 488, 490 Phosphorylation, 56, 490, 496 Photocoagulation, 445, 490 Physical Examination, 312, 326, 490 Physical Fitness, 378, 490 Physical Therapy, 69, 490 Physiologic, 23, 48, 71, 87, 106, 117, 189, 220, 429, 444, 469, 476, 479, 491, 499, 500, 512 Pilot study, 29, 35, 97, 99, 107, 121, 136, 138, 322, 491

530 Menopause

Pineal Body, 491 Pineal gland, 124, 491 Pituitary Gland, 449, 460, 464, 491, 512 Placebos, 335, 491 Placenta, 434, 458, 461, 491, 495, 513 Plague, 52, 491 Plants, 258, 337, 430, 434, 435, 436, 445, 463, 464, 481, 484, 491, 501, 511, 514 Plaque, 20, 52, 64, 179, 491 Plasma cells, 432, 491 Plasma protein, 138, 429, 456, 491, 503 Plasmin, 491, 492 Plasminogen, 93, 491, 492 Plasminogen Activators, 491, 492 Plasticity, 58, 102, 492 Platelet Activation, 492, 504 Platelet Aggregation, 431, 484, 492 Platelets, 484, 492 Platinum, 476, 492 Pleural, 485, 492 Pleural cavity, 485, 492 Plexus, 116, 492 Pneumonia, 71, 448, 492 Poisoning, 472, 482, 492 Policy Making, 76, 464, 492 Polycystic, 221, 222, 399, 413, 492 Polycystic Ovary Syndrome, 413, 492 Polymerase, 127, 492 Polymerase Chain Reaction, 127, 492 Polymorphic, 72, 443, 451, 493 Polymorphism, 67, 90, 93, 147, 185, 493 Polyposis, 446, 493 Polysaccharide, 433, 442, 493 Portal System, 477, 493 Posterior, 19, 431, 435, 454, 480, 486, 487, 491, 493, 502, 512 Postprandial, 48, 210, 493 Postsynaptic, 483, 493, 504 Post-translational, 431, 493, 503 Post-traumatic, 128, 465, 493 Post-traumatic stress disorder, 128, 493 Postural, 100, 493 Potassium, 429, 480, 493 Potentiation, 476, 493, 504 Practicability, 493, 512 Practice Guidelines, 397, 409, 410, 493 Precursor, 25, 64, 431, 432, 434, 453, 455, 456, 457, 484, 491, 494, 511, 512, 513, 514 Predisposition, 67, 72, 73, 77, 91, 337, 494 Prednisolone, 494 Prednisone, 315, 494 Pre-eclamptic, 455, 494

Premenstrual, 224, 272, 286, 341, 366, 404, 494 Premenstrual Syndrome, 272, 286, 341, 404, 494 Presumptive, 115, 494 Presynaptic, 41, 482, 483, 494, 508 Presynaptic Terminals, 482, 494, 508 Primary endpoint, 319, 321, 494 Primary Prevention, 29, 54, 98, 107, 322, 410, 494 Primary tumor, 24, 34, 494 Private Sector, 494 Privatization, 158, 494 Probe, 18, 312, 494 Progestogen, 78, 232, 260, 334, 335, 340, 346, 372, 410, 495 Progressive, 27, 60, 65, 113, 434, 442, 444, 451, 454, 458, 465, 472, 482, 486, 492, 495, 513 Projection, 484, 495, 499 Prolactin, 165, 239, 423, 495 Prolapse, 17, 94, 108, 249, 495 Proline, 445, 468, 495 Promoter, 60, 75, 93, 495 Prone, 57, 60, 495 Prophase, 115, 485, 495, 508 Prophylaxis, 17, 18, 451, 495, 501 Prospective study, 16, 18, 50, 78, 86, 96, 112, 148, 159, 171, 180, 226, 239, 251, 475, 495 Prostaglandins, 197, 434, 495 Prostaglandins D, 197, 495 Prostaglandins F, 495 Prostate, 45, 133, 399, 437, 464, 485, 495, 500, 512 Prostate-Specific Antigen, 133, 495 Protease, 70, 105, 446, 496 Protease Inhibitors, 70, 105, 496 Protein Binding, 496, 510 Protein C, 124, 135, 264, 429, 430, 433, 436, 474, 475, 486, 496 Protein Kinases, 37, 79, 496 Protein S, 376, 399, 400, 438, 458, 486, 496, 501, 509 Protein-Tyrosine Kinase, 462, 496 Proteinuria, 463, 496 Proteolytic, 446, 460, 491, 492, 496 Protocol, 42, 69, 117, 123, 138, 142, 335, 491, 496 Protons, 430, 468, 496, 497 Proximal, 18, 66, 86, 103, 453, 494, 496, 503

Index 531

Psychiatric, 53, 54, 74, 86, 122, 123, 205, 224, 242, 263, 437, 479, 496 Psychiatry, 30, 36, 41, 42, 57, 61, 106, 107, 121, 123, 124, 129, 130, 242, 259, 347, 496 Psychic, 444, 473, 479, 496, 502 Psychoactive, 496, 515 Psychological Tests, 42, 496 Psychomotor, 62, 496 Psychomotor Performance, 62, 496 Psychophysiology, 275, 496 Psychosexual, 111, 227, 497 Psychotherapy, 188, 497, 498 Puberty, 68, 70, 81, 104, 126, 127, 144, 344, 349, 389, 497, 512 Public Policy, 395, 396, 497 Pulmonary, 144, 222, 322, 438, 447, 448, 497, 514 Pulmonary Artery, 438, 497, 514 Pulmonary Embolism, 322, 497 Pulmonary hypertension, 222, 448, 497 Pulse, 16, 132, 146, 481, 497 Purulent, 427, 497, 513 Q Quinones, 32, 497 R Race, 54, 55, 71, 78, 83, 101, 108, 139, 142, 143, 228, 303, 473, 484, 497 Racemic, 473, 484, 497 Radiation, 34, 42, 111, 428, 432, 457, 459, 460, 461, 471, 477, 497, 498, 501, 516 Radiation therapy, 35, 428, 459, 461, 471, 497 Radioactive, 69, 438, 439, 468, 470, 471, 475, 477, 484, 497, 498, 501, 513 Radiography, 19, 448, 497 Radioimmunoassay, 127, 497 Radioisotope, 498, 511 Radiolabeled, 497, 498 Radiopharmaceutical, 462, 498 Radiotherapy, 439, 497, 498 Radius, 20, 51, 112, 174, 218, 498 Raloxifene, 36, 57, 61, 62, 66, 68, 94, 95, 113, 180, 184, 196, 295, 310, 314, 319, 323, 498, 503 Random Allocation, 498 Randomization, 125, 498 Randomized clinical trial, 12, 83, 125, 137, 315, 323, 498 Randomized Controlled Trials, 44, 498 Rape, 493, 498 Reagent, 476, 498 Reassurance, 131, 498

Receptors, Serotonin, 499, 503 Recombinant, 61, 101, 499, 514 Recombination, 39, 462, 499 Rectal, 52, 499 Rectum, 433, 439, 446, 450, 452, 460, 462, 470, 473, 495, 499 Recurrence, 24, 138, 309, 313, 317, 444, 499 Red blood cells, 458, 499, 501 Red Nucleus, 435, 499 Reductase, 249, 434, 499 Refer, 1, 8, 19, 439, 446, 453, 456, 461, 475, 477, 483, 484, 499, 511 Refraction, 499, 505 Regeneration, 460, 499 Regimen, 5, 28, 68, 77, 334, 340, 444, 455, 488, 490, 499 Regression Analysis, 8, 84, 499 Relapse, 47, 499 Relative risk, 4, 15, 16, 427, 499 Reliability, 230, 244, 499 Remission, 315, 499, 500 Renal pelvis, 473, 500 Renin, 67, 432, 441, 500 Renin-Angiotensin System, 441, 500 Reproductive cells, 463, 500 Reproductive History, 55, 139, 142, 143, 500 Reproductive system, 106, 500 Research Support, 272, 500 Resorption, 36, 65, 68, 100, 128, 160, 430, 439, 486, 500 Respiration, 433, 481, 500 Resting metabolic rate, 49, 91, 138, 500 Restoration, 449, 490, 500, 516 Retina, 473, 477, 486, 500, 501 Retinoblastoma, 399, 500 Retinoids, 501, 515 Retrograde, 472, 501 Retroperitoneal, 428, 501, 515 Retrospective, 3, 30, 259, 501 Retrospective study, 3, 501 Rheumatic Diseases, 29, 163, 501 Rheumatism, 166, 501 Rheumatoid, 29, 317, 318, 487, 501 Rheumatoid arthritis, 29, 318, 501 Ribosome, 501, 512 Rigidity, 56, 488, 491, 501 Risk factor, 5, 6, 14, 15, 17, 19, 20, 22, 23, 29, 31, 32, 35, 37, 47, 49, 51, 52, 54, 71, 73, 75, 77, 78, 79, 83, 84, 86, 88, 90, 93, 95, 100, 106, 107, 108, 109, 111, 118, 120, 124, 125, 130, 135, 161, 162, 170, 199,

532 Menopause

200, 204, 222, 224, 230, 231, 236, 274, 312, 320, 339, 343, 387, 408, 457, 475, 495, 499, 501 Rod, 436, 444, 501 S Sagittal, 12, 501 Saliva, 8, 501 Salivary, 9, 114, 130, 452, 459, 487, 501, 516 Salivary glands, 452, 459, 501 Saponins, 133, 501, 506 Scans, 36, 71, 91, 148, 318, 501 Schizoid, 502, 515 Schizophrenia, 502, 515 Schizotypal Personality Disorder, 502, 515 Sclera, 502 Sclerosis, 60, 222, 399, 434, 502 Sclerotic, 60, 502 Screening, 29, 68, 73, 107, 108, 166, 233, 274, 312, 318, 352, 410, 445, 502 Sebaceous, 452, 502, 514 Sebaceous gland, 452, 502, 514 Second cancer, 34, 502 Secondary tumor, 479, 502 Secretin, 117, 502 Secretory, 81, 96, 483, 502 Sedative, 124, 502 Sedentary, 12, 66, 76, 500, 502 Segmental, 25, 230, 463, 502 Segmentation, 502 Segregation, 436, 499, 502 Seizures, 183, 185, 386, 488, 502 Selective estrogen receptor modulator, 59, 62, 68, 95, 113, 135, 274, 498, 503, 508, 511 Semen, 495, 503 Seminiferous tubule, 431, 471, 503 Semisynthetic, 458, 503 Senescence, 29, 63, 101, 301, 503 Senile, 286, 377, 486, 503 Septal, 116, 474, 503 Septic, 435, 503 Sequencing, 493, 503 Serine, 456, 464, 495, 503 Serotonin, 39, 311, 483, 490, 499, 503, 512 Serous, 456, 503 Serum Albumin, 498, 503 Sex Characteristics, 428, 431, 485, 497, 503, 509 Sex Determination, 399, 503 Sex Hormone-Binding Globulin, 83, 148, 173, 503

Sexually Transmitted Diseases, 96, 99, 382, 503 Shock, 503, 512 Signal Transduction, 38, 504 Signs and Symptoms, 33, 499, 500, 504 Skeletal, 20, 45, 59, 96, 431, 444, 482, 504, 505, 509 Skeleton, 20, 100, 128, 427, 439, 460, 472, 504 Sleep apnea, 87, 124, 198, 235, 504 Small intestine, 38, 444, 454, 467, 469, 472, 504 Smoking Cessation, 97, 322, 504 Smooth muscle, 61, 430, 431, 440, 447, 460, 473, 482, 484, 495, 500, 504, 505, 507 Smooth Muscle Tumor, 460, 504 Sneezing, 408, 504, 506, 507 Social Class, 92, 504 Social Environment, 497, 504 Social Security, 498, 504 Social Support, 113, 504, 507 Sodium, 83, 334, 429, 480, 483, 504, 508 Soft tissue, 438, 504, 505 Solid tumor, 432, 505 Solitary Nucleus, 435, 505 Solvent, 437, 464, 479, 505 Soma, 193, 505 Somatic, 86, 101, 115, 428, 444, 474, 478, 480, 489, 505 Somatic cells, 101, 115, 478, 480, 505 Sonogram, 505, 512 Sound wave, 312, 447, 505, 512 Soy Proteins, 271, 505 Spasm, 438, 505, 509 Spatial disorientation, 453, 505 Specialist, 99, 213, 264, 280, 413, 452, 505 Specificity, 40, 377, 429, 456, 505, 510 Spectrum, 108, 117, 505 Sperm, 431, 444, 500, 503, 505, 509 Sphincter, 51, 505, 507 Spinal cord, 439, 442, 443, 462, 478, 482, 489, 505, 508 Spleen, 431, 476, 506 Sporadic, 501, 506 Spotting, 335, 506 Staging, 70, 126, 233, 501, 506 Statistically significant, 6, 506 Steel, 35, 444, 506 Stem cell transplantation, 315, 506 Stem Cells, 506 Sterile, 435, 488, 506

Index 533

Sterility, 147, 153, 154, 179, 189, 202, 213, 222, 228, 234, 250, 252, 471, 506 Stimulant, 440, 506, 514 Stimulus, 122, 454, 459, 473, 506, 509 Stomach, 427, 452, 458, 462, 463, 467, 482, 489, 502, 504, 506 Stool, 446, 470, 473, 506 Strand, 32, 446, 492, 506 Stress incontinence, 69, 136, 408, 506 Stress management, 31, 507 Stress urinary, 136, 507 Stroke, 4, 19, 23, 57, 62, 72, 84, 162, 208, 286, 320, 322, 328, 336, 394, 405, 408, 441, 507 Stromal, 65, 344, 456, 507 Styptic, 340, 507 Subacute, 471, 507 Subarachnoid, 465, 507 Subclinical, 52, 71, 107, 111, 120, 322, 323, 471, 502, 507 Subcutaneous, 12, 61, 237, 341, 428, 455, 473, 485, 488, 507, 515 Subfornical Organ, 57, 507 Subiculum, 467, 507 Subspecies, 505, 507 Substance P, 438, 458, 479, 495, 502, 507 Substrate, 47, 70, 457, 507 Subtrochanteric, 467, 507 Suction, 23, 507 Supine, 69, 507 Supplementation, 14, 49, 60, 125, 137, 261, 280, 301, 332, 345, 378, 507 Support group, 7, 507 Suppression, 47, 48, 65, 95, 316, 317, 324, 449, 507 Suprachiasmatic Nucleus, 124, 507 Survival Rate, 111, 507 Sweat, 300, 452, 490, 508 Sympathetic Nervous System, 57, 110, 435, 508 Sympathomimetic, 453, 457, 484, 508 Symphysis, 443, 495, 508 Symptomatic, 3, 14, 52, 85, 122, 133, 139, 142, 143, 308, 508 Symptomatology, 90, 108, 209, 227, 341, 377, 508 Synapse, 428, 483, 494, 508, 512 Synapsis, 508 Synaptic, 58, 102, 476, 483, 504, 508 Synaptic Vesicles, 508 Synergistic, 495, 508

Systemic lupus erythematosus, 72, 175, 508 Systolic, 468, 508 T Tachycardia, 331, 335, 343, 508 Tamoxifen, 34, 42, 61, 62, 66, 68, 112, 114, 155, 273, 316, 317, 318, 319, 321, 503, 508, 511 Tarsal Bones, 440, 508 Telangiectasia, 399, 509 Telomere, 132, 509 Temporal, 431, 465, 467, 477, 509 Temporal Lobe, 431, 509 Testicles, 477, 509 Testicular, 434, 509 Testis, 431, 458, 485, 509 Testosterone, 83, 87, 119, 120, 148, 162, 238, 242, 368, 372, 423, 431, 499, 503, 509 Tetany, 488, 509 Tetracycline, 80, 509 Thalamic, 435, 509 Thalamic Diseases, 435, 509 Thermal, 453, 483, 492, 509 Thigh, 12, 18, 20, 109, 460, 509 Third Ventricle, 469, 477, 491, 509, 512 Thorax, 427, 476, 509 Threshold, 26, 338, 459, 468, 509 Thrombin, 460, 492, 496, 509, 510 Thromboembolism, 17, 509 Thrombolytic, 492, 510 Thrombomodulin, 496, 510 Thrombosis, 62, 79, 170, 190, 210, 226, 336, 496, 507, 510 Thymus, 469, 476, 510 Thyroid, 59, 90, 296, 365, 440, 469, 488, 510, 513 Thyroid Gland, 488, 510 Thyroiditis, 90, 510 Thyrotropin, 469, 510 Thyroxine, 14, 59, 429, 510 Time Management, 507, 510 Tin, 330, 347, 492, 510 Tissue Culture, 25, 510 Tissue Distribution, 132, 510 Tolerance, 69, 90, 109, 427, 463, 510 Tomography, 107, 447, 501, 510 Tone, 80, 262, 484, 510 Tonic, 438, 510 Tonicity, 466, 510 Tonus, 510, 511 Tooth Loss, 20, 21, 511 Tooth Preparation, 428, 511

534 Menopause

Topical, 292, 427, 435, 511 Toremifene, 333, 511 Toxic, iv, 35, 435, 437, 457, 469, 479, 511 Toxicity, 32, 34, 214, 323, 454, 511 Toxicology, 396, 511 Toxin, 456, 510, 511 Trace element, 460, 510, 511 Tracer, 47, 511 Trachea, 439, 510, 511 Traction, 444, 511 Transcription Factors, 66, 129, 511 Transdermal, 93, 109, 132, 148, 176, 184, 202, 235, 260, 262, 264, 511 Transduction, 61, 62, 504, 511 Transfection, 438, 462, 511 Transfer Factor, 469, 511 Transforming Growth Factor beta, 168, 511 Translation, 76, 430, 458, 511 Translocation, 458, 512 Transmitter, 427, 453, 477, 479, 484, 508, 512 Transplantation, 444, 469, 512 Transvaginal ultrasound, 67, 198, 312, 512 Trauma, 51, 136, 512 Treatment Outcome, 19, 69, 512 Tremor, 488, 512 Triglyceride, 13, 16, 69, 93, 121, 332, 345, 468, 512 Triptorelin, 318, 319, 512 Trisomy, 25, 39, 432, 512 Trophic, 62, 512 Tryptophan, 445, 503, 512 Tuber Cinereum, 432, 512 Tuberous Sclerosis, 399, 512 Tumor marker, 437, 512 Tumor Necrosis Factor, 318, 512 Tumorigenic, 32, 513 Tumour, 227, 462, 513 Tunica, 481, 513 Type 2 diabetes, 13, 14, 15, 16, 19, 95, 150, 513 Tyrosine, 453, 496, 513 U Umbilical Veins, 63, 513 Unconscious, 432, 469, 513 Urban Population, 225, 513 Ureters, 473, 513 Urethra, 408, 489, 495, 513 Urethritis, 17, 340, 513 Urinary tract, 5, 7, 14, 17, 55, 145, 246, 436, 513

Urinary tract infection, 5, 14, 17, 55, 145, 436, 513 Urinate, 513, 515 Urodynamics, 17, 513 Urogenital, 8, 17, 244, 249, 339, 463, 513 Uterine Prolapse, 220, 513 V Vaccine, 428, 496, 513 Vagina, 28, 56, 94, 95, 308, 312, 344, 347, 443, 469, 479, 500, 506, 512, 513 Vaginitis, 17, 286, 422, 513 Valine, 334, 514 Vascular Resistance, 31, 514 Vasoconstriction, 57, 59, 457, 514 Vasodilatation, 342, 514 Vasodilation, 62, 119, 514 Vasodilator, 439, 440, 453, 483, 514 Vasomotor, 28, 36, 79, 122, 123, 135, 163, 184, 249, 264, 331, 335, 339, 343, 458, 514 VE, 19, 154, 155, 157, 161, 376, 514 Vector, 511, 514 Vegetative, 338, 514 Vein, 318, 432, 472, 484, 488, 514 Venous, 17, 378, 484, 485, 496, 514 Ventricle, 431, 448, 467, 497, 508, 509, 514 Ventricular, 30, 58, 131, 164, 183, 448, 514 Venules, 438, 440, 456, 514 Vertebrae, 104, 506, 514 Vertebral, 130, 514 Vertigo, 330, 514 Vesicular, 465, 514 Veterinary Medicine, 395, 514 Viral, 38, 48, 70, 105, 511, 513, 514, 515 Virilization, 227, 514 Virulence, 511, 515 Virus, 38, 48, 70, 436, 443, 457, 468, 491, 511, 514, 515 Visceral, 12, 88, 91, 95, 121, 258, 277, 435, 474, 515 Visceral Afferents, 435, 515 Visceral fat, 12, 91, 95, 121, 515 Vitamin A, 332, 336, 345, 515 Vitreous, 473, 500, 515 Vitro, 60, 129, 515 Vivo, 48, 60, 515 Void, 118, 135, 515 W Waist circumference, 16, 515 War, 493, 515 Warts, 468, 515 Weight Gain, 10, 21, 97, 138, 149, 220, 236, 239, 252, 322, 381, 389, 406, 515

Index 535

Weight-Bearing, 179, 515 White blood cell, 132, 432, 470, 473, 476, 491, 515 Windpipe, 510, 515 Withdrawal, 119, 129, 317, 515 Womb, 500, 513, 515 Wound Healing, 460, 477, 516 X Xenobiotics, 55, 516 Xenograft, 432, 516

Xerostomia, 9, 516 X-ray, 28, 109, 113, 214, 318, 438, 447, 448, 460, 461, 477, 484, 497, 498, 501, 516 Y Yeasts, 461, 490, 516 Z Zoledronate, 319, 516 Zygote, 447, 516 Zymogen, 496, 516

536 Menopause

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