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

ORAL CONTRACEPTIVES A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES ...

Author: ICON Health Publications

40 downloads 796 Views 4MB Size Report

This content was uploaded by our users and we assume good faith they have the permission to share this book. If you own the copyright to this book and it is wrongfully on our website, we offer a simple DMCA procedure to remove your content from our site. Start by pressing the button below!

Report copyright / DMCA form

DOWNLOAD PDF

ORAL

CONTRACEPTIVES A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

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

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 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., 1960Oral Contraceptives: 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: 0-597-84537-9 1. Oral Contraceptives-Popular works. I. Title.

iii

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.

iv

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 oral contraceptives. 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.

v

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.

vi

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

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ORAL CONTRACEPTIVES........................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Oral Contraceptives ...................................................................... 6 E-Journals: PubMed Central ....................................................................................................... 35 The National Library of Medicine: PubMed ................................................................................ 37 CHAPTER 2. NUTRITION AND ORAL CONTRACEPTIVES ................................................................. 83 Overview...................................................................................................................................... 83 Finding Nutrition Studies on Oral Contraceptives..................................................................... 83 Federal Resources on Nutrition ................................................................................................... 86 Additional Web Resources ........................................................................................................... 87 CHAPTER 3. ALTERNATIVE MEDICINE AND ORAL CONTRACEPTIVES .......................................... 91 Overview...................................................................................................................................... 91 National Center for Complementary and Alternative Medicine.................................................. 91 Additional Web Resources ........................................................................................................... 96 General References ..................................................................................................................... 102 CHAPTER 4. DISSERTATIONS ON ORAL CONTRACEPTIVES .......................................................... 103 Overview.................................................................................................................................... 103 Dissertations on Oral Contraceptives........................................................................................ 103 Keeping Current ........................................................................................................................ 104 CHAPTER 5. CLINICAL TRIALS AND ORAL CONTRACEPTIVES ..................................................... 105 Overview.................................................................................................................................... 105 Recent Trials on Oral Contraceptives........................................................................................ 105 Keeping Current on Clinical Trials ........................................................................................... 106 CHAPTER 6. PATENTS ON ORAL CONTRACEPTIVES ..................................................................... 109 Overview.................................................................................................................................... 109 Patents on Oral Contraceptives ................................................................................................. 109 Patent Applications on Oral Contraceptives ............................................................................. 118 Keeping Current ........................................................................................................................ 124 CHAPTER 7. BOOKS ON ORAL CONTRACEPTIVES ......................................................................... 125 Overview.................................................................................................................................... 125 Book Summaries: Federal Agencies............................................................................................ 125 Book Summaries: Online Booksellers......................................................................................... 127 Chapters on Oral Contraceptives............................................................................................... 129 CHAPTER 8. MULTIMEDIA ON ORAL CONTRACEPTIVES .............................................................. 137 Overview.................................................................................................................................... 137 Audio Recordings....................................................................................................................... 137 CHAPTER 9. PERIODICALS AND NEWS ON ORAL CONTRACEPTIVES ........................................... 139 Overview.................................................................................................................................... 139 News Services and Press Releases.............................................................................................. 139 Newsletter Articles .................................................................................................................... 143 Academic Periodicals covering Oral Contraceptives ................................................................. 145 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 147 Overview.................................................................................................................................... 147 U.S. Pharmacopeia..................................................................................................................... 147 Commercial Databases ............................................................................................................... 148 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 151 Overview.................................................................................................................................... 151 NIH Guidelines.......................................................................................................................... 151 NIH Databases........................................................................................................................... 153

Contents

viii

Other Commercial Databases..................................................................................................... 155 APPENDIX B. PATIENT RESOURCES ............................................................................................... 157 Overview.................................................................................................................................... 157 Patient Guideline Sources.......................................................................................................... 157 Finding Associations.................................................................................................................. 168 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 171 Overview.................................................................................................................................... 171 Preparation................................................................................................................................. 171 Finding a Local Medical Library................................................................................................ 171 Medical Libraries in the U.S. and Canada ................................................................................. 171 ONLINE GLOSSARIES................................................................................................................ 177 Online Dictionary Directories ................................................................................................... 178 ORAL CONTRACEPTIVES DICTIONARY............................................................................. 179 INDEX .............................................................................................................................................. 243

1

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 oral contraceptives 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 oral contraceptives, 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 oral contraceptives, 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 oral contraceptives. 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 oral contraceptives, 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 oral contraceptives. The Editors

1

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

3

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and oral contraceptives, 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 “oral contraceptives” (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: •

Oral Contraceptives in Women With Diabetes Source: Diabetes Care. 13(8): 895-898. August 1990. Summary: The authors of this article evaluated the association of oral contraceptive use with the presence and severity of diabetic retinopathy, hypertension, and glycosylated hemoglobin in women of childbearing age who have diabetes. Neither current or past use of oral contraceptives, nor duration of of oral contraceptive use was associated with severity of retinopathy, hypertension, or current glycosylated hemoglobin. In conclusion, further study of various birth control methods in young women of childbearing age should be considered. 2 tables. 16 references. (AA).

4

•

Oral Contraceptives

Are Oral Contraceptives Safe for Diabetic Women? Source: Contraceptive Technology Update. p. 134-138. September 1990. Summary: This article discusses the safety of prescribing oral contraceptives (OCs) for women who have diabetes mellitus. The author notes that the higher-dose OCs commonly prescribed during the 1960s and 1970s were found to adversely affect glucose metabolism. Some experts now believe that newer low-dose formulations cause only minimal insulin and glucose changes and thus are much safer for women with diabetes and for women at risk for developing diabetes. Topics discussed include prescribing practices based on the severity of the patient's diabetes; contraindications to long-term use of OCs; the spectrum of individual responses to the use of OCs; and the importance of active follow-up of the patient. 6 figures. 8 references.

•

Increased Risk of Inflammatory Bowel Disease Associated with Oral Contraceptive Use Source: American Journal of Epidemiology. 140(3): 268-278. August 1, 1994. Summary: This article reports on a population-based case-control study that evaluated the effects of oral contraceptive use on ulcerative colitis and Crohn's disease risk. Cases were women enrollees, aged 15-68 years, in a prepaid health plan based in western Washington State, who had ulcerative colitis (n=211) or Crohn's disease (n=91). Agematched controls were randomly selected from the health plan enrollment file. Results showed that women who reported oral contraceptive use within 6 months before disease onset were at increased risk for both diseases compared with women who had never used contraceptives. Women who had used oral contraceptives for more than 6 years had the highest risk of Crohn's disease. In contrast, duration of use was not associated with increased risk of ulcerative colitis. Higher ulcerative colitis risk tended to occur among users of high estrogen dose oral contraceptives, while Crohn's disease risk was not related to estrogen potency. 4 tables. 36 references. (AA-M).

•

Oral Contraceptive Use and Association with Glucose, Insulin, and Diabetes in Young Adult Women: The CARDIA Study Source: Diabetes Care. 25(6): 1027-1032. June 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 of the associations between current use of oral contraceptives (OCs) and glucose levels, insulin levels, and diabetes in young women. Subjects were women (n = 1,940) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective observational study of African Americans and whites aged 18 to 30 years at enrollment in 1985 to 1986. Current use of OCs was associated with lower fasting glucose levels and reduction in the odds of diabetes, but not lower fasting insulin levels, compared with nonuse in both African-American and white women. No association existed between pattern of use of OCs and incident diabetes at year 10, although the total number of new persons with diabetes at year 10 was small (n = 17). The authors conclude that current use of OCs is associated with lower glucose levels in young African American and white women and may be associated with lower odds of diabetes. 2 tables. 30 references.

Studies

•

5

Oral Contraceptives and Renal and Retinal Complications in Young Women with Insulin-Dependent Diabetes Mellitus Source: JAMA. Journal of the American Medical Association. 271(14): 1099-1102. April 13, 1994. Summary: This article reports on a study undertaken to evaluate the effects of oral contraceptives (OCs) as a possible risk factor for early diabetic renal and/or retinal complications. Forty-three women with diabetes who used OCs for 1 year or longer were compared with a computer-matched control group of 43 women with diabetes who never used OCs. Outcome measures included hemoglobin A1C levels, albumin excretion rates, and mean retinopathy scores. The mean longitudinal hemoglobin A1C values were similar for study subjects and control subjects. The final mean albumin excretion rates, reflecting diabetic renal damage, and the mean eye grades were not significantly different between the groups. The researchers concluded that the use of OCs among young women with insulin-dependent diabetes mellitus does not pose an additional risk for the development of early diabetic retinopathy and/or nephropathy. 4 figures. 3 tables. 26 references. (AA-M).

•

Antibiotic Interference with Oral Contraceptives Source: JADA. Journal of the American Dental Association. 133(7): 880. July 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: This brief article reminds dental health practitioners of the possible interference of antibiotics with oral contraceptives. The ADA Council on Scientific Affairs recommends that, considering the possible consequences of an unwanted pregnancy, when prescribing antibiotics to a patient using oral contraceptives, the dentist should do the following: advise the patient of the potential risk of the antibiotic's reducing the effectiveness of the oral contraceptive; recommend that the patient discuss with her physician with use of an additional nonhormonal means of contraception; and advise the patient to maintain compliance with oral contraceptives when concurrently using antibiotics. The article briefly reviews research studies that support these recommendations. 4 references.

•

Smoking, the Oral Contraceptive Pill, and Crohn's Disease Source: Digestive Diseases and Sciences. 36(8): 1147-1150. August 1991. Summary: This review article focuses on the relationship between smoking, oral contraceptives, and Crohn's disease. Both cigarette smoking and oral contraceptives have been implicated as aggravating factors in Crohn's disease. Based upon the recent demonstration of multifocal gastrointestinal infarction in Crohn's disease, a possible pathogenic mechanism for this condition, the authors propose how smoking and oral contraceptives may potentiate a tendency for focal thrombosis and exacerbate the activity of Crohn's disease. The authors recommend that patients who suffer from Crohn's disease should be advised to abstain from smoking and females should seek expert guidance concerning the type of oral contraceptive they use. 51 references.

6

Oral Contraceptives

Federally Funded Research on Oral Contraceptives The U.S. Government supports a variety of research studies relating to oral contraceptives. 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 oral contraceptives. 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 oral contraceptives. The following is typical of the type of information found when searching the CRISP database for oral contraceptives: •

Project Title: 17DEACETYLNORGESTIMATE, ETHINYL ESTRADIOL W/ ORAL TRIPHA Principal Investigator & Institution: Creinin, Mitchell D.; Associate Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This is a phase III efficacy study for the contraceptive patch. Participants are randomly assigned to use either Triphasil or the contraceptive patch as their contraceptive method for up to 13 months. The first 21 patients were assigned to 13 cycles, and the next 10 were to use the product for 7 cycles. Physical exams with pap and bloodwork are done at the initial visit and after completion of the last cycle of study medication. Participants are also seen at regular intervals to check for adverse events and review diary cards during the course of the study. The contraceptive patch may offer improved ease of use with equal efficacy when compared to traditional oral contraceptives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ACCUTANE/ORAL NODULAR ACNE

CONTRACEPTIVES

IN

WOMEN

WITH

Principal Investigator & Institution: Hendrix, Craig W.; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: The clinical study will systematically evaluate whether isotretinoin affects the pharmacokinetics of ethinyl estradiol and norethindrone. We will also assess surrogate pharmacodynamic markers for oral contraceptive effectiveness, LH and FSH, to detect whether breakthrough ovulation occurred during the menstrual cycle. Finally, this study will describe the single dose and steady state pharmacokinetics of isotretinoin and its metabolites in these study patients. This is an open label, drug interaction study which will be done in two parts. The study design includes a screening/baseline 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).

Studies

7

evaluation followed by the administration of Ortho Novum 7/7/7+ and Accutane + 1.0 mg/kg/day in twice daily divided doses for 16 to 20 weeks. Pharmacokinetic/pharmacodynamic assessments will be made to compare periods with isotretinoin (month 4) to those periods without isotretinoin (month 2). Comparisons will be made both for the low dose phase (day 6) and high dose phase (day 20) of Ortho Novum 7/7/7. A second comparison will be made between single dose (beginning of month 3) and multiple dose isotretinoin pharmacokinetics (month 4, concurrent with hormonal kinetics). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BACKUP CONTRACEPTIVES

METHODS

FOR

NEW

START

USING

ORAL

Principal Investigator & Institution: Schwartz, Jill; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002 Summary: The aim of this study is to determine the recommendations for the use of a backup method for new start oral contraceptive users. While oral contraceptive are commonly prescribed, there is no consensus of recommendations for a backup method for new start patients. Package insert instructions are confusing; this may lead to noncompliance and undesired pregnancies. Experts generally agree that starting pills no later than day 5 of menses ensures immediate protection. However, a Sunday start adds the risk of breakthrough ovulation since the first pill can be started as late as day 7 of the menstrual cycle. Clinical practice favors advising new start patients to use a backup in the first week to month, regardless of start regimen. This study is a prospective and randomized clinical trial. One hundred and twenty subjects will be recruited. It is designed to compare three pill start regimens of Lo/Ovral, day 1 of menses, (the shortest window), day 4, (the intermediate window), and day 7, (the longest window) in regard to ovulation rate and ovarian follicle formation. The primary analysis will be to test the null hypotheses that the averages of the maximum follicular diameter and the ovulation rates are equal for the three groups. Descriptive analyses of follicular diameter assessments and changes, and endometrial lining will also be provided. Serum progesterone levels will be summarized and evaluated for evidence of ovulation. Comparing these regimens will provide information about how the pill works in the initial cycle of use and may lead to improved patient compliance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRCA1, ORAL CONTRACEPTIVES, AND HORMONAL RISK FACTORS Principal Investigator & Institution: Bernstein, Leslie; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 07-MAY-1999; Project End 29-FEB-2004 Summary: Mutations in the breast cancer susceptibility gene BRCA1 may be involved in a substantial number of breast cancer diagnosed at an early age. However, the age at which breast cancer occurs appears to vary substantially, even in women from the same family with the same mutation. Further recent evidence suggests that breast cancer risk in BRCA1 mutation carriers is much lower than the previously reported 85%. This suggests that other, genetic or non-genetic, factors play a role in whether or when breast cancer occurs in women with a BRCA1 mutation. Epidemiological evidence suggests that oral contraceptive (OC) use at an early age may increase risk of breast cancer.

8

Oral Contraceptives

Further, OC use appears to be particularly. Detrimental in young women with a family history. We have preliminary data suggesting that BRCA1 mutation carriers have a much higher risk associated with OC use than non- carriers. Such a detrimental effect of OC use in BRCA1 mutation carriers could be due to increased breast cell proliferation in these women. Experimental evidence suggests that BRCA1 may be a hormonally induced negative growth regulator. We propose to conduct a population-based study to determine the ration of relative risk of breast cancer associated with OC use in BRCA1 mutation carriers and the relative risk of breast cancer associated with OC use in noncarriers. This information can subsequently be used to determine the relative risk of breast cancer associated with OC use in BRCA1 mutation carriers. The secondary aims of this study are to determine whether other hormonal risk factors such as selected reproductive factors and physical exercise differentially affects breast cancer risk in BRCA1 mutation carriers and non-carriers, to determine whether BRCA1 mutation carriers have different mammographic density profiles that on carriers, and to determine whether mammographic densities are affected by OC use differentially in BRCA1 mutation carriers than non-carriers. This study will provide valuable epidemiologic information regarding the role of BRCA1 in breast cancer etiology, and could yield important results in developing intervention regimens and appropriate counseling for women with a BRCA1 mutation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CATSPER: NOVEL TARGET FOR AN ORAL CONTRACEPTIVE Principal Investigator & Institution: Chong, Jayhong A.; Hydra Biosciences, Inc. 790 Memorial Dr, Ste 203 Cambridge, Ma 02139 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 14-FEB-2004 Summary: (provided by applicant): Hydra Biosciences Inc. will develop a novel class of non-hormonal, oral contraceptives based on the discovery by our co-founder, David Clapham, M.D./ Ph.D., of a sperm specific ion channel, CatSper. Male mice lacking CatSper have poor sperm motility and are sterile. These and other studies carried out by Dr. Clapham suggest that pharmacological agents that block CatSper may serve as an ideal contraceptive: first, because CatSper expression is confined to sperm, its disruption may exhibit few side effects; second, a drug that specifically blocks CatSper may be effectively delivered to both males and females; third, a CatSper blocker may be fast acting and only need to be used just before or after intercourse. A stable cell line that functionally expresses CatSper is required for screening for CatSper blockers. Though native CatSper is expressed on the cell surface of sperm, CatSper fails to localize to the plasma membrane in heterologous systems. In this fast track application we propose two strategies for producing a cell line that functionally expresses CatSper. The first is to bypass the obstacle by making chimeric ion channels. The second is to overcome the obstacle by identifying, through a yeast two-hybrid screen, proteins that are required to traffic CatSper to the cell surface. In Phase I, the milestones are to generate the basic molecular biology reagents required for both strategies. First, we will clone chimeric CatSper channels. Second, we will clone four bait vectors needed for a yeast two-hybrid screen (Y-2-H) to identify accessory proteins that bind and guide CatSper to the cell surface. In Phase II, we will test whether the chimeric clones or the co-expression of binding proteins facilitate functional expression. First, we wilt determine whether CatSper mediated current can be measured in cell lines expressing chimeric CatSper channel. Second, we will identify proteins that bind CatSper and determine whether coexpression with CatSper produces a functional cell line. Third, we will optimize the cell line to maximize its use in high throughput screening. Once a functional cell line is

Studies

9

established, Hydra Biosciences Inc. in collaboration with a pharmaceutical company will screen small molecule libraries for CatSper blockers and develop a novel non-hormonal, oral contraceptive. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOPREVENTION OF BREAST AND OVARIAN CANCER Principal Investigator & Institution: Brown, Powel; Associate Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2005 Summary: The long-term goal of the proposed studies is to identify specific biomarkers in breast and ovarian tissue from high-risk individuals who are modulated by effective chemopreventive agents, and may therefore serve as surrogate endpoints in future chemoprevention trials. The studies will involve the collaboration of clinical investigators at several institutions, including the University of Texas Health Science Center at San Antonio, MD Anderson Cancer Center, Baylor Medical College, and the University of Texas Southwestern Medical Center. These institutions have previously formed the Texas Cancer Genetics Consortium, and have active high-risk cancer genetics clinics. Specific projects include: (1) Modulation of Breast Biomarkers using an RXR-Selective Retinoid. This project is a clinical trial in which the novel RXR-selective retinoid LGD1069 (Targretin) will be used to modulate potential biomarkers in breast biopsies from women with high risk of breast cancer. (2) Chemoprevention of Ovarian Cancer: Marker Modulation using Fenretinide and Oral Contraceptives. This project will investigate whether oral contraceptives, the synthetic retinoid 4HPR or their combination, will modulate fiber-optically detected ovarian surface spectral properties associated with neoplasia and with apoptosis, and will change the expression of Breast and Ovarian Cells. In this project, we will characterize specific genes which are up or down-regulated in normal and malignant human breast cells by LGD1069, using cDNA expression arrays. We will define the biological effects of changes in expression of these retinoid-regulated genes and determine whether certain changes are markers of successful chemoprevention in existing tissues from an animal model. These LGD1069regulated genes identified in this project will then be included in Project 1 to determine whether they are also modulated in retinoid-treated human breast tissue. The proposed studies will be supported by three core facilities: a pathology/immuno- histochemistry core, a biostatistics core, and an administrative core. These highly interactive projects will determine whether these novel chemopreventive strategies modulate specific biomarkers and are therefore promising agents for the prevention of breast and ovarian cancer, as well as indicating which of these markers might be most useful as endpoints in later, large-sale prevention trials in women at high risk of familial breast and ovarian cancer. Thus, these studies should ultimately serve to reduce the incidence and mortality of these common cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: CHEMOPREVENTION OF OVARIAN CANCER IN WOMEN USING FENRETINIDE/ORAL CONTRACEPTIVES Principal Investigator & Institution: Bast, Robert C.; Professor of Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002 Summary: Epidemiologic and experimental studies suggest that oral contraceptives (OCP) as well as the retinoid fenretinide (4-HPR) may reduce the risk of ovarian cancer,

10

Oral Contraceptives

but mechanisms underlying the chemopreventive activity of these agents are not well understood. Conventional and molecular epidemiology has not correlated risk of ovarian cancer with frequency of ovulation, but the decreased risk from OCP is not directly proportional to the fraction of cycles suppressed, suggesting that other mechanisms might also contribute to chemoprevention. Retinoids increase the production of TGFbeta by stromal cells in other tissues; further, we have demonstrated that retinoids and TGFbeta induce synergistic death in ovarian cancer cell lines as well as in freshly isolated tumor cells. 4-HPR decreased the incidence of ovarian cancer in a large Italian breast chemoprevention trial. Women with BRCA1 or BRCA2 mutations and a family history of ovarian cancer have a much higher risk of developing ovarian cancer than the general low risk population. Studies have shown that prior OCP use reduces the risk of ovarian cancer in both low and high risk women by about 50%. A recent study in primates indicates that treatment with oral contraceptives or progestins can increase apoptosis in ovarian surface epithelial cells, thus perhaps lessening the chance that a genetic alteration will occur which could lead to cancer. TGFbeta is thought both to suppress the proliferation of ovarian surface epithelial cells and to induce apoptosis in transformed cells, thus providing a primitive surveillance mechanism for eliminating emerging clones of malignant cells. We hypothesize that both OCP and retinoids increase the production of TGFbeta from ovarian stromal cells and induce apoptosis in epithelial cells. Preliminary studies suggest that fiber-optic spectroscopy may be able to identify cancerous and precancerous changes on the ovarian surface and subsurface, and thus may provide a unique marker for assessment in chemoprevention trials. We will explore the hypotheses that: 1) 4-HPR and OCP induce apoptosis in ovarian surface epithelial cells. 2) TGFbeta produced by ovarian stromal cells contributes to apoptosis and differentially affects normal and transformed cells. 3) OCP and 4-HPR may affect low and high risk ovarian epithelium differently; these differences will be detectable through variations in intermediary markers. 4) Spectroscopy provides a unique intermediary marker to detect early dysplastic or premalignant changes in ovarian epithelial cells as well as reliably identifying both early proliferative changes and apoptotic changes that may change with chemoprevention. To investigate these hypotheses, we propose two randomized placebo- controlled chemoprevention trials in women at low risk (no history, no known mutations) or at high risk (BRCA1 or BRCA2 mutations, or family history), optical spectroscopy. These pilot studies should elucidate mechanisms of chemoprevention in ovarian cancer, identify relevant intermediate biomarkers, and help in development of definitive chemoprevention trials for high risk women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTRACEPTIVE IN WOMEN WITH PRIOR GESTATIONAL DIABETES Principal Investigator & Institution: Xiang, Anny H.; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): This application is submitted in response to PA-02077, "Secondary Analyses in Diabetes, Digestive and Kidney Diseases". We propose to analyze data from an existing observational cohort database to assess the impact of different types of contraception on the risk of diabetes and on glucose levels, blood pressure and serum lipids in Latino women with prior gestational diabetes mellitus (GDM). We have previously shown that those women are at high risk of developing type 2 diabetes during their reproductive years. They require effective contraception

Studies

11

because a) pregnancy planning is required to minimize the risk of conceiving with undetected hyperglycemia, which imparts a risk of congenital malformations to the baby and (b) additional pregnancies increase their risk of diabetes. Contraception should be safe regarding effects on glycemia and risk of diabetes, as well as on blood pressure and lipid levels, which can be elevated in association with the insulin resistance that is common in women with GDM. Using data from a subset of the current cohort available through 1994, we found that low-dose combination oral contraceptives (OCs) did not increase the risk of diabetes, but that a progestin-only oral preparation did increase that risk. Effects on lipids and blood pressure were not evaluated. Approximately 20% of hormonal contraception users in our patients elect to use an injectable progestin preparation, depomedroxyprogesterone acetate (DMPA) for longterm contraception. The impact of that preparation on the risk of diabetes is unknown. Accordingly, we now propose to use an expanded version of the cohort, including all patients through 1998 when accrual ended, to assess the impact of DMPA as compared to OCs and non-hormonal contraception, on the risk of diabetes and on glucose levels, blood pressure and lipid levels. Survival analysis will be use to compare diabetes rates among forms of contraception. Generalized linear models will be used to compare effects on glucose, blood pressure and lipid levels. Successful completion of these analyses will provide novel and clinically important information about the safety of several forms of hormonal contraception that are crucial for young Latino women at high risk for type 2 diabetes. The observational results will also be important to the design of future direct comparisons of different forms of contraception in this high-risk population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COOPERATIVE CENTER FOR RESEARCH IN REPRODUCTION Principal Investigator & Institution: Coney, Ponjola; Professor and Chair; Obstetrics and Gynecology; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The collaborative partnership of Pennsylvania State University (PSU) and Meharry Medical College (MMC) proposes the development of a Cooperative Center for Research in Reproduction at MMC. The proposal addresses two goals. First, the Center will conduct scientifically sound, clinically relevant research in a thematically focused area of gynecologic endocrinology. Specifically, the research development core will study: 1) the role of sex steroid hormones as determinants of bone mineral density score in Black females, 2) the influence of oral contraceptives on the growth of uterine fibroids, and 3) the efficacy and safety of metformin and lifestyle factors in the amelioration of hyperandrogenemia and its associated symptomatology. These studies will generate knowledge and comparisons across race. Secondly, the compelling need to strengthen research infrastructure at a historically Black medical school through development of minority-initiated research proposals, collaboration and mentorship with a research intensive institutional network of experienced investigators, toward the eventual capacity to build an independent clinical research team at MMC will be facilitated. Additionally, core research support resources will be enhanced at MMC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

12

•

Oral Contraceptives

Project Title: ECTOPY, HORMONAL CONTRACEPTION AND STD'S IN ADOLESCENTS Principal Investigator & Institution: Peralta, Ligia; Chief; Pediatrics; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 20-SEP-2000; Project End 30-JUN-2005 Summary: Adolescents are at high risk for sexually transmitted diseases (STDs), which can have serious consequences for their future health and fertility, and which can increase their vulnerability to HIV infection. Cervical ectopy and use of oral contraceptives (OC), both common in adolescence, are risk factors for chlamydia, the most common inflammatory STD. Standardized, reliable measurements of ectopy have not been employed across studies. The independent risk of OC use stratified by ectopy has not been well studied. The association among Depot Medroxy Progesterone Acetate (DMPA), a contraceptive widely used among adolescents, ectopy and STD acquisition has not been reported. The aims of this proposal are to study prospectively: 1) the natural history of cervical ectopy and the transformation zone (T zone) in sexually active adolescents, 2) the impact of DMPA and a combined estrogen-progestins (OC) over time on cervical ectopy/T zone; 3) the relation between the size of the area of ectopy/T zone and STD acquisition, including chlamydia, gonorrhea, trichomonas and HPV; and 4) the risk of STDs in OC users compared to DMPA users stratified by the extent of cervical ectopy/T zone. Design: This is a 5 year prospective study on 500 inner-city sexually active nonparous females aged 12-18, some of whom will initiate DMPA or OC. They will be recruited consecutively from the Adolescent, Pediatric and community-based OB/Gyn Clinics of the University of Maryland, Baltimore, where the study will be conducted. Participants will be seen every 6 months for medical/sexual history, complete physical and pelvic examinations, and specimen collection of STDs. Cervicography will be used to determine the areas of ectopy and T zone, measured by computerized planimetry. This is an innovative reliable, sensitive and standardized method of measurement. Behavioral data will be collected anonymously by audio assisted computer interview (A-CASI). Interim follow up visits (every 3 months) will include behavioral risk by ACASI, medical history and incidence of STDs by urine screening and from the City STD registry. Summary. This proposal will 1) use a standardized measure of ectopy in young nonparous adolescents before and during hormonal contraceptive use; 2) address the relation between STDs and OCs, especially those OCs containing new progestins; 3) be one of the few studies to examine the association among DMPA, STDs and ectopy in adolescents; 4) recruit a difficult cohort with one of the highest rates of STDs, especially chlamydia infection. The team of researchers has expertise on STDs, adolescent health, and cervical anatomy. They have collaborated on the preliminary study and have experience in planning, implementing and managing successful longitudinal studies on high-risk youth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: EFFECT CATARACTOGENESIS

OF

ESTROGEN

ON

RADIATION-INDUCED

Principal Investigator & Institution: Dynlacht, Joseph R.; Radiation Oncology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): The induction of cataracts is often an unfortunate and unavoidable consequence of conventional radiation therapy for head and neck or

Studies

13

ocular tumors, whole-brain irradiation, and total-body irradiation prior to autologous bone marrow transplantation. Though not life-threatening, radiation-induced cataractogenesis represents a potentially serious sequelae of radiotherapy which can require surgical intervention. While the cellular and molecular mechanism(s) of radiation-induced cataractogenesis have not been clearly elucidated, damage to the genome at the time of exposure and subsequent proliferation of the radiosensitive cells in the germinative zone of the lens epithelium likely play a role in the process. Using a rat model, we have recently accumulated preliminary data which indicate that estrogen reduces the latent period and may increase the incidence and severity of radiationinduced cataracts. High estrogen levels are artificially induced in nonpregnant women using oral contraceptives, or in post-menopausal women on estrogen replacement therapy, and these groups may be at an increased risk for developing cataracts which are more severe or occur with a more rapid onset. Estrogens regulate several proteins involved in cell cycle control and apoptosis, and its metabolism results in the production of free radicals which may be genotoxic and mutagenic to mammalian cells. Thus, a novel hypothesis to be tested in the proposed studies is that estrogen alters cell cycle regulation, DNA double strand break induction or repair, and proliferation in irradiated lens cells. We shall also investigate the dose-time interactions of radiation and estradiol to better understand the mechanism of estrogen action, and we will determine whether estrogen-modulation of radiation cataractogenesis is estrogen receptor (ER)-mediated using knockout mice that are deficient in either ERalpha or ERbeta. The lens has frequently been used as a model for predicting delayed (late) effects in other irradiated tissues. Data obtained from the proposed study may demonstrate that the lens is a useful model for predicting late effects in other estrogen-responsive target tissues. Finally, the efficacy of utilizing a novel technique for small animal irradiations shall also be tested; in this study, using the Leksell Gamma Knife, only one eye shall be irradiated in each of the animals, with the contralateral eye serving as a control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF HORMONAL CONTRACEPTION ON BONE MINERAL DENSITY Principal Investigator & Institution: Berenson, Abbey B.; Obstetrics and Gynecology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 11-SEP-2001; Project End 31-AUG-2006 Summary: Recent studies have suggested that use of depot medroxyprogesterone acetate (DMPA) may have an adverse effect on bone mineral density (BMD). In contrast, use of oral contraceptives has been reported to have a beneficial effect or no effect. In a preliminary study, we observed a decrease of 3.0 percent in BMD among users of DMPA as compared with an increase of 0.1 percent-2.9 percent among users of 30-35 mug pills. Questions regarding the specific relationship between BMD and DMPA, however, have not been fully addressed. Furthermore, almost no data are available on the effects of the recently marketed pills containing only 20 mug of estradiol. Considering that over 11 million women in the US use hormonal contraception each year, it seems imperative to obtain accurate information on the effects of these medications on skeletal health. To address this important question, we propose to conduct a prospective clinical trial comparing changes in BMD over a 2-year interval experienced by women using DMPA or oral contraceptives containing 20 mug estradiol as compared with women not using hormonal contraception. Each cohort will be comprised of 229 women aged 16 to 33 years of white, black, or Hispanic race/ethnicity. The primary outcomes (ie, BMD and biomarkers of bone metabolism) will be analyzed

14

Oral Contraceptives

to assess changes from baseline within each contraceptive group at 6, 12, 18, and 24 months as compared to changes observed among controls. Furthermore, we will be able to assess the reversibility of potential adverse effects of hormonal contraception on BMD among those who discontinue their method by conducting a bone scan and measuring biomarkers at the point of discontinuation and at 6-month intervals from this point. This study will be among the first to investigate the role of race/ethnicity and age in contraceptive-related BMD changes while accounting for behavioral correlates (eg, prior contraceptive use, nutritional intake, exercise habits, alcohol use, smoking) in a multivariate fashion. Ultimately, this study will determine which women, if any, are placed at increased risk of osteopenia or osteoporosis as a result of using these hormonal contraceptives during their reproductive years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISPENSING

EFFECTIVENESS

OF

NURSE

HOME

CONTRACEPTIVE

Principal Investigator & Institution: Melnick, Alan L.; Assistant Professor; Family Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2005 Summary: (provided by the applicant): The purpose of our study is to determine whether an innovative way of providing contraception, in the home, could reduce the incidence of unintended pregnancy for low income and minority women who have already had one birth. Women with a first-borne infant found to be at high risk for medical and social problems through a community-based screening program who are interested in delaying a subsequent pregnancy will be randomized into two groups. The first group will receive a home visit by a community health nurse, who will provide contraceptive counseling, including a referral to publicly funded family planning clinic. The second group will receive the same services, but will also receive either a threemonth supply of oral contraceptives or a depo-medroxyprogesterone injection. The study has two objectives: to determine whether this practice reduces subsequent unintended pregnancies in this population and whether this practice encourages or discourages utilization of clinic-based preventive services, such as sexually transmitted disease and cervical cancer screening. The results of our study have important implications for public health. Most local public health departments throughout the United States already use community health nurses to deliver many services at home, including case management for families with infants at risk for medical and social problems. If delivery of contraceptives at home is effective in reducing subsequent unintended pregnancies for these families, local health departments across the country could add this service for very little added cost. To the extent that home contraceptive delivery model proves successful at widening the interval between births for lowincome and minority women, and increases the likelihood that subsequent pregnancies are intended, it will increase the likelihood of having babies born healthier. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS CONTRACEPTIVES

OF

HYPERICUM

PERFORATUM

ON

ORAL

Principal Investigator & Institution: Murphy, Patricia A.; Obstetrics and Gynecology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 10-SEP-2001; Project End 31-AUG-2004

Studies

15

Summary: (provided by applicant): This study will evaluate the effects of chronic use of a common herbal remedy, St. John's Wort (Hypericum perforatum) on metabolism of contraceptive steroids and ovarian suppression during oral contraceptive use. St. John's Wort is one of the more popular herbal remedies. It has been implicated as an inducer of the cytochrome P450 enzyme (CYP) system, and as such may cause increased metabolism of certain drugs, including oral contraceptives. Women using oral contraceptives have been warned against using St. John's Wort, although there are to date no data demonstrating risk of contraceptive failure if they do. This will be an openlabel, non-randomized, unblinded, sequential treatment clinical trial of reproductiveaged women. Eligible women will take low dose oral contraceptives containing ethinyl estradiol and norethindrone for two months, followed by two months taking the same oral contraceptive and St. John's Wort. Several markers of hormonal and ovarian activity will be evaluated. Parameters to be compared between these two exposure periods are: 1. the pharmacokinetics of contraceptive steroids 2. follicular development in the ovary 3. evidence of ovulation, 4. evidence of the potential for ovulation, 5. the quality of cervical mucus, 6. endometrial proliferation, and 7. irregular vaginal bleeding. This preliminary study will identify possible undesired interactions between a common botanical remedy and oral contraceptives. A concurrent aim is the development and refinement of a methodology for evaluating the risk of ovulation and unintended pregnancy from use of other herbs or medications during oral contraceptive use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ETHINYL ESTRADIOL AND HEPATOCARCINOGENESIS Principal Investigator & Institution: Yager, James D.; Professor; Environmental Health Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JAN-1984; Project End 30-APR-2004 Summary: Prolonged use by women of oral contraceptives containing the synthetic ethinyl estradiol (EE) is associated with a modest increased risk of developing liver tumors. Our original hypothesis was that the non- directly mutagenic EE was a promoter of hepatocarcinogenesis. Since then, our laboratory and others demonstrated that EE is a strong promoter and weak complete carcinogen of hepatocarcinogenesis in female rats, confirming this hypothesis. During the previous project period (years 6-9) we observed that at non-hepatotoxic doses, following the initial transient stimulation of growth, continued EE exposure was associated with the onset of a mitosuppressed state, characterized by reduced basal growth and decreased responsiveness to growth stimulation. Our overall hypothesis was/is that mitosuppression represents a growthnegative, selective environment and that the altered hepatic foci that develop represent clonal outgrowths of hepatocytes that became resistant to mitosuppression through spontaneous or carcinogen-induced mutagenesis ("initiation"). In other words, initiated hepatocytes would be differentially resistant to EE-induced mitosuppression. Our hypothesis during the current project period (years 10-14) was that mitosuppression was caused by EE-induced altered gene expression. At the time the project began (January 1995), using differential display, we had just detected several cDNAs representing mRNA transcripts increased in amount during EE-induced mitosuppression. These transcripts, and others, originate from nuclear and mitochondrial genome-encode genes encoding proteins of the respiratory chain. The induction by EE of these transcripts in human hepatoma HepG2 cells, cultured rat hepatocytes and cultured precision-cut liver slices requires estrogen metabolism, most likely to catechols, and the estrogen receptor. In vivo and in culture, the increase in mitochondrial transcripts precedes an increase in mitochondrial superoxide production, reflecting increased respiratory chain activity. We

16

Oral Contraceptives

do not known whether this response is mechanistically related to mitosuppression, although EE inhibited basal and transforming growth factor beta (TGF-induced apoptosis in cultured hepatocytes and liver slices. We hypothesize that mitosuppression reflects reduced hepatocyte growth/turnover due to the inhibition of apoptosis by EE. We further hypothesize that the inhibition of apoptosis results from EE catechol metabolites signaling through the estrogen receptor to stimulate mitochondrial respiration. Since mitochondria are integral to some signaling processes leading to induction of apoptosis, we propose that increased mitochondrial respiration renders hepatocytes less sensitive to apoptosis inducing signals. During the next project period (years 15-20) we would investigate these hypotheses through 3 Specific Aims. 1) To determine the mechanism of inhibition of apoptosis by EE; 2) to determine whether altered hepatic foci are resistant to inhibition of apoptosis by EE, and 3) To define in detail the signal transduction pathway mediating the induction by EE of mitochondrial respiratory chain activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FOLLOW-UP STUDY FOR CAUSES OF ILLNESS IN BLACK WOMEN Principal Investigator & Institution: Rosenberg, Lynn; Professor and Associate Director; Slone Epidemiology Unit; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 02-SEP-1994; Project End 31-JUL-2004 Summary: We propose to continue the largest follow-up study of the health of AfricanAmerican women yet undertaken, the Black Women's Health Study (BWHS). The aim is to determine the effects on breast cancer incidence (and eventually other cancers) of potential risk factors, including physical activity, obesity, alcohol, diet, oral contraceptives, and postmenopausal female hormones. Most of these factors have not been studied in black women. In addition, factors specific to African-American women, including experiences and perceptions of racism and use of hair straightening products (which is very common) will be assessed. Because prevention programs require an understanding of the determinants of risk factors, we will also assess correlates of important risk factors. The BWHS cohort was established in 1995 when 64,554 black women aged 21-69 years from all regions of the U.S. completed mail questionnaires, providing data on demographic factors, medical and reproductive history, use of oral contraceptives and other drugs, physical activity, smoking, alcohol use, diet, and other factors. Methods for following participants, collecting, processing and managing the data, and validating cancer outcomes have been developed, and results of analyses of the baseline data have been published. The first round of follow-up (every 2 years) to determine incident cancer and changes in exposures has been carried out, with a followup rate of 83 percent. After further cycles of follow-up through the end of the proposed grant, 600 plus cases of breast cancer will be available for analysis. Hypotheses to be assessed include whether physical activity reduces the incidence, and whether dietary fat intake and alcohol consumption increase it. African-American women suffer a greater burden of cancer morbidity than white women but there have been few studies in black women. The BWHS will contribute to the effort to improve the health of African-American women by providing insight into causes and preventives of breast cancer and other cancers and useful information for intervention programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

17

Project Title: GENES AND THE ESTROGEN EFFECT ON ENDOMETRIAL CANCER Principal Investigator & Institution: Ross, Ronald K.; Professor; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The etiology of endometrial cancer is relatively well understood. Estrogen stimulation of the endometrium without the modulatory effects of progestins is the major cause. Estrogen replacement therapy (ERT) in menopause and obesity are the principal risk factors. The effect of the latter is probably due to the association between postmenopausal obesity and circulating bioavailable estrogen levels. Oral contraceptives and pregnancy, both of which deliver estrogen stimulation to the endometrium but with the continuous modulatory influence of progestins, are associated with reduction in risk. Combination hormone replacement therapy in which a progestin is added to estrogen for all or part of the monthly cycle results in no increase in endometrial cancer risk over that of a non-user of hormone replacement. Despite the fact that ERT and obesity are the major risk factors, only a small proportion of women using ERT or even with extreme obesity will develop endometrial cancer. It would be important from a public health as well as from a mechanistic view to be able to predict which women those will be. We propose to evaluate a series of eight candidate genes (CYP17, CYP19, HSD17B1, ER, CYP1A1, CYP1B1, COMT andPR) in the estrogen biosynthesis, transactivation and metabolism pathways to determine if the effects of these risk factors might be mediated or modified by genetic variability. We will evaluate this question in the context of a prospective epidemiologic study of 133,000 female California teachers (the California Teachers Study) using a nested case-control design. We will also examine in detail the possible impact of phytoestrogens on endometrial cancer risk reduction in conjunction with HRT, obesity and the eight candidate genes under evaluation. 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; Medicine; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 01-MAR-1998; Project End 31-AUG-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

18

Oral Contraceptives

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 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 VARIANTS OF HORMONE RECEPTORS IN OVARIAN CANCER Principal Investigator & Institution: Terry, Kathryn L.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Epidemiologic and in vitro data suggest a role for reproductive hormones in ovarian cancer development. The tissue specific effect of these hormones is controlled by the expression of hormone receptors. Normal ovarian epithelium contains both estrogen and progesterone receptors. Animal models and cell lines demonstrate that estrogen increases ovarian epithelial proliferation and induce ovarian tumors, whereas, progesterone inhibits growth and increases apoptosis of the ovarian epithelium. In addition, epidemiologic literature suggests a protective effect for the combination of estrogen and progesterone in oral contraceptives, which are consistently protective. Unopposed estrogen in the form of menopausal therapy appears to increase ovarian caner risk but formulations with estrogen and progesterone have no consistent relationship with ovarian cancer. Our goal is to examine the effect of genetic variation in hormone receptors on the risk of ovarian cancer, using a New England based case-control study. Specifically, this study will test whether common haplotypes of estrogen receptor genes (estrogen receptor alpha and estrogen receptor beta) or the progesterone receptor gene are associated with an increased risk of ovarian cancer. In addition, this study will test whether the association between a functional polymorphism in the progesterone receptor, +331 G/A, increases ovarian cancer risk. Variables such as parity, menopausal status, body mass index, and exogenous hormones affect estrogen and progesterone levels, therefore, interaction with these variables will be considered. Ovarian cancer is particularly deadly due to its asymptomatic progression and poor prognosis at late stages of disease. Advances in prevention and detection may come from a better understanding of the genetic determinants of ovarian cancer, which might inform decisions about lifestyle modifications that could lower risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

19

Project Title: HORMONES, DIET AND RISK OF OVARIAN CANCER Principal Investigator & Institution: Hankinson, Susan E.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: We propose to conduct detailed analyses of both hormonal and dietary frisk factors for ovarian cancer using data collected since 1976 in the prospective Nurses' Health Study cohort. From 1976-2004, we expect 737 incident ovarian cancer cases to be confirmed in total. Specifically, we propose to evaluate body mass index, waist-to-hip ratio, antioxidant intake, time since last use of oral contraceptives and duration of postmenopausal hormone use in relation to ovarian cancer risk. In addition, using a nested case-control design, we will examine relationships between plasma insulin-like growth factor I (and its binding proteins) and ovarian cancer using blood samples collected from 32,826 cohort members in 1989-90. Using germline DNA from either archived buffy coat, buccal cell specimens or tissue (the latter two to be collected as part of this program project), we propose to evaluate ovarian cancer risk in relation to several specific genetic polymorphisms and gene- environment interactions (galactose-1phosphate uridyl transferase [GALT] and lactose intake; GAG repeats in the androgen receptor gene and oral contraceptive use). In addition, we propose to establish a bank of tumor tissue from women with incident ovarian cancer, and to assess several ovarian cancer risk factors according to over-expression of mutant p53 protein in the tumor tissue. Overall, the prospective nature and large size of the cohort, the high follow-up rates over more than 24 years, the detailed and repeated measured exposure data, and the availability of both germline DNA and tumor tissue from a subset of the cohort provide a unique opportunity to test several important hypotheses related to risk of ovarian cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HPV METHYLATION: A BIOMARKER OF CERVICAL LESION PROGRESS Principal Investigator & Institution: Giuliano, Anna R.; Associate Professor; None; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 30-JUN-2004 Summary: (provided by applicant)Epidemiologic research has shown that infection with the human papillomavirus (HPV) is a cause of most cases of cervical cancer and that specific HPV types (e.g., 16 and 18) are associated with high risk of progression to cervical cancer. However, HPV infection is an insufficient cause of cervical cancer and appears to require the presence of other factors for the infection to progress to a significant cervical lesion. One factor that may modify progression of HPV to cervical neoplasia is DNA methylation. In support of this hypothesis, in vitro work from zur Hausen's laboratory indicated that methylation in the Upstream Regulatory Region (URR) of oncogenic HPV exerts a powerful effect on transcriptional activity and hence carcinogenicity of the virus. HPV DNA methylation patterns may modify the virulence resulting in increased risk for progression of HPV infection to high grade SIL. However, the association between HPV methylation patterns specifically has only been tested in vitro. In this application, we propose to conduct the first epidemiological study of the association between HPV methylation status and cervical cancer risk. The overall goal of this application is to examine in vivo methylation patterns of oncogenic HPV and determine if these patterns are associated with SIL. The primary aims of this study are to determine: 1) the overall methylation status and site-specific methylation in the URR of

20

Oral Contraceptives

oncogenic HPV among women previously identified with normal, ASCUS, LgSIL, and HgSIL cytology; 2) whether methylation patterns of HPV are related to viral load; 3) the factors (such as smoking, oral contraceptives, and co-infections) associated with HPV methylation status; 4) whether HPV DNA methylation status is independently associated with risk of SIL Study Design: Data and biological samples collected from the USA-Mexico Border HPV, Cervical Dysplasia and Chlamydia trachomatis study (19971998) will be used for this proposed study. A population of 2,246 women, 246 of whom are HPV positive for one of eight oncogenic HPV types, 15 years and older were recruited from family planning clinics in 3 pairs of contiguous communities at the Arizona (US) - Sonora (Mexico) border, and in Tucson, AZ and Hermosillo, Sonora, Mexico. HPV DNA methylation status will be assessed among 246 women positive for one of eight HPV types (HPV types 16, 18, 31, 39, 45, 51, 52, and 58) utilizing the Bisulfite Genomic Sequencing technique. Data available from the completed study include laboratory measures (HPV typing, HPV viral load, C. trachomatis status, and cytology), and risk factor data (reproductive, sexual and medical histories, and demographic data). Results from this study may provide a novel biomarker for women at risk of progression of HPV infection to SIL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENSTRUAL CYCLE EFFECTS ON TMD PAIN AND OTHER SYMPTOMS Principal Investigator & Institution: Leresche, Linda A.; Research Professor; Oral Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 20-SEP-1998; Project End 19-SEP-2004 Summary: Temporomandibular disorders (TMD's) are musculoskeletal pain conditions characterized by pain in the muscles of mastication and/or the temporomandibular joint. These pain problems are about twice as common in women as in men in the community, and prevalence peaks during the reproductive years. About 80 percent of patients treated in tertiary care settings are women. The investigators propose a 5-year program of clinical epidemiologic and experimental research to examine the possible interactive influences of hormonal status, other gender factors in pain sensitivity, the presence of non-TMD somatic symptoms and psychological distress on TMD pain in women. Study 1 will assess variations in self report of clinical TMD pain, other physical symptoms and psychosocial state in relation to hormonal status across three consecutive ovulatory menstrual cycles for normally cycling female TMD patients, as well as appropriate comparison groups (male TMD patients, female TMD patients who use oral contraceptives and normally cycling pain-free females controls). Studies 2 and 3 will assess variability in responses to standardized experimental pain stimuli at critical points (menses, ovulatory, mid-luteal and late luteal/premenstrual phases) across three consecutive ovulatory cycles in female TMD cases and appropriate controls, to ascertain the extent to which variability and level of pain experience may be attributable to female gender, hormonal status, experience of pain during the menstrual period (i.e., dysmenorrhea) and/or presence of clinical TMD pain. Study 4 assesses clinical pain, pain in response to palpation of muscles of mastication and the temporomandibular joint, psychosocial variables and hormonal status during each trimester of pregnancy, as well as postpartum in TMD cases and age-matched controls. Finally, Study 5 compares hormone levels, pain report and psychological factors over the menstrual cycle in women diagnosed with joint pain only and women diagnosed only with muscle pain. Thus, the proposed studies will: 1) provide important descriptive information concerning the course of clinical pain across the menstrual cycle and during pregnancy;

Studies

21

2) illuminate relationships between clinical pain, generalized pain sensitivity, psychological state, gender and hormonal status; and 3) explore whether central or peripheral mechanisms may be involved in pain-hormone relationships. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENSTRUAL PHASE AND NEURAL CONTROL OF SKIN BLOOD FLOW Principal Investigator & Institution: Johnson, John M.; Professor; Physiology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 14-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from the applicant's abstract): Reflex control of the cutaneous circulation is both of thermoregulatory and of non-thermoregulatory origin and occurs via sympathetic vasoconstrictor and sympathetic active vasodilatory mechanisms. The applicant has previously shown that each of these 2 efferent systems is subject to control by internal temperature, skin temperature, exercise-associated reflexes, and baroreflexes. Steroidal changes accompanying the phases of the menstrual cycle are known to act as background modifiers of the thermoregulatory control of skin blood flow. The PI's working hypothesis is that in the luteal phase, progesterone inhibits active vasodilation by shifting to a higher internal temperature threshold for its initiation and elevates vasoconstrictor activity for any given body temperature as well. Elevated estrogen levels in the ovulatory phase are hypothesized to have directionally opposite effects on vasoconstriction and active vasodilator function. Through selective local blockade of vasoconstrictor function the applicant will examine changes in active vasodilator function among menstrual phases. Such effects would provide mechanisms for the well-documented phasic changes in basal internal temperature and in the control of the cutaneous circulation through the menstrual cycle. The applicant will also seek evidence for the roles of progesterone and estrogen in these phasic changes by taking advantage of the normal fluctuations of steroid levels among follicular (both low), ovulatory (estrogen elevated), and luteal (both elevated) phases to find how those hormonal patterns affect the control of the vasodilator and vasoconstrictor pathways. These studies will be complemented by examinations of alterations in control of the vasoconstrictor and vasodilator pathways between active and placebo phases of oral contraceptives. The applicant will evaluate peripheral contributions by these steroids in vasomotor function by testing whether vasoconstrictor responses to controlled application of norepinephrine or vasodilator responses to direct application of acetylcholine are dependent on the phase of the menstrual cycle. This question will be further addressed by finding if the level of skin blood flow in areas free of autonomic influences (via cutaneous nerve block) and in areas with intact innervation vary among phases of the menstrual cycle or between phases of oral contraceptive use. The role of prostaglandin synthesis in the upward shift of the thermoregulatory control of the active vasodilator system will also be evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MINORITY PREDOCTORAL FELLOWSHIP PROGRAM Principal Investigator & Institution: Cheng, Georgina; Animal Sciences and Veterinary Pathobiology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007

22

Oral Contraceptives

Summary: (provided by applicant): Vaginal candidiasis affects approximately 75% of all women. Hormone levels have been associated with an increased incidence of vaginal candidiasis, especially during pregnancy, and for individuals who use oral contraceptives or hormone replacement therapy. C. albicans is the etiological agent in over 80% of vaginal candidiasis cases, thus making the relationship between estrogen and C. albicans an important one to study. Research into the effect of estrogen on C. albicans has been limited and the signaling mechanisms involved are unknown. Because great variability exists in various estrogen response elements in mammalian genes and because of the differences between mammalian systems and yeast, it is unlikely that a genome database search will identify all of the estrogen response mechanisms at work in C. albicans. This proposal seeks to determine the cellular growth characteristics of C. albicans in the presence of estrogen, identify C. albicans genes responsive to estrogen and define estrogen-responsive promoter elements using molecular biology techniques. Upon completion of these studies, we will have significant new knowledge about the interaction between C. albicans and estrogen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUTATIONS, THROMBOEMBOLISM

HORMONE

THERAPY,

AND

VENOUS

Principal Investigator & Institution: Psaty, Bruce M.; Professor, Medicine and Epidemiology; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: (Adapted from Investigator's Abstract) Epidemiologic studies have identified Factor V Leiden as the most common cause of heritable thrombophilia a prothrombotic mutation associated with a 5 to 7-fold increase in the risk of venous thromboembolism (VTE). In pre-menopausal women, the use of oral contraceptives is associated with a 4fold increase in VTE risk, and the joint effects of oral contraceptive use and Factor V Leiden carriership increase the VTE risk of by a factor of 35 (95% IC = 8 154). Recently, the results of several observational studies and randomized clinical trials suggest that in post-menopausal women, the use of hormone replacement therapy is associated with a 3-fold increase in VTE risk. Whether post-menopausal women with prothrombotic mutations experience a similar 20-fold increase in risk when they take post-menopausal hormones remains unknown. The primary aim of this ancillary study is to assess the interaction between hormone replacement therapy and the prothrombotic mutations, Factor V Leiden and the recently described prothrombin mutation (20210A) on the incidence of VTE in a population-based case-control study conducted at Group Health Cooperative of Puget Sound (GHC). The investigators state that using a variety of computerized surveillance systems at GHC will enable them to identify both in-patient and out-patient episodes of venous thromboembolism. They anticipate recruiting 300 post-menopausal women with a first episode of objectively confirmed venous thromboembolism, and 1,200 population-based controls will be identified and recruited from the GHC enrollment files. Controls will be frequency matched to the cases on age and calendar-year. Data collection includes a review of ambulatory medical record and a telephone interview. The GHC computerized pharmacy database will be used to assess exposure to hormone replacement therapy. A venous blood specimen will be obtained from consenting subjects, processed into aliquots of white cells, plasma, and red cells, and stored at 70 degrees C prior to laboratory analysis. DNA will be extracted from white cells, and molecular genotyping assays will be conducted to assess carriership of prothrombotic mutations. Data from these various sources will be entered,

Studies

23

linked and analyzed to address the specific aims. Under an additive model, the expected joint effects of HRT and carriership of prothrombotic mutations is 7. Compared with the null hypothesis for the additive model of a joint effect of 7, the investigators have 80% power to detect a difference between the alternative hypothesis of 18 and the null hypothesis of 7. If there is an important interaction between hormone replacement therapy and prothrombotic mutations, such a finding would offer important opportunities of VTE risk reduction by pre-treatment screening in the clinical setting for the prothrombotic mutations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MX EXPRESSION AND UTERINE MUCCOSAL IMMUNITY Principal Investigator & Institution: Ott, Troy L.; University of Idaho Moscow, Id 838443020 Timing: Fiscal Year 2002 Summary: The long term goal of this project is to define mechanisms involved in regulating the uterine mucosal immune system. Pregnancy or use of oral contraceptives can alter the mucosal immune system and increase susceptibility to infectious diseases. Additionally, the fetus alters uterine immune function resulting in protection of the fetal agents from crossing the utero-placenta and infecting the fetus. The role that steroid hormones play in implications to treatment of sexually transmitted diseases, to blocking transmission of viruses such as the human immunodeficiency virus from mother to fetus, and to our understanding of how pharmacological manipulation of cycling females may be impacted by cyclic changes in endogenous steroid hormones. Our preliminary results demonstrate that one component of the uterine anti-viral mechanisms, expression of the anti-viral protein Mx, is dramatically affected by steroid hormones and interferon. To test this hypothesis we propose to utilize cell cell lines derived from the bovine uterine lumenal (LE) and glandular (GE) epithelium and stroma (ST) and peripheral blood mononuclear cells (PBMC) filtered through the uterus to address the following specific aims: 1.) Determine the effects of steroids and IFN on Mx expression and anti-viral activity of LE, GE, ST and PBMC; 2.) Determine the effects of paracrine interaction between PBMC and LE, GE and ST cells on Mx expression and antiviral activity; and 3.) Determine the effect of level of Mx expression in the presence and absence of IFN and steroid hormones on antiviral activity of LE, GE and ST. Cell culture and co-culture in the presence and absence of interferon and steroid hormones will be utilized to assess affects on steady-state levels of Mx mRNA and protein and antiviral activity of the uterine cell lines against challenge with Vesicular Stomatitis virus. Paracrine (physical and biochemical) interactions between the uterine cell lines and PBMC will be evaluated to address the potentially complex cellular interactions that occur in the uterus in response to viral infection. Results will provide novel information on the role played by steroid hormones in regulating the antiviral response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: NIGHT SHIFT WORKERS AND HORMONE LEVELS IN WOMEN Principal Investigator & Institution: Davis, Scott; Professor of Epidemiology; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 11-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The primary objective of the proposed study is to determine whether working at night is associated with decreased levels of the nocturnal urinary concentration of 6-sulphatoxymelatonin, and increased levels of luteinizing

24

Oral Contraceptives

hormone (LH), follicle stimulating hormone (FSH), and estradiol in a sample of healthy women of reproductive age. Secondarily, this study is designed to investigate whether urinary levels of melatonin are lower and levels of reproductive hormones are higher during daytime sleep relative to nighttime sleep among women who work at night. Approximately 200 nurses who work the night shift exclusively and 150 nurses who work the day shift exclusively will be recruited as volunteers in the Seattle metropolitan area. Eligible participants must be between the ages of 20 and 40, employed for at least 20 hours/week, resident of King or Snohomish County, do not take oral contraceptives or other hormone preparations, and have no personal history of breast cancer. In addition, the night shift nurses must normally sleep at night during off days. This study will employ a design which allows for both between-subject comparisons of night shift v. day shift workers, and within-subject comparisons during day sleep v. night sleep among the night shift workers. Participation will span two months. In the first month the study will evaluate menstrual cycle regularity, determine the day of ovulation using a commercial kit, conduct a personal interview regarding employment and reproductive history, assess the participant's ability to adjust to shift work, and collect a blood sample. In the second month urine sample collections will be scheduled during both work and sleep periods, and will take place in the early to mid-luteal phase of each participant's cycle. Sleep patterns will be measured via actigraphy during the sleep periods corresponding to urine collection. Oral temperature data will be collected during waketime in the night shift workers to determine temperature amplitude. Information will be collected on factors which may be related to the hormones under study, such as alcohol consumption, medication use, and hours of daylight during sample collection. Urine samples will be assayed for the primary urinary metabolite of melatonin, 6sulphatoxymelatonin, and levels of LH, FSH, and estradiol. 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 2002 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: ORAL CONTRACEPTIVE AND HORMONE REPLACEMENT IN SLE Principal Investigator & Institution: Petri, Michelle A.; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: The overall goal of the current study is to address the effect of exogenous female hormones on disease activity and severity in patients with systemic lupus erythematosus (SLE), a disease which largely affects minority women. Oral

Studies

25

contraceptives and estrogen replacement are generally not prescribed due to the practice is based only on the predominance of female gender, biologic abnormalities of estrogen metabolism, murine models of lupus, several anecdotes of patients having disease flares while receiving exogenous hormones, and one retrospective study in patients with pre-existing renal disease. In contrast, a more recent retrospective study suggests that the rate of flare is not statistically increased in patients taking oral contraceptives. The pre-existing data are insufficient to warrant the dismissal of a potentially important birth control option in a disease which predominantly affects women in their reporductive years and whose fertility is not appreciably altered by the disease. Moreover, the use of synthetic estrogens to preserve fertility in patients taking cyclophosphamide and the use of estrogens to prevent post-menopausal and steroid induced osteoporosis are timely considerations. Women with lupus who are fertile who choose to participate will be randomly divided into a group that takes birth control pills (oral contraceptives) and a group that does not. The women and their doctors will not know what grouop they are in, because both groups will take tablets that appear identical. Women with high blood pressure, a history of a blood clot, lupus antibodies that cause clot, cancer, heart disease, liver disease, diabetes, complicated migraines, and very active lupus cannot participate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORAL CONTRACEPTIVE USE AND BONE DENSITY IN YOUNG WOMEN Principal Investigator & Institution: Scholes, Delia; Center for Health Studies Seattle, Wa 98101 Timing: Fiscal Year 2004; Project Start 15-JUL-1994; Project End 31-MAR-2009 Summary: (provided by applicant): For the more than 10 million US women using oral contraceptives (OCs), clear evidence regarding the health effects of OCs is a major public health concern. Several recent studies suggest that current OC formulations may act to suppress peak bone mass accrual in young women. However, this possibility has not been fully evaluated, particularly with regard to OC use among adolescents, the group most actively gaining bone. This application is focused on a thorough evaluation of the impacts of OC use on bone in young women. We include consideration of different skeletal sites, varying durations of use, and differing OC estrogen content. Importantly, this would be the first prospective study to our knowledge to document changes in bone mineral density (BMD) after OC discontinuation. We propose a prospective epidemiologic study of the effects on bone of new and ongoing OC use and of OC discontinuation in a cohort of adolescent and young adult women. The cohort (n=600) will be recruited from a defined population of HMO enrollees between the ages of 14 and 30, with 300 participants aged 14-18 years and 300 aged 19-30. Each age group will include 200 OC users and 100 comparison women. We will evaluate possibly different effects from a low-dose (20 mcg EE) and a higher-dose (35 mcg EE) formulation. The HMO's automated pharmacy and membership files will be used to select women who are new and ongoing users of OCs and to randomly select comparison women who are not using hormonal contraception, frequency matching on age and clinic. Participants will be followed longitudinally for 24-36 months. The primary outcome, bone mineral density, will be measured every 6 months at selected anatomic sites (hip, spine, whole body) using dual-energy x-ray absorptiometry. In our work to date investigating the association between injectable contraception and BMD in adolescents and young adult women, we have achieved excellent participant recruitment and retention with similar methods and have developed relevant

26

Oral Contraceptives

measurement and analytic strategies. OC use is highest among sexually active adolescents and women in their 20s. These are also women who are actively gaining bone. Given the increasing public health importance of osteoporosis and the prevalence of OC exposure at a crucial stage of growth, focused evaluation of the potentially adverse effects of OC use on the skeletal health of these young women--and their possible amelioration upon cessation of this exposure--is essential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORAL CONTRACEPTIVES /LEIOMYOMA

/ENDOGENOUS

SEX

STEROIDS

Principal Investigator & Institution: Sweet, Stephanie; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2008 Summary: The presence of uterine leiomyomas, benign smooth muscle tumors of the uterus, has long perplexed clinicians and the patients who develop them. Their enigmatic appearance is usually silent, but in some women they can precipitate substantial symptoms that do not consistently respond to medical therapy. Leiomyomas develop almost exclusively in women during their reproductive years and their growth, seems to be influenced by endogenous sex steroids. Our hypothesis is that the addition of exogenous hormones via oral contraceptives will accelerate the growth rate of leiomyomas. This supposition is important because, to date, a key component of various medical treatments for menorrhagia caused by leiomyomas are the use of oral contraceptives. Additionally, Black women, who are believed to produce higher levels of estrogens and progestins during the menstrual cycle, have a greater propensity for developing leiomyomas. The oral contraceptives could, therefore, have an additive affect. Studies to determine the influence of leiomyoma growth by oral contraceptives have been largely speculative, conflicting, and infrequently used a case control study design. Their impact on the growth of leiomyomas in Black women, who have the largest percentage of these symptomatic tumors (3 times greater), has never been investigated. In our two-center, case-control observational study, we will directly monitor the growth of uterine leiomyomas in women using oral contraceptives by using serial ultrasound evaluations (every 6 months for 36 months). In addition, all subjects will have serum and urine assays to establish if Black women produce higher levels of sex steroids. Our deliberate effort to recruit a large number of Black subjects provides an excellent opportunity to corroborate those findings. Women selected for this study will be premenopausal and have reproducible evidence of uterine leiomyomas. The case population (n=240) will consist of women using oral contraceptives and the controls (n=80) will be women who have never used hormonal therapy. The patient base in Meharry's urban center will be an abundant resource for the inclusion of Black case subjects sufficient to detect if there truly is a racial difference in this populations' leiomyoma growth rate. This collaborative effort will be a monumental step in ascertaining if oral contraceptive pills accelerate leiomyoma growth. Additionally, this will become a landmark study evaluating the seemingly exaggerated growth of leiomyomas in Black women and possibly correlating that growth difference with their increases in hormone levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

27

Project Title: ORAL CONTRACEPTIVES AND HORMONAL REPLACEMENT IN SLE Principal Investigator & Institution: Dooley, Mary A.; Professor; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ORAL ADOLESCENT GIRLS

CONTRACEPTIVES

FOR

DYSMENORRHEA

IN

Principal Investigator & Institution: Davis, Anne R.; Obstetrics and Gynecology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (Adapted from applicant's description) This is an initial application submitted by a new investigator. Primary dysmenorrhea is defined as pain during the menses in the absence of a pathologic lesion and is probably caused by prostaglandin effects on the uterus. Primary dysmenorrhea is highly prevalent among adolescents. More than 50% of adolescent girls in various populations report dysmenorrhea which is severe in about 15%. Dysmenorrhea is a major cause of morbidity in adolescents leading to activity restriction and school absence. Combined oral contraceptives (COC) are a common treatment for primary dysmenorrhea. Some small laboratory studies show decreased prostaglandins associated with COC use compared to non-COC use. Larger observational studies show a lower prevalence of dysmenorrhea among COC users compared to non-COC users and improved dysmenorrhea after initiating open-label COC use. In the only randomized, double blind, placebo-controlled trial, Matthews showed modest improvement of dysmenorrhea among a small number of women using a high- dose COC compared to placebo (1968). None of the existing studies compare the efficacy of a low-dose COC with placebo in the treatment of primary dysmenorrhea. The proposed study is a double blind, randomized, placebo-controlled trial to determine the efficacy of a low-dose COC in the treatment of primary dysmenorrhea among urban, adolescent girls. Healthy girls aged 19 years or less with moderate to severe dysmenorrhea as determined by the Robinson modification of the Andersch scale will be eligible (Robinson, 1992). 150 girls will be randomized to receive either a COC containing 20 micrograms ethinyl estradiol and 0.1 milligrams levonorgestrel or a placebo. The main effect will be change in score on the pain sub-scale of the Moos Menstrual Distress Questionnaire (MDQ) after three months of treatment. This study will have 80% power to detect a 50% reduction in pain score with an alpha of.05 and a drop-out rate of 40%. Secondary outcome measures will be changes in school absence, activity restriction and medication use. Also, we plan to determine if psychological measures of depression, life-crisis events or self- concept ratings predict response to treatment. Given their efficacy in pregnancy prevention, safety, and non-contraceptive health benefits, COC may be an ideal therapy for primary dysmenorrhea in adolescent girls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORAL CONTRACEPTIVES, HORMONAL RISK FACTORS AND BRCA1 Principal Investigator & Institution: Ursin, Giske; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033

28

Oral Contraceptives

Timing: Fiscal Year 2002 Summary: (Applicant's Description) Project C: Oral Contraceptives, Hormonal Risk Factors, and BRCA1. Mutations in the breast cancer susceptibility gene BRCA1 may be involved in a substantial number of breast cancers diagnosed at an early age. However, the age at which breast cancer occurs appears to vary substantially, even in women from the same family with the same mutation. This suggests that other, genetic or nongenetic, factors play a role in whether or when breast cancer occurs in women with a BRCA1 mutation. Epidemiological evidence suggests that oral contraceptive (OC) use at an early age may increase risk of breast cancer. Further, OC use may be particularly detrimental in women with a family history. A number of environmental risk factors other than exogenous hormone use probably also work through a hormonal mechanism; these include age at first birth, parity, possibly abortion, and physical exercise. All these factors can be manipulated, and therefore have implications for prevention. These "hormonal" risk factors appear to have different, if not opposite, effects in women with a family history than in women with no such history. The reason for this is unknown. However, BRCA1 expression appears to be regulated by hormones in experimental studies. Further, women with a family history are more likely to have a BRCA1 mutation. It is therefore possible that the apparent effect modification by family history is caused by BRCA1 status. We propose to conduct a population-based study that investigates whether the presence of specific BRCA1 mutations modify 1) the effects of oral contraceptive use, 2) the effects of "hormonal" risk factors such as age at first birth, number of pregnancies, and number of abortions, and 3) the protective effect of physical exercise, on breast cancer risk. In addition, this study will provide information as to the frequency of these mutations in younger breast cancer patients, and we will explore the associations between BRCA1 status and other breast cancer risk factors such as mammographic densities. This study will provide valuable epidemiologic information regarding the role of BRCA1 in breast cancer etiology, and could yield important results in developing intervention regimens and appropriate counseling for women with a BRCA1 mutation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVARIAN CANCER RISK AND SURVIVAL IN BRCA CARRIERS Principal Investigator & Institution: Modugno, Francesmary; Assistant Professor; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: The goal of this K07 Career Award training is to acquire expertise in the requisite disciplines for molecular and genetic cancer epidemiology research, with an emphasis on femal cancers. Two interlocking areas of study will be pursued. First, a series of independent studies, laboratory projects and seminars/conferences will provide an understanding of the laboratory techniques employed in genetic epidemiology studies, the underlying biology of female cancers, and the clinical relevance of genetic epidemiology research. Second, studies in epidemiology and biostatistics will ensure the development of study design, management and analysis skills. The cornerstone of this training will be a study investigating ovarian cancer risks and survival among BRCA1/2 mutation carriers. Because the case fatality rate of ovarian cancer is so high, many doctors advise these high-risk women to engage in the two behaviors that most strongly prevent ovarian cancer: using oral contraceptives (Ocs) and bearing more children. While one recent study did find Ocs to be protective for BRCA1/2 carriers, concerns about the study's design question its validity. Moreover,

Studies

29

one report suggests that for BRCA1/2 mutation carriers, OC use substantially increases breast cancer risk. Another study suggests that having more children increases (rather than decreases) ovarian cancer risk in these women. There are also contradictory findings on the survival of BRCA1/2-associated ovarian cancer patients. Therefore, a well-designed study investigating the effect of OC use and parity on ovarian cancer risk and survival in BRCA1/2 carriers is urgently needed. We will use a case-only study to determine the protectiveness of Ocs and parity against ovarian cancer among women carrying BRCA1/2 mutations versus among women not carrying these mutations, and we will determine whether there is a survival difference between the two groups. We will obtain BRCA1/2 mutation status from banked tissue specimens of about 400 Ashkenazi Jewish women with ovarian cancer identified from tumor registries in Pennsylvania, Ohio, New York and Florida or who participated in an NIH-sponsored study. We will link these results to information on OC use and parity. The protection afforded by OC use and parity will then be compared among BRCA1/2 mutation carriers versus among non-carriers. Survival status will be obtained from the National Death Index and the differences in survival between the two groups will be compared. The information from this study will have immediate implications for clinical practice and for the design of clinical trials. Additionally, this training will provide the skills and experience needed to become an independent researcher in the molecular and genetic epidemiology of female cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVARIAN HORMONE EFFECTS OF MUSCLE INJURY AND RECOVERY Principal Investigator & Institution: Schneider, Barbara A.; None; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2005 Summary: (provided by applicant): In the United States, there are about 57.6 million athletic and physically active women. More women are participating in high-intensity sports activities than ever before. Consequently, women as well as men are at risk for eccentric contraction-induced injury. Eccentric contraction-induced injury occurs when the extrinsic load on a stretched muscle exceeds the amount of force produced by that muscle. However, there are no criteria that enable health care providers to effectively predict which group(s) of women (e.g., premenopausal women and/or women taking oral contraceptives or hormone replacement therapy) have an increased susceptibility to develop eccentric contraction-induced injury. The long-term objective of our research program is to understand how personal factors, such as gender, influence eccentric contraction-induced injury and recovery. Limited study suggests that female gender may be one personal factor. The specific aims of the proposal are to determine the independent and interactional effects of estradiol and progesterone on 1) susceptibility to develop eccentric contraction-induced injury and 2) host defense (inflammatory) response to eccentric contraction-induced injury. The hypotheses are 1) estradiol alone increases injury susceptibility; 2) progesterone attenuates the estradiol increased injury susceptibility; and 3) a combination of estradiol and progesterone delays recovery by inhibiting and delaying the host defense response to eccentric contraction-induced injury. The hypotheses will be tested using intact mice (mice that have ovaries) and ovariectomized mice (mice that have had their ovaries surgically removed). The ovariectomized mice will be treated with placebo, estradiol alone, progesterone alone, or a combination of estradiol and progesterone. Slow-twitch and fast-twitch muscles of both intact and ovariectomized mice will undergo eccentric contraction-induced injury.

30

Oral Contraceptives

Then functional and structural changes and magnitude of macrophage infiltration will be measured in injured muscles. Findings may have implications for women of varying ovarian hormone status when they engage in high-intensity eccentric contractions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PAIN AND ANALGESIC RESPONSE--SEX AND HORMONE VARIATIONS Principal Investigator & Institution: Comer, Sandra D.; Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 30-JUN-2004 Summary: The majority of studies involving experimentally-induced pain have shown that women are more sensitive to pain than men. Unfortunately, many of the pain procedures that have found sex differences confound sensory (the ability to discriminate pain) and emotional (subjective reports of pain) variables by treating pain as a single dimension, when in fact pain varies along a range of dimensions. Further, while data suggest that sex differences in pain response may be related to circulating gonadal hormones, the definition and measurement of menstrual cycle phase has been inadequate. The purpose of the present application is to more fully investigate sex differences in response to painful stimuli, specifically focusing on 1) the influence of gonadal hormones on pain responsivity and 2) the analgesic response to mu (morphine) and kappa (butorphanol) opioid agonists. Each study will use two pain procedures: the cold pressor test, which combines sensory and emotional aspects of pain, and the mechanical pressure test, which yields data amenable to Signal Detection Theory analysis (i.e., can distinguish between sensory and emotional pain). Further, each study will compare normally-cycling women to women maintained on oral contraceptives and to men. Phase of the cycle will be verified via documentation of ovulation in normally-cycling women and hormone levels (estradiol and progesterone) in all participants. The first study will measure pain response at five different phases of the menstrual cycle (menstrual, follicular, ovulatory, luteal, and late luteal) in normallycycling women; women on oral contraceptives and men will be tested during the same five "phases." Studies 2 and 3 will compare the analgesic effect of butorphanol and morphine in the three groups across two menstrual-cycle phases (based on Study 1). A dose- response function for each drug will be obtained and blood samples will be collected to determine any pharmacokinetic differences across the three groups and cycle phases. These studies will provide important information regarding sex differences in analgesic response, which may be due to cyclical fluctuations in gonadal hormones. In addition, they will more carefully examine sex differences in analgesic response to butorphanol and morphine, two agonists with differing selectivities for mu and kappa opioid receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: RCT OF A NOVEL ORAL CONTRACEPTIVE INITIATION METHOD Principal Investigator & Institution: Westhoff, Carolyn L.; Associate Professor; Obstetrics and Gynecology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 29-AUG-2002; Project End 30-JUN-2005 Description (provided by applicant): Pregnancy rates are high among acceptors of oral contraceptives despite the effectiveness of the method. These pregnancies occur due to incorrect use and due to premature discontinuation of oral contraceptives. Failure to begin one contraceptives after receiving a prescription is a large subcategory. Up to 25%

Studies

31

of adolescents who seek oral contraceptives from family planning clinics never take the first pill. Failure to begin oral contraceptives may occur due to ambivalence, confusion about starting instructions, or due to intervening pregnancy. Conventional starting instructions for oral contraceptives require waiting until the next menstrual period, which may leave the client at high risk of pregnancy. Novel approaches to initiation may improve continuation and decrease pregnancy rates among young women seeking oral contraceptives. In order to increase initiation rates we developed a quick start approach in which the client swallows the first pill during the clinic visit under direct observation and then continues daily pill use without waiting for her next menses. Pregnancy tests emergency contraception are used as clinically indicated. In a pilot study of 250 women, those who swallowed the first pill in the clinic were more likely to continue to their second pack of pills than women who received conventional starting instructions (adjusted CR 2.74, 2.74, 95% C.I. 1.1-6.8). We also carried out a randomized trial comparing 90-day bleeding patterns in 113 women who were randomized to quick start or conventional start of a monophasic 35ug EE OC. 104 women completed the study. Bleeding patterns were identical in the quick start and conventional start groups with excellent power to rule out clinically important differences. To further evaluate the usefulness of quick start we propose a multi-enter randomized clinical trial in which we will enroll 2l00 women aged less than 25 years. Subjects will be recruited from 3 publicly funded clinics that primarily serve Hispanic and African-American urban populations of low socio-economic status. They will complete a baseline, 3 month and 6 month questionnaire. The primary aim of the trial is to assess oral contraceptive continuation rates and pregnancy rates. We anticipate 75% low up at 6 months. The major secondary aim is to evaluate the predictive power of the Transtheoretical Model constructs relevant to adoption of and adherence to oral contraceptives. We will also assess dual method use for STD prevention in the study to adoption of and adherence to oral contraceptives. We will also assess dual method use for STD prevention in the study population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RISK FACTORS FOR BREAST CANCER AMONG YOUNGER NURSES Principal Investigator & Institution: Willett, Walter C.; Professor and Chairman; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 17-JUL-1989; Project End 31-DEC-2003 Summary: We propose to continue the follow-up of over 116,000 women who in 1989 were enrolled in a prospective study to evaluate potentially modifiable risk factors for major health problems among younger women. In this unique cohort, the Nurses' Health Study II (NHS II), exposure information has been collected at two-year intervals in early adult life, and we have maintained over 90% response to follow-up questionnaires. The proposed specific aims build upon and extend the original objectives. Specifically, we will tet the following hypothesis for breast cancer and melanoma, the two most important malignancies in this age group, and will quantify and characterize associations that are observed: 1) higher intakes of specific carotenoids, dietary fiber, and unsaturated fat during adolescent and early adult life reduce risk of premenopausal breast cancer, whereas higher dietary glycemic load and intake of saturated fat increase risk; 2) higher levels of physical activity reduce risk of breast cancer (for this aim we will evaluate contributions of different activity levels during different stages of life, and assess the degree to which error in measuring activity or

32

Oral Contraceptives

recall bias can account for major inconsistencies in the literature); 3) current use of lower- dose oral contraceptives does not increase breast cancer risk, but long-term use before first pregnancy increases risk; 4) breast-feeding reduces risk of breast cancer among premenopausal women; 5) long duration of oral contraceptive use and low intake of specific antioxidants increase the risk of melanoma; and 6) higher plasma levels of IGF-1 increase breast cancer risk. In the proposed follow-up, we will continue to mail questionnaires to participants at two year intervals to update information on the primary exposures and relevant covariates, and to ascertain incident cases of cancer and other major illness. For all reported cancers, we seek medical records for confirmation and more detailed characteristics. Through 2003, we expect to ascertain 1,685 cases of invasive breast cancers and 301 invasive melanomas, thus providing substantial statistical power to address the above hypotheses. A nested case-control study of IGF-1 in relation to breast cancer will utilize the blood specimens currently being collected from approximately 30,000 participants. In addition to the above aims, the NHS II provides the exposure data and initial case identification to examine many other important outcomes among young women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF STROMA IN MAMMARY GLAND CELL PROLIFERATION Principal Investigator & Institution: Haslam, Sandra Z.; Professor; Physiology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2003; Project Start 01-JUL-1985; Project End 30-JUN-2008 Summary: (provided by applicant): Progestins (P) are major mitogens in the adult human breast and contribute significantly to breast cancer risk. Since P are widely used in oral contraceptives and in postmenopausal hormone replacement therapy it is critically important that their mechanims of action be understood. It is the goal of the proposed research to delineate the mechanisms of P-dependent proliferation in the normal mammary gland. In the current grant period, using the mouse mammary gland model, we have developed a minimally-supplemented, serum-free collagen gel primary culture system in which mammary epithelial organoids, made up from both luminal epithelial and myoepithelial cells, proliferate and undergo alveolar morphogenesis in response to P. In addition to P, these responses require mammary stroma derivedhepatocyte growth factor (HGF). Treatment with HGF alone induces proliferation and tubulo-ductal morphogenesis, whereas P alone does not induce proliferation but induces lumen formation that is associated with increased apoptosis. HGF+P increase proliferation above HGF alone and cause a change from ductal to alveolar morphology. This is a novel in vitro demonstration of a mitogenic and morphological response to P that recapitulates the proliferative and alveologenesis response to P in vivo. In addition a pro-apoptotic response to P in normal mammary cells has been identified. In this proposal we will determine whether and how P acts in the cytoplasm, possibly through an SH3 binding domain on the progesterone receptor (PR), to affect HGF/Met-activated pathways associated with mammary-specific tublogenesis (FAK, SHIP-1, PI3-K) and proliferation (ERK, Src/Myc) to inhibit tubulogenesis, promote proliferation and cause alveologenesis. We will also determine the effect of PR action in the nucleus, via its transcriptional activation function, on the expression of P-responsive target genes relevant to alveologenesis (Wnt-4) and proliferation (Met, cyclin D1, Myc). In addition will also identify the specific cells types (luminal epithelial, myoepithelial cells) in which these effects of P occur. Using cultures derived from PRA null or PRB null mice we will also determine the role of the two PR isoforms (A and B) in proliferation and alveologenesis. The long-term goal of this proposal is the delineation of the mechanisms

Studies

33

of P-dependent growth regulation in the adult normal mammary gland that may lead to novel strategies for the prevention and treatment of breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEX AND MENSTRUAL CYCLE EFFECTS ON PAIN AND ANALGESIA Principal Investigator & Institution: Fillingim, Roger B.; Associate Professor; Operative Dentistry; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-MAR-2004 Summary: The influence of sex and gender on pain perception and pain modulatory systems is a research topic of substantial basic science and clinical import. Studies in nonhuman animals and humans indicate greater sensitivity to experimental pain among females. Sex differences in opioid analgesia have also been reported, but are not well characterized in humans. The mechanisms underlying these sex-related differences in pain modulator have not been determined; although, considerable evidence from animals suggests that baseline pain sensitivity and opioid-mediated analgesia vary across the estrous cycle. However, among humans, findings relating pain sensitivity to menstrual cycle phase are inconsistent, and the effects of menstrual cycle phase an opioid analgesia have not been investigated. The studies proposed in this application are designed to further elucidate the nature and mechanisms of sex- related differences in pain modulation by investigating baseline pain sensitivity and opioid analgesia as a function of sex, menstrual cycle phase and oral contraceptive use. Two clinically relevant laboratory pain induction procedures will be used in these studies: 1) temporal summation of thermal pain, and 2) ischemic arm pain. In the proposed study, responses to temporal summation and isochemic procedures will be obtained in females and males before and after administration of morphine, pentazocine and placebo (saline). In addition, two groups of females will be studies: females not taking oral contraceptives (OC) and females taking OC. Both groups of females will participate in each drug condition once during the follicular and once during the luteal phase of the menstrual cycle, and males will participate at similar time intervals. It is hypothesized that: 1) females, regardless of OC status, will exhibit greater baseline pain sensitivity than males, 2) females not taking OC will be more pain sensitive during the luteal compared to the follicular phase of the menstrual cycle, while females taking OC will show no change in pain responses across cycle phase; 3) males will exhibit greater morphine analgesia than females, while females will exhibit greater analgesia to pentazocine than males, and 4) females not taking OC will exhibit less opioid analgesia during the luteal versus the follicular phase of the menstrual cycle, while no menstrual cycle effects on analgesia will emerge for females taking OC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TREATMENT OF ENDOMETRIOSIS-ASSOCIATED PELVIC PAIN Principal Investigator & Institution: Guzick, David S.; Professor and Chair; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Approximately one-third of women with chronic pelvic pain have endometriosis. Surgical treatment of endometriosis with laparoscopic excision of implants and lysis of adhesions is often successful in reducing pain in the short term. Furthermore, several postoperative medical treatments have been shown to be efficacious in maintaining pain reduction for as long as the medication is continued.

34

Oral Contraceptives

After stopping the medication, however, the level of pain tends to trend upwards towards pre-treatment levels. The desired postoperative treatment is one that is can be used for a long period of time, so as to minimize the chance of pain recurrence. Simplicity of administration and cost-effectiveness are other desirable characteristics of an ideal postoperative regimen. The only FDA approved 12-month treatment for endometriosis-associated pain is a combination of leuprolide acetate (a GnRH analog), 11.25 mg IM q 12 weeks, and norethindrone acetate, 5 mg PO daily. Use of this regimen has been constrained by its complexity and cost. As an alternative, the continuous use of oral contraceptives has been advocated as a practical, inexpensive strategy for longterm medical treatment of endometriosis-associated pain. Although such an approach is frequently used in clinical practice, there has been no clinical trial of its efficacy. The goal of this project is to compare the efficacy and cost-effectiveness of continuous oral contraceptives and leuprolide+norethindrone in the postoperative treatment of endometriosis-associated pelvic pain. Investigators at the University of Rochester School of Medicine and Harvard Medical School will recruit 194 women for randomization to one of the two treatments, each of which will continue for 48 weeks. Randomization will occur after biopsy-proven endometriosis is established. Pelvic pain and quality-of-life assessments will be obtained at regular intervals. The recruitment goal is 88 subjects per arm after a 10% drop-our rate. Change scores for these measures will be compared between the two treatments. The study has 80% power to test non-inferiority of oral contraceptives at the 5% level of significance, using a 1-point difference in the change scores for pain as the threshold. In addition, a cost-effectiveness analysis will be performed by calculating the cost per unit reduction in pain score for each treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: URINARY EXCRETION OF DEOXYPYRIDINOLINE CROSSLINKS AND N-TELOPEPTIDES Principal Investigator & Institution: Phelps, John; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: The purpose of this study is to investigate the influence of low dose oral contraceptives on bone resorption in perimenopausal women as determined by urinary markers of bone metabolism. Twenty healthy perimenopausal women will be enrolled. The perimenopausal women will meet all inclusion criteria prior to enrollment. Inclusion criteria Will include 1) age between 45-50 years, 2) change in menstrual cycle interval, 3) complaints of hot flashes, 4) elevated follicular or luteal phase FSH and 5) serum creatinine < 1.5 mg/dI. Patients who have been longer than 6 months without a menstrual cycle or have taken hormonal therapy within the preceding 6 months will be excluded. In addition, women who smoke, have a history of taking bisphosphonates, calcitonin, or calcitriol, or who have a history of parathyroid disease will be excluded. Two baseline urine specimens from the first morning void will be collected on two separate days from patients enrolled in the study. Urinary concentrations of deoxypyridinoline crosslinks will be measured using Pyrlinks-D (Metra Biosystems, Mountain View, CA) enzyme-linked immunoassay. Urinary concentrations of Ntelopeptides will be measures using Osteomark (Ostex, Seattle, WA) enzyme-linked immunoassay. Concentrations of deoxypyridinoline crosslinks and N-telopeptides from the two baseline urine specimens will be averaged to determine the baseline excretion prior to initiating hormonal therapy. Patients will then be given Loestrin (Parke-Davis, Morris Plains, NJ), containing 20 mcg ethinyl estradiol with I mg norethindrone acetate the following Sunday. Urinary specimens obtained from the first morning void will be

Studies

35

collected on a weekly basis for a total of four weeks after initiation of Loestrin. The urinary specimens will be assayed for both deoxypyridinoline crosslinks and Ntelopeptides. Concentrations of urinary deoxypyridinoline crosslinks and Ntelopeptides prior to and after each successive week of oral contraceptive pill use win then be compared. A one-tailed Student's t-test will be used for statistical analysis. Significance will be defined as a P value < 0.05. The power of the study is anticipated to be greater than 0.80 based on previous responses to estrogen therapy on urinary niarkers of bone metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WOMEN'S MELANOMA RISK Principal Investigator & Institution: Karagas, Margaret R.; Professor; Community and Family Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-AUG-1995; Project End 30-JUN-2004 Summary: (Adapted from applicant's abstract): We propose to continue our collaborative study of melanoma risk factors in women. We hypothesize that some of the risk factors for breast cancer also may influence women's risk of melanoma. In the initial grant period, we found evidence of a reduced risk of melanoma associated with higher parity and earlier age at first birth. We propose to extend our investigation to two other hormone-related factors associated with breast cancer risk -- body weight and alcohol use. Recent results also indicate an excess melanoma risk among current or recent oral contraceptive users. To provide a more detailed analysis of the effects of oral contraceptives, we will add data from two large case-control studies completed since our study began. Additionally, we will systematically examine whether artificial tanning devices, used by an increasing number of women worldwide, affect risk of melanoma. We will perform a standard set of analyses on data collected on over 6,500 women (about 3,000 melanoma cases and over 3,500 controls). The proposed work will encompass the largest group to date of women melanoma case and control subjects who have had risk factor information collected through personal interviews. Therefore, we will be able to explore hypotheses that have not been previously considered and could not be fully addressed in a single study. Our findings will help identify the factors that place women at greatest risk for melanoma and ultimately aid the prevention of these malignancies. 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 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 “oral contraceptives” (or synonyms) into the search box. This search gives you 3 4

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

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.

36

Oral Contraceptives

access to full-text articles. The following is a sample of items found for oral contraceptives in the PubMed Central database: •

Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users who are carriers of hereditary prothrombotic conditions. by de Bruijn SF, Stam J, Koopman MM, Vandenbroucke JP.; 1998 Feb 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28462

•

Effect of 1995 pill scare on rates of venous thromboembolism among women taking combined oral contraceptives: analysis of General Practice Research Database. by Farmer RD, Williams TJ, Simpson EL, Nightingale AL.; 2000 Aug 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27461

•

Influence of the third generation pill controversy on prescriptions for oral contraceptives among first time users: population based study. by de Jong-van den Berg L, Tobi H, Bijker B, van den Berg P.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140762

•

Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General Practitioners' oral contraception study. by Beral V, Hermon C, Kay C, Hannaford P, Darby S, Reeves G.; 1999 Jan 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27684

•

No Interaction between Ciprofloxacin and an Oral Contraceptive. by Scholten PC, Droppert RM, Zwinkels MG, Moesker HL, Nauta JJ, Hoepelman IM.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106032

•

Oral contraceptive use and bone mineral density in premenopausal women: crosssectional, population-based data from the Canadian Multicentre Osteoporosis Study. by Prior JC, Kirkland SA, Joseph L, Kreiger N, Murray TM, Hanley DA, Adachi JD, Vigna YM, Berger C, Blondeau L, Jackson SA, Tenenhouse A.; 2001 Oct 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81536

•

Oral contraceptive use before first birth and risk of breast cancer: a case control study. by Hemminki E, Luostarinen T, Pukkala E, Apter D, Hakulinen T.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122097

•

Oral contraceptives and myocardial infarction. by Hoey J.; 2002 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100931

•

Oral contraceptives and myocardial infarction: results of the MICA case-control study. by Dunn N, Thorogood M, Faragher B, de Caestecker L, MacDonald TM, McCollum C, Thomas S, Mann R.; 1999 Jun 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28136

•

Oral contraceptives and the risk of breast cancer. by Farquhar D.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126514

•

Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis. by Jick H, Kaye JA, VasilakisScaramozza C, Jick SS.; 2000 Nov 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27524

•

Third generation oral contraceptives and risk of venous thrombosis: meta-analysis. by Kemmeren JM, Algra A, Grobbee DE.; 2001 Jul 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34722

Studies

•

37

Using epidemiological data to guide clinical practice: review of studies on cardiovascular disease and use of combined oral contraceptives. by Hannaford PC, Owen-Smith V.; 1998 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28503

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 oral contraceptives, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “oral contraceptives” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for oral contraceptives (hyperlinks lead to article summaries): •

A comparison of cycle control, efficacy, and side effects among healthy Thai women between two low-dose oral contraceptives containing 20 microg ethinylestradio1/75 microg gestodene (Meliane) and 30 microg ethinylestradio1/75 microg gestodene (Gynera). Author(s): Taneepanichskul S, Kriengsinyot R, Jaisamrarn U. Source: Contraception. 2002 December; 66(6): 407-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499032

•

A pilot study on the effect of oral contraceptives on electromyography and mechanomyography during isometric muscle actions. Author(s): Drake SM, Evetovich T, Eschbach C, Webster M. Source: Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. 2003 June; 13(3): 297-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12706609

•

A prospective study evidencing rhinomanometric and olfactometric outcomes in women taking oral contraceptives. Author(s): Cochrane Database Syst Rev. 2003;(2):CD002032 Source: Human Reproduction (Oxford, England). 2001 November; 16(11): 2288-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804421

6

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.

38

Oral Contraceptives

•

A prospective study of the effects of oral contraceptives on sexuality and well-being and their relationship to discontinuation. Author(s): Sanders SA, Graham CA, Bass JL, Bancroft J. Source: Contraception. 2001 July; 64(1): 51-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11535214

•

A randomized controlled trial of second- versus third-generation oral contraceptives in the treatment of acne vulgaris. Author(s): Rosen MP, Breitkopf DM, Nagamani M. Source: American Journal of Obstetrics and Gynecology. 2003 May; 188(5): 1158-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748463

•

A randomized study over 13 cycles to assess the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on carbohydrate metabolism. Author(s): Gaspard U, Scheen A, Endrikat J, Buicu C, Lefebvre P, Gerlinger C, Heithecker R. Source: Contraception. 2003 June; 67(6): 423-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814810

•

A scheme of combined oral contraceptives for women more than 40 years old. Author(s): Blumel JE, Castelo-Branco C, Binfa L, Aparicio R, Mamani L. Source: Menopause (New York, N.Y.). 2001 July-August; 8(4): 286-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11449087

•

Acceptability of emergency contraception in Brazil, Chile, and Mexico: 1 - Perceptions of emergency oral contraceptives. Author(s): Diaz S, Hardy E, Alvarado G, Ezcurra E. Source: Cadernos De Saude Publica / Ministerio Da Saude, Fundacao Oswaldo Cruz, Escola Nacional De Saude Publica. 2003 September-October; 19(5): 1507-17. Epub 2003 December 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14666232

•

Acute renal artery occlusion in a 15-year-old girl taking oral contraceptives. Author(s): Saint F, Quintela R, Salomon L, Cicco A, Olsson E, Chopin D, Abbou CC. Source: Bju International. 2002 May; 89(7): 787-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966649

•

Advance provision of oral contraceptives to family planning clients in Kenya. Author(s): Stanback J, Qureshi ZP, Sekkade-Kigondu C. Source: East Afr Med J. 2002 May; 79(5): 257-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12638810

Studies

39

•

Alcohol intake, androgen and glucocorticoid steroids in premenopausal women using oral contraceptives: an interventional study. Author(s): Sarkola T, Adlercreutz H, Heinonen S, Eriksson CJ. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 August; 78(2): 157-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11566440

•

Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives. Author(s): Mastorakos G, Koliopoulos C, Creatsas G. Source: Fertility and Sterility. 2002 May; 77(5): 919-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12009344

•

Antibiotic interference with oral contraceptives. Author(s): ADA Council on Scientific Affairs. Source: The Journal of the American Dental Association. 2002 July; 133(7): 880. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12148681

•

Antibiotics and oral contraceptives. Author(s): DeRossi SS, Hersh EV. Source: Dent Clin North Am. 2002 October; 46(4): 653-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12436822

•

Antiepileptic drugs: coprescription of proconvulsant drugs and oral contraceptives: a national study of antiepileptic drug prescribing practice. Author(s): Shorvon SD, Tallis RC, Wallace HK. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 January; 72(1): 114-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11784837

•

APC resistance and third-generation oral contraceptives: Acquired resistance to activated protein C, oral contraceptives and the risk of thromboembolic disease. Author(s): Gris JC, Jamin C, Benifla JL, Quere I, Madelenat P, Mares P. Source: Human Reproduction (Oxford, England). 2001 January; 16(1): 3-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11139527

•

Are oral contraceptives (OCPs) with anti-androgenic progestins preferred over other OCPs in patients with acne? Author(s): Johnson KH. Source: The Journal of Family Practice. 2002 January; 51(1): 86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927074

40

Oral Contraceptives

•

Assessment of DNA damage in women using oral contraceptives. Author(s): Biri A, Civelek E, Karahalil B, Sardas S. Source: Mutation Research. 2002 November 26; 521(1-2): 113-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438009

•

Attitudes of female patients regarding oral contraceptives for treatment of acne. Author(s): Tan JK, Vasey K, Fung KY. Source: Journal of Cutaneous Medicine and Surgery. 2001 November-December; 5(6): 471-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907854

•

Auditory brainstem response in premenopausal women taking oral contraceptives. Author(s): Caruso S, Maiolino L, Rugolo S, Intelisano G, Farina M, Cocuzza S, Serra A. Source: Human Reproduction (Oxford, England). 2003 January; 18(1): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525445

•

Barriers to use of oral contraceptives in ethnic Chinese women presenting for abortion. Author(s): Wiebe ER, Sent L, Fong S, Chan J. Source: Contraception. 2002 February; 65(2): 159-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927119

•

Benefits and risks of combined oral contraceptives. Author(s): Vessey MP. Source: Methods of Information in Medicine. 1993 April; 32(3): 222-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8341154

•

Beyond ovulation: oral contraceptives and epithelial ovarian cancer. Author(s): Siskind V, Green A, Bain C, Purdie D. Source: Epidemiology (Cambridge, Mass.). 2000 March; 11(2): 106-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11021605

•

Biological coagulation findings in third-generation oral contraceptives. Author(s): Conard J. Source: Human Reproduction Update. 1999 November-December; 5(6): 672-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10652977

•

Biphasic versus monophasic oral contraceptives for contraception. Author(s): Van Vliet HA, Grimes DA, Helmerhorst FM, Schulz KF. Source: Cochrane Database Syst Rev. 2003; (2): Cd002032. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804421

Studies

41

•

Biphasic versus monophasic oral contraceptives for contraception. Author(s): Cochrane Database Syst Rev. 2003;(2):CD003283 Source: Cochrane Database Syst Rev. 2001; (4): Cd002032. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804457

•

Biphasic versus monophasic oral contraceptives for contraception. Author(s): Van Vliet H, Grimes DA, Helmerhorst F, Schulz K. Source: Cochrane Database Syst Rev. 2001; (2): Cd002032. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406026

•

Biphasic versus monophasic oral contraceptives for contraception: a Cochrane review. Author(s): Van Vliet HA, Grimes DA, Helmerhorst FM, Schulz KF. Source: Human Reproduction (Oxford, England). 2002 April; 17(4): 870-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11925375

•

Biphasic versus triphasic oral contraceptives for contraception. Author(s): Van Vliet HA, Grimes DA, Helmerhorst FM, Schulz KF. Source: Cochrane Database Syst Rev. 2003; (2): Cd003283. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804457

•

Biphasic versus triphasic oral contraceptives for contraception. Author(s): van Vliet HA, Grimes DA, Helmerhorst FM, Schulz KF. Source: Contraception. 2002 May; 65(5): 321-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12057781

•

Biphasic versus triphasic oral contraceptives for contraception. Author(s): Van Vliet H, Grimes D, Helmerhorst F, Schulz K. Source: Cochrane Database Syst Rev. 2001; (4): Cd003283. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687185

•

Bleeding patterns of women using Lunelle monthly contraceptive injections (medroxyprogesterone acetate and estradiol cypionate injectable suspension) compared with those of women using Ortho-Novum 7/7/7 (norethindrone/ethinyl estradiol triphasic) or other oral contraceptives. Author(s): Garceau RJ, Wajszczuk CJ, Kaunitz AM; Lunelle Study Group. Source: Contraception. 2000 December; 62(6): 289-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11239615

•

Blood coagulation and oral contraceptives. A critical review. Author(s): Winkler UH. Source: Contraception. 1998 March; 57(3): 203-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9617536

42

Oral Contraceptives

•

Bone mineral density at various anatomic bone sites in women receiving combined oral contraceptives and depot-medroxyprogesterone acetate for contraception. Author(s): Wanichsetakul P, Kamudhamas A, Watanaruangkovit P, Siripakarn Y, Visutakul P. Source: Contraception. 2002 June; 65(6): 407-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12127638

•

Bone mineral density in adolescent and young Thai girls receiving oral contraceptives compared with depot medroxyprogesterone acetate: a cross-sectional study in young Thai women. Author(s): Tharnprisarn W, Taneepanichskul S. Source: Contraception. 2002 August; 66(2): 101-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12204782

•

Bone mineral density in young, hypothalamic oligoamenorrheic women treated with oral contraceptives. Author(s): Castelo-Branco C, Vicente JJ, Pons F, Martinez de Osaba MJ, Casals E, Vanrell JA. Source: J Reprod Med. 2001 October; 46(10): 875-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11725730

•

Breast cancer and oral contraceptives: patterns of risk among parous and nulliparous women--further analysis of the Swedish-Norwegian material. Author(s): Meirik O, Farley TM, Lund E, Adami HO, Christoffersen T, Bergsjo P. Source: Contraception. 1989 May; 39(5): 471-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2721197

•

Breast cancer and specific types of oral contraceptives: a large Norwegian cohort study. Author(s): Dumeaux V, Alsaker E, Lund E. Source: International Journal of Cancer. Journal International Du Cancer. 2003 July 20; 105(6): 844-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12767072

•

Breastfeeding and oral contraceptives. Exploring opinions on the options. Author(s): Adams DM. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2000 June-July; 4(3): 45-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11249388

Studies

43

•

Budd-Chiari syndrome: combination of genetic defects and the use of oral contraceptives leading to hypercoagulability. Author(s): Minnema MC, Janssen HL, Niermeijer P, de Man RA. Source: Journal of Hepatology. 2000 September; 33(3): 509-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11020010

•

Cardiovascular events associated with different combined oral contraceptives: a review of current data. Author(s): Hannaford P. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2000 May; 22(5): 361-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10830253

•

Cardiovascular issues with oral contraceptives: evidenced-based medicine. Author(s): Burkman RT. Source: Int J Fertil Womens Med. 2000 March-April; 45(2): 166-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10831186

•

Changes in GABAA receptor gamma 2 subunit gene expression induced by long-term administration of oral contraceptives in rats. Author(s): Follesa P, Porcu P, Sogliano C, Cinus M, Biggio F, Mancuso L, Mostallino MC, Paoletti AM, Purdy RH, Biggio G, Concas A. Source: Neuropharmacology. 2002 March; 42(3): 325-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897111

•

Changes in prescription patterns of oral contraceptives in a northern Italian province: relation with venous thromboembolism. Author(s): Girolami A, Spiezia L, Vianello F, Girolami B, Fabris F. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2003 April; 9(2): 125-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812381

•

Chapter 3: Cofactors in human papillomavirus carcinogenesis--role of parity, oral contraceptives, and tobacco smoking. Author(s): Castellsague X, Munoz N. Source: J Natl Cancer Inst Monogr. 2003; (31): 20-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807941

44

Oral Contraceptives

•

Clinical comparative study of oral contraceptives containing 30 microg ethinylestradiol/150 microg levonorgestrel, and 35 microg ethinylestradiol/250 microg norgestimate in Thai women. Author(s): Tantbirojn P, Taneepanichskul S. Source: Contraception. 2002 December; 66(6): 401-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499031

•

Clinical practice. Combination estrogen-progestin oral contraceptives. Author(s): Petitti DB. Source: The New England Journal of Medicine. 2003 October 9; 349(15): 1443-50. Review. Erratum In: N Engl J Med. 2004 January 1; 350(1): 92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534338

•

Clozapine and oral contraceptives: a possible drug interaction. Author(s): Gabbay V, O'Dowd MA, Mamamtavrishvili M, Asnis GM. Source: Journal of Clinical Psychopharmacology. 2002 December; 22(6): 621-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12454563

•

Combined estrogen-progestin oral contraceptives. Author(s): Sutherland SE, Munarriz RM, Goldstein I. Source: The New England Journal of Medicine. 2004 January 15; 350(3): 307-8; Author Reply 307-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732939

•

Combined estrogen-progestin oral contraceptives. Author(s): Martinelli I, Battaglioli T, Mannucci PM. Source: The New England Journal of Medicine. 2004 January 15; 350(3): 307-8; Author Reply 307-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724315

•

Combined oral contraceptives and the risk of myocardial infarction. Author(s): Keeling D. Source: Annals of Medicine. 2003; 35(6): 413-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572165

•

Combined oral contraceptives do not increase the risk of back and pelvic pain during pregnancy or after delivery. Author(s): Bjorklund K, Nordstrom ML, Odlind V. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2000 November; 79(11): 979-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11081684

Studies

45

•

Combined oral contraceptives do not influence post-exercise hypotension in women. Author(s): Birch K, Cable N, George K. Source: Experimental Physiology. 2002 September; 87(5): 623-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12481937

•

Communication about contraception and knowledge of oral contraceptives amongst Norwegian high school students. Author(s): Hansen T, Skjeldestad FE. Source: Journal of Adolescence. 2003 August; 26(4): 481-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12887936

•

Comparison of the lipoprotein, carbohydrate, and hemostatic effects of phasic oral contraceptives containing desogestrel or levonorgestrel. Author(s): Knopp RH, Broyles FE, Cheung M, Moore K, Marcovina S, Chandler WL. Source: Contraception. 2001 January; 63(1): 1-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11257242

•

Concurrent use of oral contraceptives with antidepressants for premenstrual syndromes. Author(s): Freeman EW, Rickels K, Sondheimer SJ, Polansky M. Source: Journal of Clinical Psychopharmacology. 2001 October; 21(5): 540-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11593086

•

Congenital and acquired thrombotic risk factors in women using oral contraceptives: clinical aspects. Author(s): Mira Y, Aznar J, Estelles A, Vaya A, Villa P, Ferrando F. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2000 July; 6(3): 162-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10898277

•

Crohn's disease activity not affected by oral contraceptives. Author(s): Green BT, DiPalma JA. Source: The American Journal of Gastroenterology. 2000 June; 95(6): 1585-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10894603

•

Cycle characteristics after discontinuation of oral contraceptives. Author(s): Gnoth C, Frank-Herrmann P, Schmoll A, Godehardt E, Freundl G. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 August; 16(4): 307-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12396560

46

Oral Contraceptives

•

Cycle control, tolerability, and satisfaction among women switching from 30-35 microg ethinyl estradiol-containing oral contraceptives to the triphasic norgestimate/25 microg ethinyl estradiol-containing oral contraceptive Ortho TriCyclen LO. Author(s): Poindexter AN, Burkman R, Fisher AC, LaGuardia KD. Source: Int J Fertil Womens Med. 2003 July-August; 48(4): 163-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13677549

•

Data from transnational study of oral contraceptives have been misused. Author(s): Spitzer WO. Source: Bmj (Clinical Research Ed.). 1995 October 28; 311(7013): 1162. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7580717

•

Deaths fom venous thromboembolism associated with combined oral contraceptives. Author(s): Price H. Source: Lancet. 1997 August 9; 350(9075): 450. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9289596

•

Decline in cerebral thromboembolism among young women after introduction of low-dose oral contraceptives: an incidence study for the period 1980-1993. Author(s): Lidegaard O. Source: Contraception. 1995 August; 52(2): 85-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8536452

•

Decreased plasma tissue factor pathway inhibitor in women taking combined oral contraceptives. Author(s): Harris GM, Stendt CL, Vollenhoven BJ, Gan TE, Tipping PG. Source: American Journal of Hematology. 1999 March; 60(3): 175-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10072106

•

Desogestrel versus gestodene in oral contraceptives: influence on the clinical and histomorphological features of benign breast disease. Author(s): Di Lieto A, De Rosa G, Albano G, Pagnano AM, Campanile M, Terracciano L, Pontillo M, Cimmino E, Covelli A, Paladini A. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1994 May 31; 55(1): 71-83. Erratum In: Eur J Obstet Gynecol Reprod Biol 1995 January; 58(1): 101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7958144

Studies

47

•

Differences in the use of combined oral contraceptives amongst women with and without acne. Author(s): Seaman HE, de Vries CS, Farmer RD. Source: Human Reproduction (Oxford, England). 2003 March; 18(3): 515-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615817

•

Different effects of oral contraceptives containing levonorgestrel or desogestrel on plasma lipoproteins and coagulation factor VII. Author(s): van Rooijen M, von Schoultz B, Silveira A, Hamsten A, Bremme K. Source: American Journal of Obstetrics and Gynecology. 2002 January; 186(1): 44-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810082

•

Disturbance of withdrawal bleeding during concomitant use of itraconazole and oral contraceptives. Author(s): Meyboom RH, van Puijenbroek EP, Vinks MH, Lastdrager CJ. Source: N Z Med J. 1997 August 8; 110(1049): 300. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9293288

•

Diurnal rhythm and effects of oral contraceptives on serum dehydroepiandrosterone sulfate (DHEAS) are related to alterations in serum albumin rather than to changes in adrenocortical steroid secretion. Author(s): Carlstrom K, Karlsson R, Von Schoultz B. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2002; 62(5): 361-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12387582

•

Do antibiotics decrease effectiveness of oral contraceptives? Author(s): Cottet C. Source: Oreg Nurse. 1996 September; 61(3): 4-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9006212

•

Do different brands of oral contraceptives differ in their effects on cardiovascular disease? Author(s): Crook D. Source: British Journal of Obstetrics and Gynaecology. 1997 May; 104(5): 516-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9166189

•

Do oral contraceptives improve vocal quality? Limited trial on low-dose formulations. Author(s): Amir O, Biron-Shental T, Muchnik C, Kishon-Rabin L. Source: Obstetrics and Gynecology. 2003 April; 101(4): 773-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12681885

48

Oral Contraceptives

•

Do third-generation oral contraceptives (OCs) increase the risk of venous thrombosis? Author(s): Sapp AV, Lindbloom EJ. Source: The Journal of Family Practice. 2001 October; 50(10): 893. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11674894

•

Does anovulation induced by oral contraceptives favor pregnancy during the following two menstrual cycles? Author(s): Fukuda M, Fukuda K, Yding Andersen C, Byskov AG. Source: Fertility and Sterility. 2000 April; 73(4): 742-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10731535

•

Does evidence-based medicine provide evidence? The evidence on breast cancer and the safety of oral contraceptives suggests that unorthodox interpretations may be just as valid. Author(s): Reynolds TM, Wierzbicki AS. Source: The Breast Journal. 2003 January-February; 9(1): 66-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12558680

•

Does the menstrual cycle and use of oral contraceptives influence the risk of low back pain? A prospective study among female soccer players. Author(s): Brynhildsen JO, Hammar J, Hammar ML. Source: Scandinavian Journal of Medicine & Science in Sports. 1997 December; 7(6): 34853. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9458501

•

DoH seems to have underestimated incidence of venous thromboembolism in users of combined oral contraceptives. Author(s): Lawrenson RA, Whalley A, Simpson E, Farmer RD. Source: Bmj (Clinical Research Ed.). 1999 August 7; 319(7206): 387. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10435982

•

Drug interactions between oral contraceptives and antibiotics. Author(s): Lindsey JL, Hugin M. Source: Obstetrics and Gynecology. 2002 May; 99(5 Pt 1): 841-2; Author Reply 842. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978298

•

Drug interactions between oral contraceptives and antibiotics. Author(s): Dickinson BD, Altman RD, Nielsen NH, Sterling ML; Council on Scientific Affairs, American Medical Association. Source: Obstetrics and Gynecology. 2001 November; 98(5 Pt 1): 853-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704183

Studies

49

•

Dual suppression with oral contraceptives and gonadotrophin releasing-hormone agonists improves in-vitro fertilization outcome in high responder patients. Author(s): Damario MA, Barmat L, Liu HC, Davis OK, Rosenwaks Z. Source: Human Reproduction (Oxford, England). 1997 November; 12(11): 2359-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9436663

•

Effect of combined oral contraceptives on bone mineral density in pre and postmenopausal women. Author(s): Sultana S, Choudhury S, Choudhury SA. Source: Mymensingh Med J. 2002 January; 11(1): 12-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12148389

•

Effect of four different oral contraceptives on various sex hormones and serumbinding globulins. Author(s): Wiegratz I, Kutschera E, Lee JH, Moore C, Mellinger U, Winkler UH, Kuhl H. Source: Contraception. 2003 January; 67(1): 25-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12521654

•

Effect of four oral contraceptives on thyroid hormones, adrenal and blood pressure parameters. Author(s): Wiegratz I, Kutschera E, Lee JH, Moore C, Mellinger U, Winkler UH, Kuhl H. Source: Contraception. 2003 May; 67(5): 361-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742558

•

Effect of oral contraceptives and intrauterine devices on midcycle myometrial contractions. Author(s): Maslow KD, Lyons EA. Source: Fertility and Sterility. 2003 November; 80(5): 1224-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607579

•

Effect of oral contraceptives on lacrimal fluid peroxidase activity in women. Author(s): Liberati V, de Feo G, Madia F, Marcozzi G. Source: Ophthalmic Research. 2002 July-August; 34(4): 251-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12297698

•

Effect of oral contraceptives on respiratory function. Author(s): Resmi SS, Samuel E, Kesavachandran C, Shashidhar S. Source: Indian J Physiol Pharmacol. 2002 July; 46(3): 361-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12613402

50

Oral Contraceptives

•

Effect of oral contraceptives on the transport of chlorpromazine across the CACO-2 intestinal epithelial cell line. Author(s): Brown D, Goosen TC, Chetty M, Hamman JH. Source: European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V. 2003 September; 56(2): 159-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957628

•

Effect of second- and third-generation oral contraceptives on the protein C system in the absence or presence of the factor VLeiden mutation: a randomized trial. Author(s): Kemmeren JM, Algra A, Meijers JC, Tans G, Bouma BN, Curvers J, Rosing J, Grobbee DE. Source: Blood. 2004 February 1; 103(3): 927-33. Epub 2003 October 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551147

•

Effects of oral contraceptives on acute cocaine response in female volunteers. Author(s): Kouri EM, Lundahl LH, Borden KN, McNeil JF, Lukas SE. Source: Pharmacology, Biochemistry, and Behavior. 2002 December; 74(1): 173-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376165

•

Effects of oral contraceptives on glucose flux and substrate oxidation rates during rest and exercise. Author(s): Suh SH, Casazza GA, Horning MA, Miller BF, Brooks GA. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 January; 94(1): 28594. Epub 2002 September 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12391078

•

Effects of oral contraceptives on peak exercise capacity. Author(s): Casazza GA, Suh SH, Miller BF, Navazio FM, Brooks GA. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2002 November; 93(5): 1698-702. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12381756

•

Effects of oral contraceptives on total serum proteins, albumin, globulins and cholesterol levels in Ibadan, Nigeria. Author(s): Obisesan KA, Adenaike FA, Okunlola MA, Adenaike AA. Source: West Afr J Med. 2002 July-September; 21(3): 197-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12744566

Studies

51

•

Effects of oral contraceptives with low-dose estrogen and desogestrel on leptin concentrations. Author(s): Sagsoz N, Akcay F, Bayram M. Source: J Reprod Med. 2002 July; 47(7): 545-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12170530

•

Effects of putative male pheromones on female ratings of male attractiveness: influence of oral contraceptives and the menstrual cycle. Author(s): Thorne F, Neave N, Scholey A, Moss M, Fink B. Source: Neuroendocrinol Lett. 2002 August; 23(4): 291-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195229

•

Effects of two oral contraceptives on plasma levels of nitric oxide, homocysteine, and lipid metabolism. Author(s): Merki-Feld GS, Imthurn B, Keller PJ. Source: Metabolism: Clinical and Experimental. 2002 September; 51(9): 1216-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200770

•

Efficacy of second versus third generation oral contraceptives in the treatment of hirsutism. Author(s): Breitkopf DM, Rosen MP, Young SL, Nagamani M. Source: Contraception. 2003 May; 67(5): 349-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742556

•

Emerging evidence on oral contraceptives and arterial disease. Author(s): Heinemann LA. Source: Contraception. 2000 August; 62(2 Suppl): 29S-36S; Discussion 37S-38S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11102600

•

Estrogen fluctuations, oral contraceptives and borderline personality. Author(s): DeSoto MC, Geary DC, Hoard MK, Sheldon MS, Cooper L. Source: Psychoneuroendocrinology. 2003 August; 28(6): 751-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812862

•

Estrogen-containing oral contraceptives are allowable in young women with factor V Leiden heterozygosity without a history of thrombosis. Author(s): Budev MM, Abu-Hajir M, Deitcher SR, Gomes MP. Source: The Medical Clinics of North America. 2003 November; 87(6): 1225-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14680303

52

Oral Contraceptives

•

Evolution and treatment of migraine with oral contraceptives. Author(s): Massiou H, MacGregor EA. Source: Cephalalgia : an International Journal of Headache. 2000 April; 20(3): 170-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10997770

•

Factor V Leiden and third-generation oral contraceptives. Author(s): Westhoff C. Source: Lancet. 1996 February 10; 347(8998): 396-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8598719

•

Factor VII activation and oral contraceptives. Author(s): Plu-Bureau G, Scarabin PY, Bara L, Malmejac A, Guize L, Samama M. Source: Thrombosis Research. 1993 May 1; 70(3): 275-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8327993

•

Factors influencing the reliability of oral contraceptives. Author(s): Hansen TH, Lundvall F. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1997 January; 76(1): 61-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9033246

•

Failure of hepatic adenomas (HCA) to regress after discontinuance of oral contraceptives. An association with focal nodular hyperplasia (FNH) and uterine leiomyoma. Author(s): Marks WH, Thompson N, Appleman H. Source: Annals of Surgery. 1988 August; 208(2): 190-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2840865

•

Fatal cerebral venous sinus thrombosis associated with the factor V Leiden mutation and the use of oral contraceptives. Author(s): Bridey F, Wolff M, Laissy JP, Morin V, Lefebvre M, de Prost D. Source: Thrombosis and Haemostasis. 1995 November; 74(5): 1382. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8607129

•

Fatal pulmonary venoocclusive disease after use of oral contraceptives. Author(s): Townend JN, Roberts DH, Jones EL, Davies MK. Source: American Heart Journal. 1992 December; 124(6): 1643-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1462933

•

Fatal stroke and use of oral contraceptives: findings from a case-control study. Author(s): Thorogood M, Mann J, Murphy M, Vessey M. Source: American Journal of Epidemiology. 1992 July 1; 136(1): 35-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1415130

Studies

53

•

Female adolescents' perceptions of benefits of and barriers to using oral contraceptives. Author(s): Hanna KM. Source: Issues in Comprehensive Pediatric Nursing. 1994 January-March; 17(1): 47-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7928454

•

Female workforce participation, use of oral contraceptives, and the sex ratio of Crohn's disease incidence. Author(s): Alic M. Source: The American Journal of Gastroenterology. 2000 January; 95(1): 328-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10638625

•

First-time use of newer oral contraceptives and the risk of venous thromboembolism. Author(s): Suissa S, Blais L, Spitzer WO, Cusson J, Lewis M, Heinemann L. Source: Contraception. 1997 September; 56(3): 141-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9347203

•

Fluid retention with oral contraceptives. Author(s): Smals AG. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 December; 14(6): 476-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11228070

•

Folic acid deficiency, megaloblastic anemia and peripheral polyneuropathy due to oral contraceptives. Author(s): Kornberg A, Segal R, Theitler J, Yona R, Kaufman S. Source: Isr J Med Sci. 1989 March; 25(3): 142-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2540115

•

Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives. Author(s): London BM, Lookingbill DP. Source: Archives of Dermatology. 1994 March; 130(3): 392-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8129425

•

FSH and ovarian response: spontaneous recovery of pituitary-ovarian activity during the pill-free period vs. exogenous recombinant FSH during high-dose combined oral contraceptives. Author(s): van Heusden AM, Coelingh Bennink HJ, Fauser BC. Source: Clinical Endocrinology. 2002 April; 56(4): 509-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966744

54

Oral Contraceptives

•

Functional ovarian cysts in relation to the use of monophasic and triphasic oral contraceptives. Author(s): Robinson JC. Source: Obstetrics and Gynecology. 1992 September; 80(3 Pt 1): 472-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1495708

•

Functional ovarian cysts in relation to the use of monophasic and triphasic oral contraceptives. Author(s): Holt VL, Daling JR, McKnight B, Moore D, Stergachis A, Weiss NS. Source: Obstetrics and Gynecology. 1992 April; 79(4): 529-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1553170

•

Gender, menstrual cycle, oral contraceptives and red blood cell deformability in healthy adult subjects. Author(s): Guillet R, Driss F, Perrotin P, Pautou C, Nalpas B, Boynard M. Source: Clinical Hemorheology and Microcirculation. 1998 October; 19(2): 83-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9849921

•

Generalized peliosis hepatis and cirrhosis after long-term use of oral contraceptives. Author(s): van Erpecum KJ, Janssens AR, Kreuning J, Ruiter DJ, Kroon HM, Grond AJ. Source: The American Journal of Gastroenterology. 1988 May; 83(5): 572-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3129933

•

Genetic testing for breast and ovarian cancer for women with a family history of breast cancer: weighing conflicting evidence about oral contraceptives. Author(s): Friedenson B, Friedenson H. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2002 August 30; 4(3): 3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466746

•

Gestational trophoblastic disease and use of oral contraceptives. Author(s): Rosenberg L, Palmer JR, Shapiro S. Source: American Journal of Obstetrics and Gynecology. 1989 October; 161(4): 1087-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2552806

•

Gestodene and desogestrel do not have a different influence on concentration profiles of ethinylestradiol in women taking oral contraceptives--results of isotope dilution mass spectrometry measurements. Author(s): Siekmann L, Siekmann A, Bidlingmaier F, Brill K, Albring M. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1998 August; 139(2): 167-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9724072

Studies

55

•

Glucose and lipid metabolism with triphasic oral contraceptives in women with history of gestational diabetes. Author(s): Kung AW, Ma JT, Wong VC, Li DF, Ng MM, Wang CC, Lam KS, Young RT, Ma HK. Source: Contraception. 1987 March; 35(3): 257-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3111786

•

Glucose metabolism and insulin resistance in women with polycystic ovary syndrome during therapy with oral contraceptives containing cyproterone acetate or desogestrel. Author(s): Cagnacci A, Paoletti AM, Renzi A, Orru M, Pilloni M, Melis GB, Volpe A. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3621-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915645

•

Glucose tolerance during moderate prolonged exercise in women with oral contraceptives as compared to non-users. Author(s): Boisseau N, Rannou F, Delamarche P, Bentue-Ferrer D, Gratas-Delamarche A. Source: The Journal of Sports Medicine and Physical Fitness. 2001 June; 41(2): 203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11447363

•

Gonadotropin suppression with oral contraceptives before in vitro fertilization. Author(s): Gonen Y, Jacobson W, Casper RF. Source: Fertility and Sterility. 1990 February; 53(2): 282-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2105244

•

Good news about oral contraceptives. Author(s): Davidson NE, Helzlsouer KJ. Source: The New England Journal of Medicine. 2002 June 27; 346(26): 2078-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087145

•

Group comparison of serum ethinyl estradiol, SHBG and CBG levels in 83 women using two low-dose combination oral contraceptives for three months. Author(s): Dibbelt L, Knuppen R, Jutting G, Heimann S, Klipping CO, Parikka-Olexik H. Source: Contraception. 1991 January; 43(1): 1-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1825969

•

Guidelines for prescribing combined oral contraceptives. Author(s): Mills AM, Wilkinson CL, Bromham DR, Elias J, Fotherby K, Guillebaud J, Kubba A, Wade A. Source: Bmj (Clinical Research Ed.). 1996 January 13; 312(7023): 121-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8555906

56

Oral Contraceptives

•

Have oral contraceptives reduced the prevalence of acne? a population-based study of acne vulgaris, tobacco smoking and oral contraceptives. Author(s): Jemec GB, Linneberg A, Nielsen NH, Frolund L, Madsen F, Jorgensen T. Source: Dermatology (Basel, Switzerland). 2002; 204(3): 179-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037444

•

Health benefits of oral contraceptives. Author(s): Jensen JT, Speroff L. Source: Obstetrics and Gynecology Clinics of North America. 2000 December; 27(4): 70521. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11091985

•

Health consequences of combined oral contraceptives. Author(s): Hannaford P. Source: British Medical Bulletin. 2000; 56(3): 749-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11255559

•

Health policy and third-generation oral contraceptives. Author(s): Michaels MA, Norpoth T. Source: Human Reproduction (Oxford, England). 1996 April; 11(4): 691-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8671302

•

Hemorrhage caused by ruptured liver cell adenoma following long-term oral contraceptives: a case report. Author(s): Meissner K. Source: Hepatogastroenterology. 1998 January-February; 45(19): 224-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9496518

•

Hemostatic and metabolic effects of lowering the ethinyl-estradiol dose from 30 mcg to 20 mcg in oral contraceptives containing desogestrel. Author(s): Basdevant A, Conard J, Pelissier C, Guyene TT, Lapousterle C, Mayer M, Guy-Grand B, Degrelle H. Source: Contraception. 1993 September; 48(3): 193-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8222650

•

Hemostatic effects of oral contraceptives in women who developed deep-vein thrombosis while using oral contraceptives. Author(s): Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Koster T, Bertina RM, Vandenbroucke JP. Source: Thrombosis and Haemostasis. 1998 September; 80(3): 382-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9759614

Studies

57

•

Hemostatic effects of third- and second-generation oral contraceptives: absence of a causal mechanism for a difference in risk of venous thromboembolism. Author(s): Winkler UH. Source: Contraception. 2000 August; 62(2 Suppl): 11S-20S; Discussion 37S-38S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11102598

•

Hemostatic effects of two oral contraceptives containing low doses of ethinyl estradiol and either gestodene or norgestimate: an open, randomized, parallel-group study. Author(s): Winkler UH, Oberhoff C, Bier U, Schindler AE, Gillain D. Source: Int J Fertil Menopausal Stud. 1995 September-October; 40(5): 260-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8556031

•

Hepatocellular carcinoma associated with precocious puberty and oral contraceptives. A case report. Author(s): Mansvelt B, Etienne PY, Bertrand C, Henrion J, Gerard R. Source: Acta Chir Belg. 2003 August; 103(4): 412-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14524163

•

High concentrations of prostate-specific antigen in urine of women receiving oral contraceptives. Author(s): Mannello F, Condemi L, Cardinali A, Bianchi G, Gazzanelli G. Source: Clinical Chemistry. 1998 January; 44(1): 181-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9550578

•

High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives. Author(s): Martinelli I, Sacchi E, Landi G, Taioli E, Duca F, Mannucci PM. Source: The New England Journal of Medicine. 1998 June 18; 338(25): 1793-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9632445

•

Higher risk of venous thrombosis during early use of oral contraceptives in women with inherited clotting defects. Author(s): Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Source: Archives of Internal Medicine. 2000 January 10; 160(1): 49-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10632304

•

Hormonal content and potency of oral contraceptives and breast cancer risk among young women. Author(s): Althuis MD, Brogan DR, Coates RJ, Daling JR, Gammon MD, Malone KE, Schoenberg JB, Brinton LA. Source: British Journal of Cancer. 2003 January 13; 88(1): 50-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556959

58

Oral Contraceptives

•

Hormonal oral contraceptives, urinary porphyrin excretion and porphyrias. Author(s): Gross U, Honcamp M, Daume E, Frank M, Dusterberg B, Doss MO. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1995 August; 27(8): 379-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7590628

•

Hormone replacement therapy and previous use of oral contraceptives among Swedish women. Author(s): Hammar M, Brynhildsen J, Dabrosin L, Frisk J, Lindgren R, Nedstrand E, Wyon Y. Source: Maturitas. 1996 November; 25(3): 193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8981336

•

Human immunodeficiency virus transmission and oral contraceptives. Author(s): Nicolosi A. Source: The Journal of Infectious Diseases. 1993 May; 167(5): 1256-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8486967

•

Human papillomavirus infection and use of oral contraceptives. Author(s): Green J, Berrington de Gonzalez A, Smith JS, Franceschi S, Appleby P, Plummer M, Beral V. Source: British Journal of Cancer. 2003 June 2; 88(11): 1713-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771986

•

Hyperglycaemic episodes in a young woman after taking levonorgestrel-containing oral contraceptives. Author(s): Rennie NJ. Source: N Z Med J. 1994 October 26; 107(988): 440-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7970351

•

Hypertension, genotype and oral contraceptives. Author(s): Mulatero P, Morra di Cella S, Veglio F. Source: Pharmacogenomics. 2002 January; 3(1): 57-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966403

•

Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk. Author(s): Schildkraut JM, Calingaert B, Marchbanks PA, Moorman PG, Rodriguez GC. Source: Journal of the National Cancer Institute. 2002 January 2; 94(1): 32-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11773280

Studies

59

•

Importance of levonorgestrel dose in oral contraceptives for effects on coagulation. Author(s): Kluft C, de Maat MP, Heinemann LA, Spannagl M, Schramm W. Source: Lancet. 1999 September 4; 354(9181): 832-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10485729

•

Incidence of venous thromboembolism in users of combined oral contraceptives. Methods for identifying cases and estimating person time at risk must be detailed. Author(s): Jick H. Source: Bmj (Clinical Research Ed.). 2000 January 1; 320(7226): 57; Author Reply 57-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10617543

•

Incidence of venous thromboembolism in users of combined oral contraceptives. Risk is particularly high with first use of oral contraceptives. Author(s): Vandenbrouke JP, Bloemenkamp KW, Rosendaal FR, Helmerhorst FM. Source: Bmj (Clinical Research Ed.). 2000 January 1; 320(7226): 57-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10671043

•

Incomplete compensation following the ban on third generation oral contraceptives. Author(s): Leader A. Source: Human Reproduction (Oxford, England). 1998 May; 13(5): 1118. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9647525

•

Inconsistent use of oral contraceptives in rural Bangladesh. Author(s): Khan MA, Trottier DA, Islam MA. Source: Contraception. 2002 June; 65(6): 429-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12127643

•

Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized crossover study of two low-dose oral contraceptives. Author(s): Meijers JC, Middeldorp S, Tekelenburg W, van den Ende AE, Tans G, Prins MH, Rosing J, Buller HR, Bouma BN. Source: Thrombosis and Haemostasis. 2000 July; 84(1): 9-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10928462

•

Increased serum FSH in female fragile X premutation carriers with either regular menstrual cycles or on oral contraceptives. Author(s): Hundscheid RD, Braat DD, Kiemeney LA, Smits AP, Thomas CM. Source: Human Reproduction (Oxford, England). 2001 March; 16(3): 457-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11228211

60

Oral Contraceptives

•

Influence of gender and oral contraceptives on CYP2D6 and CYP2C19 activity in healthy volunteers. Author(s): Hagg S, Spigset O, Dahlqvist R. Source: British Journal of Clinical Pharmacology. 2001 February; 51(2): 169-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11259990

•

Influence of gestodene and desogestrel as components of low-dose oral contraceptives on the pharmacokinetics of ethinyl estradiol (EE2), on serum CBG and on urinary cortisol and 6 beta-hydroxycortisol. Author(s): Hammerstein J, Daume E, Simon A, Winkler UH, Schindler AE, Back DJ, Ward S, Neiss A. Source: Contraception. 1993 March; 47(3): 263-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8462317

•

Influence of low-dose oral contraceptives, alcohol, and grapefruit on. Author(s): Van Vlierberghe H, Van Durme F, Verdievel H, Dhont M, de Vos M, Elewaut A. Source: Digestive Diseases and Sciences. 2001 January; 46(1): 133-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11270777

•

Influence of menstrual cycle and oral contraceptives on tolerance to uncompensable heat stress. Author(s): Tenaglia SA, McLellan TM, Klentrou PP. Source: European Journal of Applied Physiology and Occupational Physiology. 1999 July; 80(2): 76-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10408316

•

Influence of smoking and oral contraceptives on bone mineral density and bone remodeling in young women: a 2-year study. Author(s): Elgan C, Samsioe G, Dykes AK. Source: Contraception. 2003 June; 67(6): 439-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814812

•

Influence of the third generation pill controversy on prescriptions for oral contraceptives among first time users: population based study. Author(s): de Jong-van den Berg L, Tobi H, Bijker B, van den Berg P. Source: Bmj (Clinical Research Ed.). 2003 February 1; 326(7383): 254. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12560275

Studies

61

•

Influence of two low-dose oral contraceptives on pulsatile gonadotropin secretion. Author(s): Schleussner E, Brueckner T, Brautigam J, Michels W. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2001 August; 15(4): 259-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11560098

•

Inhibition of follicular growth by two different oral contraceptives (monophasic and triphasic) containing ethinylestradiol and gestodene. Author(s): Lete I, Morales P. Source: The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception. 1997 September; 2(3): 187-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9678091

•

Insulin sensitivity in non-obese women with polycystic ovary syndrome during treatment with oral contraceptives containing low-androgenic progestin. Author(s): Cibula D, Sindelka G, Hill M, Fanta M, Skrha J, Zivny J. Source: Human Reproduction (Oxford, England). 2002 January; 17(1): 76-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11756365

•

International Headache Society (IHS) Task Force on oral contraceptives (OCs) and hormone replacement therapy (HRT) used in migraine sufferers. Author(s): Bousser MG. Source: Cephalalgia : an International Journal of Headache. 2000 April; 20(3): 147; Discussion 145-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10997765

•

Is there an increased risk of stroke associated with oral contraceptives? Author(s): Zeitoun K, Carr BR. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1999 June; 20(6): 467-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10392664

•

Ischemic stroke risk with oral contraceptives: A meta-analysis. Author(s): Gillum LA, Mamidipudi SK, Johnston SC. Source: Jama : the Journal of the American Medical Association. 2000 July 5; 284(1): 72-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10872016

•

Kudos to the Food and Drug Administration: reversal of the package insert warning for birth defects for oral contraceptives. Author(s): Brent RL. Source: Teratology. 1989 January; 39(1): 93-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2718144

62

Oral Contraceptives

•

Lack of effect of rosiglitazone on the pharmacokinetics of oral contraceptives in healthy female volunteers. Author(s): Cochrane Database Syst Rev. 2001;(4):CD002032 Source: Journal of Clinical Pharmacology. 2001 June; 41(6): 683-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687135

•

Lack of objectivity in the debate concerning third-generation oral contraceptives and venous thrombosis. Author(s): Egermayer P, Frampton C. Source: Archives of Internal Medicine. 2001 February 12; 161(3): 484-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11176782

•

Lamotrigine plasma levels reduced by oral contraceptives. Author(s): Sabers A, Buchholt JM, Uldall P, Hansen EL. Source: Epilepsy Research. 2001 November; 47(1-2): 151-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11673029

•

Lansoprazole does not affect the bioavailability of oral contraceptives. Author(s): Fuchs W, Sennewald R, Klotz U. Source: British Journal of Clinical Pharmacology. 1994 October; 38(4): 376-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7833230

•

Latin american experience with two low-dose oral contraceptives containing 30 microg ethinylestradiol/75 microg gestodene and 20 microg ethinylestradiol/150 microg desogestrel. Author(s): Bassol S, Alvarado A, Celis C, Cravioto MC, Peralta O, Montano R, Novelli J, Albornoz H, Kesseru E, Soares A, Petracco A, Isaia B, Mendes J, Bahamondes L, de Melo NR, Reyes-Marquez R, Albrecht G. Source: Contraception. 2000 September; 62(3): 131-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11124360

•

Lipid and lipoprotein changes in women taking low-dose, triphasic oral contraceptives: a controlled, comparative, 12-month clinical trial. Author(s): Notelovitz M, Feldman EB, Gillespy M, Gudat J. Source: American Journal of Obstetrics and Gynecology. 1989 May; 160(5 Pt 2): 1269-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2655452

•

Lipid metabolism effects with desogestrel-containing oral contraceptives. Author(s): Burkman RT. Source: American Journal of Obstetrics and Gynecology. 1993 March; 168(3 Pt 2): 103340. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8447357

Studies

63

•

Liver adenoma and focal nodular hyperplasia associated with oral contraceptives. Author(s): Tajada M, Nerin J, Ruiz MM, Sanchez-Dehesa M, Fabre E. Source: The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception. 2001 December; 6(4): 227-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11848652

•

Liver damage from low-dose oral contraceptives. Author(s): Lindgren A, Olsson R. Source: Journal of Internal Medicine. 1993 September; 234(3): 287-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8354979

•

Long-term effects of combined oral contraceptives on markers of endothelial function and lipids in healthy premenopausal women. Author(s): Merki-Feld GS, Rosselli M, Dubey RK, Jager AW, Keller PJ. Source: Contraception. 2002 March; 65(3): 231-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11929645

•

Long-term effects of oral contraceptives on ovarian cancer risk. Author(s): Bosetti C, Negri E, Trichopoulos D, Franceschi S, Beral V, Tzonou A, Parazzini F, Greggi S, La Vecchia C. Source: International Journal of Cancer. Journal International Du Cancer. 2002 November 20; 102(3): 262-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397647

•

Low dose oral contraceptives and quality of life. Author(s): Egarter C, Topcuoglu MA, Imhof M, Huber J. Source: Contraception. 1999 May; 59(5): 287-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10494481

•

Low goitre prevalence among users of oral contraceptives in a population sample of 3712 women. Author(s): Knudsen N, Bulow I, Laurberg P, Perrild H, Ovesen L, Jorgensen T. Source: Clinical Endocrinology. 2002 July; 57(1): 71-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100072

•

Low-dose oral contraceptives and 24-hour ambulatory blood pressure. Author(s): Cardoso F, Polonia J, Santos A, Silva-Carvalho J, Ferreira-de-Almeida J. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1997 December; 59(3): 237-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9486514

64

Oral Contraceptives

•

Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study. Author(s): Rosing J, Middeldorp S, Curvers J, Christella M, Thomassen LG, Nicolaes GA, Meijers JC, Bouma BN, Buller HR, Prins MH, Tans G. Source: Lancet. 1999 December 11; 354(9195): 2036-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10636369

•

Low-dose oral contraceptives and bone mineral density: an evidence-based analysis. Author(s): Kuohung W, Borgatta L, Stubblefield P. Source: Contraception. 2000 February; 61(2): 77-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10802271

•

Low-dose oral contraceptives. Author(s): Rough GJ. Source: The Medical Journal of Australia. 1993 July 5; 159(1): 69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8316130

•

Low-dose oral contraceptives: health consequences of discontinuation. Author(s): Ansbacher R. Source: Contraception. 2000 December; 62(6): 285-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11239614

•

Low-dose oral contraceptives: protective effect on ovarian cancer risk. Author(s): Royar J, Becher H, Chang-Claude J. Source: International Journal of Cancer. Journal International Du Cancer. 2001 November 20; 95(6): 370-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11668519

•

Low-oestrogen oral contraceptives as a major risk factor for cerebral venous and sinus thrombosis: evidence from a clinical series. Author(s): Buccino G, Scoditti U, Pini M, Tagliaferri AR, Manotti C, Mancia D. Source: Italian Journal of Neurological Sciences. 1999 August; 20(4): 231-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10551909

•

Malignant melanoma and the prognostic implications of pregnancy, oral contraceptives, and exogenous hormones. Author(s): Slingluff CL Jr, Reintgen D. Source: Seminars in Surgical Oncology. 1993 May-June; 9(3): 228-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8516609

Studies

65

•

Managing the transition from oral contraceptives to hormone replacement therapy. Author(s): Burkman RT. Source: Am J Manag Care. 2001 November; 7(18 Suppl): S575-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11727396

•

Markers for cardiovascular disease in monozygotic twins discordant for the use of third-generation oral contraceptives. Author(s): Loos RJ, Verhaeghe J, De Zegher F, Beunen G, Derom C, Fagard R, Mathieu C, Vlietinck R. Source: Journal of Human Hypertension. 2003 July; 17(7): 481-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821955

•

Masculinizing effects on otoacoustic emissions and auditory evoked potentials in women using oral contraceptives. Author(s): McFadden D. Source: Hearing Research. 2000 April; 142(1-2): 23-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10748325

•

Maternal use of oral contraceptives and Down syndrome. Author(s): Kallen B. Source: Contraception. 1989 May; 39(5): 503-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2524361

•

Menstrual cycle symptom variation in a community sample of women using and not using oral contraceptives. Author(s): Sveinsdottir H, Backstrom T. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2000 September; 79(9): 757-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10993099

•

Menstrual nirvana: amenorrhea through the use of continuous oral contraceptives. Author(s): Edelman A. Source: Curr Womens Health Rep. 2002 December; 2(6): 434-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12429077

•

Metabolic and fibrinolytic response to changed insulin sensitivity in users of oral contraceptives. Author(s): Petersen KR, Christiansen E, Madsbad S, Skouby SO, Andersen LF, Jespersen J. Source: Contraception. 1999 December; 60(6): 337-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10715368

66

Oral Contraceptives

•

Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives. Author(s): Devenport MH, Crook D, Wynn V, Lees LJ. Source: British Journal of Clinical Pharmacology. 1989 June; 27(6): 851-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2547410

•

Metabolic effects of oral contraceptives. Implications for exercise responses of premenopausal women. Author(s): Bemben DA. Source: Sports Medicine (Auckland, N.Z.). 1993 November; 16(5): 295-304. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8272685

•

Methodological problems in the evaluation of drug induced sexual dysfunction for oral contraceptives. Author(s): Guichoux JY. Source: Therapie. 1993 September-October; 48(5): 447-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8146823

•

Migraine and stroke in young women. Authors' results suggest that all types of migraine are contraindications to oral contraceptives. Author(s): MacGregor EA, Guillebaud J. Source: Bmj (Clinical Research Ed.). 1999 May 29; 318(7196): 1485; Author Reply 1486. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10346783

•

Modern combined oral contraceptives for pain associated with endometriosis. Author(s): Moore J, Kennedy S, Prentice A. Source: Cochrane Database Syst Rev. 2000; (2): Cd001019. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10796731

•

Monocyte tissue factor expression is enhanced in women who smoke and use oral contraceptives. Author(s): Holschermann H, Terhalle HM, Zakel U, Maus U, Parviz B, Tillmanns H, Haberbosch W. Source: Thrombosis and Haemostasis. 1999 December; 82(6): 1614-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10613644

•

More on oral contraceptives, drug interactions, herbal medicines, and hormone replacement therapy. Author(s): Shader RI, Greenblatt DJ. Source: Journal of Clinical Psychopharmacology. 2000 August; 20(4): 397-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10917398

Studies

67

•

Multicenter, comparative study of cycle control, efficacy and tolerability of two lowdose oral contraceptives containing 20 microg ethinylestradiol/100 microg levonorgestrel and 20 microg ethinylestradiol/500 microg norethisterone. Author(s): Endrikat J, Hite R, Bannemerschult R, Gerlinger C, Schmidt W. Source: Contraception. 2001 July; 64(1): 3-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11535206

•

Myocardial infarction and oral contraceptives. Author(s): Arscott A, Nettelfield P. Source: Prof Nurse. 2001 February; 16(5): 1117-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12029914

•

Myocardial infarction and oral contraceptives. Author(s): SoRelle R. Source: Circulation. 2002 January 1; 105(1): E9063. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11772890

•

Myocardial infarction and stroke in young women: what is the impact of oral contraceptives? Author(s): Lewis MA. Source: American Journal of Obstetrics and Gynecology. 1998 September; 179(3 Pt 2): S68-77. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9753313

•

Myocardial infarction and third generation oral contraceptives: aggregation of recent studies. Author(s): Spitzer WO, Faith JM, MacRae KD. Source: Human Reproduction (Oxford, England). 2002 September; 17(9): 2307-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12202417

•

Neonatal choreoathetosis following prenatal exposure to oral contraceptives. Author(s): Profumo R, Toce S, Kotagal S. Source: Pediatrics. 1990 October; 86(4): 648-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2216639

•

Neoplastic effects of oral contraceptives. Author(s): Grimes DA. Source: Int J Fertil. 1991; 36 Suppl 1: 19-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1678377

68

Oral Contraceptives

•

New contraceptive eligibility checklists for provision of combined oral contraceptives and depot-medroxyprogesterone acetate in community-based programmes. Author(s): Stang A, Schwingl P, Rivera R. Source: Bulletin of the World Health Organization. 2000; 78(8): 1015-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10994285

•

New developments and practice guidelines: oral contraceptives and intrauterine devices. Author(s): Mishell DR Jr. Source: Contraception. 1998 September; 58(3 Suppl): 7S-8S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9807686

•

New generation oral contraceptives of nineties. Author(s): Chowdhury NN. Source: J Indian Med Assoc. 1992 February; 90(2): 26-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1588112

•

New progestin oral contraceptives and the female condom. Author(s): Gold MA. Source: Pediatric Annals. 1995 April; 24(4): 211-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7596650

•

New progestogens in oral contraceptives. Author(s): Runnebaum B, Rabe T. Source: American Journal of Obstetrics and Gynecology. 1987 October; 157(4 Pt 2): 105963. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2960242

•

Newer oral contraceptives and the risk of venous thromboembolism. Author(s): Walker AM. Source: Contraception. 1998 March; 57(3): 169-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9617533

•

No sex-related differences but significant inhibition by oral contraceptives of CYP2C19 activity as measured by the probe drugs mephenytoin and omeprazole in healthy Swedish white subjects. Author(s): Laine K, Tybring G, Bertilsson L. Source: Clinical Pharmacology and Therapeutics. 2000 August; 68(2): 151-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10976546

Studies

69

•

Noncontraceptive benefits of modern low-dose oral contraceptives. Author(s): Thorneycroft IH. Source: Advances in Contraception : the Official Journal of the Society for the Advancement of Contraception. 1992 October; 8 Suppl 1: 5-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1442250

•

Noncontraceptive benefits of oral contraceptives. Author(s): Mishell DR Jr. Source: J Reprod Med. 1993 December; 38(12 Suppl): 1021-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8120859

•

Noncontraceptive benefits of oral contraceptives. Author(s): Haas GG Jr. Source: J Okla State Med Assoc. 1992 March; 85(3): 135-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1564594

•

Noncontraceptive clinical benefits of oral contraceptives. Author(s): Burkman RT. Source: Int J Fertil. 1989; 34 Suppl: 50-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2576260

•

Non-protein bound dienogest in serum and salivary dienogest in women taking the oral contraceptives Certostat and Valette. Author(s): Klinger G, Piater T, Jager R, Kuntzel B, Schon R, Hobe G. Source: Pharmazie. 2001 April; 56(4): 325-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11338674

•

Norplant vs oral contraceptives. Author(s): Slawson DC, Shaughnessy AF. Source: The Journal of Family Practice. 1994 June; 38(6): 631-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8195741

•

Nutrient intakes of women who use oral contraceptives. Author(s): Masse PG. Source: Journal of the American Dietetic Association. 1991 September; 91(9): 1118-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1918767

•

Oral contraceptives and breast cancer: A note of caution for high-risk women. Author(s): Burke W. Source: Jama : the Journal of the American Medical Association. 2000 October 11; 284(14): 1837-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11025837

70

Oral Contraceptives

•

Oral contraceptives and cardiovascular outcomes: cause or bias? Author(s): Spitzer WO. Source: Contraception. 2000 August; 62(2 Suppl): 3S-9S; Discussion 37S-38S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11102597

•

Oral contraceptives and cardiovascular risk-an end to the debate? Author(s): Westhoff CL. Source: Contraception. 2000 August; 62(2 Suppl): 1S-2S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11102596

•

Oral contraceptives and compliance: reaction to cardiovascular alarm among users. Author(s): Tyden T, Bingefors K, Odlind V. Source: Advances in Contraception : the Official Journal of the Society for the Advancement of Contraception. 1999; 15(2): 133-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10997895

•

Oral contraceptives and epithelial ovarian cancer. Does dose matter? Author(s): Sanderson M, Williams MA, Weiss NS, Hendrix NW, Chauhan SP. Source: J Reprod Med. 2000 September; 45(9): 720-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11027080

•

Oral contraceptives and risk of breast cancer in women with a family history of breast cancer. Author(s): Kirkland LR. Source: Jama : the Journal of the American Medical Association. 2001 January 3; 285(1): 39, 40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11150095

•

Oral contraceptives and venous thromboembolism. Author(s): Skegg D. Source: N Z Med J. 2000 September 8; 113(1117): 385. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11050907

•

Oral contraceptives can cause falsely low vitamin B(12) levels. Author(s): Gardyn J, Mittelman M, Zlotnik J, Sela BA, Cohen AM. Source: Acta Haematologica. 2000; 104(1): 22-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11111117

Studies

71

•

Oral contraceptives do not affect magnesium in breast milk. Author(s): Dorea JG. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2000 October; 71(1): 25-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11044538

•

Oral contraceptives. Risks. Author(s): Shulman LP. Source: Obstetrics and Gynecology Clinics of North America. 2000 December; 27(4): 695704, V-Vi. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11091984

•

Pharmacology of progestogens used in oral contraceptives: an historical review to contemporary prescribing. Author(s): Kovacs GT. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2003 February; 43(1): 4-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12755340

•

Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil. Author(s): McGready R, Stepniewska K, Seaton E, Cho T, Cho D, Ginsberg A, Edstein MD, Ashley E, Looareesuwan S, White NJ, Nosten F. Source: European Journal of Clinical Pharmacology. 2003 October; 59(7): 553-7. Epub 2003 August 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955370

•

Prescribing oral contraceptives for women older than 35 years of age. Author(s): Seibert C, Barbouche E, Fagan J, Myint E, Wetterneck T, Wittemyer M. Source: Annals of Internal Medicine. 2003 January 7; 138(1): 54-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12513046

•

Prescribing oral contraceptives. Focusing on each woman as an individual case. Author(s): Tufts KA, Chung C. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2003 August-September; 7(4): 332-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528590

72

Oral Contraceptives

•

Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives. Author(s): Runnebaum IB, Wang-Gohrke S, Vesprini D, Kreienberg R, Lynch H, Moslehi R, Ghadirian P, Weber B, Godwin AK, Risch H, Garber J, Lerman C, Olopade OI, Foulkes WD, Karlan B, Warner E, Rosen B, Rebbeck T, Tonin P, Dube MP, Kieback DG, Narod SA. Source: Pharmacogenetics. 2001 October; 11(7): 635-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11668223

•

Pro-inflammatory effects of oestrogens during use of oral contraceptives and hormone replacement treatment. Author(s): Kluft C, Leuven JA, Helmerhorst FM, Krans HM. Source: Vascular Pharmacology. 2002 August; 39(3): 149-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12616983

•

Prospectively reported symptom change across the menstrual cycle in users and nonusers of oral contraceptives. Author(s): Ross C, Coleman G, Stojanovska C. Source: Journal of Psychosomatic Obstetrics and Gynaecology. 2003 March; 24(1): 15-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12685336

•

Prothrombotic activity of oral contraceptives in patients with congenital thrombophilia. Author(s): Aznar J, Mira Y. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2002 January; 8(1): 91-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11991247

•

Prothrombotic effects and clinical implications of third-generation oral contraceptives use. Author(s): Lippi G, Manzato F, Brocco G, Franchini M, Guidi G. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2002 January; 13(1): 69-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11994571

•

Provider resistance to advance provision of oral contraceptives in Africa. Author(s): Stanback J, Janowitz B. Source: The Journal of Family Planning and Reproductive Health Care / Faculty of Family Planning & Reproductive Health Care, Royal College of Obstetricians & Gynaecologists. 2003 January; 29(1): 35-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626181

Studies

73

•

Quantitation of plasma levels of tetranectin--effects of oral contraceptives, pregnancy, treatment with L-asparaginase and liver cirrhosis. Author(s): Kluft C, Los P, Clemmensen I, Brommer EJ, Gevers Leuven JA, Boks AL, Vellenga E. Source: Thrombosis and Haemostasis. 1989 September 29; 62(2): 792-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2814926

•

Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism. Author(s): Ludicke F, Gaspard UJ, Demeyer F, Scheen A, Lefebvre P. Source: Contraception. 2002 December; 66(6): 411-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499033

•

Re: Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Author(s): Rookus MA, Brohet R, van Leeuwen FE. Source: Journal of the National Cancer Institute. 2003 July 2; 95(13): 1012. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837843

•

Re: Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Author(s): de Bock GH, Tollenaar RA, Papelard H, Vliet Vlieland TP, Devilee P, Cornelisse CJ, Vandenbroucke JP. Source: Journal of the National Cancer Institute. 2003 July 2; 95(13): 1011-2; Author Reply 1012-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837842

•

Re: Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Author(s): Hopper JL, Baron JA. Source: Journal of the National Cancer Institute. 2003 July 2; 95(13): 1010-1; Author Reply 1012-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837841

•

Recommendations on the risk of ischaemic stroke associated with use of combined oral contraceptives and hormone replacement therapy in women with migraine. The International Headache Society Task Force on Combined Oral Contraceptives & Hormone Replacement Therapy. Author(s): Bousser MG, Conard J, Kittner S, de Lignieres B, MacGregor EA, Massiou H, Silberstein SD, Tzourio C. Source: Cephalalgia : an International Journal of Headache. 2000 April; 20(3): 155-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10997767

74

Oral Contraceptives

•

Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy. Author(s): Bork K, Fischer B, Dewald G. Source: The American Journal of Medicine. 2003 March; 114(4): 294-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12681457

•

Risk of invasive cancer of the cervix in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen oral contraceptives (South Africa). Author(s): Shapiro S, Rosenberg L, Hoffman M, Kelly JP, Cooper DD, Carrara H, Denny LE, du Toit G, Allan BR, Stander IA, Williamson AL. Source: Cancer Causes & Control : Ccc. 2003 June; 14(5): 485-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946044

•

Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives. Author(s): Martinelli I, Taioli E, Battaglioli T, Podda GM, Passamonti SM, Pedotti P, Mannucci PM. Source: Archives of Internal Medicine. 2003 December 8-22; 163(22): 2771-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662632

•

Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis. Author(s): Jick H, Kaye JA, Vasilakis-Scaramozza C, Jick SS. Source: Bmj (Clinical Research Ed.). 2000 November 11; 321(7270): 1190-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11073511

•

Risk of venous thrombosis in carriers of the prothrombin G20210A variant and factor V Leiden and their interaction with oral contraceptives. Author(s): Aznar J, Vaya A, Estelles A, Mira Y, Segui R, Villa P, Ferrando F, Falco C, Corella D, Espana F. Source: Haematologica. 2000 December; 85(12): 1271-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11114134

•

Selection of oral contraceptives or hormone replacement therapy: patient communication and counseling issues. Author(s): La Valleur J, Wysocki S. Source: American Journal of Obstetrics and Gynecology. 2001 August; 185(2 Suppl): S5764. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11521123

Studies

75

•

Serum concentrations of markers of type I collagen metabolism in women taking monophasic oral contraceptives. Author(s): Rechberger T, Baranowski W, Bogusiewicz M, Postawski K, Jakimiuk AJ, Tomaszewski J, Kulik-Rechberger B, Jakowicki JA. Source: Ginekol Pol. 2002 February; 73(2): 81-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12001776

•

Serum folate and Vitamin B12 levels in women using modern oral contraceptives (OC) containing 20 microg ethinyl estradiol. Author(s): Sutterlin MW, Bussen SS, Rieger L, Dietl J, Steck T. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2003 March 26; 107(1): 57-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593896

•

Short note: oral contraceptives and sleep in depressed and healthy women. Author(s): Burdick RS, Hoffmann R, Armitage R. Source: Sleep. 2002 May 1; 25(3): 347-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12003166

•

Should a patient with a history of melanoma be advised against the use of oral contraceptives? The relatives are worried. Author(s): Katz V, Balderston K. Source: Skinmed. 2003 November-December; 2(6): 382-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673253

•

Skin patch and vaginal ring versus combined oral contraceptives for contraception. Author(s): Gallo MF, Grimes DA, Schulz KF. Source: Cochrane Database Syst Rev. 2003; (1): Cd003552. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535478

•

Solar urticaria due to progesterone compounds in oral contraceptives. Author(s): Morison WL. Source: Photodermatology, Photoimmunology & Photomedicine. 2003 June; 19(3): 155-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12914601

•

St. John's wort and oral contraceptives: reasons for concern? Author(s): Murphy PA. Source: Journal of Midwifery & Women's Health. 2002 November-December; 47(6): 44750. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12484666

76

Oral Contraceptives

•

Successful use of oral contraceptives. Author(s): Burke AE, Blumenthal PD. Source: Seminars in Reproductive Medicine. 2001 December; 19(4): 313-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11727173

•

Sympathetic activity and baroreflex sensitivity in young women taking oral contraceptives. Author(s): Minson CT, Halliwill JR, Young TM, Joyner MJ. Source: Circulation. 2000 September 26; 102(13): 1473-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11004135

•

Termination of pregnancy following panic-stopping of oral contraceptives. Author(s): Goodyear-Smith F, Arroll B. Source: Contraception. 2002 September; 66(3): 163-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12384204

•

The effect of oral contraceptives on voice: preliminary observations. Author(s): Amir O, Kishon-Rabin L, Muchnik C. Source: Journal of Voice : Official Journal of the Voice Foundation. 2002 June; 16(2): 26773. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12150379

•

The patched polymorphism Pro1315Leu (C3944T) may modulate the association between use of oral contraceptives and breast cancer risk. Author(s): Chang-Claude J, Dunning A, Schnitzbauer U, Galmbacher P, Tee L, Wjst M, Chalmers J, Zemzoum I, Harbeck N, Pharoah PD, Hahn H. Source: International Journal of Cancer. Journal International Du Cancer. 2003 March 1; 103(6): 779-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516098

•

The place of combined oral contraceptives in contraception. Author(s): MacGregor EA, de Lignieres B. Source: Cephalalgia : an International Journal of Headache. 2000 April; 20(3): 157-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10997768

•

The RATIO study: oral contraceptives and the risk of peripheral arterial disease in young women. Author(s): Van Den Bosch MA, Kemmeren JM, Tanis BC, Mali WP, Helmerhorst FM, Rosendaal FR, Algra A, Van Der Graaf Y. Source: Journal of Thrombosis and Haemostasis : Jth. 2003 March; 1(3): 439-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12871447

Studies

77

•

The risk of cardiovascular disease with second- and third-generation oral contraceptives. Author(s): Kovacs P. Source: Medscape Women's Health [electronic Resource]. 2002 July-August; 7(4): 3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466735

•

The use of low dose oral contraceptives for the management of acne. Author(s): Lemay A, Langley RG. Source: Skin Therapy Letter. 2002 December; 7(10): 1-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658330

•

Timing within the menstrual cycle, sex, and the use of oral contraceptives determine adrenergic suppression of NK cell activity. Author(s): Shakhar K, Shakhar G, Rosenne E, Ben-Eliyahu S. Source: British Journal of Cancer. 2000 December; 83(12): 1630-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11104557

•

To what extent do oral contraceptives influence mood and affect? Author(s): Oinonen KA, Mazmanian D. Source: Journal of Affective Disorders. 2002 August; 70(3): 229-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12128235

•

Treatment of acne with oral contraceptives: criteria for pill selection. Author(s): Koulianos GT. Source: Cutis; Cutaneous Medicine for the Practitioner. 2000 October; 66(4): 281-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11109151

•

Ultra-low-dose oral contraceptives: are they right for your patient? Author(s): Thorneycroft IH, Cariati SL. Source: Medscape Women's Health [electronic Resource]. 2001 August; 6(4): 3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11811135

•

Ultrasound evaluation of ovarian activity under oral contraceptives. Author(s): Hoogland HJ, Skouby SO. Source: Contraception. 1993 June; 47(6): 583-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8334892

78

Oral Contraceptives

•

Use of multiphasic oral contraceptives and hospitalizations of women with functional ovarian cysts in the United States. Author(s): Grimes DA, Hughes JM. Source: Obstetrics and Gynecology. 1989 June; 73(6): 1037-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2726107

•

Use of oral contraceptives and breast cancer risk: The Norwegian-Swedish Women's Lifestyle and Health Cohort Study. Author(s): Kumle M, Weiderpass E, Braaten T, Persson I, Adami HO, Lund E. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 November; 11(11): 1375-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12433714

•

Use of oral contraceptives and endometrial cancer risk (Sweden). Author(s): Weiderpass E, Adami HO, Baron JA, Magnusson C, Lindgren A, Persson I. Source: Cancer Causes & Control : Ccc. 1999 August; 10(4): 277-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10482486

•

Use of oral contraceptives and risk of breast cancer in young women. Author(s): Ursin G, Ross RK, Sullivan-Halley J, Hanisch R, Henderson B, Bernstein L. Source: Breast Cancer Research and Treatment. 1998 July; 50(2): 175-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9822222

•

Use of oral contraceptives and uterine fibroids: results from a case-control study. Author(s): Chiaffarino F, Parazzini F, La Vecchia C, Marsico S, Surace M, Ricci E. Source: British Journal of Obstetrics and Gynaecology. 1999 August; 106(8): 857-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10453838

•

Use of oral contraceptives blunts the calciuric effect of caffeine in young adult women. Author(s): Ribeiro-Alves MA, Trugo LC, Donangelo CM. Source: The Journal of Nutrition. 2003 February; 133(2): 393-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12566473

•

Use of oral contraceptives by women who smoke. Author(s): Schiff I. Source: American Journal of Obstetrics and Gynecology. 1999 June; 180(6 Pt 2): S341-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10368518

Studies

79

•

Use of oral contraceptives in patients with migraine. Author(s): Becker WJ. Source: Neurology. 1999; 53(4 Suppl 1): S19-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10487509

•

Venous thromboembolic disease and combined oral contraceptives: A re-analysis of the MediPlus database. Author(s): Todd J, Lawrenson R, Farmer RD, Williams TJ, Leydon GM. Source: Human Reproduction (Oxford, England). 1999 June; 14(6): 1500-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10357966

•

Venous thromboembolism among new users of different oral contraceptives. Author(s): Herings RM, Urquhart J, Leufkens HG. Source: Lancet. 1999 July 10; 354(9173): 127-8. Erratum In: Lancet 1999 October 23; 354(9188): 1478. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10408492

•

Venous thromboembolism and combined oral contraceptives: does the type of progestogen make a difference? Author(s): Lawrenson R, Farmer R. Source: Contraception. 2000 August; 62(2 Suppl): 21S-28S; Discussion 37S-38S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11102599

•

Venous thromboembolism and oral contraceptives. Author(s): Lewis MA, MacRae KD, Kuhl-Habich D, Heinemann LA. Source: Lancet. 1999 October 23; 354(9188): 1470. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10543691

•

Venous thromboembolism and oral contraceptives. Author(s): D'Souza R, Guillebaud J. Source: Lancet. 1999 October 23; 354(9188): 1469; Author Reply 1469-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10543690

•

Venous thromboembolism and oral contraceptives. Author(s): Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Source: Lancet. 1999 October 23; 354(9188): 1469; Author Reply 1469-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10543689

•

Venous thromboembolism, oral contraceptives and high prothrombin levels. Author(s): Legnani C, Cosmi B, Valdre L, Boggian O, Bernardi F, Coccheri S, Palareti G. Source: Journal of Thrombosis and Haemostasis : Jth. 2003 January; 1(1): 112-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12871547

80

Oral Contraceptives

•

Venous thrombosis, oral contraceptives and high factor VIII levels. Author(s): Bloemenkamp KW, Helmerhorst FM, Rosendaal FR, Vandenbroucke JP. Source: Thrombosis and Haemostasis. 1999 September; 82(3): 1024-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10494758

•

What are the risks of third-generation oral contraceptives? Are third-generation oral contraceptives safe? Author(s): Rosenberg L, Begaud B, Bergman U, Brown B, Buist AS, Cramer D, Daling J, Grimes D, Kemper F, Mills A. Source: Human Reproduction (Oxford, England). 1996 April; 11(4): 687-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8724792

•

What is the risk of venous thromboembolism (VTE) among women taking thirdgeneration oral contraceptives (OCs) in comparison with those taking contraceptives containing levonorgestrel? Author(s): Meurer LN, Slawson JG. Source: The Journal of Family Practice. 2001 February; 50(2): 108. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11219554

•

When is it safe to switch from oral contraceptives to hormonal replacement therapy? Author(s): Castracane VD, Gimpel T, Goldzieher JW. Source: Contraception. 1995 December; 52(6): 371-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8749601

•

Women with thrombophilia: assessing the risks for thrombosis with oral contraceptives or hormone replacement therapy. Author(s): Waselenko JK, Nace MC, Alving B. Source: Seminars in Thrombosis and Hemostasis. 1998; 24 Suppl 1: 33-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9840690

•

Women's satisfaction with birth control: a population survey of physical and psychological effects of oral contraceptives, intrauterine devices, condoms, natural family planning, and sterilization among 1466 women. Author(s): Oddens BJ. Source: Contraception. 1999 May; 59(5): 277-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10494480

•

Women's satisfaction with Norplant as compared with oral contraceptives. Author(s): Eilers GM, Swanson TK. Source: The Journal of Family Practice. 1994 June; 38(6): 596-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8195734

Studies

81

83

CHAPTER 2. NUTRITION AND ORAL CONTRACEPTIVES Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and oral contraceptives.

Finding Nutrition Studies on Oral Contraceptives 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 “oral contraceptives” (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.

84

Oral Contraceptives

The following is a typical result when searching for recently indexed consumer information on oral contraceptives: •

The Journal of the American Medical Association, Volume 226, 1973: Megaloblastic changes in cervical epithelium. Association with oral contraceptive therapy and reversal with folic acid. Source: Whitehead, N Reyner, F Lindenbaum, J Nutr-Revolume 1989 October; 47(10): 318-21 0029-6643

The following information is typical of that found when using the “Full IBIDS Database” to search for “oral contraceptives” (or a synonym): •

A large observational clinical evaluation of a desogestrel-containing combiphasic oral contraceptive in Germany. Author(s): Medical Services, NV Organon, OSS, The Netherlands. Source: Vree, M L Schmidt, J Eur-J-Contracept-Reprod-Health-Care. 2001 June; 6(2): 10814 1362-5187

•

Application of the erythrocyte glutathione reductase test to the evaluation of vitamin B2 status in normal female subjects and in females taking oral contraceptive agents. Source: Tonkin, S.Y. Recent vitamin research / editor, Michael H. Briggs. Boca Raton, Fla. : CRC Press, c1984. page 127-176. ISBN: 0849356180

•

Approaches to the replacement of ethinylestradiol by natural 17beta-estradiol in combined oral contraceptives. Author(s): Jenapharm & Co. KG, Department R & D, Jena, Germany. Source: Hoffmann, H Moore, C Zimmermann, H Elger, W Schwarz, S Graser, T Oettel, M Exp-Toxicol-Pathol. 1998 September; 50(4-6): 458-64 0940-2993

•

Blood pressure stability in a normotensive population during intake of a monophasic oral contraceptive containing 20 microg ethinylestradiol and 75 g gestodene. Author(s): Schering AG, Berlin, Germany. Source: Endrikat, J Gerlinger, C Cronin, M Ruebig, A Schmidt, W Dusterberg, B Eur-JContracept-Reprod-Health-Care. 2001 September; 6(3): 159-66 1362-5187

•

Body weight change during use of a monophasic oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene with a comparison of the women who completed versus those who prematurely discontinued intake. Author(s): Schering AG, Berlin, Germany. Source: Endrikat, J Gerlinger, C Cronin, M Wessel, J Ruebig, A Rosenbaum, P Dusterberg, B Eur-J-Contracept-Reprod-Health-Care. 2001 December; 6(4): 199-204 13625187

•

Comparison of the effect on acne with a combiphasic desogestrel-containing oral contraceptive and a preparation containing cyproterone acetate. Author(s): Laakarikeskus Materna Oy, Kajaani, Finland. Source: Vartiainen, M de Gezelle, H Broekmeulen, C J Eur-J-Contracept-Reprod-HealthCare. 2001 March; 6(1): 46-53 1362-5187

•

Effects of an oral contraceptive combination with or without androgen on mammary tissues: a study in rats. Author(s): Pathology Associates International, Advance, NC 27006, USA. [email protected] Source: Jayo, M J Register, T C Hughes, C L Blas Machado, U Sulistiawati, E Borgerink, H Johnson, C S J-Soc-Gynecol-Investig. 2000 Jul-August; 7(4): 257-65 1071-5576

Nutrition

85

•

Effects of menstrual cycle phase and oral contraceptive use on intermittent exercise. Author(s): Scottish School of Sport Studies, University of Strathclyde, Glasgow, UK. Source: Lynch, N J Nimmo, M A Eur-J-Appl-Physiol-Occup-Physiol. 1998 November; 78(6): 565-72 0301-5548

•

Effects of second and third generation oral contraceptives and their respective progestagens on the coagulation system in the absence or presence of the factor V Leiden mutation. Author(s): Julius Center for General Practice and Patient Oriented Research, University Medical Center Utrecht, The Netherlands. Source: Kemmeren, J M Algra, A Meijers, J C M Bouma, B N Grobbee, D E ThrombHaemost. 2002 February; 87(2): 199-205 0340-6245

•

Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder. Author(s): Department of Obstetrics/Gynecology, University of Pennsylvania, Philadelphia, PA, USA. Source: Freeman, E W Kroll, R Rapkin, A Pearlstein, T Brown, C Parsey, K Zhang, P Patel, H Foegh, M J-Womens-Health-Gend-Based-Med. 2001 Jul-August; 10(6): 561-9 1524-6094

•

Noncontraceptive benefits and therapeutic uses of the oral contraceptive pill. Author(s): Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA. Source: Dayal, M Barnhart, K T Semin-Reprod-Med. 2001 December; 19(4): 295-303 15268004

•

Nutritional consequences of oral contraceptives. Source: Emery, Maurice G. De Lia, Julian E. Fam-Community-Health. aithersburg : Aspen Systems Corporation. November 1983. volume 6 (3) page 23-30. 0160-6379

•

Oral contraceptives and bone mineral density in white and black women in CARDIA. Coronary Risk Development in Young Adults. Author(s): Division of Epidemiology, Department of Health Research and Policy, Stanford University, Stanford, California 94305, USA. [email protected] Source: Cobb, K L Kelsey, J L Sidney, S Ettinger, B Lewis, C E Osteoporos-Int. 2002 November; 13(11): 893-900 0937-941X

•

Platelet-vessel wall interactions with third-generation oral contraceptives: no evidence of detrimental effects. Author(s): Department of Obstetrics and Gynecology, the University of Pisa, Italy. Source: Fruzzetti, F Giannessi, D Ricci, C Bernini, W Puntoni, R Genazzani, A R De Caterina, R Thromb-Haemost. 1999 September; 82(3): 1164-70 0340-6245

•

Preference threshold for maltose solutions in rats treated chronically with the components of an oral contraceptive. Source: Fregly, M.J. Interaction of the chemical senses with nutrition / edited by Morley R. Kare, Joseph G. Brand. Orlando, Fla. : Academic Press, 1986. page 71-86. ISBN: 0123978556

•

Prescribing and managing oral contraceptive pills and emergency contraception for adolescents. Author(s): Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, School of Medicine, Pennsylvania, USA. [email protected] Source: Gold, M A Pediatr-Clin-North-Am. 1999 August; 46(4): 695-718 0031-3955

86

Oral Contraceptives

•

Serum alkaline phosphatase and bone mineral density: to assess bone loss in oral contraceptive pill user. Author(s): Department of Pharmacology, Mymensingh Medical College. Source: Sultana, S Choudhury, S Choudhury, S A Mymensingh-Med-J. 2002 July; 11(2): 107-9 1022-4742

•

Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intraepithelial neoplasia in relation to human papillomavirus infection. Author(s): Department of Obstetrics and Gynecology, University Hospital of Northern Sweden, Umea. Source: Kjellberg, L Hallmans, G Ahren, A M Johansson, R Bergman, F Wadell, G Angstrom, T Dillner, J Br-J-Cancer. 2000 April; 82(7): 1332-8 0007-0920

•

The effects of postmenopausal hormone replacement therapy and oral contraceptives on the endogenous estradiol metabolism. Author(s): Section of Endocrinology and Menopause, Department of Obstetrics and Gynecology, University of Tubingen, Schleichstrasse 4, 72076 Tubingen, Germany. Source: Mueck, A O Seeger, H Graser, T Oettel, M Lippert, T H Horm-Metab-Res. 2001 December; 33(12): 744-7 0018-5043

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

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

•

The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

•

The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

•

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/

•

Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

•

Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

•

Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Nutrition

87

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

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

•

Google: http://directory.google.com/Top/Health/Nutrition/

•

Healthnotes: http://www.healthnotes.com/

•

Open Directory Project: http://dmoz.org/Health/Nutrition/

•

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

•

WebMDHealth: http://my.webmd.com/nutrition

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to oral contraceptives; 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 Ascorbic Acid Source: Integrative Medicine Communications; www.drkoop.com Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Niacin Source: Integrative Medicine Communications; www.drkoop.com Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B1 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B2 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B2 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B3 Source: Healthnotes, Inc.; www.healthnotes.com

88

Oral Contraceptives

Vitamin B3 (Niacin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C (Ascorbic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com •

Minerals Alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Beta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Healthnotes, Inc.; www.healthnotes.com Copper Source: Healthnotes, Inc.; www.healthnotes.com Copper Source: Integrative Medicine Communications; www.drkoop.com D-alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Source: Integrative Medicine Communications; www.drkoop.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: Healthnotes, Inc.; www.healthnotes.com

Nutrition

Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Manganese Source: Healthnotes, Inc.; www.healthnotes.com Manganese Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com

89

91

CHAPTER 3. ALTERNATIVE CONTRACEPTIVES

MEDICINE

AND

ORAL

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to oral contraceptives. At the conclusion of this chapter, we will provide additional sources.

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 oral contraceptives 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 “oral contraceptives” (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 oral contraceptives: •

“Fish on Steroids”? Author(s): Czap A. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2003 November; 8(4): 358. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14653764

•

A progressive rise in serum copper levels in women taking oral contraceptives: a potential hazard? Author(s): Rubinfeld Y, Maor Y, Simon D, Modai D. Source: Fertility and Sterility. 1979 November; 32(5): 599-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=499590

92

Oral Contraceptives

•

A trial of daily vitamin supplementation as a means of reducing oral contraceptive side effects and discontinuation in Sri Lanka. Author(s): Basnayake S, de Silva SV, Miller PC, Rogers S. Source: Contraception. 1983 May; 27(5): 465-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6349926

•

Antifertility investigations on embelin -- an oral contraceptive of plant origin. Part I -Biological properties. Author(s): Prakash AO. Source: Planta Medica. 1981 March; 41(3): 259-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7232554

•

Can combined oral contraceptives be made more effective by means of a nursing care model? Author(s): Lindell M, Olsson H. Source: Journal of Advanced Nursing. 1991 April; 16(4): 475-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2061511

•

China invents male birth control pill. Author(s): Wen W. Source: The American Journal of Chinese Medicine. 1980 Spring-Summer; 8(1-2): 195-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7395797

•

Combined oral contraceptives: acceptability and effective use. Author(s): Kubba A, Guillebaud J. Source: British Medical Bulletin. 1993 January; 49(1): 140-57. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8324604

•

Cover illustration: regional sources of saponins, and their role in the development of oral contraceptive steroids. Author(s): Huxtable RJ. Source: Proc West Pharmacol Soc. 1996; 39: 1-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8895952

•

Effect of betel chewing on the frequency of sister chromatid exchanges in pregnant women and women using oral contraceptives. Author(s): Ghosh PK, Ghosh R. Source: Cancer Genetics and Cytogenetics. 1988 June; 32(2): 211-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3365681

•

Effect of HR (O-(beta-hydroxyethyl)-rutosides) on the impaired venous function of young females taking oral contraceptives. A strain gauge plethysmographic and

Alternative Medicine 93

clinical open controlled study. Author(s): Forconi S, Guerrini M, Pecchi S, Cappelli R, Bruni F. Source: Vasa. Zeitschrift Fur Gefasskrankheiten. Journal for Vascular Diseases. 1980; 9(4): 324-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7008418 •

Effect of oral contraceptives and vitamin B6 supplements on alanine and glycine metabolism. Author(s): Rose DP, Leklem JE, Brown RR, Potera C. Source: The American Journal of Clinical Nutrition. 1976 September; 29(9): 956-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=961624

•

Effects of oral contraceptives on affective fluctuations associated with the menstrual cycle. Author(s): Paige KE. Source: Psychosomatic Medicine. 1971 November-December; 33(6): 515-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5148982

•

Efficacy of O-(beta-hydroxyethyl)-rutosides at high dosage in counteracting the unwanted activity of oral contraceptives on venous function. Author(s): Cappelli R, Pecchi S, Oberhauser V, Forconi S, Di Perri T. Source: Int J Clin Pharmacol Res. 1987; 7(4): 291-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3596872

•

Erythrocyte aminotransferase activities in women using oral contraceptives and the effect of vitamin B 6 supplementation. Author(s): Rose DP, Strong R, Folkard J, Adams PW. Source: The American Journal of Clinical Nutrition. 1973 January; 26(1): 48-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4682816

•

Folic acid deficiency enhances oral contraceptive-induced platelet hyperactivity. Author(s): Durand P, Prost M, Blache D. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1997 October; 17(10): 193946. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9351357

•

Heterogeneity of renin substrate in human plasma: effect of pregnancy and oral contraceptives. Author(s): Gordon DB, Sachin IN, Dodd VN. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1976 November; 153(2): 314-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=995964

94

Oral Contraceptives

•

Influence of dietary lipids on plasma and hepatic lipids and on blood clotting properties in rats fed oral contraceptives. Author(s): Tabacchi MH, Kirksey A. Source: The Journal of Nutrition. 1973 September; 103(9): 1270-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4725717

•

Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial. Author(s): Pfrunder A, Schiesser M, Gerber S, Haschke M, Bitzer J, Drewe J. Source: British Journal of Clinical Pharmacology. 2003 December; 56(6): 683-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616430

•

Interactions of the oral contraceptive pill with antibiotics and St John's work: knowledge of female college students. Author(s): Hindmarch M, Oakeshott P. Source: Family Practice. 2002 December; 19(6): 708. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12429683

•

Letter: supplementary pyridoxine given to women using oral contraceptives. Author(s): Winston F. Source: American Journal of Obstetrics and Gynecology. 1975 July 15; 122(6): 793. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1155524

•

Megaloblastic anemia in a vegetarian taking oral contraceptives. Author(s): Green JD. Source: Southern Medical Journal. 1975 February; 68(2): 249-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1118760

•

More on oral contraceptives, drug interactions, herbal medicines, and hormone replacement therapy. Author(s): Shader RI, Greenblatt DJ. Source: Journal of Clinical Psychopharmacology. 2000 August; 20(4): 397-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10917398

•

Multivitamin supplementation in oral contraceptive users. Author(s): Mooij PN, Thomas CM, Doesburg WH, Eskes TK. Source: Contraception. 1991 September; 44(3): 277-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1764944

•

Oral contraceptives and early-term abortifacients during classical antiquity and the Middle Ages. Author(s): Riddle JM.

Alternative Medicine 95

Source: Past Present. 1991 August; No. 132: 3-32. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11656135 •

Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin's disease. Author(s): Chapman RM, Sutcliffe SB. Source: Blood. 1981 October; 58(4): 849-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7272513

•

Psychiatric aspects of oral contraceptives. Author(s): Orchard WH. Source: The Medical Journal of Australia. 1969 April 26; 1(17): 872-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5787054

•

Psychosomatic medicine. Side effects of oral contraceptive medication: a psychosomatic problem. Author(s): Fortin JN, Wittkower ED, Paiement J, Tetreault L. Source: Can Psychiatr Assoc J. 1972 February; 17(1): 3-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5063376

•

Response to short-duration signals, pre- and postmenses, in subjects using oral contraceptives and subjects not using oral contraceptives. Author(s): Schubert GW, Meyer RC, Washer SH. Source: J Am Audiol Soc. 1975 November-December; 1(3): 112-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1228162

•

Serum folate and Vitamin B12 levels in women using modern oral contraceptives (OC) containing 20 microg ethinyl estradiol. Author(s): Sutterlin MW, Bussen SS, Rieger L, Dietl J, Steck T. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2003 March 26; 107(1): 57-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593896

•

St. John's wort and oral contraceptives: reasons for concern? Author(s): Murphy PA. Source: Journal of Midwifery & Women's Health. 2002 November-December; 47(6): 44750. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12484666

•

The effects of oral contraceptives and multivitamin supplementation on serum ferritin and hematological parameters. Author(s): Mooij PN, Thomas CM, Doesburg WH, Eskes TK.

96

Oral Contraceptives

Source: Int J Clin Pharmacol Ther Toxicol. 1992 February; 30(2): 57-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1551747 •

The in vitro effect of aspirin on increased whole blood platelet aggregation in oral contraceptive users. Author(s): Norris LA, Bonnar J. Source: Thrombosis Research. 1994 May 1; 74(3): 309-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8042198

•

The interaction between St John's wort and an oral contraceptive. Author(s): Hall SD, Wang Z, Huang SM, Hamman MA, Vasavada N, Adigun AQ, Hilligoss JK, Miller M, Gorski JC. Source: Clinical Pharmacology and Therapeutics. 2003 December; 74(6): 525-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663455

•

Thyroid status in long-term, high-dose oral contraceptive users. Author(s): Vega-De Rodriguez G, Fuertes-De la Haba A, Pelegrina I. Source: Obstetrics and Gynecology. 1972 May; 39(5): 779-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4112427

•

Vitamin metabolism and the effects of multivitamin supplementation in oral contraceptive users. Author(s): Amatayakul K, Uttaravichai C, Singkamani R, Ruckphaopunt S. Source: Contraception. 1984 August; 30(2): 179-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6437739

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/

•

AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

•

Chinese Medicine: http://www.newcenturynutrition.com/

•

drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

•

Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

•

Google: http://directory.google.com/Top/Health/Alternative/

•

Healthnotes: http://www.healthnotes.com/

•

MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

•

Open Directory Project: http://dmoz.org/Health/Alternative/

Alternative Medicine 97

•

HealthGate: http://www.tnp.com/

•

WebMDHealth: http://my.webmd.com/drugs_and_herbs

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

•

Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to oral contraceptives; 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 Abnormal Pap Smear Source: Healthnotes, Inc.; www.healthnotes.com Acne Source: Integrative Medicine Communications; www.drkoop.com Acne Vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Amenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Amenorrhea Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Breast Cancer Source: Integrative Medicine Communications; www.drkoop.com Candida/Yeast Hypersensitivity Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Cervical Dysplasia Source: Integrative Medicine Communications; www.drkoop.com Cervical Dysplasia Source: Prima Communications, Inc.www.personalhealthzone.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

98

Oral Contraceptives

Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Dysmenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Dysmenorrhea Source: Integrative Medicine Communications; www.drkoop.com Dysmenorrhea Alternative names: Painful Menstruation Source: Prima Communications, Inc.www.personalhealthzone.com Endometriosis Source: Healthnotes, Inc.; www.healthnotes.com Endometriosis Source: Integrative Medicine Communications; www.drkoop.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Fibrocystic Breast Disease Source: Healthnotes, Inc.; www.healthnotes.com Gallstones Source: Healthnotes, Inc.; www.healthnotes.com Hair Disorders Source: Integrative Medicine Communications; www.drkoop.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Hirsuitism Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Hypochondriasis Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine 99

Lupus Source: Integrative Medicine Communications; www.drkoop.com Menorrhagia Source: Healthnotes, Inc.; www.healthnotes.com Menstrual Pain Source: Integrative Medicine Communications; www.drkoop.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com Myocardial Infarction 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 Raynaud's Disease Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com Urinary Tract Infection in Women Source: Integrative Medicine Communications; www.drkoop.com UTI Source: Integrative Medicine Communications; www.drkoop.com Vaginal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Vaginitis Source: Integrative Medicine Communications; www.drkoop.com Viral Hepatitis Source: Prima Communications, Inc.www.personalhealthzone.com Yeast Infection Source: Healthnotes, Inc.; www.healthnotes.com

100

•

Oral Contraceptives

Herbs and Supplements Angelica sinensis Source: Integrative Medicine Communications; www.drkoop.com Black Cohosh Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10009,00.html Carotenoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,763,00.html 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 Chinese Angelica Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Danggui Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Dioscorea Villosa Source: Integrative Medicine Communications; www.drkoop.com Dong Quai Alternative names: Angelica sinensis Source: Integrative Medicine Communications; www.drkoop.com Estrogen Source: Prima Communications, Inc.www.personalhealthzone.com Estrogens (Combined) 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

Alternative Medicine 101

Glycyrrhiza glabra Alternative names: Licorice Source: Integrative Medicine Communications; www.drkoop.com Licorice Alternative names: Glycyrrhiza glabra Source: Integrative Medicine Communications; www.drkoop.com Medroxyprogesterone Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Source: Prima Communications, Inc.www.personalhealthzone.com Oral Contraceptives Source: Healthnotes, Inc.; www.healthnotes.com Oral Contraceptives Source: Prima Communications, Inc.www.personalhealthzone.com Progesterone Source: Healthnotes, Inc.; www.healthnotes.com Red Clover Source: Integrative Medicine Communications; www.drkoop.com Red Clover Source: Prima Communications, Inc.www.personalhealthzone.com SAMe (S-Adenosylmethionine) Source: Prima Communications, Inc.www.personalhealthzone.com Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com Tang Kuei Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Wild Yam Alternative names: Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com Wild Yam Source: Prima Communications, Inc.www.personalhealthzone.com

102

Oral Contraceptives

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.

103

CHAPTER 4. DISSERTATIONS ON ORAL CONTRACEPTIVES Overview In this chapter, we will give you a bibliography on recent dissertations relating to oral contraceptives. 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 “oral contraceptives” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on oral contraceptives, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Oral Contraceptives 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 oral contraceptives. 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: •

Adolescents and Birth Control: A Study of Oral Contraceptive Use by BALASSONE, MARY LOU, DSW from University of California, Berkeley, 1987, 240 pages http://wwwlib.umi.com/dissertations/fullcit/8726121

•

Guidelines for Teaching Clinic Patients How to Utilize Oral Contraceptives Safely and Effectively by JACOBSON, LINBANIA, EDD from Columbia University, 1971, 184 pages http://wwwlib.umi.com/dissertations/fullcit/7208824

•

On the Pill: A Social History of Oral Contraceptives in America, 1950-1970 (Sexual Revolution, Birth Control, Feminism) by WATKINS, ELIZABETH ROSE SIEGEL, PHD from Harvard University, 1996, 336 pages http://wwwlib.umi.com/dissertations/fullcit/9631613

104

Oral Contraceptives

•

The Effects of an Exercise Training Program on Serum Cholesterol and Triglyceride Levels in Women Using Oral Contraceptives. by RITCHEY, ELIZABETH ANN, EDD from Virginia Polytechnic Institute and State University, 1976, 78 pages http://wwwlib.umi.com/dissertations/fullcit/7619889

•

The Effects of Current and Prior Oral Contraceptive Treatment on the Behavior and Neurobiology of Cynomolgus Monkeys by Henderson, Jessica Ann; PhD from Wake Forest University, the Bowman Gray School of Medicine, 2003, 158 pages http://wwwlib.umi.com/dissertations/fullcit/3102482

•

The Relationship of Knowledge to Perceived Benefits and Risks of Oral Contraceptives among College Women by LIVELY, BUFORD THEODORE, EDD from West Virginia University, 1979, 176 pages http://wwwlib.umi.com/dissertations/fullcit/8012902

•

The Relationship of Static Muscle Strength and Endurance with the Use of Oral Contraceptives, Phase of the Menstrual Cycle, and Vitamin B-6 Status. by WIRTH, JOHN CHRISTIAN, PHD from University of Illinois at Urbana-champaign, 1978, 179 pages http://wwwlib.umi.com/dissertations/fullcit/7913661

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.

105

CHAPTER 5. CLINICAL CONTRACEPTIVES

TRIALS

AND

ORAL

Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning oral contraceptives.

Recent Trials on Oral Contraceptives The following is a list of recent trials dedicated to oral contraceptives.8 Further information on a trial is available at the Web site indicated. •

Quick Start Approach to Birth Control Pills Condition(s): Pregnancy; Contraception Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Women who choose to take birth control pills are currently instructed to begin taking the pills at the end of a menstrual cycle. This creates a window of time between when the woman is given the pills and when she begins taking them. Some women fail to begin taking the pills, placing them at increased risk of pregnancy. This study will evaluate a new approach to beginning birth control pills. Women will take the first pill in the doctor's office rather than waiting until the next menstrual cycle. Phase(s): Phase IV; MedlinePlus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068848

8

These are listed at www.ClinicalTrials.gov.

106

Oral Contraceptives

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 “oral contraceptives” (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/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

•

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

•

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

•

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

•

For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

•

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/

•

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

•

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

•

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

•

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

Clinical Trials 107

•

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

•

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

109

CHAPTER 6. PATENTS ON ORAL CONTRACEPTIVES 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 “oral contraceptives” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on oral contraceptives, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Oral Contraceptives By performing a patent search focusing on oral contraceptives, 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. 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

110

Oral Contraceptives

The following is an example of the type of information that you can expect to obtain from a patent search on oral contraceptives: •

Birth control pill dispenser in the form of a hair brush Inventor(s): Hochberg; Charles (508 Jeffords St., Clearwater, FL 33516) Assignee(s): None Reported Patent Number: 4,690,279 Date filed: March 13, 1986 Abstract: A package for oral contraceptives that has the outward appearance of a hair brush. A first compartment serves as a pill storage compartment; it retains a three week supply of pills of the type that are individually packaged under a flexible bubble and collectively mounted on a frangible support surface. The floor of the first compartment is apertured and each aperture is pill-sized and positioned in registration with a pill under a bubble. A closure member such as a hinged lid masks the presence of the pillstorage compartment, but when the lid is open and a bubble is pressed against, the frangible support surface for the pill breaks and allows the pill to fall into a second compartment with an imperforate bottom. The second compartment is enclosed on three sides but open on a fourth so that a pill driven through its frangible support surface may be retrieved from such second compartment by tilting the brush. Excerpt(s): This invention generally relates to birth control pill dispensers and more particularly relates to a device that provides such a dispenser in the form of a hair brush. It is well known that birth control pills of the type intended to be taken orally by females must be taken daily and in the proper dosage if they are to be effective. For this reason, the manufacturers of such pills typically provide packaging for the same that is designed to remind the individual taking the medication to do so on a daily basis. Web site: http://www.delphion.com/details?pn=US04690279__

•

Chewable oral contraceptive Inventor(s): Boissonneault; Roger M. (Long Valley, NJ), deVries; Tina M. (Long Valley, NJ) Assignee(s): Galen (chemicals) Limited (dunlaoghaire, Ie) Patent Number: 6,667,050 Date filed: June 12, 2001 Abstract: The present invention relates to a chewable, palatable oral contraceptive tablet, comprising an oral contraceptive agent, a chewable carrier suitable for human consumption, and not comprising a ferrocene compound, as well as use of these tablets in a method of human female oral contraception, and in a method of enhancing compliance with a human female oral contraceptive regimen. Excerpt(s): Not Applicable. The present invention generally relates to an oral contraceptive delivery system, and in particular an oral contraceptive delivery system involving novel alternate dose forms to improve compliance. Web site: http://www.delphion.com/details?pn=US06667050__

Patents 111

•

Combined pharmaceutical estrogen-androgen-progestin oral contraceptive Inventor(s): Hughes, Jr.; Claude L. (Mebane, NC), Jayo; Manuel J. (Winston-Salem, NC) Assignee(s): Wake Forest University (winston-salem, Nc) Patent Number: 5,770,226 Date filed: July 10, 1996 Abstract: Disclosed are methods and compositions for oral contraception. Certain compositions of the invention contain androgens, preferably methyltestosterone to be taken by younger users of the contraceptives to inhibit adverse effects of oral contraceptive use on bone mineral density. Excerpt(s): The present invention relates generally to the field of pharmaceutical preparations and in particular to the field of oral contraceptives. In particular the present invention addresses the field of peak bone mass accrual in young oral contraceptive users. Due to the relatively high rate of teenage pregnancy in the United States, pediatric and adolescent gynecologists often recommend that young women take some form of contraception to prevent unwanted pregnancies (The Contraception Report, 1995). The most common method of contraception among adolescents is oral contraceptives, taken by approximately 46% of the sexually active population. Consequently, almost half of all premenopausal women (<44 years) are potentially taking oral contraceptives while their skeleton is still maturing and before reaching peak bone mass, which occurs at about age 30-35. Peak bone mass is a term that describes a point at which the maximum bone density is reached. For a woman, bone density increases until about age 30-35, and then slowly decreases for the remainder of her life. This peak is known as the peak bone mass. As the bone density decreases in later years, osteoporosis or bone breakage are more likely to occur. It is important, therefore, to forestall these problems by attaining as high a peak as possible. Although estrogen is necessary for maintaining bone density in premenopausal women, the role of androgens or their combined effect is unclear. It is generally accepted that low-dose estrogens are potent bone growth promoters and probably provide the major growth stimulus in girls, while in boys, estrogens may be involved in the growth spurt along with testosterone (Kulin, 1991). However, some recent evidence suggests that androgens play an important role in building and maintaining bone in the female as well as in the male. During puberty, androgens influence bone growth and peak bone mass, but after puberty, during adolescence and early adulthood, androgens are also involved in the maintenance of bone mass. Peak bone mass is acquired by age 30-35 (Recker, et al., 1992), but 15% of the adult height and 48% of the skeletal mass are attained during adolescence. Web site: http://www.delphion.com/details?pn=US05770226__

•

Dispensing container for triphasic Inventor(s): Curtis; H. Edward (Perkasie, PA), Gaffney; Thomas J. (West Chester, PA) Assignee(s): American Home Products Corporation (new York, Ny) Patent Number: 4,706,815 Date filed: August 23, 1982 Abstract: A dispenser for solid dosage form pharmaceutical preparations for selfadministration on a daily basis related to the menstrual cycle is made up of a blister

112

Oral Contraceptives

pack in a carrying case. The case has a septagonal post and the blister pack a cooperating septagonal opening. The dose form to be taken on the first day is indicated and is aligned with the day taken. The remaining dose forms are taken sequentially. Once inserted on the starting day, the blister pack is not moved. A triphasic, 21-day regimen for oral contraceptives is described which may be followed by seven days of iron tablets. Excerpt(s): This invention relates to a pharmaceutical dispensing container in which a regimen of treatment is contained in dose forms, which are contained in a blister pack that is held in a compact carrying case. The present dispensing container is intended principally for use with a triphasic contraceptive regimen. That is, three different compositions are used to mimic as closely as possible the characteristic fluctuations in the plasma levels of.beta.-oestradiol and progesterone. Much research has been conducted in the time since the contraceptive pill was first introduced towards improving the patient tolerance and cycle control of the preparations, and to increase their safety from a medical point of view by reducing the effect on certain parameters of the hemostatic system and metabolic functions. Improvements have been achieved by reducing the dose size and by changing the oesterogen:progestagen ratio in the dose form. It is known that during the normal menstrual cycle, there are plasma levels of.beta.-oestradiol and progesterone that fluctuate in characteristic fashion. For a time, the estrogen content of the oral contraceptive was considered to be a problem portion and reduction in its amount was an early goal. Later, however, the role of progesterone was determined to be beneficial and dose forms and regimens of treatment were prepared to reflect this advantage. In the last ten years, attempts have been made to develop a step-up preparation containing the lowest possible quantities of both hormone components. From this evolved three-phase regimens of treatment which would provide increased estrogen doses for five days in mid-cycle, which fits in with the normal pre-ovulatory estrogen peak. As in the normal cycle, the follicular phase is sub-divided into a post menstrual phase of six days' duration, and a peri-ovulatory one of five days' duration which retains the ten-day luteal phase which proved so successful in the biphasic regimen. It is an object of the present invention to provide a pharmaceutical dispensing container for use in a three-phase oral contraceptive regimen of treatment. Web site: http://www.delphion.com/details?pn=US04706815__ •

Low estrogen oral contraceptives Inventor(s): Bergink; Engelhart W. (Oss, NL) Assignee(s): Akzo N.v. (arnhem, Nl) Patent Number: 5,262,408 Date filed: December 12, 1991 Abstract: Disclosed is a contraceptive regimen, and method of using the regimen, comprising 24 daily sequential dosage units of: a first phase comprising about 7 to 9 separate first dosage units containing a progestogen at a daily dosage equivalent in progestogenic activity to 100 desogestrel and an estrogen at a daily dosage equivalent in estrogenic activity to 25.mu.g ethinyl estradiol ("EE"). A second phase of 7 to 9 second dosage units, each of the second dosage units containing a progestogen equivalent to 125.mu.g desogestrel and an estrogen equivalent lent to 20.mu.g EE. A third phase of 7 to 9 third dosage units, each unit containing a progestogen equivalent to 50.mu.g desogestrel and an estrogen equivalent to 20.mu.g EE. The kit generally has 28 daily

Patents 113

dosage units wherein four of the daily dosage units contain no contraceptive steroid, or, alternatively, have only 24 dosage units with a four day "pill-free" period. The fourth phase may also be four dosage units containing a progestogen equivalent to 25-35.mu.g desogestrel. Excerpt(s): The invention relates generally to oral contraceptive preparations, and more specifically to a low estrogen oral contraceptive regimen. Since the first birth control pill regimen was described, attempts have been made to lower the total steroid dosage in the regimen, while maintaining the regimen's reliability in providing contraception. For example, U.S. Pat. No. 4,628,051 to Ortho Pharm. Corp. discloses a three phase oral contraceptive containing estrogen and progestogen for administration over 21 days having a lower total monthly steroid dose having the same amount of estrogen in each phase. In the first phase, 5 to 8 tablets containing 0.02 to 0.05 milligrams (mg) ethinyl estradiol ("EE") and 0.065 to 0.75 mg of norethindorone ("NE") are administered daily. In the second phase, 7 to 11 tablets containing the same dosage of EE and 0.25 to 1 mg of NE are administered. In the third phase, 3 to 7 tablets containing the same dosage of EE and 0.35 to 2 mg of NE are administered. While an adequate contraceptive regimen, a 7 day pill free interval can lead to follicular development and thus pregnancy. Furthermore the preferred and described regimens administer 0.735 mg of EE, which to some is considered too large a dosage. Similar regimens are described in U.S. Pat. Nos. 4,616,006, 4,544,554, and 4,530,839 also to Ortho Pharm. Corp. Web site: http://www.delphion.com/details?pn=US05262408__ •

Male oral contraceptive Inventor(s): Nassar; Michael F. (8731 Dewey Dr., Garden Grove, CA 92641) Assignee(s): None Reported Patent Number: 4,148,892 Date filed: May 8, 1978 Abstract: A simple, nontoxic, effective male oral contraceptive is disclosed which directly effects the metabolism of the sperm by causing an acidotic state in the fluid medium surrounding the sperm thereby inhibiting the sperm's activity. Excerpt(s): Social scientists recognize that over population is one of the most serious problems which mankind must face and solve. As an example, in the United States the Department of Health, Education and Welfare released statistics recently which showed that 3.3 million babies were born in the United States in 1977, up 5% from the previous year. This marked an increase in the nation's birth rate for the first time since 1970. (1) The problem is even more critical in underdeveloped countries. In order to control our increasing world population, there exists a myriad of contraceptive devices to prevent unwanted pregnancy. Each method attempts to achieve a contraceptive possessing the qualities of simplicity, acceptability, efficacy, nontoxicity and absence of adverse side effects. One class of such measures are mechanical contraceptives, such as the diaphragm, which are inserted into the vagina to completely occlude the orifice of the cervix, thus obstructing the migration of spermatozoa upward into the fallopian tubes. Such contraceptives have serious application problems due to the wide variation in size and geometry of the vaginal canal and the cervical opening. These devices often require special insertion instruments and careful fitting, usually by a trained physician. Furthermore, since trained help in application is often necessary, these devices are illsuited for the underdeveloped countries where they are needed most.

114

Oral Contraceptives

Web site: http://www.delphion.com/details?pn=US04148892__ •

Novel cyclic progestogen-interrupted estrogen oral contraceptive regimens Inventor(s): Segre; Eugene J. (Los Altos, CA) Assignee(s): Syntex Corporation (panama, Pm) Patent Number: 3,932,635 Date filed: May 5, 1972 Abstract: This invention relates to a method of fertility control by use of novel cyclic progestogen-interrupted estrogen oral contraceptive regimens. Considering the first day of menstrual flow as day one of a 28 day medication administration cycle, a combined formulation of estrogen and progestogen substances is administered on the 3rd, 4th, 5th or 6th day of the cycle and every second or third day thereafter through, and including, the 23rd, 24th, 25th, 26th, 27th or 28th day of the cycle, and a formulation having only a progestogen substance as the active component is administered on the 4th, 5th, 6th, or 7th day of the cycle and every day thereafter on which a combination formulation is not administered, through, and including, the 22nd, 23rd, 24th, 25th, 26th, 27th or 28th day of the cycle.In a particular regimen, a combination of estrogen and progestogen is administered starting with the 5th day of the cycle and continuing every other day through the 25th day of the cycle, and starting with the 6th day of the cycle and continuing every other day through the 24th day of the cycle only progestogen is administered. The remaining seven days are dosage-free or the regimen is completed by use of placebos or other nonhormonal supplements.Dispensing packages for holding unit dosage forms for oral ingestion of one unit dosage form daily in the appropriate sequence during a single cycle of medication administration are also described. Excerpt(s): The present invention relates to a method of fertility control in the human female by adherence to a novel oral contraceptive regimen. The regimen includes the administration of a combination of an estrogen and a progestogen during certain days of the reproductive cycle, and the administration of only the progestogen on certain of the other days of the cycle. Research and development in the area of human contraception or fertility control has heretofore concentrated almost exclusively on preventative methods, whether in the form of chemical or physical diversions of or barriers to sperm transport, e.g., vaginal creams and foams, condoms, diaphragms, and intrauterine devices, or in the form of chemically based oral contraceptive. The former methods have been largely supplanted by the use of oral contraceptives which have proven to be extremely effective in the prevention of conception. This effectiveness, however, necessarily requires the administration of the oral contraceptive tablets over approximately 21 days of each reproductive cycle. During the remaining 7 days of the 28 day cycle, no hormone-containing tablets are given and it is during this period, if the reproductive cycle is accurately regulated, that normal menstrual flow takes place. The most common form of oral contraception is based upon the daily administration of a combination of estrogen and progestogen substances for about 21 successive days, starting generally on the 5th day of the menstrual cycle. After the 21 day period, there follows a 7 day period during which neither the estrogen or progestogen substances are taken. If the reproductive cycle of the female has been properly regulated, the normal and characteristic menstrual flow is supposed to, and generally does, occur within the 7 day period. Web site: http://www.delphion.com/details?pn=US03932635__

Patents 115

•

Oral contraceptive regimen Inventor(s): Pasquale; Samuel A. (Basking Ridge, NJ) Assignee(s): Ortho Pharmaceutical Corporation (raritan, Nj) Patent Number: 4,066,757 Date filed: March 26, 1973 Abstract: An oral contraceptive regimen in which a progestin is administered from the fifth through the twenty-fifth day of the physiological cycle is described. The amount of progestin administered is serially increased during the period of administration; regular menses occurs when administration of the regimen is complete. Excerpt(s): The oral contraceptive methods which are currently accepted fall into three categories, i.e. combination cyclic regimens, sequential cyclic regimens and continuous low dose progestin regimens. In the combination oral contraceptive regimen, an individual daily dose containing both a progestin and estrogen is prescribed for daily use over a period of 20 or 21 days, followed by a 5 to 7 day period when neither is taken to allow for uterine bleeding of a menstrual type. After the bleeding phase, administration of the combination is continued. It is generally accepted that the administration of the ovarian hormones progesterone and estrogen is primarily responsible for suppressing ovulation through inhibition of gonadotropin secretion by the pituitary, as indicated by the reduced urinary pregnanediol excretion during the period of administration. Progestational change in the endometrium is stimulated to the extent that the stroma development progresses occasionally even to the decidual stage. In the sequential oral contraceptive regimen, an individual daily dosage of estrogen is administered to the patient during the first part of the cycle, i.e. from about day 5 through day 15. Then, in the last 6 or 7 days of the cycle, a combination of estrogen and a progestin is administered as in the combination type. This therapy thus mimics the normal menstrual pattern which is characterized by a rise in estrogen levels during the first part of the cycle, the proliferative phase, and a rise in progestin levels during the second part of the cycle after ovulation, the secretory phase. In the sequential regimen, it is the estrogen which suppresses ovulation by depressing the follicle-stimulating hormone (F.S.H.) levels which in turn prevents the follicles from maturing. Therefore, the luteinizing hormone (L.H.) output of the pituitary has no opportunity to induce ovulation. This is in contrast to the combination oral contraceptive regimen in which both F.S.H. and L.H. pituitary secretion are suppressed. The progestin is also administered during the last six or seven days of treatment to induce changes in the endometrium closely resembling the progesterone influence in the secretory stage of the normal cycle; thus the irregular withdrawal bleeding which is associated with the use of estrogens alone is avoided. At the end of the administration of medication there is a sluffing-off of the endometrial lining in a fashion which mimics normal menstruation. Web site: http://www.delphion.com/details?pn=US04066757__

•

Oral contraceptives Inventor(s): Gast; Michael J. (Phoenixville, PA) Assignee(s): American Home Products Corporation (madison, Nj) Patent Number: 5,888,543 Date filed: July 2, 1997

116

Oral Contraceptives

Abstract: This invention provides a method of contraception which comprises administering to a female of child bearing age for 23-25 consecutive days, a first phase combination of a progestin at a daily dosage of 40-500.mu.g trimegestone, 250.mu.g-4 mg dienogest, or 250.mu.g-4 mg drospirenone, and an estrogen at a daily dosage equivalent in estrogenic activity to 10-20.mu.g ethinyl estradiol for 9-13 days beginning on day 1 of the menstrual cycle, wherein the same dosage of the progestin and estrogen combination is administered in each of the 9-13 days, and a second phase combination of a progestin at a daily dosage of 40-500.mu.g trimegestone, 250.mu.g-4 mg dienogest, or 250.mu.g-4 mg drospirenone, and an estrogen at a daily dosage equivalent in estrogenic activity to 10-20.mu.g ethinyl estradiol, for 11-15 days beginning on the day immediately following the last day of administration of the first phase combination, wherein the same dosage of the progestin and estrogen combination is administered in each of the 11-15 days, provided that the daily dosage of second phase progestin is greater than the daily dosage of the first phase progestin and that the daily dosage of the second phase estrogen is greater than or equal to the daily dosage of the first phase estrogen. Excerpt(s): This application claims the benefit of U.S. Provisional application Ser. No. 60/022,681, filed Jul. 26, 1996. The vast majority of oral contraceptives consist of a combination of a progestin and estrogen that are administered concurrently for 21 days followed either by a 7 day pill free interval or by the administration of a placebo for 7 days in each 28 day cycle. The most important aspects of a successful oral contraceptive product are effective contraception, good cycle control (absence of spotting and breakthrough bleeding and occurrence of withdrawal bleeding), and minimal side effects. Combination oral contraceptives have traditionally acted by suppression of gonadotropins. In addition, it appears that the progestin component is primarily responsible for contraceptive efficacy through inhibition of ovulation, and other peripheral effects which include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation). The estrogenic component intensifies the anovulatory effect of the progestin, and is also important for maintaining cycle control. Since the introduction of oral contraceptives (OCs) over a quarter-century ago, research has been directed toward developing preparations that minimize the potential for side effects while maintaining efficacy and normal menstrual patterns. The first-generation OCs contained more progestin and estrogen than was necessary to prevent conception. Adverse hemostatic and metabolic changes, clinical problems, and side effects were associated with these high-dose preparations. In 1978, the World Health Organization (WHO) recommended that the focus of OC research should be the development of products containing the lowest possible dose levels of estrogen and progestin. Web site: http://www.delphion.com/details?pn=US05888543__ •

Package for oral contraceptive tablet Inventor(s): Urheim; John E. (Lincolnshire, IL) Assignee(s): Gynex, Inc. (deerfield, Il) Patent Number: 4,958,736 Date filed: March 18, 1986 Abstract: The present invention contemplates a package for oral contraceptive tablets. The package contains four rows of seven tablets per row. Three adjacent rows contain active contraceptive tablets, while the fourth row contains placebo tablets. A line of

Patents 117

severability is provided between the row of placebo tablets and an adjacent row of active tablets, thereby enabling dispensing 21-day and 28-day oral contraceptive formulations using a single package. Excerpt(s): This invention relates to packages for oral contraceptive tablets. Conventional oral contraceptives are administered on a repeating 28 day cycle. Contraceptive tablet taking generally begins on the fifth day of the menstrual cycle or on the first Sunday after menstruation begins, continues for a total of 21 days and begins again after seven days without contraceptive tablets. The patient thereafter takes a tablet each day for three weeks, takes no contraceptives for one week, and begins another 28 day cycle of three weeks of tablet taking and one week without tablets for the desired duration of contraceptive treatment. Some physicians prefer to prescribe 21 tablet packages and have the patient go without tablets for seven days each cycle. Other physicians prefer 28 tablet packages containing seven placebo tablets to facilitate proper tablet administration. Web site: http://www.delphion.com/details?pn=US04958736__ •

Ultra low dose oral contraceptives with less menstrual bleeding and sustained efficacy Inventor(s): Hodgen; Gary D. (Virginia Beach, VA) Assignee(s): Medical College of Hampton Roads (norfolk, Va) Patent Number: 5,898,032 Date filed: June 23, 1997 Abstract: A method of female contraception involves administering a combination of estrogen and progestin for 60-110 consecutive days in which the daily amounts of estrogen and progestin are equivalent to about 5-35 mcg of ethinyl estradiol and about 0.025 to 10 mg of norethindrone acetate, respectively. The advantages include less menstrual bleeding, less patient anemia, less total exposure to medication, higher compliance rates and more lifestyle convenience for patients. Excerpt(s): The ovarian/menstrual cycle is a complex event characterized by an estrogen rich follicular phase and, after ovulation, a progesterone rich luteal phase. Each has a duration of approximately 14 days resulting in an intermenstrual interval of about 28 days. The endometrial tissue responds to the changes in hormonal milieu. The onset of menstruation is the beginning of a new menstrual cycle and is counted as day 1. During a span of about 5 to 7 days, the superficial layers of the endometrium, which grew and developed during the antecedent ovarian/menstrual cycle, are sloughed because demise of the corpus luteum in the non-fertile menstrual cycle is associated with a loss of progesterone secretion. Ovarian follicular maturation occurs progressively resulting in a rise in the circulating levels of estrogen, which in turn leads to new endometrial proliferation. The dominant ovarian follicle undergoes ovulation at mid-cycle, generally between menstrual cycle days 12 to 16 and is converted from a predominantly estrogen source to a predominantly progesterone source (the corpus luteum). The increasing level of progesterone in the blood converts the proliferative endometrium to a secretory phase in which the tissue proliferation has promptly abated, leading to the formation of endometrial glands or organs. When the ovulated oocyte is viably fertilized and continues its progressive embryonic cleavage, the secretory endometrium and the conceptus can interact to bring about implantation (nidation), beginning about 6 to 8 days after fertilization.

118

Oral Contraceptives

Web site: http://www.delphion.com/details?pn=US05898032__

Patent Applications on Oral Contraceptives 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 oral contraceptives: •

Anti-estrogen plus progestin containing oral contraceptives Inventor(s): Gast, Michael J.; (Phoenixville, PA), Miller, Christopher P.; (Wayne, PA) Correspondence: American Home Products Corporation; Five Giralda Farms; Patent Law; Madison; NJ; 07940; US Patent Application Number: 20020061875 Date filed: November 21, 2001 Abstract: This invention provides a method of providing contraception which comprises administering to a female of child bearing age a combination of a non-uterotrophic antiestrogen and a progestin for 28 days per 28-day menstrual cycle. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/093,051, which was converted from U.S. patent application Ser. No. 08/965,083, filed Nov. 6, 1997, pursuant to a petition filed under 37 C.F.R. 1.53(c)(2)(i) on Apr. 15, 1998. This invention relates to oral contraceptive regimens containing a nonuterotrophic antiestrogen (i.e., a tissue selective estrogen) and a progestin. The vast majority of oral contraceptives consist of a combination of a progestin and estrogen that are administered concurrently for 21 days followed either by a 7 day pill free interval or by the administration of a placebo for 7 days in each 28 day cycle. The most important aspects of a successful oral contraceptive product are effective contraception, good cycle control (absence of spotting and breakthrough bleeding and occurrence of withdrawal bleeding), and minimal side effects. Combination oral contraceptives have traditionally acted by suppression of gonadotropins. In addition, it appears that the progestin component is primarily responsible for contraceptive efficacy through inhibition of ovulation, and other peripheral effects which include changes in the cervical mucus (which increase the difficulty-of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation). The estrogenic component intensifies the anovulatory effect of the progestin, and is also important for maintaining cycle control. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

10

This has been a common practice outside the United States prior to December 2000.

Patents 119

•

CRYSTALLINE PROGESTAGENS Inventor(s): BOOY, CORNELIUS J.; (OSS, NL), BRANDS, FRANCISCUS T. L.; (HAREN, NL), DE WILDT, WILHELMUS P. H. M.; (WYCHEN, NL), VAN DER SCHANS, MARIA J. A.; (SPRANG-CAPELLE, NL) Correspondence: Rothwell, Figg, Ernst & Manbeck, P.C.,; 555 13th Street, N.W.; Suite 701-east; Washington; DC; 20004; US Patent Application Number: 20020010166 Date filed: August 4, 1998 Abstract: The disclosed invention resides in the polymorphism found with the progestagenic steroidal compound (17.alpha.)-17-hydroxy-11-methylene-19-norpregna-4,15-diene-20-yn-3-one. More particularly, the invention resides in crystalline forms of said compound having unexpectedly favorable thermodynamic stability. These crystalline compounds, which can be suitably described with reference to spectral data, can advantageously be employed as an active ingredient in solid pharmaceutical compositions. The crystalline compounds can be used in oral contraceptives and in hormone replacement therapy (HRT). Excerpt(s): The invention pertains to crystalline (17.alpha.)-17-hydroxy-11-met- hylene19-norpregna-4,15-diene-20-yn-3-one, hereinafter referred to as Org 30659. Org 30659 is a progestational steroid with high progestagenic activity and with low estrogenic and low androgenic activity. Org 30659 is suitable for being utilised in hormone replacement therapy (HRT) and in contraception. Org 30659 as a crystalline chemical compound is known from EP 210 678. A drawback to the Org 30659 produced therein is that it is not obtained in one single, reproducible crystalline form. Further, the thermodynamic stability of the crystals obtainable needs to be improved. Another background disclosure on Org 30659 is WO 96/09056, which pertains to a process of making dosage units comprising e.g. Org 30659 in a relatively low amount, which process involves wet granulation. WO 96/09056 refers to Org 30569 as a known compound without specifically teaching its crystallinity or the selection of a particular preparation method. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Non-steroidal progesting Inventor(s): Fuhrmann, Ulrike; (Berlin, DE), Hegele-Hartung, Christa; (Muelheim/Ruhr, DE), Klotzbuecher, Michael; (Berlin, DE), Lehmann, Manfred; (Berlin, DE), Muhn, Peter; (Berlin, DE), Schmees, Norbert; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030232824 Date filed: March 11, 2003 Abstract: The present invention relates to non-steroidal progestins of the general formula (I) 1whereinR.sub.1 and R.sub.2 are independently of each other --H or -F,R.sub.3 is --CH.sub.3 or --CF.sub.3, andAr is 2or a pharmaceutically acceptable derivative or analogue thereof. These progestins are suitable for selectively modulating progesterone receptor mediated effects in different target tissues, particularly in uterine tissue versus breast tissue. Therefore, the progestins of the present invention, optionally in combination with estrogens, may be used for contraception (in particular in estrogen-

120

Oral Contraceptives

free oral contraceptives), hormone replacement therapy and the treatment of gynecological disorders. The present invention furthermore relates to methods for selectively modulating progesterone receptor mediated effects in different target tissues or organs. Excerpt(s): This application claims the benefit of the filing date of U.S. Provisional Application Serial No. 60/363,044 filed Mar. 11, 2002. The present invention relates to non-steroidal progestins of the general formula (I) as well as to uses of said compounds for selectively modulating progesterone receptor mediated effects in different target tissues, i.e., to progestins having a dissociated activity profile regarding different target tissues, preferably a uterus/breast dissociated profile. The present invention further relates to uses of said compounds as well as to methods for selectively enhancing progesterone receptor mediated effects in uterine tissue with respect to progesterone receptor mediated effects in breast tissue. Due to the unique dissociated activity and selectivity profile of the progestins according to the present invention, the invention in particular relates to the use of said compounds for fertility control, in particular for oral contraception, hormone replacement therapy and the treatment of gynecological disorders. The progestins according to the present invention are especially suitable for use in estrogen-free oral contraceptives. Progesterone is a unique reproductive hormone, and it plays a decisive role for tissues of female reproduction. Its principal target organs are uterus, ovary, breast and the hypothalamus-pituitary axis. In addition to the primary use as pregnancy control for women (e.g., oral contraception (OC)), progestins, optionally combined with estrogens, are widely used in hormone replacement therapy (HRT). Progestins are also used to treat several gynecological disorders, e.g., dysmenorrhea, endometriosis, and dysfunctional uterine bleeding caused by hormonal deficiency or imbalance. Due to certain effects of progestins, which may be undesirable for some applications, or cross-reactivities with receptors other than the progesterone receptor, the development of new generations of progestins to improve their activity profile has been a great challenge. Additionally, the exploration of therapeutic applications such as oncology demands progestins with new activity profiles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Oral contraceptives symptomatology

to

prevent

pregnancy

and

diminish

premenstrual

Inventor(s): Bell, Robert G.; (Palm Harbor, FL), Ben-Maimon, Carole; (Merion, PA), Iskold, Beata; (Livingston, NJ) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W.; Washington; DC; 20005; US Patent Application Number: 20030139381 Date filed: December 4, 2002 Abstract: This invention relates to a method of preventing pregnancy and treating PMS including PMDD. More particularly, the invention relates to a method, which involves administering one of several combination oral contraceptive regimens in combination with an antidepressant and a kit containing the same. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/335,807, filed Dec. 5, 2001, the disclosure of which is hereby incorporated herein by reference. This invention relates to oral contraceptives that prevent pregnancy and

Patents 121

diminish or eliminate premenstrual symptomatology, including PMS and PMDD, and to a method of preventing pregnancy and diminishing or eliminating premenstrual symptomatology, including PMS and PMDD. The human menstrual cycle involves a repetitive sequence of hormonal changes that result in episodic uterine bleeding. Normally, each menstrual cycle has a mean interval of 21 to 35 days, conventionally beginning with the first day of menstrual flow and ending on the day before the next onset of bleeding. Duration of the menstrual flow is usually 2 to 6 days with loss of 20 to 60 ml of blood. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

PHARMACEUTICAL FORMULATIONS CONTAINING SOLUBILIZED HYDROQUINONE, SALICYLIC ACID AND HYDROCORTISONE FOR THE TREATMENT OF MELASMA AND RELATED DERMATOLOGICAL PROBLEMS Inventor(s): Gruber, Murray; (Roslyn, NY) Correspondence: Darby & Darby P.C.; P. O. Box 5257; New York; NY; 10150-5257 Patent Application Number: 20030194385 Date filed: January 29, 2003 Abstract: There are provided dermatological compositions achieved by combining solubilized, stabilized hydroquinone salicylic acid and hydrocortisone by dissolving the three ingredents in dimethyl isosorbide. These preparations are intended for the treatment of melasma and related disorders of the skin such as freckles, senile lentigines, chloasma, ultraviolet induced dyschromia and discoloration resulting from ingestion of oral contraceptives or hormonal replacement therapy. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 119(e) from Provisional Application No. 60/352,651, filed January 29, 2002. The present invention relates generally to pharmaceutical and cosmetic products, more specifically to those preparations incorporating solubized, stabilized hydroquinone, salicylic acid and hydrocortisone which when applied topically produces reversible depigmentation of human skin. Hyperpigmentation of the skin in humans can be the cause of much mental distress. Hypermelanotic areas, especially on the face, can result in a marked psychological and cosmetic disability. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Starter kit for low dose oral contraceptives Inventor(s): Grubb, Gary S.; (Newtown Square, PA) Correspondence: Arnold S. Milowsky; American Home Products Corporation; Patent Law Department - 2B; Five Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20020010167 Date filed: June 1, 2001 Abstract: The present invention provides a contraceptive kit which helps to overcome or ameliorate the problem of breakthrough bleeding and spotting associated with lowest dose (15-20 ug EE) estrogen contraceptives.

122

Oral Contraceptives

Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/210,310, filed Jun. 8, 2000. Since the introduction of oral contraceptives (OCs) over a quarter-century ago, research has been directed toward developing preparations that minimize the potential for side effects while maintaining efficacy and normal menstrual patterns. During the first three to four months oral contraceptive use, the incidence rate of breakthrough bleeding and spotting rates in the first cycle are about two times higher than the rate that remains generally steady after cycle 4. This is due to the change in endometrial histology over several months of OC use that is due to a progestin effect from an OC. Several months of OC use produces a more secretory endometrium which is less prone to breakthrough bleeding. Breakthrough bleeding and spotting are the most common complaint by women first using OCs and is a common reason for discontinuing use of OCs. Breakthrough bleeding and spotting rates are higher with OCs containing amounts of estrogen less than about 30 ug, particularly in the first several months of use. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Topical administration of pharmacologically active bases for skin lightening Inventor(s): Hsu, Tsung-Min; (San Diego, CA), Luo, Eric C.; (Plano, TX), Maibach, Howard I.; (San Francisco, CA) Correspondence: Reed & Eberle Llp; 800 Menlo Avenue, Suite 210; Menlo Park; CA; 94025; US Patent Application Number: 20030235542 Date filed: June 21, 2002 Abstract: Provided are methods and topical pharmaceutical formulations for skin lightening. The invention involves the topical administration of a pharmacologically active base in a formulation having a pH of about 7.5 to about 13.0, preferably about 8.0 to 11.5, and most preferably about 8.5 to 10.5. These basic formulations can be used to treat regions of hyperpigmented skin, comprising, as examples, age spots, freckles, disease-related hyperpigmented skin, melasma related to pregnancy or the use of oral contraceptives, and hyperpigmented skin due to chemical exposure or ingestion. Excerpt(s): This invention relates generally to methods and pharmaceutical formulations for skin lightening, and relates more particularly to the use of a pharmacologically active base in such methods and formulations. Cosmetically disfiguring skin pigmentation irregularities and disorders are common and widespread, leading to a large demand for skin lightening products. The color of normal human skin is due primarily to melanin, hemoglobin, and carotenoids. Of these pigments, melanin is of particular importance in regard to skin pigmentation and cosmetology. The type and amount of melanin synthesized by the melanocyte (melanin-producing skin cell), and its distribution pattern in the surrounding keratinocytes, largely determine skin color. Two types of melanin are present in human skin: (1) eumelanin, which is the dark brown pigment found in most skin, hair, and eyes, and whose production is stimulated by exposure to ultraviolet light, and (2) pheomelanin, which is a yellow-orange pigment found mainly in the skin of very fair-skinned people, particularly those with red hair. A basic understanding of the pigmentation pathway is helpful prior to the discussion of the skin-lightening agent used in conjunction with the method of the present invention. Melanin forms through a series of oxidative reactions involving the amino acid tyrosine in the presence of the enzyme tyrosinase. Tyrosinase converts tyrosine to dihydroxyphenylalanine (DOPA) and then to dopaquinone. Subsequently, dopaquinone

Patents 123

is converted to dopachrome through auto-oxidation, and finally to dihydroxyindole or dihydroxyindole-2-carboxylic acid (DHICA) to form eumelanin. The latter reaction occurs in the presence of dopachrome tautomerase and DHICA oxidase. In the presence of cysteine or glutathione, dopaquinone is converted to cysteinyl DOPA or glutathione DOPA; subsequently, pheomelanin is formed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Ultra low dose oral contraceptives with sustained efficacy and induced amenorrhea Inventor(s): Anderson, Freedolph D.; (Virginia Beach, VA), Hodgen, Gary D.; (Virginia Beach, VA), Williams, Robert F.; (Norfolk, VA) Correspondence: Ostrolenk Faber Gerb & Soffen; 1180 Avenue OF The Americas; New York; NY; 100368403 Patent Application Number: 20030018018 Date filed: July 10, 2001 Abstract: A method of female contraception involves administering a combination of estrogen and progestin continuously for more than a year in which the daily amounts of estrogen and progestin are equivalent to about 5-35 mcg of ethinyl estradiol and about 0.025 to 10 mg of norethindrone acetate, respectively. The advantages include lack of menstrual bleeding, less patient anemia, less total exposure to medication when compared to a 35 microgram (low dose) containing oral contraceptive, reduced risk of endometrial cancer, higher compliance rates and more lifestyle convenience for patients who desire less uterine bleeding each year or longer. Excerpt(s): The ovarian/menstrual cycle is a complex event characterized by an estrogen rich follicular phase and, after ovulation, a progesterone rich luteal phase. Each has a duration of approximately 14 days resulting in an intermenstrual interval of about 28 days. The endometrial tissue responds to the changes in hormonal milieu. The onset of menstruation is the beginning of a new menstrual cycle and is counted as day 1. During a span of about 5 to 7 days, the superficial layers of the endometrium, which grew and developed during the antecedent ovarian/menstrual cycle, are sloughed because demise of the extant corpus luteum in the non-fertile menstrual cycle is associated with a loss of progesterone secretion. Ovarian follicular maturation occurs progressively resulting in a rise in the circulating levels of estrogen, which in turn leads to new endometrial proliferation. The dominant ovarian follicle undergoes ovulation near mid-cycle, generally between menstrual cycle days 12 to 16 and is converted from a predominantly estrogen source to a predominantly progesterone source (the corpus luteum). The increasing level of progesterone in the blood converts the proliferative endometrium to a secretory phase in which the tissue proliferation has promptly abated, leading to the formation of endometrial glands or organs. When the ovulated oocyte is viably fertilized and continues its progressive embryonic cleavage, the secretory endometrium and the conceptus can interact to bring about implantation (nidation), beginning about 6 to 8 days after fertilization. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

124

Oral Contraceptives

Keeping Current In order to stay informed about patents and patent applications dealing with oral contraceptives, 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 “oral contraceptives” (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 oral contraceptives. You can also use this procedure to view pending patent applications concerning oral contraceptives. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

125

CHAPTER 7. BOOKS ON ORAL CONTRACEPTIVES Overview This chapter provides bibliographic book references relating to oral contraceptives. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on oral contraceptives 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 “oral contraceptives” (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 oral contraceptives: •

Good Bones: The Complete Guide To Building and Maintaining the Healthiest Bones Source: Palo Alto, CA: Bull Publishing Company. 1999. 184 p. Contact: Available from Bull Publishing Company. P.O. Box 208, Palo Alto, CA 943020208. (650) 322-2855. Fax (650) 327-3300. Website: www.bullpub.com. PRICE: $14.95 plus shipping and handling. ISBN 0923521445. Summary: This book provides women with guidelines on building and maintaining healthy bones. By examining 17 major risk factors for bone health, the book helps women assess their overall risk for osteoporosis. A chapter on normal bone physiology is followed by a chapter that discusses risk factors in the prenatal and infancy periods, childhood, adolescence, young adulthood, middle age, and older adulthood. Chapter three examines hereditary risk factors: race, ethnicity, and family history. The next chapter is devoted to factors affecting women: age at menarche, menstrual cycles, age at

126

Oral Contraceptives

menopause, and total reproductive years. Other topics include oral contraceptives, treatments for endometriosis, pregnancy and breast feeding, and hysterectomy. The fifth chapter evaluates the role of body build, weight, and fat in bone health. Chapter six focuses on the effect of exercise and physical activity on bone health and presents an example of an exercise routine that includes both endurance and strength training. The next chapter discusses the impact of hormones, prescription medications, and calcium supplements on bone health, and presents the advantages and disadvantages of hormone replacement therapy (HRT), highlights alternatives to HRT, and explains how to select the best calcium supplements and use them most effectively. Other chapters examine lifestyle factors, such as alcohol and caffeine consumption and smoking that affects bone health; identify factors influencing calcium absorption; present calcium requirements for various age groups; and discuss the importance of good nutrition in building strong bones. The final chapter applies the 17 risk factors to case studies presented in the previous chapters. A glossary of terms and a list of suggested readings and resources are included. 15 figures, 21 tables, and numerous references. •

Medical Management of Pregnancy Complicated by Diabetes. 3rd ed Source: Alexandria, VA: American Diabetes Association. 2000. 176 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $39.95 plus shipping and handling. ISBN: 1580400132. Summary: This book, which is part of the American Diabetes Association's Clinical Education Series, provides health professionals with protocols that have resulted in healthy infants in pregnancies complicated by type 1, type 2, or gestational diabetes. The first section focuses on prepregnancy counseling and management of women with preexisting diabetes or previous gestational diabetes. The next section discusses contraceptive methods, including oral contraceptives, the norplant system, barrier methods, intrauterine devices, the rhythm method, and permanent sterilization. This is followed by a section that examines the psychological impact of diabetes and pregnancy. Topics include the response to pregnancy in women with preexisting diabetes, the response to a diagnosis of gestational diabetes, long term adaptation, personality types and individualizing treatment, pregnancy crises, and the importance of a team approach and a support system. The fourth section focuses on blood glucose monitoring. Topics include glycosylated hemoglobin measurements in pregnancy for women with preexisting or gestational diabetes, self monitoring of blood glucose and urine ketones, and medical tests to evaluate maternal status in women with preexisting or gestational diabetes. The next section offers guidelines for managing morning sickness with dietary remedies, insulin adjustments, and medical management. The sixth section discusses nutritional management during pregnancy in women with preexisting diabetes. Topics include patient responsibility; the nutrient needs of pregnancy; diet and eating habits; vitamin and mineral supplementation; calorie level; weight gain; meal planning; recordkeeping; use of sodium, caffeine, and artificial sweeteners; the management of hypoglycemia; and postpartum nutritional management. Section seven focuses on the use of insulin during pregnancy in women with preexisting diabetes. Topics include metabolic alterations during normal gestation, therapeutic insulin use, dosage adjustment, insulin during labor and delivery, postpartum insulin requirements, and oral hypoglycemic agents. The next section describes diagnostic tests and methods of fetal surveillance, including ultrasonography, alpha fetoprotein testing, genetic testing, fetal monitoring, and amniocentesis. The ninth

Books

127

section discusses gestational diabetes, focusing on epidemiology, screening, diagnosis, nutritional management, insulin therapy, exercise, and obstetric management. Section ten addresses the issue of neonatal care of infants of women with diabetes. Topics include perinatal mortality and morbidity, resuscitation, nursery care, and long term followup. The final section discusses postpartum followup of women with gestational diabetes. The book includes an index and resources for health care professionals. 3 figures. 39 tables. Numerous references. •

Women's Oral Health Issues Source: Chicago, IL: Council on Access, Prevention and Interprofessional Relations; American Dental Association (ADA). December 1995. 46 p. Contact: Available from American Dental Association (ADA). 211 East Chicago Avenue, Chicago, IL 60611. (800) 947-4746; Fax (630) 443-9970. PRICE: $8.00 plus shipping and handling. Order Number J076. Summary: This document summarizes oral health care recommendations for women. The authors discuss hormonal effects on the oral cavity during various stages in women's lives as well as the special dental needs and considerations that may be encountered in each stage (puberty, menses, pregnancy, using oral contraceptives, and menopause). Osteoporosis and eating disorders, two problems prevalent in the female population, are also addressed. A final section considers temporomandibular disorders. The document is designed to be a resource tool, not an outline of standards of care. 5 tables. 108 references. (AA-M).

•

Epidemic: How Teen Sex Is Killing Our Kids Contact: Regnery Publishing, 1 Massachusetts Ave NW, Washington, DC, 20001, (202) 216-0600, http://www.regnery.com. Summary: This monograph examines the threat posed to adolescents by sexually transmitted diseases (STDs). It provides information on common STDs, including human papillomavirus, genital herpes, gonorrhea, syphilis, trichomoniasis, hepatitis B, chlamydia, and human immunodeficiency virus, and discusses depression as the emotional STD. Several chapters are devoted to the causes of the STD epidemic among adolescents, including media hype about sex, lack of education about STDs, confusion about what constitutes a sex act, the sexual freedom provided by oral contraceptives, and the myth of safe sex. In addition, the monograph offers advice to parents. The monograph includes many personal anecdotes.

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 Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “oral contraceptives” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “oral contraceptives” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “oral contraceptives” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com):

128

Oral Contraceptives

•

Bedrest in healthy women effects of menstrual function and oral contraceptives (SuDoc NAS 1.26:171946) by Suzanne M. Fortney; ISBN: B000103MOU; http://www.amazon.com/exec/obidos/ASIN/B000103MOU/icongroupinterna

•

Carcinogenicity tests of oral contraceptives; ISBN: 0113204906; http://www.amazon.com/exec/obidos/ASIN/0113204906/icongroupinterna

•

Extragenital Effects of Oral Contraceptives by Max Elstein (Editor); ISBN: 1850709394; http://www.amazon.com/exec/obidos/ASIN/1850709394/icongroupinterna

•

Gestoden: The Development of a New Gestoden -Containing Low Dose Oral Contraceptive by M. Elstein (Editor); ISBN: 1850701008; http://www.amazon.com/exec/obidos/ASIN/1850701008/icongroupinterna

•

Hepatic tumors and oral contraceptives by Randall Murray; ISBN: 0842241280; http://www.amazon.com/exec/obidos/ASIN/0842241280/icongroupinterna

•

Long-term studies on side-effects of contraception, state and planning : symposium of the Study Group "Side-Effects of Oral Contraceptives, Pilot Phase", Munich, September 27-29, 1977; ISBN: 0387090932; http://www.amazon.com/exec/obidos/ASIN/0387090932/icongroupinterna

•

Neurological Compl Oral Contraceptives by Bickerstaff; ISBN: 0198572077; http://www.amazon.com/exec/obidos/ASIN/0198572077/icongroupinterna

•

On the Pill: A Social History of Oral Contraceptives, 1950-1970 by Elizabeth Siegel Watkins; ISBN: 0801858763; http://www.amazon.com/exec/obidos/ASIN/0801858763/icongroupinterna

•

Optimizing the Estrogen Dose in Oral Contraceptives by J.R. Newton (Editor), M. op ten Berg (Editor); ISBN: 1850704457; http://www.amazon.com/exec/obidos/ASIN/1850704457/icongroupinterna

•

Oral Contraceptive User Guide by Richard Dickey; ISBN: 0917634268; http://www.amazon.com/exec/obidos/ASIN/0917634268/icongroupinterna

•

Oral Contraceptives by Michael Briggs; ISBN: 0920792146; http://www.amazon.com/exec/obidos/ASIN/0920792146/icongroupinterna

•

Oral Contraceptives & Breast Cancer by Committee on Relationship Between Oral Contracteption, et al; ISBN: 0309044936; http://www.amazon.com/exec/obidos/ASIN/0309044936/icongroupinterna

•

Oral contraceptives abstracts : a guide to the literature, 1977-1979 by Helen K. Kolbe; ISBN: 0306651920; http://www.amazon.com/exec/obidos/ASIN/0306651920/icongroupinterna

•

Oral Contraceptives and Breast Cancer: The Implications of the Present Findings for Informed Consent and Informed Choice by R.D. Mann (Editor); ISBN: 0929858344; http://www.amazon.com/exec/obidos/ASIN/0929858344/icongroupinterna

•

Oral Contraceptives and Cardiovascular Disease: An Analysis of the Recent Discussions on the Safety of the Pill by Jean Cohen (Editor), Spai European Society of Contraception World Congress 1996 Barcelona; ISBN: 1850707871; http://www.amazon.com/exec/obidos/ASIN/1850707871/icongroupinterna

•

Oral Contraceptives and Their Link to Depression and Suicide #357 by Anne D'Arcy Jorgensen; ISBN: 9996762491; http://www.amazon.com/exec/obidos/ASIN/9996762491/icongroupinterna

Books

129

•

Oral Contraceptives: Technical and Safety Aspects (WHO Offset Publications); ISBN: 9241700645; http://www.amazon.com/exec/obidos/ASIN/9241700645/icongroupinterna

•

Pathological effects of oral contraceptives; ISBN: 0842270817; http://www.amazon.com/exec/obidos/ASIN/0842270817/icongroupinterna

•

Report of the Joint Working Group on Oral Contraceptives; ISBN: 0113202385; http://www.amazon.com/exec/obidos/ASIN/0113202385/icongroupinterna

•

Summary of Contraindications to Oral Contraceptives by S. C. M. Knijff, et al; ISBN: 1850706913; http://www.amazon.com/exec/obidos/ASIN/1850706913/icongroupinterna

•

Summary of Drug Interactions with Oral Contraceptives by E.M. Goorissen, et al; ISBN: 1850705186; http://www.amazon.com/exec/obidos/ASIN/1850705186/icongroupinterna

•

The Benefits and Risks of Oral Contraceptives Today by James Owen Drife; ISBN: 1850707073; http://www.amazon.com/exec/obidos/ASIN/1850707073/icongroupinterna

•

The Development of a New Triphasic Oral Contraceptive by R.B. Greenblatt (Editor); ISBN: 0852003765; http://www.amazon.com/exec/obidos/ASIN/0852003765/icongroupinterna

•

The Metabolic effects of a low-estrogen/low-progestogen oral contraceptive : proceedings from a sYmposium published by the editors of Drug therapy; ISBN: 0935404430; http://www.amazon.com/exec/obidos/ASIN/0935404430/icongroupinterna

•

The Pill, Pygmy Chimps, and Degas' Horse/the Remarkable Autobiography of the Award-Winning Scientist Who Synthesized the Birth Control Pill by Carl Djerassi; ISBN: 0465057586; http://www.amazon.com/exec/obidos/ASIN/0465057586/icongroupinterna

•

The pill: facts and fallacies about today's oral contraceptives by Robert W. Kistner; ISBN: 009103650X; http://www.amazon.com/exec/obidos/ASIN/009103650X/icongroupinterna

•

The second International Norgestrel Symposium : some metabolic considerations of oral contraceptive usage : proceedings of the 1974 symposium held at the Royal College of Physicians, London, England; ISBN: 0444151591; http://www.amazon.com/exec/obidos/ASIN/0444151591/icongroupinterna

•

Understanding the Pill: A Consumer's Guide to Oral Contraceptives by Greg Juhn; ISBN: 1560248513; http://www.amazon.com/exec/obidos/ASIN/1560248513/icongroupinterna

Chapters on Oral Contraceptives In order to find chapters that specifically relate to oral contraceptives, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and oral contraceptives 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

130

Oral Contraceptives

the dates and language you prefer, and the format option “Book Chapter.” Type “oral contraceptives” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on oral contraceptives: •

Epidemiology of Inflammatory Bowel Disease Source: in Lichtenstein, G.R. The Clinician's Guide to Inflammatory Bowel Disease. Thorofare, NJ: SLACK Incorporated. 2003. p. 1-8. Contact: Available from SLACK Incorporated. 6900 Grove Road, Thorofare, NJ 080869447. (856) 848-1000. Fax (856) 853-5991. Website: www.slackbooks.com. PRICE: $44.95; plus shipping and handling. ISBN: 556425546. Order number: 75546. Summary: Although the term inflammatory bowel disease (IBD) describes a wide range of inflammatory states, it generally refers to ulcerative colitis (UC) and Crohn's disease. This chapter on epidemiology of IBD is from a handbook that presents an up to date guide on selected topics in IBD, focusing on those clinically important areas that have undergone recent changes or discoveries. In this chapter, the authors note that methodologically rigorous studies, which evaluate the epidemiology of these disorders, are relatively rare. Furthermore, much of the available literature is limited by referral bias and inadequate case definition. The latter issue is particularly relevant since the current concept that Crohn's disease and ulcerative colitis are unique entities has been challenged by recent genetic discoveries. Nonetheless, the current phenotypic-based classification is clinically useful and provides a valuable framework for research. The authors cover incidence and prevalence rates, morbidity and mortality, and environmental risk factors, including cigarette smoking, oral contraceptives, geography, diet, nonsteroidal antiinflammatory drugs (NSAIDs), mycobacteria, measles virus, and appendectomy. The authors also briefly consider genetic risk factors, covering familial aggregation, race and ethnicity, and gene identification. 19 references.

•

Endocrine Disorders Source: in Wilson, T.G., Jr.; Kornman, K.S. Fundamentals of Periodontics. 2nd ed. Chicago, IL: Quintessence Publishing Co., Inc. 2003. p. 195-203. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $82.00 plus shipping and handling. ISBN: 0867154055. Summary: Endocrine glands secrete hormones that are integrally involved in the regulation of cell metabolism and the maintenance of physiologic homeostasis. Endocrine dysfunctions, such as hyperparathyroidism and diabetes mellitus, are associated with an increased susceptibility to periodontitis or to accelerated destruction in coexistent periodontal diseases. Additionally, physiology fluctuations of sex hormones during various life stages may exert direct effects on the tissues of the periodontium, perhaps altering patient response to plaque-induced periodontal inflammation. This chapter on endocrine disorders is from a periodontics textbook that focuses on diagnosis and clinical management. The authors discuss hyperparathyroidism; alterations in sex hormones, due to puberty, menstruation, pregnancy, oral contraceptives, and menopause; and diabetes mellitus, including classification and epidemiology, clinical features, oral manifestations, patient treatment, and diabetic emergencies. 140 references.

Books

•

131

How Can We Predict Prognosis in Inflammatory Bowel Disease? Source: Jewell, D.P.; Warren, B.F.; Mortensen, N.J., eds. Challenges in Inflammatory Bowel Disease. Malden, MA: Blackwell Science, Inc. 2001. p.269-284. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $145.95. ISBN: 0632051698. Summary: Patients who have recently been diagnosed with inflammatory bowel disease (IBD) will have many questions for their physicians regarding the clinical course and prognosis of their disease. This chapter on prognosis is from a book that offers an approach to the subject of IBD that highlights current areas of controversy. The authors review the literature concerning the clinical course of ulcerative colitis and Crohn's disease and how physicians can predict prognosis. Topics include prognosis following the first attack of ulcerative colitis, risk for relapse, the need for colectomy, the risk of progression of proctitis and proctosigmoiditis to more extensive disease, relapse of specific Crohn's disease patterns, the need for surgery, the role of smoking, and the role of oral contraceptives. 3 tables. 95 references.

•

Endocrine Conditions Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 263-297. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: The endocrine system is a widespread system consisting of glands that exert their effects, usually at some distance, by means of chemicals (hormones) secreted into the circulation. Endocrine and nervous system mechanisms thus normally maintain homeostasis. This chapter on endocrine conditions is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include the hypothalamus and pituitary, posterior pituitary hypofunction, anterior pituitary hypo and hyperfunction, adrenocortical hypofunction, systemic corticosteroid therapy, acute adrenal insufficiency, adrenocortical hyperfunction (including Cushing's syndrome), hyperaldosteronism, pheochromocytoma, the thyroid, goiter, lingual thyroid, hypo and hyperthyroidism, the parathyroids, hypo and hyperparathyroidism, the pancreas, diabetes mellitus, hormone-secreting pancreatic tumors, the gonads, oral contraceptives, pregnancy, lactation, prematurity, menopause, hormone replacement therapy, multiple endocrine adenoma (MEA), and endocrine and metabolic manifestations of cancer and other diseases. For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 appendix. 5 figures. 23 tables. 53 references.

•

Solving Women's Problems Source: in Touchette, N. Diabetes Problem Solver. Alexandria, VA: American Diabetes Association. 1999. p. 325-356. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 442-

132

Oral Contraceptives

9742. Website: www.diabetes.org. PRICE: $19.95 for members; plus shipping and handling. ISBN: 1570400091. Summary: This chapter deals with solving problems in women who have diabetes. Diabetes can pose both physical and emotional challenges to women. For example, women who have diabetes are more likely than women who do not have diabetes to have urinary tract and vaginal infections, to experience problems associated with pregnancy, and to notice that diabetes affects their menstrual cycle. The emotional challenges of diabetes are of particular concern to women, especially as they relate to sexuality. Women who feel emotionally unhealthy are less likely to feel sexually comfortable. Women who have diabetes often report problems with sexual desire. In addition, they may have problems with physical arousal or problems with achieving orgasm. The chapter presents the symptoms of these sexual problems and explains what action women should take if they experience any of the symptoms of these problems. Other topics include the impact of sexual activity on blood glucose control, the affect of ovulation on blood glucose control, and the control of blood glucose levels during the menstrual cycle. The chapter identifies the risks associated with using oral contraceptives, an intrauterine device, and barrier methods, as well as undergoing sterilization. The issue of pregnancy is addressed by discussing the risks associated with pregnancy for a woman who has diabetes; and providing guidelines for preparing for pregnancy, maintaining good blood glucose control during pregnancy, giving birth, managing blood glucose levels following delivery, and breastfeeding. In addition, the chapter discusses gestational diabetes, menopause, and osteoporosis in terms of risks and the action women should take if they experience any of the symptoms of these conditions. •

Prevalence and Incidence of Secondary and Other Types of Diabetes Source: in Harris, M.I., et al., eds., for the National Diabetes Data Group (NDDG). Diabetes in America. 2nd ed. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. 1995. p. 69-84. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. Fax (301) 634-0716. E-mail: [email protected]. Also available at http://www.niddk.nih.gov/. PRICE: Full-text book and chapter available online at no charge; book may be purchased for $20.00. Order number: DM-96 (book). Summary: This chapter on the prevalence and incidence of secondary and other types of diabetes is from a compilation and assessment of data on diabetes and its complications in the United States. The prevalence of these secondary types is approximately 1 to 2 percent of all diabetes. The extent of glucose intolerance in patients with secondary forms of diabetes can vary widely, presenting as overt diabetes that is insulin-requiring or noninsulin-requiring, simulating IDDM or NIDDM, or as milder forms such as impaired glucose tolerance (IGT) or minimally abnormal glucose tolerance. Topics include diabetes secondary to pancreatic diseases, malnutrition-related diabetes, hemochromatosis, acromegaly, isolated growth hormone deficiency, Cushing's syndrome, pheochromocytoma, primary hyperaldosteronism, hyperthyroidism, tumors of endocrine pancreas or gut, polyendocrine autoimmunity syndromes, and POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) syndrome. The author also discusses diabetogenic drugs, chemical agents, and toxins, including diuretics and beta-adrenergic antagonists, diphenylhydantoins, glucocorticoids, oral contraceptives, progestins, pentamidine, Vacor, nicotinic acid,

Books

133

cyclosporin, and opiates. The author concludes with a discussion of genetic syndromes related to secondary diabetes. 2 figures. 7 tables. 147 references. (AA-M). •

Ulcerative Colitis Source: in Corman, M.L.; Allison, S.I.; Kuehne, J.P. Handbook of Colon and Rectal Surgery. Philadelphia, PA: Lippincott Williams and Wilkins. 2002. p.701-776. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2365. PRICE: $79.00 plus shipping and handling. ISBN: 0781725860. Summary: This chapter on ulcerative colitis (UC) is from a handbook that addresses the entire range of diseases affecting the colon, rectum, and anus. The authors consider the historical perspective, epidemiology and etiology (genetics, autoimmunity, infection, diet, oxidative metabolism, stool, smoking, oral contraceptives, psychological factors, age, sex, race), differential diagnosis of UC versus Crohn's disease (the other type of inflammatory bowel disease or IBD), pathology, signs, symptoms and presentations, course and prognosis, the interrelationship of IC and cancer, medical management, and surgical management. 31 figures. 3 tables.

•

Chapter 73: Diseases of the Sebaceous Glands Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 1. New York, NY: McGraw-Hill. 1999. p. 769-784. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 759-3749 or (614) 759-3641. E-mail: [email protected]. PRICE: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with information on acne vulgaris, its epidemiology, etiology, pathogenesis, clinical manifestations, laboratory findings, pathology, diagnosis, and treatment. This self limited disease, seen mainly in adolescents, involves the sebaceous follicles. Acne is often an early manifestation of puberty, and most cases are seen during the middle to late adolescent period. The disease seems to be familial. Although the basic cause of acne is unknown, there is considerable information on the various factors involved in its pathogenesis. The primary site is the face, but the back, chest, and shoulders may also be affected. Acne is characterized by various noninflammatory or inflammatory clinical lesions. Laboratory studies are not usually indicated for patients who have acne unless hyperandrogenism is suspected. The diagnosis of acne vulgaris is usually made from the finding of a mixture of comedones, pustules, papules, and nodules on the face, back, or chest. Therapeutic options include local, physical, or systemic therapy. Local therapy involves cleansing and applying topical agents such as vitamin A acid, benzoyl peroxide, and azelaic acid. Physical therapy includes superficial x ray therapy, ultraviolet light therapy, cryotherapy, surgery, and intralesional injection of glucocorticoids. The major systemic modalities that are currently being used include antibiotics and antibacterial agents; hormones such as estrogens, oral contraceptives, glucocorticoids, gonadotropin releasing hormone agonists, and antiandrogens; and the oral synthetic retinoid isotretinoin. The prognosis vulgaris is favorable, with scarring being the only physical sequela. The article also describes miscellaneous types of acne, including neonatal acne; excoriated acne; acne induced by steroids, iodides, bromides, and other drugs; occupational acne; tropical acne; acne aestivalis; acne cosmetica; pomade acne; acne

134

Oral Contraceptives

detergicans; acne mechanica; acne with facial edema; acne conglobata; acne fulminans; and steatocystoma multiplex. 10 figures and 114 references. •

Chapter 206: Pigment Disorders Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 3 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have skin pigment disorders with information on the symptoms and treatment of albinism, vitiligo, and melasma. The main skin pigment is melanin. Abnormally low pigment is usually restricted to small areas of skin. Increased amounts of melanin can be a response to hormonal changes or particular drugs or can occur as a result of certain diseases. Albinism is a rare, inherited disorder in which a person produces no melanin. People with this disorder are prone to sunburn and, thus, to skin cancers. They can minimize these problems by avoiding direct sunlight, wearing sunglasses, and applying sunscreen with a sun protection factor higher than 15. Vitiligo, a condition in which a loss of melanocytes results in smooth, whitish patches of skin, may occur after unusual physical trauma and tends to accompany certain other diseases. The condition is most striking in darkly pigmented people. There is no cure for vitiligo, but small areas can be camouflaged with various dyes. Psoralens plus ultraviolet A light treatment is sometimes effective. Melasma, which usually affects the face, is characterized by a roughly symmetric group of dark brown patches of pigmentation that are often clearly delineated. The condition is most likely to occur during pregnancy and may also appear in women taking oral contraceptives. Sunscreens and avoidance of sun exposure may prevent the condition from getting worse.

•

Gastrointestinal Tract Disorders Source: in Last, J.M. and Wallace, R.B. Public Health and Preventive Medicine. East Norwalk, CT: Appleton and Lange. 1992. p. 897-912. Contact: Available from Appleton and Lange. 25 Van Zant Street, East Norwalk, CT 06855. (800) 423-1359. PRICE: $120; plus shipping and handling. ISBN: 0838561888. Summary: This chapter, from a book about public health and preventive medicine, discusses recent advances in the epidemiology and prevention of four diseases of the gastrointestinal tract, including duodenal ulcer, gastric ulcer, ulcerative colitis, and Crohn's disease. In the gastric and duodenal ulcer section include the underlying role of prostaglandins; the role of consumption of linoleic acid; epidemiologic trends over time; sex ratios; risk factors, including cigarette smoking, nonsteroidal anti-inflammatory drugs, coffee, alcohol, diet and eating habits, stress and occupation, Helicobacter pylori, and prostaglandins; and genetics. The section on ulcerative colitis and Crohn's disease covers incidence; risk factors, including age, seasonality, trauma, smoking, person-toperson transmission, genetic factors, religion, psychological factors, oral contraceptives, environmental factors, and diet; cancer risk; and prevention. 7 figures. 4 tables. 270 references.

Books

•

135

Preconception, Conception, and Contraception Source: in Reece, E.A. and Coustan, D.R., eds. Diabetes Mellitus in Pregnancy. 2nd ed. New York, NY: Churchill Livingstone. 1995. p. 417-427. Contact: Available from Churchill Livingstone. 300 Lighting Way, Secaucus, NJ 07094. (800) 553-5426. PRICE: $92.00. ISBN: 0443089795. Summary: This chapter, from a text on diabetes mellitus in pregnancy, covers preconception, conception, and contraception. Topics include prepregnancy counseling; the aims and practices of prepregnancy care; prepregnancy care in women with NIDDM and previous gestational diabetes; identification of the date of conception and the 'early growth delay' hypothesis; and contraception for women with IDDM, including the use of oral contraceptives, intrauterine contraceptive devices, barrier methods, natural family planning, and sterilization. The author reports in detail on the experiences of the Edinburgh prepregnancy clinic. 1 table. 59 references.

137

CHAPTER 8. MULTIMEDIA ON ORAL CONTRACEPTIVES Overview In this chapter, we show you how to keep current on multimedia sources of information on oral contraceptives. 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.

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 “oral contraceptives” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on oral contraceptives: •

Listen Carefully Contact: Emory University, School of Medicine, Department of Gynecology/Obstetrics, 1462 Clifton Rd, Atlanta, GA, 30322, (404) 589-3556. Summary: This cassette contains information in a question-and-answer format about birth control pills and other forms of contraception. Special instructions for beginning oral contraceptives are given, as well as instructions on steps to be taken if pills are missed. Side effects and danger signs are also explained. While oral contraceptives are effective in preventing pregnancy, condoms are urged as an effective means of preventing sexually transmitted diseases (STD's), including HIV and AIDS.

139

CHAPTER 9. PERIODICALS CONTRACEPTIVES

AND

NEWS

ON

ORAL

Overview In this chapter, we suggest a number of news sources and present various periodicals that cover oral contraceptives.

News Services and Press Releases One of the simplest ways of tracking press releases on oral contraceptives 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 “oral contraceptives” (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 oral contraceptives. 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 “oral contraceptives” (or synonyms). The following was recently listed in this archive for oral contraceptives: •

Oral contraceptives lower risk of developing rheumatoid arthritis Source: Reuters Medical News Date: March 02, 2004

140

Oral Contraceptives

•

Birth control pill doesn't cause weight gain-study Source: Reuters Industry Breifing Date: January 30, 2004

•

Oral contraceptives do not appear to alter premenstrual mood Source: Reuters Industry Breifing Date: January 22, 2004

•

Patent issued for chewable oral contraceptive Source: Reuters Industry Breifing Date: December 24, 2003

•

Teva and Andrx set oral contraceptives deal Source: Reuters Industry Breifing Date: December 11, 2003

•

Oral contraceptive shown to fight acne Source: Reuters Health eLine Date: November 24, 2003

•

Continuous oral contraceptive use decreases endometriosis symptoms Source: Reuters Industry Breifing Date: September 11, 2003

•

Extended oral contraceptive formulation approved by FDA Source: Reuters Medical News Date: September 08, 2003

•

Barr gets approval for extended oral contraceptive Source: Reuters Health eLine Date: September 08, 2003

•

Death rate low in former oral contraceptive users Source: Reuters Health eLine Date: July 18, 2003

•

Lower mortality seen in oral contraceptive users decades later Source: Reuters Industry Breifing Date: July 17, 2003

•

Oral contraceptive use may enhance lung mechanics Source: Reuters Industry Breifing Date: June 13, 2003

•

Modern low-dose oral contraceptives do not raise stroke risk Source: Reuters Industry Breifing Date: June 13, 2003

•

HRT or oral contraceptives may induce or exacerbate angioedema symptoms Source: Reuters Industry Breifing Date: April 22, 2003

•

Oral contraceptives complicate wisdom tooth extraction Source: Reuters Industry Breifing Date: April 16, 2003

•

Review confirms link between oral contraceptive use and cervical cancer Source: Reuters Industry Breifing Date: April 03, 2003

Periodicals and News

•

Licorice caution issued to oral contraceptive users Source: Reuters Health eLine Date: January 31, 2003

•

After stopping oral contraceptives, protection against ovarian cancer persists Source: Reuters Industry Breifing Date: December 05, 2002

•

Schering, Akzo Nobel partner on oral contraceptive for men Source: Reuters Industry Breifing Date: November 21, 2002

•

Concomitant use of fluoxetine, oral contraceptives is safe Source: Reuters Industry Breifing Date: October 31, 2002

•

Watson to market Johnson Johnson oral contraceptives under own brand Source: Reuters Industry Breifing Date: October 28, 2002

•

Barr gets FDA approval for generic oral contraceptive Source: Reuters Industry Breifing Date: September 25, 2002

•

Low-dose oral contraceptive safe and effective treatment for acne Source: Reuters Industry Breifing Date: September 10, 2002

•

Third generation oral contraceptives do not raise risk of myocardial infarction Source: Reuters Industry Breifing Date: August 29, 2002

•

FDA approves Ortho's intermediate-dose oral contraceptive Source: Reuters Medical News Date: August 23, 2002

•

Highest rates of oral contraceptive use reported in Germany Source: Reuters Medical News Date: August 16, 2002

•

German women lead world in oral contraceptive use Source: Reuters Industry Breifing Date: August 14, 2002

•

Barr fiscal Q4 profit rises on oral contraceptives, generics Source: Reuters Industry Breifing Date: August 14, 2002

•

Oral contraceptive use by teens changes lipid profile, but not body composition Source: Reuters Industry Breifing Date: August 06, 2002

•

Oral contraceptives modulate cell proliferation, apoptosis in endometriosis Source: Reuters Medical News Date: June 26, 2002

•

Oral contraceptive use does not increase breast cancer risk Source: Reuters Medical News Date: June 26, 2002

141

142

Oral Contraceptives

•

Oral contraceptive plus recombinant IGF-1 reverses bone loss in anorexics Source: Reuters Medical News Date: June 26, 2002

•

Oral contraceptives might be protective against diabetes Source: Reuters Industry Breifing Date: June 05, 2002

•

New oral contraceptive effective, offers fewer menstrual periods Source: Reuters Medical News Date: May 08, 2002

•

Birth control pill reduces periods to four a year Source: Reuters Health eLine Date: May 07, 2002

•

Barr's oral contraceptive clears initial phase III hurdle Source: Reuters Industry Breifing Date: May 06, 2002

•

Nevirapine may impair oral contraceptive effectiveness Source: Reuters Industry Breifing Date: April 30, 2002 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 “oral contraceptives” (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.

Periodicals and News

143

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 “oral contraceptives” (or synonyms). If you know the name of a company that is relevant to oral contraceptives, 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/. 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 “oral contraceptives” (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 “oral contraceptives” (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 oral contraceptives: •

Update on the Epidemiology of IBD Source: Progress in Inflammatory Bowel Disease. 15(3): 1, 3-8. Fall 1994. Contact: Available from CCFA. 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 932-2423 or (800) 343-3637 or (212) 685-3440. Summary: In this article, the authors summarize the information on the epidemiology of inflammatory bowel disease (IBD) that has been published in the past 5 years and place it in context for the practicing physician and IBD researcher. After a discussion of the epidemiological challenges of IBD, the authors cover incidence of ulcerative colitis (UC) and Crohn's disease; prevalence; mortality; morbidity; the geographic variation in IBD rates; race factors; gender; age factors; urban versus rural findings; ethnicity; diet as an etiologic factor; early life events in children with IBD; oral contraceptives as risk factors for Crohn's disease; cigarette smoking; passive smoking exposure; the use of nonsteroidal anti-inflammatory drugs (NSAIDs); and colon cancer risk in patients with UC. The authors conclude with a brief discussion of the use of outcomes research in the future of research on the epidemiology of IBD. 55 references.

•

Carpal Tunnel Syndrome: Make Way for Relief Source: Mayo Clinic Health Letter. 20(1):4-5. January 2002.

144

Oral Contraceptives

Contact: Available from Mayo Clinic Health Letter. 200 First Street SW, Rochester, MN 55905. (800) 333-9037 or (303) 604-1465. Email: [email protected]. Summary: This newsletter article presents an overview of the symptoms, risk factors, and treatment of patients with carpal tunnel syndrome. Carpal tunnel syndrome is caused by compression of the median nerve in the wrist. Carpal tunnel occurs most frequently in middle-aged women and is associated with work that requires repetitive grasping, wrist bending, or prolonged gripping. Patients with obesity, osteoarthritis, diabetes, rheumatoid arthritis, or thyroid disorders are at greater risk. People with previous wrist fractures, using oral contraceptives, experiencing hormonal changes due to pregnancy, or have hand or arm swelling after exercise are also at risk. Symptoms may include swelling, numbness, tingling, burning sensation, hand weakness, and muscle shrinkage. The doctor, after examination, may recommend conservative treatment options such as NSAIDs, night splints to immobilize the wrist, or corticosteroid injections to decrease inflammation. If the symptoms do not improve, then surgery may be performed. The surgical procedure is known as carpal tunnel release and is done on an outpatient basis. The transverse carpal is severed to relieve the pressure on the median nerve. Recovery usually takes 6 weeks, and 75 percent of those who have the surgery experience complete relief. •

Systemic Lupus Erythematosus: Women's Health Issues Source: Bulletin on the Rheumatic Diseases. 49(8): 1-3. 2001. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (404) 872-7100. Fax (404) 872-9559. Summary: This newsletter article provides health professionals with information on systemic lupus erythematosus (SLE) in relation to issues specific to women's health, including pregnancy, contraception, fertility, sexuality, management of menopause, osteoporosis, coronary artery disease, and chronic fatigue. Pregnancy is high risk for both the woman with SLE and her fetus. Pregnant women with SLE are at higher risk for both preeclampsia and premature membrane rupture. Fetal problems associated with SLE include preterm birth, intrauterine growth retardation, placental insufficiency, pregnancy loss, and congenital heart block. Although barrier contraception is the safest method in SLE, other options include oral contraceptives, the intrauterine device, and tubal ligation. Fertility is usually not a problem in women with SLE, but some SLE treatment regimens, such as monthly pulse intravenous cyclophosphamide, put fertility at risk. Women with SLE may face sexuality issues because their body image is affected both by the disease and by its treatment. More women with SLE are reaching menopause, and studies have suggested that estrogen replacement therapy does not increase SLE flares. Both premenopausal and postmenopausal women with SLE are at risk for osteoporosis because of the use of prednisone. The major cause of death in women with SLE is cardiovascular disease, so they should be considered as candidates for screening for early atherosclerosis. Chronic fatigue is a major complaint of women with SLE. 4 tables and 18 references.

•

Epidemiology and IBD: An Intriguing Conundrum Source: Foundation Focus. p. 3-5. July 1995. Contact: Available from Crohn's and Colitis Foundation of America, Inc. 386 Park Avenue South, New York, NY 10016-8804. (800) 932-2423 or (212) 685-3440.

Periodicals and News

145

Summary: This newsletter article provides readers with basic information about the epidemiology of inflammatory bowel disease (IBD). Topics include the search for genetic risk factors for IBD; incidence; prevalence; geographic variation in IBD rates; rates of IBD in urban versus rural settings; dietary factors; early life events, such as breastfeeding and other perinatal factors; the role of oral contraceptives, cigarette smoking, and nonsteroidal anti-inflammatory drugs (NSAIDs); and ways to potentially reduce the colon cancer risk associated with IBD. 2 figures.

Academic Periodicals covering Oral Contraceptives Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to oral contraceptives. In addition to these sources, you can search for articles covering oral contraceptives 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.”

147

CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for oral contraceptives. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with oral contraceptives. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).

148

Oral Contraceptives

The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to oral contraceptives: Estrogens and Progestins Oral Contraceptives •

Systemic - U.S. Brands: Alesse; Brevicon; Demulen 1/35; Demulen 1/50; Desogen; Estrostep; Estrostep Fe; Genora 0.5/35; Genora 1/35; Genora 1/50; Intercon 0.5/35; Intercon 1/35; Intercon 1/50; Jenest; Levlen; Levlite; Levora 0.15/30; Lo/Ovral; Loestrin 1.5/30; Loestrin 1/20 http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202228.html

Progestins for Contraceptive Use •

Systemic - U.S. Brands: Depo-Provera Contraceptive Injection; Micronor; NORPLANT System; Nor-QD; Ovrette; Plan B http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202757.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

149

APPENDICES

151

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 Institute11: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

11

These publications are typically written by one or more of the various NIH Institutes.

152

Oral Contraceptives

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

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

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

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

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources

153

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 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:13 •

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

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

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/

•

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

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

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/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

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

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

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

12

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). 13 See http://www.nlm.nih.gov/databases/databases.html.

154

Oral Contraceptives

•

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 NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “oral contraceptives” (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 26379 5907 995 84 111 33476

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “oral contraceptives” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

15

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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

The HSTAT URL is http://hstat.nlm.nih.gov/.

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.

Physician Resources

155

Coffee Break: Tutorials for Biologists19 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.20 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.21 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/.

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/.

19 Adapted 20

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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. 21 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.

157

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 oral contraceptives can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased 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 oral contraceptives. 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 oral contraceptives. 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 “oral contraceptives”:

158

Oral Contraceptives

Acne http://www.nlm.nih.gov/medlineplus/acne.html Cervical Cancer http://www.nlm.nih.gov/medlineplus/cervicalcancer.html Ovarian Cancer http://www.nlm.nih.gov/medlineplus/ovariancancer.html Pituitary Disorders http://www.nlm.nih.gov/medlineplus/pituitarydisorders.html Teen Sexual Health http://www.nlm.nih.gov/medlineplus/teensexualhealth.html 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 oral contraceptives. 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: •

Birth control pills Source: Washington, DC: American College of Obstetricians and Gynecologists. 1994. 4 pp. Contact: Available from Rebecca Rinehart, American College of Obstetricians and Gynecologists, 409 12th Street, S.W., Washington, DC 20024-2188. Telephone: (202) 6385577 or (202) 863-2518 reference desk / Web site: http://www.acog.org/. Single copies available at no charge; Copies of 50 available for $15.00. Summary: This brochure, part of the American College of Obstetricians and Gynecologists' Patient Education series, is designed to educate women about oral contraceptives. It covers topics such as how they work, how they should be taken, and what side effects may occur. Line drawings illustrate the reproductive cycle. The authors used the SMOG formula to determine that the brochure is written at a sixthgrade reading level.

Patient Resources

159

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 “oral contraceptives” (or synonyms). The following was recently posted: •

(1) Best practice evidence-based guideline for the appropriate prescribing of hormone replacement therapy. (2) Guideline update: hormone replacement therapy Source: Effective Practice Institute, University of Auckland - Academic Institution; 2001 May (revised information released on 2002 September 30); 185 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3107&nbr=2333&a mp;string=oral+AND+contraceptives

•

(1) Targeted tuberculin testing and treatment of latent tuberculosis infection Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2000 June 9 (addendum released 2003 August 8); 54 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4004&nbr=3134&a mp;string=oral+AND+contraceptives

•

2001 consensus guidelines for the management of women with cervical cytological abnormalities Source: American Society for Colposcopy and Cervical Pathology - Medical Specialty Society; 2002 April 24; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3286&nbr=2512&a mp;string=oral+AND+contraceptives

•

2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1999 August (updated 2001 November 28); 64 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3080&nbr=2306&a mp;string=birth+AND+control+AND+pill

•

2002 national guideline for the management of Chlamydia trachomatis genital tract infection Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3029&nbr=2255&a mp;string=oral+AND+contraceptive

160

•

Oral Contraceptives

2002 national guideline on the management of vulvovaginal candidiasis Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3033&nbr=2259&a mp;string=oral+AND+contraceptive

•

2002 national guidelines on the management of adult victims of sexual assault Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3050&nbr=2276&a mp;string=oral+AND+contraceptive

•

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=oral+AND+contraceptives

•

AACE medical guidelines for clinical practice for the diagnosis and treatment of hyperandrogenic disorders Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 2001 Mar-April; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2847&nbr=2073&a mp;string=oral+AND+contraceptives

•

Acne Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3389&nbr=2615&a mp;string=oral+AND+contraceptives

•

American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients-2002 update Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1996 (revised 2002); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3524&nbr=2750&a mp;string=oral+AND+contraceptive

Patient Resources

•

161

American Gastroenterological Association medical position statement: evaluation and management of occult and obscure gastrointestinal bleeding Source: American Gastroenterological Association - Medical Specialty Society; 1999 July 18 (reviewed 2001); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3062&nbr=2288&a mp;string=oral+AND+contraceptive

•

Antithrombotic therapy. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 March; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2907&nbr=2133&a mp;string=oral+AND+contraceptives

•

Cardiovascular disease in women: a guide to risk factor screening, prevention and management Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 2002; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3487&nbr=2713&a mp;string=oral+AND+contraceptives

•

Cervical cancer screening Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 September (revised 2002 Jun); 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3405&nbr=2631&a mp;string=oral+AND+contraceptive

•

Cervical cytology practice guidelines Source: American Society of Cytopathology - Professional Association; 2000; 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2811&nbr=2037&a mp;string=oral+AND+contraceptive

•

Chemoprevention of breast cancer: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 2002 July; 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3229&nbr=2455&a mp;string=oral+AND+contraceptives

•

Chemotherapy and biotherapy: guidelines and recommendations for practice Source: Oncology Nursing Society - Professional Association; 2001; 226 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3209&nbr=2435&a mp;string=oral+AND+contraceptives

162

•

Oral Contraceptives

Chlamydial urethritis and cervicitis Source: Finnish Medical Society Duodecim - Professional Association; 2001 June 5; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3401&nbr=2627&a mp;string=oral+AND+contraceptives

•

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=oral+AND+contraceptives

•

Clinical prevention guidelines. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3230&nbr=2456&a mp;string=oral+AND+contraceptives

•

Common gynecologic problems: a guide to diagnosis and treatment Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 2002; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3486&nbr=2712&a mp;string=oral+AND+contraceptives

•

Deep venous thrombosis Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2002 Apr 20); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3384&nbr=2610&a mp;string=oral+AND+contraceptives

•

Depression. A guide to diagnosis and treatment Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 2001; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3432&nbr=2658&a mp;string=oral+AND+contraceptives

Patient Resources

•

163

Diagnosis and management of epilepsy in adults. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2003 April; 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3737&nbr=2963&a mp;string=oral+AND+contraceptives

•

Evidence-based guidelines for breastfeeding management during the first fourteen days Source: International Lactation Consultant Association - Professional Association; 1999 April; 31 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2109&nbr=1335&a mp;string=birth+AND+control+AND+pills

•

Facilities and equipment for the care of pediatric patients in a community hospital Source: American Academy of Pediatrics - Medical Specialty Society; 2003 May; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3840&nbr=3056&a mp;string=birth+AND+control+AND+pill

•

Gestational diabetes mellitus Source: American Diabetes Association - Professional Association; 1986 (revised 2000; republished 2003 Jan); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3580&nbr=2806&a mp;string=oral+AND+contraceptives

•

Guidelines for the management of heavy menstrual bleeding Source: New Zealand National Health Committee - National Government Agency [NonU.S.]; 1998 http://www.guideline.gov/summary/summary.aspx?doc_id=2184&nbr=1410&a mp;string=oral+AND+contraceptives

•

Guidelines for the management of uterine fibroids Source: New Zealand Guidelines Group - Private Nonprofit Organization; 1999 August; 120 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2279&nbr=1505&a mp;string=oral+AND+contraceptives

164

•

Oral Contraceptives

HIV infection: detection, counseling, and referral. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3232&nbr=2458&a mp;string=oral+AND+contraceptive

•

Lipid management in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1997 October (revised 2002 Jul); 61 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3410&nbr=2636&a mp;string=oral+AND+contraceptives

•

Major depression, panic disorder and generalized anxiety disorder in adults in primary care Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 January (revised 2002 May); 55 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3350&nbr=2576&a mp;string=oral+AND+contraceptives

•

Massachusetts guidelines for adult diabetes care Source: Massachusetts Department of Public Health, Bureau of Family and Community Health, Diabetes Control Program - State/Local Government Agency [U.S.]; 1999 June (revised 2001 Jun); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3429&nbr=2655&a mp;string=oral+AND+contraceptives

•

Migraine headache Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 November (revised 2002 Jul); 74 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3441&nbr=2667&a mp;string=oral+AND+contraceptives

•

Osteoporosis: prevention and treatment Source: University of Michigan Health System - Academic Institution; 2002 March; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3541&nbr=2767&a mp;string=oral+AND+contraceptives

Patient Resources

•

165

Parameter on periodontitis associated with systemic conditions Source: American Academy of Periodontology - Professional Association; 1996 October (revised 2000 May); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2333&nbr=1559&a mp;string=oral+AND+contraceptives

•

Practice guideline for the treatment of patients with borderline personality disorder Source: American Psychiatric Association - Medical Specialty Society; 2001 October; 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2972&nbr=2198&a mp;string=birth+AND+control+AND+pills

•

Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2001 May; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2818&nbr=2044&a mp;string=oral+AND+contraceptives

•

Practice parameters for the prevention of venous thromboembolism Source: American Society of Colon and Rectal Surgeons - Medical Specialty Society; 2000 August; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2593&nbr=1819&a mp;string=oral+AND+contraceptives

•

Preconception care of women with diabetes Source: American Diabetes Association - Professional Association; 1995 (revised 2000; republished 2003 Jan); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3577&nbr=2803&a mp;string=oral+AND+contraceptive

•

Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP) Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2000 June 30; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2364&nbr=1590&a mp;string=oral+AND+contraceptives

166

•

Oral Contraceptives

Prophylaxis of venous thromboembolism. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2002 October; 47 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3485&nbr=2711&a mp;string=oral+AND+contraceptives

•

Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1998 January 30 (revised 2003 November 26); 46 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4378&nbr=3300&a mp;string=oral+AND+contraceptive

•

Recommendation for the management of stress and urge urinary incontinence in women Source: University of Texas at Austin School of Nursing, Family Nurse Practitioner Program - Academic Institution; 2002 May; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3227&nbr=2453&a mp;string=oral+AND+contraceptive

•

Recommendations for the treatment of dysmenorrhea Source: University of Texas at Austin School of Nursing, Family Nurse Practitioner Program - Academic Institution; 2001 February; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2737&nbr=1963&a mp;string=oral+AND+contraceptives

•

Recommendations for using smallpox vaccine in a pre-event smallpox vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 February 26; 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3623&nbr=2849&a mp;string=oral+AND+contraceptive

•

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=oral+AND+contraceptives

Patient Resources

•

167

The diagnosis and treatment of adult asthma Source: New Zealand Guidelines Group - Private Nonprofit Organization; 2002 September; 101 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3462&nbr=2688&a mp;string=oral+AND+contraceptives

•

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1997 (revised 2003 May 21); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3744&nbr=2970&a mp;string=oral+AND+contraceptives

•

Urinary incontinence Source: American Medical Directors Association - Professional Association; 1996 (reviewed January 2001, 2002 and 2003); 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1812&nbr=1038&a mp;string=oral+AND+contraceptive

•

VHA/DOD clinical practice guideline for the management of major depressive disorder in adults Source: Department of Defense - Federal Government Agency [U.S.]; 1997 (updated 2000); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2585&nbr=1811&a mp;string=oral+AND+contraceptives 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: •

Oral Contraceptives and Cancer Risk Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7080 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 oral contraceptives. 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

168

Oral Contraceptives

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/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to oral contraceptives. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with oral contraceptives. 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 oral contraceptives. 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. 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/.

Patient Resources

169

Simply type in “oral contraceptives” (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 “oral contraceptives”. 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 “oral contraceptives” (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 “oral contraceptives” (or a synonym) into the search box, and click “Submit Query.”

171

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.22

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

22

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

172

Oral Contraceptives

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)23: •

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/

23

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

173

•

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/

174

Oral Contraceptives

•

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

175

•

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/

176

Oral Contraceptives

•

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

177

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 oral contraceptives: •

Basic Guidelines for Oral Contraceptives Birth control pills overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002599.htm

•

Signs & Symptoms for Oral Contraceptives Breast tenderness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003152.htm Discoloration of urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003139.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm

178

Oral Contraceptives

Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Mental changes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Nausea and/or vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Vaginal bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003156.htm •

Background Topics for Oral Contraceptives Birth control Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001946.htm

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

179

ORAL CONTRACEPTIVES DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-phosphate: A drug that halts cell suicide in human white blood cells. [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 Pain: Sensation of discomfort, distress, or agony in the abdominal region. [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] 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] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [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 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] Adenoma: A benign 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] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [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]

180

Oral Contraceptives

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 insufficiency: The reduced secretion of adrenal glands. [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] Adrenergic Antagonists: Drugs that bind to but do not activate adrenergic receptors. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters epinephrine and norepinephrine. [NIH] 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 Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] 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 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 Factors: Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from aging, a physiological process, and time factors which refers only to the passage of time. [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

Dictionary 181

manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonists: Drugs that trigger an action from a cell or another drug. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albinism: General term for a number of inherited defects of amino acid metabolism in which there is a deficiency or absence of pigment in the eyes, skin, or hair. [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] 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 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] Alopecia: Absence of hair from areas where it is normally present. [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] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [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] Amenorrhea: Absence of menstruation. [NIH] 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] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or

182

Oral Contraceptives

eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [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] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [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] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [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] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH]

Dictionary 183

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] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]

Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiandrogens: Drugs used to block the production or interfere with the action of male sex hormones. [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 for white blood cells to destroy the antigen. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] 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] 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] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and

184

Oral Contraceptives

dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [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] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aperture: A natural hole of perforation, especially one in a bone. [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] Appendectomy: An operation to remove the appendix. [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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Articular: Of or pertaining to a joint. [EU] Asparaginase: A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH]

Dictionary 185

Aspiration: The act of inhaling. [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] Attenuated: Strain with weakened or reduced virulence. [NIH] Auditory: Pertaining to the sense of hearing. [EU] 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] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [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] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Benzoyl Peroxide: A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy. It is used also as a bleach in the food industry. [NIH]

186

Oral Contraceptives

Bewilderment: Impairment or loss of will power. [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] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [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] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived 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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Birth Rate: The number of births in a given population per year or other unit of time. [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] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the

Dictionary 187

middle or upper lobes of the lung. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blister pack: A package consisting of a clear plastic overlay affixed to a cardboard backing for protecting and displaying a product. [EU] 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 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] 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] 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 Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, 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 Marrow Transplantation: The transference of bone marrow from one human or animal to another. [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]

188

Oral Contraceptives

Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [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]

Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Butorphanol: A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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] Calcifediol: The major circulating metabolite of vitamin D3 produced in the liver and the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. [NIH] Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. [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

Dictionary 189

many enzymatic processes. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Capsules: Hard or soft soluble containers used for the oral administration of medicine. [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] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] 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] 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] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [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] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [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] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual

190

Oral Contraceptives

patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [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 can also be man-made. [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] 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 Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [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 motility: The ability of a cell to move. [NIH] 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] Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] 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] Cerebral: Of or pertaining of the cerebrum or the brain. [EU]

Dictionary 191

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] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlamydia: A genus of the family Chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is Chlamydia trachomatis. [NIH] Chloasma: Melasma c. hepaticum a term formerly used to refer to circumscribed facial hyperpigmentation resembling melasma that may occur as a cutaneous manifestation of chronic liver disease. [EU] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [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] 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] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [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] 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]

192

Oral Contraceptives

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] Clinical series: A case series in which the patients receive treatment in a clinic or other medical facility. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other 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] 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] Colectomy: An operation to remove the colon. An open colectomy is the removal of the colon through a surgical incision made in the wall of the abdomen. Laparoscopic-assisted colectomy uses a thin, lighted tube attached to a video camera. It allows the surgeon to remove the colon without a large incision. [NIH] Colitis: Inflammation of the colon. [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] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but

Dictionary 193

now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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] 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] 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] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that

194

Oral Contraceptives

provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraceptive Agents: Chemical substances that prevent or reduce the probability of 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] Contralateral: Having to do with the opposite side of the body. [NIH] 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 study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments,

Dictionary 195

etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] 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 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] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [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] Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [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]

196

Oral Contraceptives

Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cyproterone Acetate: An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [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] 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] Cytotoxic: Cell-killing. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [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]

Dictionary 197

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] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depigmentation: Removal or loss of pigment, especially melanin. [EU] 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] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Desogestrel: A synthetic progestational hormone used often as the progestogenic component of combined oral contraceptive agents. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [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] 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] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [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

198

Oral Contraceptives

movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [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] 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] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] 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] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dispenser: Glass, metal or plastic shell fitted with valve from which a pressurized formulation is dispensed; an instrument for atomizing. [NIH] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [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] 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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [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

Dictionary 199

dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]

Duodenum: The first part of the small intestine. [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] Dysmenorrhea: Painful menstruation. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

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] 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] Elastin: The protein that gives flexibility to tissues. [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] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a

200

Oral Contraceptives

primary disorder or as a complication of or in association with another disease. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] 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] 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] 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-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [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] Enhancer: Transcriptional element in the virus genome. [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] 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] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [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] Epigastric: Having to do with the upper middle area of the abdomen. [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]

Dictionary 201

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] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [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]

Ethinyl Estradiol: A semisynthetic estrogen with high oral estrogenic potency. It is often used as the estrogenic component in oral contraceptives. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

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] Extraction: The process or act of pulling or drawing out. [EU] Extreme obesity: A body mass index [NIH] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an

202

Oral Contraceptives

infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] 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] 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] Fenretinide: A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetal Monitoring: Physiologic or biochemical monitoring of the fetus. It is usually done during labor and may be performed in conjunction with the monitoring of uterine activity. It may also be performed prenatally as when the mother is undergoing surgery. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Flagellum: A whiplike appendage of a cell. It can function either as an organ of locomotion or as a device for moving the fluid surrounding the cell. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [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,

Dictionary 203

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] Forearm: The part between the elbow and the wrist. [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [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] 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] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [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] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [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] 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] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of

204

Oral Contraceptives

fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [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] 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] 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] 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] 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]

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] 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] Goiter: Enlargement of the thyroid gland. [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] 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]

Dictionary 205

Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [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] 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] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [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] 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] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [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] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [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

206

Oral Contraceptives

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 M: A group of abnormal hemoglobins in which amino acid substitutions take place in either the alpha or beta chains but near the heme iron. This results in facilitated oxidation of the hemoglobin to yield excess methemoglobin which leads to cyanosis. [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. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatoma: A liver tumor. [NIH] Hepatotoxic: Toxic to liver cells. [EU] 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] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

Histology: The study of tissues and cells under a microscope. [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]

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

Dictionary 207

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] 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] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [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] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [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] Hyperaldosteronism: Aldosteronism. [EU] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH]

208

Oral Contraceptives

Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [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] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [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] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

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] Hypotension: Abnormally low blood pressure. [NIH] 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] Hysterectomy: Excision of the uterus. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [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 microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [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]

Dictionary 209

Immunosuppressive: Describes the ability to lower immune system responses. [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] 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] 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] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] 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, 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]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] 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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU]

210

Oral Contraceptives

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] 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] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] 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] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intravenous: IV. Into a vein. [NIH] 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]

Iodides: Inorganic binary compounds of iodine or the I- ion. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Dictionary 211

Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [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] Irradiation: The use of high-energy radiation from x-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 from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [NIH] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Lacrimal: Pertaining to the tears. [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]

212

Oral Contraceptives

Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Latent period: A seemingly inactive period, as that between exposure of tissue to an injurious agent and the manifestation of response, or that between the instant of stimulation and the beginning of response. [EU] 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] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [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] Lesion: An area of abnormal tissue change. [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 (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

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] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligation: Application of a ligature to tie a vessel or strangulate a part. [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] Linkages: 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] Lipid: Fat. [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,

Dictionary 213

and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [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] 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] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [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] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] 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.

214

Oral Contraceptives

[NIH]

Mammary: Pertaining to the mamma, or breast. [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] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [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] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Melanin: The substance that gives the skin its color. [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] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]

Membrane: A very thin layer of tissue that covers a surface. [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] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menorrhagia: Excessive menstrual flow. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the

Dictionary 215

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 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] Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy. It may cause blood dyscrasias. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltestosterone: A synthetic hormone used for androgen replacement therapy and as an hormonal antineoplastic agent. [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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microgram: A unit of mass (weight) of the metric system, being one-millionth of a gram (106 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] 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] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [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] 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

216

Oral Contraceptives

normally receive identical complements of the number of chromosomes of the somatic cells of the species. [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]

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] Mononuclear: A cell with one nucleus. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]

Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [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] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [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] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU]

Dictionary 217

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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [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] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] 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 tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] 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] 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] 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] Nidation: Implantation of the conceptus in the endometrium. [EU]

218

Oral Contraceptives

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 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] 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] 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] 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] Nursing Care: Care given to patients by nursing service personnel. [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] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] 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]

Dictionary 219

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]

Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [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] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [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]

Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [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]

Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Organoids: An organization of cells into an organ-like structure. Organoids can be generated in culture. They are also found in certain neoplasms. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH]

220

Oral Contraceptives

Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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] 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] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian Cysts: General term for cysts and cystic diseases of the ovary. [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] 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] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [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] 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] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palpation: Application of fingers with light pressure to the surface of the body to determine consistence of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior

Dictionary 221

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] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [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] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] 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] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [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] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] 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]

222

Oral Contraceptives

Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Peliosis Hepatis: A condition in which microscopic pools of blood are present throughout the liver parenchyma, which may lead to congestion and necrosis. [NIH] Pelvic: Pertaining to the pelvis. [EU] 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] Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of Pneumocystis carinii pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] 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] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontics: A dental specialty concerned with the histology, physiology, and pathology of the tissues that support, attach, and surround the teeth, and of the treatment and prevention of disease affecting these tissues. [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Pernicious: Tending to a fatal issue. [EU] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary

Dictionary 223

disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] 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] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] 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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Pheromones: Chemical substances which, when secreted by an individual into the environment, cause specific reactions in other individuals, usually of the same species. The substances relate only to multicellular organisms. This includes kairomones. Allomones are repellent pheromones. [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] 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] 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] 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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH]

224

Oral Contraceptives

Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [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] Placental Insufficiency: Failure of the placenta to deliver an adequate supply of nutrients and oxygen to the fetus. [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] 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] 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] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH]

Dictionary 225

Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] 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] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] 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] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a

226

Oral Contraceptives

designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Preventive Medicine: A medical specialty primarily concerned with prevention of disease and the promotion and preservation of health in the individual. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [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] Proctosigmoiditis: Irritation of the rectum and the sigmoid colon. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, 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] 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] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] 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] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane).

Dictionary 227

The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [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] 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 both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [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 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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU] 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

228

Oral Contraceptives

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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [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] 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]

Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [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] Quiescent: Marked by a state of inactivity or repose. [EU] 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] 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] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [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] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and

Dictionary 229

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] 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] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] 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] 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] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [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]

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]

230

Oral Contraceptives

Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [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] 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] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]

Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] 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] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] 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] 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

Dictionary 231

infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhythm Method: A contraceptive method whereby abstinence is practiced a few days before and after the estimated day of ovulation. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Safe Sex: Sex behavior that prevents or decreases the spread of sexually transmitted diseases or pregnancy. [NIH] Salicylic: A tuberculosis drug. [NIH] Saline: A solution of salt and water. [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] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [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] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [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

232

Oral Contraceptives

elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Sequential treatment: One treatment after the other. [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] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [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] 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 Ratio: The number of males per 100 females. [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 one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] 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

Dictionary 233

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] Sister Chromatid Exchange: An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in Bloom syndrome. [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] Skin Pigmentation: Coloration of the skin. [NIH] Skin Tests: Epicutaneous or intradermal application of a sensitizer for demonstration of either delayed or immediate hypersensitivity. Used in diagnosis of hypersensitivity or as a test for cellular immunity. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [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] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Problems: Situations affecting a significant number of people, that are believed to be sources of difficulty or threaten the stability of the community, and that require programs of amelioration. [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, 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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH]

234

Oral Contraceptives

Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] 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] Sperm Motility: Ability of the spermatozoon to move by flagellate swimming. [NIH] Sperm Transport: Passive transport or active migration of spermatozoa from the testes through the male genital system as well as within the female genital system. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spermatozoon: The mature male germ cell. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [NIH] Spotting: A slight discharge of blood via the vagina, especially as a side-effect of oral contraceptives. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Steady state: Dynamic equilibrium. [EU] 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] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] 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

Dictionary 235

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] 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] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [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] 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] Sun protection factor: SPF. A scale for rating the level of sunburn protection in sunscreen products. The higher the SPF, the more sunburn protection it provides. Sunscreens with an SPF value of 2 through 11 provide minimal protection against sunburns. Sunscreens with an SPF of 12 through 29 provide moderate protection, which is adequate for most people. Those with an SPF of 30 or higher provide high protection against sunburn and are sometimes recommended for people who are highly sensitive to the sun. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [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]

236

Oral Contraceptives

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] 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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synthetic retinoid: A substance related to vitamin A that is produced in a laboratory. [NIH] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

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] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [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] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] 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] Thoracic: Having to do with 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]

Dictionary 237

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 a distant site by the blood stream. [NIH] Thrombophilia: A disorder of hemostasis in which there is a tendency for the occurrence of thrombosis. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] 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] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Time Factors: Elements of limited time intervals, contributing to particular results or situations. [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] 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] 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] 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] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Total-body irradiation: Radiation therapy to the entire body. Usually followed by bone marrow or peripheral stem cell transplantation. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] 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

238

Oral Contraceptives

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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] 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] 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]

Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trichomonas: A genus of parasitic flagellate protozoans distinguished by the presence of four anterior flagella, an undulating membrane, and a trailing flagellum. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] 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] Tubal ligation: An operation to tie the fallopian tubes closed. This procedure prevents pregnancy by blocking the passage of eggs from the ovaries to the uterus. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculin: A sterile liquid containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis. [NIH]

Tuberculin Test: One of several skin tests to determine past or present tuberculosis infection. A purified protein derivative of the tubercle bacilli, called tuberculin, is introduced into the skin by scratch, puncture, or interdermal injection. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of

Dictionary 239

Mycobacterium. [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] 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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [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] Urge urinary incontinence: Urinary leakage when the bladder contracts unexpectedly by itself. [NIH] 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] 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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond

240

Oral Contraceptives

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] 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] 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] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] 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] 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] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virilism: Development of masculine traits in the female. [NIH] 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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH]

Dictionary 241

Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] 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] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Weight Gain: Increase in body weight over existing weight. [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 developed into a child. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Zygote: The fertilized ovum. [NIH]

243

INDEX 1 1-phosphate, 19, 179 A Abdomen, 179, 187, 192, 200, 213, 235, 240 Abdominal, 74, 179, 197, 221, 225, 230, 239 Abdominal Pain, 74, 179, 239 Acceptor, 179, 220 Acetylcholine, 21, 179, 218 Acne, 38, 39, 40, 47, 53, 56, 77, 84, 97, 133, 140, 141, 158, 160, 179, 185, 196, 211 Acne Vulgaris, 38, 56, 97, 133, 179, 211 Adaptation, 126, 179, 191 Adenoma, 56, 63, 131, 179 Adenosine, 179, 188, 223 Adhesions, 33, 179 Adipocytes, 179, 212 Adjustment, 126, 179 Adolescence, 12, 45, 111, 125, 179 Adrenal Cortex, 180, 195, 201, 207, 219, 226 Adrenal Glands, 180, 230 Adrenal insufficiency, 131, 180 Adrenal Medulla, 180, 200, 218 Adrenergic, 77, 132, 180, 184, 198, 200, 235 Adrenergic Antagonists, 132, 180 Adverse Effect, 13, 26, 111, 180, 211, 232 Aerobic, 180, 215, 220 Aerobic Metabolism, 180, 220 Aerobic Respiration, 180, 220 Afferent, 180, 212 Affinity, 180, 233 Agar, 180, 224 Age Factors, 143, 180 Age Groups, 126, 180 Age of Onset, 180, 239 Aged, 80 and Over, 180, 181 Agonists, 30, 49, 133, 181 Alanine, 93, 181 Albinism, 134, 181 Albumin, 5, 50, 181, 224 Alertness, 181, 188 Algorithms, 181, 186 Alimentary, 181, 197, 210 Alkaline, 86, 181, 188, 236 Alkaline Phosphatase, 86, 181 Alkaloid, 181, 192, 216 Alopecia, 181, 196 Alpha Particles, 181, 228

Alpha-fetoprotein, 181, 202 Alternative medicine, 142, 181 Amenorrhea, 65, 97, 123, 181, 218, 224 Amino Acid Sequence, 181, 183 Amino Acid Substitution, 181, 206 Amino Acids, 181, 182, 222, 225, 227, 232 Amniocentesis, 126, 182 Amniotic Fluid, 182 Amphetamines, 182, 192 Ampulla, 182, 201 Anaemia, 182, 214 Anaesthesia, 182, 209 Anal, 26, 182 Analgesic, 30, 182, 188, 216, 219 Analog, 34, 182, 212 Androgenic, 39, 61, 119, 182, 218 Androgens, 111, 180, 182, 195, 207 Anemia, 53, 94, 117, 123, 182, 203 Aneurysm, 182, 240 Angiotensinogen, 182, 230 Animal model, 9, 18, 182 Anions, 181, 182, 211, 232 Anovulation, 48, 182, 224 Antagonism, 183, 188 Antecedent, 117, 123, 183 Antiallergic, 183, 195 Antiandrogens, 133, 183 Antibacterial, 133, 183, 234 Antibiotic, 5, 39, 183, 234 Antibodies, 25, 183, 224, 228 Antibody, 180, 183, 193, 208, 209, 211, 216, 228, 241 Anticonvulsant, 183, 215 Antidepressant, 120, 183, 202 Antiemetic, 183, 184, 191 Antiepileptic, 39, 183 Antifungal, 183, 202, 211 Antigen, 180, 183, 193, 208, 209 Anti-inflammatory, 134, 143, 145, 183, 185, 195, 204, 225 Anti-Inflammatory Agents, 183, 185, 195 Antineoplastic, 183, 195, 196, 202, 215 Antioxidant, 19, 183 Antipsychotic, 183, 191 Antiseptic, 184, 190 Antiviral, 23, 184, 210 Anus, 133, 182, 184, 187, 210 Anxiety, 164, 184, 221

Oral contraceptives

Anxiety Disorders, 184, 221 Aorta, 184, 225, 230, 240 Aperture, 110, 184 Apolipoproteins, 184, 213 Apoptosis, 9, 10, 13, 16, 18, 32, 141, 184 Appendectomy, 130, 184 Aqueous, 184, 185, 196, 212 Arachidonic Acid, 184, 226 Arginine, 184, 218 Arterial, 51, 76, 184, 191, 208, 227, 236 Arteries, 184, 187, 195, 213, 215, 216 Articular, 184, 220 Asparaginase, 73, 184 Aspartate, 184 Aspergillosis, 184, 211 Aspiration, 185, 202 Aspirin, 96, 185 Assay, 185, 208 Astringent, 185, 190 Asymptomatic, 18, 185 Attenuated, 185, 198 Auditory, 40, 65, 185, 201 Autoimmune disease, 185 Autoimmunity, 132, 133, 185 Autologous, 13, 185, 222 Autologous bone marrow transplantation, 13, 185 Autonomic, 21, 179, 184, 185, 218 B Bacillus, 185, 238 Bacteria, 183, 185, 194, 199, 202, 205, 215, 234, 238, 240 Bacterial Physiology, 179, 185 Bacteriophage, 185, 224, 238 Baroreflex, 76, 185 Base, 26, 122, 185, 197, 211, 236 Benign, 26, 46, 179, 185, 202, 205, 212, 217, 227, 228, 241 Benign tumor, 185, 212 Benzoyl Peroxide, 133, 185 Bewilderment, 186, 194 Bilateral, 186, 224 Bile, 186, 203, 213, 234 Bilirubin, 181, 186 Bioavailability, 62, 186 Bioavailable, 17, 186 Biochemical, 23, 186, 202, 220, 232 Biological response modifier, 186, 210 Biomarkers, 9, 10, 13, 78, 186 Biopsy, 34, 186 Biosynthesis, 17, 184, 186, 232 Biotechnology, 35, 37, 142, 153, 186

244

Biotransformation, 71, 186 Biphasic, 40, 41, 112, 186 Birth Rate, 113, 186 Bladder, 186, 209, 217, 227, 239, 241 Blastocyst, 186, 193, 224 Blastomycosis, 186, 211 Blister, 111, 112, 187 Blister pack, 112, 187 Blood Coagulation, 72, 187, 188 Blood Glucose, 126, 132, 187, 205, 208, 210 Blood pressure, 10, 25, 49, 63, 84, 185, 187, 189, 208, 216, 218, 233 Blood vessel, 185, 187, 189, 191, 200, 212, 223, 233, 235, 237, 240 Body Composition, 141, 187 Body Fluids, 186, 187, 188, 199, 233, 239 Body Image, 144, 187, 197 Body Mass Index, 18, 19, 187, 201 Bone Density, 111, 187 Bone Marrow, 185, 187, 213, 222, 235, 237 Bone Marrow Transplantation, 187 Bone Remodeling, 60, 187 Bone Resorption, 34, 187, 188 Bone scan, 14, 187 Bowel, 4, 130, 131, 143, 182, 187, 197, 209, 217, 235, 239 Bowel Movement, 187, 198, 235 Brachial, 187, 188, 214 Brachial Plexus, 188, 214 Brachytherapy, 188, 210, 211, 228, 241 Bradykinin, 188, 218, 224 Branch, 175, 188, 221, 227, 230, 234, 236 Breast Feeding, 126, 188 Buccal, 19, 188, 213 Buffers, 185, 188 Burns, 185, 188 Butorphanol, 30, 188 Bypass, 8, 188 C Caffeine, 78, 126, 188 Calcifediol, 188 Calcitriol, 34, 188 Calcium, 88, 126, 187, 188, 193, 221, 227, 233, 236 Candidiasis, 22, 160, 189, 202 Candidosis, 189 Capsules, 189, 198, 203 Carbohydrate, 38, 45, 73, 189, 195, 204 Carbon Dioxide, 189, 203, 224, 230, 240 Carcinogen, 15, 18, 189 Carcinogenesis, 43, 189, 191 Carcinogenic, 189, 209, 219, 226, 234

245

Carcinoma, 57, 189, 196 Cardiac, 185, 188, 189, 199, 200, 216, 230, 234 Cardiac Output, 185, 189 Cardiovascular, 37, 43, 47, 65, 70, 77, 128, 144, 161, 189, 232 Cardiovascular disease, 37, 47, 65, 77, 144, 161, 189 Carotene, 189, 230 Carotenoids, 31, 100, 122, 189 Carpal Tunnel Syndrome, 143, 144, 189 Case report, 56, 57, 189, 192 Case series, 189, 192 Case-Control Studies, 35, 190 Cataracts, 12, 190 Catechol, 16, 190 Caudal, 190, 197, 208, 225 Causal, 57, 190 Cause of Death, 144, 190 Cell Aggregation, 190, 220 Cell Cycle, 13, 190, 195 Cell Death, 184, 190, 217 Cell Differentiation, 190, 233 Cell Division, 185, 190, 215, 224 Cell motility, 190, 206 Cell proliferation, 8, 141, 190, 233 Cell Respiration, 180, 190, 215, 220, 230 Cells, Cultured, 15, 190 Central Nervous System Infections, 190, 205, 207 Cerebral, 36, 46, 52, 57, 64, 190, 191, 194, 200, 201, 207, 236 Cerebrovascular, 189, 191 Cerebrum, 190, 191 Cervical, 12, 14, 15, 19, 84, 86, 97, 113, 116, 118, 140, 158, 159, 161, 188, 191, 214 Cervix, 74, 113, 191 Chemoprevention, 9, 10, 161, 191 Chemopreventive, 9, 10, 191, 202 Chemotherapy, 95, 161, 191 Chlamydia, 12, 20, 127, 191 Chloasma, 121, 191 Chlorpromazine, 50, 191 Cholesterol, 50, 98, 104, 186, 191, 195, 212, 213, 231, 234 Cholesterol Esters, 191, 212 Chromaffin System, 191, 200 Chromatin, 184, 191, 234 Chromosome, 191, 194, 211, 212, 233 Chronic, 15, 33, 144, 179, 186, 191, 192, 198, 200, 209, 213, 224, 235, 236, 239, 241 Chronic renal, 191, 224

Chylomicrons, 191, 213 Circulatory system, 191, 200 CIS, 192, 230 Clinical series, 64, 192 Clinical study, 6, 192 Clinical trial, 6, 9, 13, 15, 29, 34, 62, 105, 106, 153, 192, 194, 224, 227, 229 Clone, 8, 192 Clonic, 192, 215 Cloning, 186, 192 Coagulation, 40, 41, 47, 59, 85, 187, 192, 206, 224, 237 Coca, 192 Cocaine, 50, 192 Colectomy, 131, 192 Colitis, 4, 130, 131, 133, 134, 144, 192 Collagen, 32, 75, 192, 203, 207, 224, 226 Collagen disease, 192, 207 Colloidal, 181, 193, 232 Combination Therapy, 193, 201 Complement, 193, 211, 213, 224 Complementary and alternative medicine, 91, 102, 193 Complementary medicine, 91, 193 Computational Biology, 153, 193 Conception, 114, 116, 135, 193, 194, 202, 234 Concomitant, 47, 141, 193 Condoms, 80, 114, 137, 193 Cones, 193, 230 Confusion, 31, 127, 194, 198 Congestion, 184, 194, 201, 222 Conjugated, 194, 196 Conjugation, 186, 194 Connective Tissue, 187, 192, 194, 203, 213, 230, 235, 236 Consciousness, 182, 194, 197, 230 Constriction, 194, 240 Constriction, Pathologic, 194, 240 Consumption, 16, 24, 110, 126, 134, 194, 220 Contraceptive Agents, 84, 194, 197 Contraindications, ii, 4, 66, 129, 194 Contralateral, 13, 194, 202, 219 Control group, 5, 194, 224, 229 Controlled study, 73, 93, 194 Convulsions, 183, 194, 199, 225 Cornea, 194, 235 Coronary, 4, 85, 144, 189, 194, 195, 215, 216 Coronary heart disease, 189, 195 Coronary Thrombosis, 195, 215, 216

Oral contraceptives

Corpus, 117, 123, 195, 222, 226, 236 Corpus Luteum, 117, 123, 195, 226 Cortex, 195, 201 Corticosteroid, 131, 144, 195, 225 Cortisol, 60, 181, 195 Cortisone, 195, 225 Cranial, 195, 205 Craniocerebral Trauma, 195, 205, 207 Creatinine, 34, 195 Cryotherapy, 133, 195 Curative, 195, 236 Cutaneous, 21, 40, 77, 186, 189, 191, 195, 212, 213 Cyanosis, 195, 206 Cyclic, 23, 114, 115, 188, 195, 205, 218, 227 Cyclin, 32, 195 Cyclophosphamide, 25, 144, 196 Cyproterone, 55, 84, 196 Cyproterone Acetate, 55, 84, 196 Cysteine, 123, 196 Cystine, 196 Cytochrome, 15, 196 Cytoplasm, 32, 184, 196, 205 Cytotoxic, 196, 228, 233 D Dairy Products, 196, 231 Databases, Bibliographic, 153, 196 Decidua, 196, 224 Degenerative, 196, 206, 220, 230 Dehydroepiandrosterone, 47, 196 Deletion, 184, 196 Dementia, 165, 184, 197 Dendritic, 197, 214 Density, 8, 11, 13, 25, 36, 42, 49, 60, 64, 85, 86, 111, 187, 197, 213, 219 Depersonalization, 197, 221, 231 Depigmentation, 121, 197, 241 Depolarization, 197, 233 Depressive Disorder, 167, 197 Derealization, 197, 221 Desogestrel, 38, 45, 46, 47, 51, 54, 55, 56, 60, 62, 73, 84, 112, 197 Diabetes Mellitus, 4, 5, 10, 130, 131, 135, 163, 197, 204, 206, 222 Diabetic Retinopathy, 3, 5, 197, 223 Diagnostic procedure, 109, 142, 197 Diaphragm, 113, 197, 206 Diastolic, 197, 208 Diencephalon, 197, 208, 236 Dietary Fiber, 31, 197 Diffusion, 197, 198, 209 Digestion, 181, 186, 187, 197, 213, 235

246

Digestive system, 106, 197 Dihydrotestosterone, 196, 198, 229 Dilatation, 182, 198, 226, 240 Dilatation, Pathologic, 198, 240 Dilation, 188, 198, 207, 240 Dilution, 54, 198 Dimethyl, 121, 198 Direct, iii, 11, 21, 31, 130, 134, 147, 198, 229 Disease Progression, 198, 240 Disorientation, 194, 198 Dispenser, 110, 111, 198 Diuresis, 188, 198 Diuretic, 198, 211 Dizziness, 198, 221 Dopamine, 184, 191, 192, 198, 223 Dorsal, 198, 225 Dosage Forms, 114, 198 Drug Interactions, 66, 94, 129, 148, 198 Drug Tolerance, 198, 237 Duct, 182, 199, 201, 231 Duodenal Ulcer, 134, 199 Duodenum, 186, 199, 235 Dyes, 134, 199 Dysmenorrhea, 20, 27, 98, 120, 166, 199 Dyspareunia, 199, 201 Dysphoric, 85, 197, 199 Dyspnea, 199, 221 E Eating Disorders, 127, 199 Eclampsia, 199, 225 Edema, 134, 197, 199, 225 Effector, 179, 193, 199 Efficacy, 6, 11, 13, 27, 34, 37, 51, 67, 93, 113, 116, 117, 118, 122, 123, 199 Elastin, 192, 199 Electrocoagulation, 192, 199 Electrolyte, 195, 199, 215, 233 Electromyography, 37, 199 Electrons, 183, 185, 199, 211, 220, 228 Electroplating, 190, 199 Embolus, 199, 209 Embryo, 186, 190, 199, 209, 219 Endocarditis, 189, 199 Endocrine Glands, 200, 221 Endocrine System, 131, 200 Endocrinology, 11, 45, 53, 54, 55, 61, 63, 86, 200 Endometrial, 7, 15, 17, 78, 115, 117, 122, 123, 200 Endometriosis, 33, 66, 98, 120, 126, 140, 141, 200, 212, 218

247

Endometrium, 17, 115, 116, 117, 118, 122, 123, 196, 200, 215, 217 Endothelium, 200, 218 Endothelium-derived, 200, 218 End-stage renal, 191, 200, 224 Energy balance, 200, 212 Enhancer, 200, 230 Environmental Health, 15, 152, 154, 200 Enzymatic, 188, 189, 193, 200, 202, 230 Enzyme, 15, 34, 122, 181, 182, 184, 199, 200, 205, 222, 224, 229, 230, 232, 235, 237, 241 Epidemic, 127, 200 Epidemiological, 7, 19, 28, 37, 143, 200 Epidermal, 200, 211, 214, 241 Epidermis, 187, 200, 208, 211, 226, 228 Epigastric, 200, 221 Epinephrine, 180, 198, 200, 218, 239 Epithelial, 10, 18, 32, 40, 50, 70, 86, 179, 196, 200, 201, 206, 227 Epithelial Cells, 10, 201, 206, 227 Epithelial ovarian cancer, 40, 70, 201 Epithelium, 10, 13, 18, 23, 84, 200, 201, 221 Erythema, 98, 201, 235, 239 Erythrocytes, 182, 187, 201, 229 Esophagus, 198, 201, 235 Estradiol, 13, 24, 29, 30, 41, 46, 56, 84, 86, 116, 201 Estrogen, 4, 12, 13, 15, 17, 18, 21, 22, 24, 25, 35, 44, 51, 58, 73, 74, 100, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 128, 129, 144, 196, 201 Estrogen receptor, 13, 15, 18, 201 Estrogen Replacement Therapy, 13, 144, 201 Ethinyl Estradiol, 6, 15, 24, 27, 34, 41, 46, 55, 57, 60, 75, 95, 112, 113, 116, 117, 123, 201 Evoke, 201, 234 Evoked Potentials, 65, 201 Exocrine, 201, 220 Exogenous, 18, 24, 26, 28, 53, 64, 186, 201, 239 Expiration, 201, 230 Extensor, 201, 241 External-beam radiation, 201, 211, 228, 241 Extracellular, 194, 201, 233, 236 Extraction, 140, 201 Extreme obesity, 17, 201 Extremity, 188, 201, 214

F Facial, 134, 191, 201 Fallopian Tubes, 113, 201, 238 Family Planning, 14, 20, 31, 38, 72, 80, 135, 153, 202 Fat, 16, 31, 126, 179, 184, 187, 189, 195, 199, 202, 212, 230, 231, 233 Fatigue, 144, 202 Fatty acids, 181, 202, 226 Feces, 202, 235 Fenretinide, 9, 202 Ferritin, 95, 202 Fetal Monitoring, 126, 202 Fetoprotein, 126, 202 Fetus, 23, 144, 181, 202, 224, 225, 239 Fibrin, 187, 202, 237 Fibrinolysis, 59, 72, 202 Fibrinolytic, 59, 65, 202 Fibroid, 202, 212 Flagellum, 202, 238 Fluconazole, 66, 202 Fluoxetine, 141, 202 Foetoplacental, 202, 219 Folate, 75, 88, 95, 202, 203 Fold, 22, 202 Folic Acid, 84, 87, 202 Follicles, 115, 133, 203 Follicular Phase, 33, 112, 117, 123, 203 Forearm, 187, 203, 214 Fungus, 189, 203 G Gallbladder, 179, 198, 203 Gamma Rays, 203, 228 Ganglia, 179, 184, 203, 217 Gas, 189, 197, 203, 207, 218, 240 Gas exchange, 203, 240 Gastric, 134, 198, 203 Gastrin, 203, 206 Gastrointestinal, 5, 134, 161, 188, 200, 202, 203, 212, 232, 235, 239 Gastrointestinal tract, 134, 202, 203, 212, 232, 239 Gelatin, 203, 204 Gene, 7, 15, 18, 19, 28, 43, 57, 130, 186, 203, 219, 230, 238 Gene Expression, 15, 43, 203 Genetic testing, 54, 126, 203 Genetics, 9, 92, 133, 134, 194, 203 Genital, 127, 203, 234, 239 Genotype, 58, 203 Germ Cells, 203, 220, 233, 234, 236 Gestation, 126, 203, 222, 224

Oral contraceptives

Gestational, 10, 54, 55, 126, 132, 135, 163, 204 Gland, 32, 180, 191, 195, 204, 207, 213, 220, 221, 224, 227, 231, 234, 237 Glucocorticoid, 39, 204, 207, 225 Glucose, 4, 10, 50, 55, 126, 132, 187, 197, 204, 205, 210, 231 Glucose Intolerance, 132, 197, 204 Glucose tolerance, 55, 132, 204 Glucose Tolerance Test, 204 Glutamic Acid, 202, 204, 226 Glycine, 93, 204, 232 Glycogen, 191, 204 Glycoside, 204, 231 Goiter, 131, 204 Gonad, 204 Gonadal, 30, 204, 234 Gonadorelin, 204, 212 Gonadotropin, 55, 61, 115, 133, 204, 212 Gonorrhea, 12, 127, 205 Governing Board, 205, 225 Grade, 19, 158, 205 Graft, 205, 207 Grafting, 205, 209 Gram-negative, 191, 205 Granulocytes, 205, 233, 241 Grasses, 203, 205 Gravidity, 205, 221 Guanylate Cyclase, 205, 218 H Hair follicles, 205, 241 Haplotypes, 18, 205 Headache, 52, 61, 73, 76, 164, 178, 188, 205, 207, 225 Headache Disorders, 205 Heart attack, 189, 205 Heme, 186, 196, 205, 206 Hemochromatosis, 132, 205 Hemoglobin, 3, 5, 122, 126, 182, 195, 201, 205, 206 Hemoglobin M, 126, 195, 206 Hemorrhage, 56, 195, 199, 205, 206, 235, 241 Hemostasis, 43, 45, 72, 80, 206, 232, 237 Hepatic, 15, 52, 94, 128, 181, 204, 206, 213 Hepatitis, 99, 127, 206 Hepatocyte, 16, 32, 206 Hepatocyte Growth Factor, 32, 206 Hepatoma, 15, 206 Hepatotoxic, 15, 206 Hereditary, 36, 125, 206, 222 Heredity, 179, 203, 206

248

Herpes, 127, 206 Herpes Zoster, 206 Hiccup, 191, 206 Hirsutism, 51, 196, 206, 207, 208 Histology, 122, 206, 222 Homeostasis, 130, 131, 187, 206 Homodimer, 206, 238 Hormonal therapy, 26, 34, 206 Hormone therapy, 166, 206, 207 Host, 29, 185, 189, 207, 239, 240 Human papillomavirus, 19, 43, 58, 86, 127, 207 Hybrid, 8, 192, 207 Hydrocephalus, 207, 211 Hydrocortisone, 121, 207 Hydrogen, 179, 185, 188, 189, 207, 216, 217, 220, 223, 227 Hydrolysis, 186, 207, 223, 225 Hydrophobic, 207, 212 Hydroxylation, 188, 207 Hydroxylysine, 192, 207 Hydroxyproline, 192, 207 Hyperaldosteronism, 131, 132, 207 Hyperandrogenism, 133, 207 Hyperglycemia, 11, 207 Hyperpigmentation, 121, 191, 208 Hyperplasia, 52, 63, 208 Hypersensitivity, 97, 208, 231, 233 Hypertension, 3, 58, 65, 98, 189, 205, 207, 208, 225 Hyperthyroidism, 131, 132, 208 Hypertrichosis, 206, 208 Hypertrophy, 208 Hypoglycemia, 126, 208 Hypoglycemic, 126, 208 Hypoglycemic Agents, 126, 208 Hypogonadism, 160, 208 Hypotension, 45, 184, 194, 208 Hypothalamic, 42, 208 Hypothalamus, 120, 131, 197, 204, 208, 224, 236 Hysterectomy, 126, 208 I Id, 23, 87, 96, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 174, 176, 208 Immune function, 23, 208, 238 Immune response, 183, 185, 195, 208, 213, 235, 239, 240 Immune system, 23, 185, 208, 209, 213, 239, 241 Immunity, 181, 208, 233 Immunoassay, 34, 208

249

Immunodeficiency, 23, 58, 127, 159, 208 Immunologic, 208, 228 Immunosuppressive, 196, 204, 209 Impairment, 186, 209, 215 Implant radiation, 209, 210, 211, 228, 241 Implantation, 116, 117, 118, 123, 193, 209, 217, 219 In vitro, 18, 19, 32, 55, 96, 190, 209 In vivo, 15, 19, 32, 209 Incision, 192, 209, 210 Incontinence, 167, 207, 209 Indicative, 127, 209, 221, 240 Induction, 12, 15, 33, 182, 184, 209 Infancy, 125, 209 Infant, Newborn, 180, 209 Infarction, 5, 99, 207, 209 Infiltration, 30, 209 Inflammatory bowel disease, 130, 131, 133, 143, 145, 209 Ingestion, 114, 121, 122, 204, 209, 236 Initiation, 15, 21, 31, 35, 209, 226, 238 Innervation, 21, 188, 209, 214 Inorganic, 209, 210, 216 Insight, 16, 210 Insomnia, 210, 225 Insulin, 4, 5, 11, 19, 55, 61, 65, 126, 132, 204, 210, 231, 239 Insulin-dependent diabetes mellitus, 5, 210 Insulin-like, 19, 210 Interferon, 23, 210 Interferon-alpha, 210 Intermittent, 85, 210 Internal Medicine, 57, 62, 63, 71, 74, 200, 210 Internal radiation, 210, 211, 228, 241 Interstitial, 188, 210, 211, 241 Intervertebral, 210, 213 Intervertebral Disk Displacement, 210, 213 Intestinal, 50, 188, 189, 204, 210 Intestines, 179, 202, 203, 210 Intoxication, 210, 241 Intracellular, 188, 209, 210, 218, 227, 232 Intravenous, 144, 210 Invasive, 32, 74, 208, 210 Iodides, 133, 210 Iodine, 210 Ion Channels, 8, 211 Ionizing, 181, 211, 214, 228, 233 Ions, 185, 188, 199, 207, 211, 227 Irradiation, 13, 211, 241

Isosorbide, 121, 211 Isotretinoin, 6, 133, 211 Itraconazole, 47, 211 J Joint, 20, 22, 129, 167, 184, 211, 220, 234, 235, 236 K Karyotype, 182, 211 Kb, 152, 211 Keratin, 211, 231 Keratinocytes, 122, 211 Kinetics, 7, 211 L Lacrimal, 49, 211 Lactation, 131, 163, 211, 219 Large Intestine, 198, 210, 211, 229, 233 Latent, 13, 159, 212, 225 Latent period, 13, 212 Leiomyoma, 26, 52, 202, 212, 233 Leishmaniasis, 212, 222 Lens, 13, 190, 212 Leptin, 51, 212 Lesion, 19, 27, 186, 212, 232, 239 Leukocytes, 187, 205, 210, 212, 222 Leuprolide, 34, 212 Levonorgestrel, 27, 36, 44, 45, 47, 58, 59, 67, 74, 80, 212, 218 Libido, 182, 212 Library Services, 174, 212 Life cycle, 186, 212 Ligament, 212, 227, 234 Ligation, 212 Linear Models, 11, 212 Linkages, 205, 212 Lipid, 11, 39, 51, 55, 62, 141, 164, 184, 210, 212 Lipoprotein, 45, 62, 205, 212, 213 Liver Cirrhosis, 73, 213 Localized, 206, 208, 209, 213, 224, 239 Longitudinal Studies, 12, 213 Low Back Pain, 48, 213 Low-density lipoprotein, 213 Lumbar, 210, 213 Lumen, 32, 213 Lupus, 25, 99, 144, 213, 236 Luteal Phase, 21, 24, 33, 34, 112, 117, 123, 213 Lymph, 191, 200, 213 Lymph node, 191, 213 Lymphatic, 200, 209, 213 Lymphoid, 183, 213

Oral contraceptives

M Macrophage, 30, 213 Major Histocompatibility Complex, 205, 213 Malignancy, 213, 221 Malignant, 9, 10, 64, 183, 213, 217, 227, 228 Malnutrition, 132, 181, 213 Mammary, 32, 84, 214 Man-made, 190, 214 Mastication, 20, 214 Measles Virus, 130, 214 Meat, 214, 231 Median Nerve, 144, 189, 214 Medical Records, 32, 214, 230 MEDLINE, 153, 214 Medroxyprogesterone, 13, 14, 41, 42, 68, 101, 214 Medroxyprogesterone Acetate, 13, 41, 42, 68, 214 Megaloblastic, 53, 84, 94, 203, 214 Melanin, 122, 134, 197, 214, 223, 239 Melanocytes, 134, 208, 214 Melanoma, 31, 35, 64, 75, 214 Melanosomes, 214 Membrane, 8, 144, 193, 197, 200, 205, 211, 214, 216, 219, 220, 222, 223, 230, 233, 238 Memory, 197, 214 Menarche, 18, 125, 214 Meningitis, 202, 211, 214 Menopause, 17, 18, 38, 86, 126, 127, 130, 131, 132, 144, 160, 162, 166, 214, 219, 222, 225 Menorrhagia, 26, 99, 214 Menstruation, 98, 115, 117, 123, 130, 181, 196, 199, 203, 213, 214, 215, 219, 225 Mental Disorders, 107, 215 Mental Health, iv, 6, 107, 152, 154, 215, 228 Mephenytoin, 68, 215 Meta-Analysis, 36, 61, 215 Metabolite, 24, 186, 188, 198, 215 Methionine, 198, 215 Methyltestosterone, 111, 215 MI, 178, 215 Microbiology, 179, 215 Microcirculation, 54, 213, 215 Microgram, 123, 215 Microorganism, 215, 241 Migration, 113, 215, 234 Milligram, 215 Milliliter, 187, 215 Mineralocorticoids, 180, 195, 215

250

Mitochondria, 16, 215, 219 Mitosis, 184, 215 Modification, 27, 28, 216, 228 Modulator, 33, 216 Molecular, 8, 10, 13, 22, 28, 39, 153, 155, 186, 193, 216, 235 Molecule, 9, 183, 185, 193, 195, 199, 200, 204, 207, 216, 220, 228, 229, 232 Monitor, 26, 195, 216, 218 Monoclonal, 132, 211, 216, 228, 241 Mononuclear, 23, 216 Morbillivirus, 214, 216 Morphine, 30, 33, 216, 219 Morphogenesis, 32, 216 Morphological, 32, 199, 203, 214, 216 Morphology, 32, 216 Mucosa, 213, 216, 235 Mucus, 15, 116, 118, 216, 239 Mutagenesis, 15, 216 Mutagenic, 13, 15, 216, 233 Mutagens, 216 Myocardial infarction, 36, 44, 67, 141, 195, 215, 216 Myocardium, 215, 216 N Narcotic, 188, 216 Nausea, 178, 183, 184, 198, 217, 221, 225 NCI, 1, 106, 151, 192, 217 Necrosis, 184, 209, 215, 216, 217, 222 Need, 3, 8, 11, 125, 129, 131, 143, 169, 180, 191, 204, 217, 237 Neonatal, 42, 67, 71, 127, 133, 217 Neoplasia, 9, 19, 86, 217 Neoplasms, 183, 207, 217, 219, 228 Neoplastic, 67, 207, 217 Nephropathy, 5, 217 Nerve, 21, 144, 180, 188, 209, 214, 217, 219, 225, 230, 234, 238 Nervous System, 131, 179, 180, 181, 182, 185, 188, 190, 192, 201, 203, 204, 216, 217, 222, 232, 235 Neural, 180, 202, 217 Neural tube defects, 202, 217 Neuromuscular, 179, 217 Neuromuscular Junction, 179, 217 Neurons, 192, 203, 217, 236 Neurosecretory Systems, 200, 217 Neutrons, 181, 211, 217, 228 Nidation, 117, 123, 217 Nitric Oxide, 51, 218 Nitrogen, 181, 182, 196, 218, 238 Norepinephrine, 21, 180, 198, 218

251

Norethindrone, 6, 15, 24, 34, 41, 117, 123, 218 Norgestrel, 129, 212, 218 Normotensive, 84, 218 Nuclear, 15, 194, 199, 203, 214, 217, 218 Nucleus, 32, 184, 191, 195, 196, 203, 210, 216, 217, 218, 227, 235 Nulliparous, 42, 218 Nursing Care, 92, 218 O Observational study, 4, 26, 218 Occult, 161, 218 Ocular, 13, 218 Odds Ratio, 218, 229 Oestradiol, 112, 219 Oestrogen, 64, 219 Ointments, 198, 219 Oligomenorrhea, 219, 224 Oncogene, 206, 219 Oncogenic, 19, 219 Oncology, 12, 64, 78, 120, 161, 219 Opacity, 190, 197, 219 Opium, 216, 219 Opportunistic Infections, 159, 219 Opsin, 219, 230 Optic Chiasm, 208, 219 Optic Disk, 197, 219 Oral Health, 127, 131, 219 Oral Manifestations, 130, 219 Organelles, 196, 214, 219 Organoids, 32, 219 Orgasm, 132, 219 Osmotic, 181, 211, 220, 232 Osteoarthritis, 144, 220 Osteoporosis, 14, 25, 26, 36, 111, 125, 127, 132, 144, 164, 187, 201, 219, 220 Outpatient, 144, 220 Ovarian Cysts, 54, 78, 220 Ovarian Follicle, 7, 117, 123, 195, 220 Ovaries, 29, 201, 207, 220, 224, 232, 238 Ovary, 15, 120, 195, 201, 204, 219, 220, 235 Overdose, 177, 220 Ovulation, 6, 7, 10, 15, 24, 30, 40, 115, 116, 117, 118, 123, 132, 182, 203, 213, 218, 220, 231 Ovum, 195, 196, 204, 212, 220, 226, 241 Oxidation, 50, 123, 179, 183, 186, 196, 206, 220 Oxidation-Reduction, 186, 220 Oxidative metabolism, 133, 180, 220 Oxygen Consumption, 220, 230

P Palliative, 196, 219, 220, 236 Palpation, 20, 220 Pancreas, 131, 132, 179, 186, 198, 205, 210, 220, 221, 239 Pancreatic, 131, 132, 221 Panic, 76, 164, 221 Panic Disorder, 164, 221 Papillomavirus, 221 Parasite, 221, 238 Parasitic, 221, 238 Parathyroid, 34, 188, 221, 236 Parathyroid Glands, 221 Parathyroid hormone, 188, 221 Parenchyma, 221, 222 Paresthesias, 221 Parity, 18, 28, 29, 35, 43, 221 Patch, 6, 75, 221 Pathogenesis, 133, 221 Pathologic, 27, 184, 186, 189, 195, 208, 221, 230 Pathologic Processes, 184, 221 Patient Compliance, 7, 222 Patient Education, 158, 172, 174, 178, 222 Peliosis Hepatis, 54, 222 Pelvic, 12, 33, 44, 200, 222, 227 Penis, 193, 222 Pentamidine, 132, 222 Peptide, 211, 212, 222, 225, 227 Perception, 33, 197, 222, 231 Perforation, 184, 222 Pericardium, 222, 236 Perimenopausal, 34, 222 Perinatal, 127, 145, 166, 222 Periodontal disease, 130, 222 Periodontics, 130, 222 Periodontitis, 130, 165, 222 Peripheral blood, 23, 210, 222 Peripheral stem cell transplantation, 222, 237 Pernicious, 214, 222 Peroxidase, 49, 222 Peroxide, 185, 223 PH, 187, 223 Pharmaceutical Preparations, 111, 203, 223 Pharmaceutical Solutions, 198, 223 Pharmacodynamic, 6, 223 Pharmacokinetic, 7, 30, 223 Pharmacologic, 223, 238 Phenylalanine, 223, 239 Pheromones, 51, 223

Oral contraceptives

Phospholipases, 223, 233 Phospholipids, 202, 212, 223 Phosphorus, 188, 221, 223 Photocoagulation, 192, 223 Physiologic, 130, 186, 190, 202, 214, 215, 223, 226, 229, 230 Physiology, 21, 32, 45, 50, 60, 125, 130, 200, 222, 223 Pigment, 122, 134, 181, 186, 197, 214, 223, 224 Pigmentation, 122, 134, 208, 224 Pilot study, 31, 37, 224 Pituitary Gland, 195, 204, 224 Placebos, 114, 224 Placenta, 23, 201, 202, 224, 226 Placental Insufficiency, 144, 224 Plants, 181, 189, 192, 204, 216, 218, 224, 231, 238 Plaque, 130, 224 Plasma cells, 183, 224 Plasma protein, 181, 224, 227, 232 Platelet Activation, 224, 233 Platelet Aggregation, 96, 218, 224 Platelets, 218, 224, 232, 237 Polycystic, 39, 55, 61, 207, 224 Polycystic Ovary Syndrome, 39, 55, 61, 207, 224 Polymorphism, 18, 76, 119, 224 Polypeptide, 181, 192, 225 Posterior, 131, 182, 198, 220, 225 Postmenopausal, 16, 17, 19, 32, 49, 86, 144, 166, 201, 220, 225 Postoperative, 33, 225 Postsynaptic, 225, 233 Potentiate, 5, 225 Potentiation, 225, 233 Practice Guidelines, 68, 154, 159, 161, 225 Precancerous, 10, 191, 225 Precursor, 182, 184, 196, 198, 199, 200, 218, 223, 225, 227, 238, 239 Predisposition, 17, 225 Prednisolone, 225 Prednisone, 144, 225 Preeclampsia, 144, 225 Premalignant, 225 Premenopausal, 26, 29, 31, 36, 39, 40, 63, 66, 111, 144, 225 Premenstrual, 20, 45, 85, 99, 120, 121, 140, 225 Premenstrual Syndrome, 45, 99, 225 Prenatal, 67, 125, 199, 225 Pressoreceptors, 185, 225

252

Prevalence, 18, 20, 26, 27, 56, 63, 130, 132, 143, 145, 218, 225 Preventive Medicine, 7, 10, 17, 134, 173, 226 Prickle, 211, 226 Probe, 68, 226 Proctosigmoiditis, 131, 226 Progestogen, 74, 79, 112, 113, 114, 129, 166, 226 Progression, 18, 19, 131, 182, 226 Progressive, 91, 117, 123, 190, 191, 197, 198, 201, 205, 217, 220, 224, 226 Projection, 218, 226 Proline, 192, 207, 226 Promoter, 15, 22, 226 Promotor, 226, 230 Prone, 122, 134, 226 Prophylaxis, 166, 226, 239 Proportional, 10, 226 Prospective study, 12, 25, 31, 37, 38, 48, 226 Prostaglandin, 21, 27, 226 Prostaglandins A, 27, 226, 227 Prostaglandins D, 227 Prostate, 57, 186, 202, 219, 227, 239 Prostate-Specific Antigen, 57, 227 Protein C, 181, 184, 185, 202, 211, 212, 227 Protein S, 186, 227 Proteinuria, 225, 227 Prothrombin, 22, 57, 74, 79, 227, 237 Protocol, 224, 227 Protons, 181, 207, 211, 227, 228 Psychic, 212, 227 Psychosomatic, 72, 93, 95, 227 Puberty, 57, 111, 127, 130, 133, 227 Public Health, 14, 17, 25, 31, 134, 154, 164, 166, 227 Public Policy, 153, 228 Publishing, 5, 35, 125, 127, 130, 228 Pulmonary, 52, 187, 194, 228, 240 Pulmonary Artery, 187, 228, 240 Pulse, 144, 216, 228 Pustular, 179, 228 Q Quality of Life, 63, 228 Quiescent, 228, 241 R Race, 11, 13, 125, 130, 133, 143, 211, 212, 215, 218, 228 Radiation, 12, 201, 203, 210, 211, 214, 228, 233, 235, 237, 241

253

Radiation therapy, 12, 201, 210, 211, 228, 237, 241 Radioactive, 187, 207, 209, 210, 211, 214, 218, 219, 228, 241 Radioimmunotherapy, 228 Radiolabeled, 211, 228, 241 Radiotherapy, 13, 188, 211, 228, 241 Random Allocation, 228, 229 Randomization, 34, 229 Randomized, 7, 10, 14, 15, 22, 27, 31, 38, 50, 57, 59, 73, 94, 199, 229 Randomized clinical trial, 7, 22, 31, 229 Receptor, 16, 18, 19, 32, 43, 72, 119, 120, 179, 183, 196, 198, 201, 206, 229, 232 Recombinant, 53, 142, 229 Rectum, 133, 184, 187, 198, 203, 209, 211, 226, 227, 229, 232 Recurrence, 34, 191, 229 Red blood cells, 201, 229, 231 Reductase, 84, 229 Refer, 1, 188, 191, 193, 198, 206, 217, 228, 229 Refraction, 229, 234 Regimen, 7, 34, 110, 112, 113, 114, 115, 199, 222, 229 Registries, 29, 229 Relapse, 131, 229 Relative risk, 8, 229 Reliability, 52, 113, 229 Remission, 229 Renal Artery, 38, 230 Renin, 93, 182, 230 Research Support, 11, 230 Resorption, 187, 207, 230 Respiration, 16, 189, 216, 230 Response Elements, 22, 230 Restoration, 230 Resuscitation, 127, 230 Retina, 193, 197, 212, 219, 230, 231 Retinal, 5, 197, 219, 230 Retinoid, 9, 230 Retinol, 230 Retinopathy, 3, 5, 197, 230 Retrospective, 25, 230 Retrospective study, 25, 230 Rheumatism, 230 Rheumatoid, 139, 144, 192, 230 Rheumatoid arthritis, 139, 144, 192, 230 Rhythm Method, 126, 231 Rods, 230, 231 Rosiglitazone, 62, 231

S Safe Sex, 127, 231 Salicylic, 121, 231 Saline, 33, 231 Saliva, 231 Salivary, 69, 198, 231 Salivary glands, 198, 231 Saponins, 92, 231, 234 Saturated fat, 31, 231 Schizoid, 231, 241 Schizophrenia, 231, 241 Schizotypal Personality Disorder, 197, 231, 241 Screening, 6, 8, 12, 14, 17, 23, 127, 144, 161, 192, 231 Sebaceous, 133, 231, 241 Sebum, 179, 231 Secretion, 47, 61, 115, 117, 123, 179, 180, 195, 204, 207, 210, 211, 215, 216, 231, 232, 238 Secretory, 115, 117, 122, 123, 232 Semen, 227, 232 Seminiferous tubule, 232, 234 Semisynthetic, 201, 232 Senile, 121, 220, 232 Sequela, 133, 232 Sequential treatment, 15, 232 Serine, 227, 232 Serologic, 208, 232 Serotonin, 184, 202, 232, 238 Serum, 7, 10, 26, 32, 34, 47, 49, 50, 55, 59, 60, 69, 75, 86, 91, 95, 104, 181, 193, 204, 213, 215, 232 Serum Albumin, 47, 232 Sex Characteristics, 179, 182, 219, 227, 232, 236 Sex Ratio, 53, 134, 232 Sexually Transmitted Diseases, 12, 23, 127, 137, 231, 232 Shock, 207, 232, 238 Side effect, 8, 37, 92, 95, 113, 116, 118, 122, 137, 147, 158, 180, 184, 196, 232, 237 Sigmoid, 226, 232 Sigmoid Colon, 226, 232 Signal Transduction, 16, 232 Signs and Symptoms, 229, 233 Sister Chromatid Exchange, 92, 233 Skeletal, 13, 25, 111, 182, 233 Skeleton, 111, 187, 211, 226, 233 Skin Pigmentation, 122, 233 Skin Tests, 233, 238 Skull, 195, 217, 233, 236

Oral contraceptives

Small intestine, 191, 199, 207, 210, 233 Smallpox, 166, 233 Smooth muscle, 26, 182, 188, 202, 212, 216, 233, 235 Smooth Muscle Tumor, 26, 202, 233 Social Environment, 228, 233 Social Problems, 14, 233 Sodium, 126, 215, 233 Soft tissue, 187, 233 Soma, 233, 234 Somatic, 20, 179, 216, 233, 234 Specialist, 168, 198, 234 Species, 185, 191, 200, 207, 211, 212, 214, 215, 216, 221, 223, 228, 234, 238, 240, 241 Spectrum, 4, 234 Sperm, 8, 113, 114, 116, 118, 182, 191, 232, 234 Sperm Motility, 8, 234 Sperm Transport, 114, 234 Spermatozoa, 113, 232, 234 Spermatozoon, 234 Spinal cord, 187, 188, 190, 191, 214, 217, 234 Spinous, 200, 211, 234 Spirochete, 234, 236 Spotting, 116, 118, 121, 122, 234 Sprains and Strains, 213, 234 Steady state, 6, 234 Sterile, 8, 221, 234, 238 Sterility, 39, 48, 49, 55, 91, 196, 234 Sterilization, 80, 126, 132, 135, 234 Steroid, 11, 21, 23, 25, 39, 47, 113, 119, 195, 219, 231, 234 Stimulant, 188, 234 Stimulus, 111, 201, 209, 211, 221, 234, 236 Stomach, 179, 198, 201, 203, 204, 206, 210, 217, 233, 235 Stool, 133, 209, 211, 235 Strand, 13, 235 Stress, 60, 99, 134, 166, 195, 217, 225, 231, 235, 239 Stroke, 52, 61, 66, 67, 73, 99, 107, 140, 152, 189, 235 Stroma, 23, 32, 115, 221, 235 Stromal, 10, 200, 235 Stromal Cells, 10, 235 Subacute, 209, 235 Subarachnoid, 205, 235 Subclinical, 209, 235 Subcutaneous, 179, 199, 212, 235 Substance P, 215, 226, 232, 235 Substrate, 50, 93, 235

254

Sun protection factor, 134, 235 Sunburn, 134, 235 Superoxide, 15, 235 Supplementation, 92, 93, 94, 95, 96, 126, 235 Suppression, 15, 49, 55, 77, 116, 118, 195, 235 Sympathomimetic, 198, 200, 218, 235 Symphysis, 227, 235 Symptomatic, 26, 236 Symptomatology, 11, 120, 121, 236 Synaptic, 233, 236 Synergistic, 10, 236 Synthetic retinoid, 9, 133, 202, 236 Syphilis, 127, 236 Systemic lupus erythematosus, 24, 144, 192, 236 Systemic therapy, 133, 236 Systolic, 208, 236 T Temporal, 33, 205, 236 Teratogenic, 211, 236 Testis, 201, 219, 236 Testosterone, 111, 229, 236 Tetany, 221, 236 Therapeutics, 68, 96, 148, 236 Thermal, 33, 217, 236 Third Ventricle, 208, 236 Thoracic, 188, 197, 214, 236, 241 Threshold, 21, 34, 85, 208, 236 Thrombin, 202, 224, 227, 237 Thromboembolism, 22, 36, 43, 46, 48, 53, 57, 59, 68, 70, 74, 79, 80, 165, 166, 237 Thrombophilia, 22, 72, 74, 80, 237 Thrombosis, 5, 36, 43, 45, 51, 52, 56, 57, 59, 64, 66, 72, 73, 76, 79, 80, 93, 96, 227, 235, 237 Thrombus, 195, 209, 224, 237, 240 Thyroid, 49, 96, 131, 144, 204, 208, 210, 221, 237, 239 Thyroid Gland, 204, 208, 221, 237 Thyroid Hormones, 49, 237, 239 Thyroxine, 181, 223, 237 Time Factors, 180, 237 Tin, 144, 189, 237 Tolerance, 60, 112, 132, 204, 237 Tomography, 187, 237 Tonic, 215, 237 Tooth Preparation, 179, 237 Topical, 122, 133, 185, 211, 237 Torsion, 209, 237 Total-body irradiation, 13, 237

255

Toxaemia, 225, 237 Toxic, iv, 194, 205, 206, 208, 222, 237, 238 Toxicity, 198, 237 Toxicology, 43, 61, 154, 238 Toxins, 132, 183, 209, 228, 237, 238 Trace element, 237, 238 Trachea, 237, 238 Transcription Factors, 230, 238 Transduction, 232, 238 Transfection, 186, 238 Transforming Growth Factor beta, 16, 238 Transmitter, 179, 198, 211, 218, 238 Trauma, 134, 217, 238 Trichomonas, 12, 238 Trichomoniasis, 127, 238 Trypanosomiasis, 222, 238 Tryptophan, 192, 232, 238 Tubal ligation, 144, 238 Tubercle, 238 Tuberculin, 159, 238 Tuberculin Test, 159, 238 Tuberculosis, 159, 194, 213, 231, 238 Tumor marker, 186, 239 Type 2 diabetes, 10, 239 Tyrosine, 122, 198, 239 U Ulcer, 134, 199, 239 Ulcerative colitis, 4, 130, 131, 133, 134, 143, 209, 239 Ultrasonography, 126, 239 Unconscious, 208, 239 Urban Population, 31, 239 Ureters, 230, 239 Urethra, 222, 227, 239 Urethritis, 162, 239 Urge urinary incontinence, 166, 239 Urinary, 23, 34, 58, 60, 99, 115, 132, 167, 207, 209, 239 Urinary tract, 132, 239 Urinate, 239, 241 Urine, 12, 24, 26, 34, 57, 126, 177, 186, 195, 198, 209, 227, 239 Urogenital, 205, 239 Urticaria, 75, 239 Uterus, 23, 26, 27, 116, 118, 120, 182, 191, 195, 196, 200, 201, 202, 208, 212, 215, 220, 226, 238, 239, 240 V Vaccination, 166, 239

Vaccine, 166, 227, 239 Vagina, 113, 189, 191, 215, 234, 240 Vaginal, 15, 22, 75, 99, 113, 114, 132, 178, 240 Vaginitis, 99, 189, 240 Vascular, 72, 93, 185, 200, 205, 209, 213, 215, 218, 220, 224, 225, 237, 239, 240 Vascular Resistance, 185, 240 Vasoconstriction, 21, 200, 240 Vasodilation, 21, 240 Vasodilator, 21, 188, 198, 240 Vasomotor, 21, 201, 240 Vein, 56, 57, 182, 210, 218, 240 Venereal, 236, 240 Venous blood, 22, 240 Venous Thrombosis, 36, 48, 57, 62, 74, 162, 240 Ventricle, 228, 236, 240 Vesicular, 23, 206, 233, 240 Veterinary Medicine, 153, 240 Viral, 20, 23, 99, 219, 238, 240, 241 Viral Load, 20, 240 Virilism, 207, 240 Virulence, 19, 185, 237, 240 Virus, 19, 23, 58, 127, 159, 185, 190, 200, 207, 210, 224, 233, 238, 240 Viscera, 234, 240 Vitamin A, 87, 126, 230, 240 Vitiligo, 134, 241 Vitreous Hemorrhage, 197, 241 Vitro, 19, 49, 241 Vivo, 241 Void, 34, 241 Vulgaris, 133, 241 W Warts, 207, 241 Weight Gain, 126, 140, 241 White blood cell, 179, 183, 212, 213, 216, 224, 241 Windpipe, 237, 241 Withdrawal, 47, 115, 116, 118, 241 Womb, 239, 241 X Xenograft, 182, 241 X-ray, 25, 187, 203, 211, 214, 218, 228, 241 X-ray therapy, 211, 241 Z Zygote, 193, 194, 241

Oral contraceptives

256

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

Oral Sex: A Medical Dictionary, Bibliography, And Annotated Research Guide to Internet References

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

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

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

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

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Marburg Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Oral Sex: A Medical Dictionary, Bibliography, And Annotated Research Guide to Internet References

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

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

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

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

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Marburg Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

Recommend Documents