The 2002 Official Patient's Sourcebook on Endometriosis

THE 2002 OFFICIAL PATIENT’S SOURCEBOOK on ENDOMETRIOSIS J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E ...

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THE 2002 OFFICIAL PATIENT’S SOURCEBOOK

on

ENDOMETRIOSIS

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 Ó2002 by ICON Group International, Inc. Copyright Ó2002 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: Tiffany LaRochelle 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 as a substitute for consultation with your physician. All matters regarding your health require medical supervision. 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, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking 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., 1960The 2002 Official Patient’s Sourcebook on Endometriosis: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83131-9 1. Endometriosis-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. 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, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. 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 sourcebook.

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Dedication To the healthcare professionals dedicating their time and efforts to the study of endometriosis.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to endometriosis. All of the Official Patient’s Sourcebooks 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 sourcebook. 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 LaRochelle for her excellent editorial support.

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

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About ICON Health Publications In addition to endometriosis, Official Patient’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Antenatal Corticosteroid Therapy

·

The Official Patient's Sourcebook on Gestational Diabetes

·

The Official Patient's Sourcebook on Uterine Fibroids

·

The Official Patient's Sourcebook on Vaginitis

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

Contents vii

Table of Contents INTRODUCTION...................................................................................... 1

Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 4

PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON ENDOMETRIOSIS: GUIDELINES ........ 9

Overview............................................................................................................... 9 What Is Endometriosis?...................................................................................... 10 What Are the Symptoms?................................................................................... 12 How Is Endometriosis Related to Fertility Problems? ....................................... 13 What Is the Cause of Endometriosis? ................................................................. 13 How Is Endometriosis Diagnosed?..................................................................... 14 What Is the Treatment?...................................................................................... 14 Additional Resources .......................................................................................... 16 More Guideline Sources ..................................................................................... 17 Vocabulary Builder............................................................................................. 22

CHAPTER 2. SEEKING GUIDANCE ....................................................... 27

Overview............................................................................................................. 27 Associations and Endometriosis ......................................................................... 27 Finding More Associations................................................................................. 32 Finding Doctors.................................................................................................. 33 Finding an Obstetrician-Gynecologist ............................................................... 35 Selecting Your Doctor ........................................................................................ 35 Working with Your Doctor ................................................................................ 36 Broader Health-Related Resources ..................................................................... 37 Vocabulary Builder............................................................................................. 38

CHAPTER 3. CLINICAL TRIALS AND ENDOMETRIOSIS ........................ 41

Overview............................................................................................................. 41 Recent Trials on Endometriosis.......................................................................... 44 Benefits and Risks............................................................................................... 46 Keeping Current on Clinical Trials.................................................................... 49 General References.............................................................................................. 49 Vocabulary Builder............................................................................................. 50

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 53 CHAPTER 4. STUDIES ON ENDOMETRIOSIS.......................................... 55

Overview............................................................................................................. 55 The Combined Health Information Database ..................................................... 55

viii Contents

Federally-Funded Research on Endometriosis.................................................... 60 The National Library of Medicine: PubMed ...................................................... 76 Vocabulary Builder............................................................................................. 76

CHAPTER 5. PATENTS ON ENDOMETRIOSIS ........................................ 85

Overview............................................................................................................. 85 Patents on Endometriosis ................................................................................... 86 Patent Applications on Endometriosis ............................................................. 102 Keeping Current ............................................................................................... 105 Vocabulary Builder........................................................................................... 105

CHAPTER 6. BOOKS ON ENDOMETRIOSIS .......................................... 111

Overview........................................................................................................... 111 Book Summaries: Federal Agencies .................................................................. 111 Book Summaries: Online Booksellers ............................................................... 113 The National Library of Medicine Book Index ................................................. 116 Chapters on Endometriosis............................................................................... 121 General Home References ................................................................................. 123 Vocabulary Builder........................................................................................... 124

CHAPTER 7. MULTIMEDIA ON ENDOMETRIOSIS ............................... 125

Overview........................................................................................................... 125 Bibliography: Multimedia on Endometriosis ................................................... 125 Vocabulary Builder........................................................................................... 128

CHAPTER 8. PERIODICALS AND NEWS ON ENDOMETRIOSIS ............ 129

Overview........................................................................................................... 129 News Services & Press Releases ....................................................................... 129 Newsletter Articles ........................................................................................... 139 Academic Periodicals covering Endometriosis ................................................. 141 Vocabulary Builder........................................................................................... 142

CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES ................... 145

Overview........................................................................................................... 145 NIH Guidelines................................................................................................. 145 NIH Databases.................................................................................................. 146 Other Commercial Databases ........................................................................... 150 The Genome Project and Endometriosis........................................................... 150 Specialized References....................................................................................... 154

CHAPTER 10. DISSERTATIONS ON ENDOMETRIOSIS ......................... 157

Overview........................................................................................................... 157 Dissertations on Endometriosis........................................................................ 157 Keeping Current ............................................................................................... 159

PART III. APPENDICES .................................................. 161 APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 163

Overview........................................................................................................... 163 Your Medications: The Basics .......................................................................... 164

Contents

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Learning More about Your Medications .......................................................... 166 Commercial Databases...................................................................................... 168 Contraindications and Interactions (Hidden Dangers) ................................... 169 A Final Warning .............................................................................................. 170 General References............................................................................................ 171 Vocabulary Builder........................................................................................... 172

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 173

Overview........................................................................................................... 173 What Is CAM? ................................................................................................. 173 What Are the Domains of Alternative Medicine?............................................ 174 Can Alternatives Affect My Treatment? ......................................................... 177 Finding CAM References on Endometriosis .................................................... 178 Additional Web Resources................................................................................ 183 General References............................................................................................ 189 Vocabulary Builder........................................................................................... 190

APPENDIX C. RESEARCHING NUTRITION ......................................... 191

Overview........................................................................................................... 191 Food and Nutrition: General Principles........................................................... 191 Finding Studies on Endometriosis ................................................................... 196 Federal Resources on Nutrition........................................................................ 200 Additional Web Resources................................................................................ 200 Vocabulary Builder........................................................................................... 205

APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 207

Overview........................................................................................................... 207 Preparation ....................................................................................................... 207 Finding a Local Medical Library ...................................................................... 208 Medical Libraries Open to the Public............................................................... 208

APPENDIX E. YOUR RIGHTS AND INSURANCE ................................. 215

Overview........................................................................................................... 215 Your Rights as a Patient................................................................................... 215 Patient Responsibilities .................................................................................... 219 Choosing an Insurance Plan............................................................................. 220 Medicare and Medicaid .................................................................................... 223 NORD’s Medication Assistance Programs ..................................................... 226 Additional Resources ........................................................................................ 226 Vocabulary Builder........................................................................................... 227

APPENDIX F. MORE ON PAIN............................................................ 228

Overview........................................................................................................... 228 A Brief History of Pain..................................................................................... 228 The Two Faces of Pain: Acute and Chronic...................................................... 229 The A to Z of Pain ............................................................................................ 230 How Is Pain Diagnosed? .................................................................................. 234 How Is Pain Treated? ....................................................................................... 235 What Is the Role of Age and Gender in Pain?.................................................. 241

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Contents

A Pain Primer: What Do We Know about Pain? ............................................ 243 What Is the Future of Pain Research?.............................................................. 247 Hope for the Future........................................................................................... 249 Spine Basics: The Vertebrae, Discs, and Spinal Cord ...................................... 250 The Nervous Systems ....................................................................................... 251 Information Resources ...................................................................................... 254

ONLINE GLOSSARIES.................................................... 259 Online Dictionary Directories.......................................................................... 264

ENDOMETRIOSIS GLOSSARY .................................... 265 General Dictionaries and Glossaries ................................................................ 284

INDEX................................................................................... 286

Introduction

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INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don't know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, 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.3 Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

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Endometriosis

Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor's offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The Official Patient’s Sourcebook on Endometriosis has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to endometriosis, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on endometriosis. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on endometriosis should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate

Introduction

3

options is always up to the patient in consultation with their physician and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching endometriosis (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to endometriosis. It also gives you sources of information that can help you find a doctor in your local area specializing in treating endometriosis. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with endometriosis. Part II moves on to advanced research dedicated to endometriosis. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on endometriosis. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with endometriosis or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with endometriosis. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with endometriosis.

Scope While this sourcebook covers endometriosis, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that endometriosis is often considered a synonym or a condition closely related to the following: ·

Adenomyosis

4

Endometriosis

·

Endometrial Growths

·

Endometrial Implants

·

Endometriosis Externa

·

Endometriosis of the Cervix

·

Internal Endometriosis

·

Myometrium Endometriosis

In addition to synonyms and related conditions, physicians may refer to endometriosis using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world's illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for endometriosis:4 ·

617.0 endometriosis of uterus

·

617.1 endometriosis of ovary

·

617.2 endometriosis of fallopian tube

·

617.3 endometriosis of pelvic peritoneum

·

617.4 endometriosis of rectovaginal septum and vagina

·

617.9 endometriosis

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to endometriosis. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson's approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other 4 This list is based on the official version of the World Health Organization's 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”

Introduction

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healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with endometriosis will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with endometriosis is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of endometriosis, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors

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PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on endometriosis. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of endometriosis to you or even given you a pamphlet or brochure describing endometriosis. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

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CHAPTER 1. THE ESSENTIALS ON ENDOMETRIOSIS: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on endometriosis. 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. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on endometriosis can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on endometriosis. Originally founded in 1887, the NIH is one of the world's foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world's most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

5

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Endometriosis

There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with endometriosis and associated conditions: ·

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

·

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

·

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

Among those listed above, the National Institute of Child Health and Human Development (NICHD) is especially noteworthy. The mission of the NICHD, a part of the National Institutes of Health (NIH), is to support and conduct research on topics related to the health of children, adults, families, and populations. NICHD research focuses on the idea that events that happen prior to and throughout pregnancy as well as during childhood have a great impact on the health and well-being of adults. The following guideline is one the NICHD provides concerning endometriosis.6

What Is Endometriosis?7 Endometriosis is a common yet poorly understood disease. It can strike women of any socioeconomic class, age, or race. It is estimated that between 10 and 20 percent of American women of childbearing age have endometriosis. While some women with endometriosis may have severe pelvic pain, others who have the condition have no symptoms. Nothing about endometriosis is simple, and there are no absolute cures. The disease can affect a woman's whole existence-her ability to work, her ability to reproduce, and her relationships with her mate, her child, and every one around her. 6 This and other passages have been adapted from the NIH and NICHD: http://www.nichd.nih.gov/default.htm. “Adapted” signifies that the text has been reproduced with attribution, with some or no editorial adjustments. 7 Adapted from The National Institute of Child Health and Human Development (NICHD): http://www.nichd.nih.gov/publications/pubs/endomet.htm.

Guidelines 11

The National Institute of Child Health and Human Development (NICHD), part of the Federal Government's National Institutes of Health (NIH), conducts and supports research on the various processes that determine the health of children adults, families, and populations. As part of NICHD's mandate in the reproductive sciences, NICHD has established a Reproductive Medicine Network linking several institutions across the country. While this cooperative effort focuses on other important issues such as infertility and various male and female reproductive disorders, developing an optimal treatment for endometriosis is one of its primary goals. The name endometriosis comes from the word “endometrium,” the tissue that lines the inside of the uterus. If a woman is not pregnant this tissue builds up and is shed each month. It is discharged as menstrual flow at the end of each cycle. In endometriosis, tissue that looks and acts like endometrial tissue is found outside the uterus, usually inside the abdominal cavity.

Endometrial tissue residing outside the uterus responds to the menstrual cycle in a way that is similar to the way endometrium usually responds in the uterus. At the end of every cycle, when hormones cause the uterus to shed its endometrial lining, endometrial tissue growing outside the uterus will break apart and bleed. However, unlike menstrual fluid from the uterus, which is discharged from the body during menstruation, blood from the misplaced tissue has no place to go. Tissues surrounding the area of endometriosis may become inflamed or swollen. The inflammation may produce scar tissue around the area of endometriosis. These endometrial

12 Endometriosis

tissue sites may develop into what are called “lesions,” “implants,” “nodules,” or “growths.” Endometriosis is most often found in the ovaries, on the fallopian tubes, and the ligaments supporting the uterus, in the internal area between the vagina and rectum, on the outer surface of the uterus, and on the lining of the pelvic cavity. Infrequently, endometrial growths are found on the intestines or in the rectum, on the bladder, vagina, cervix, and vulva (external genitals), or in abdominal surgery scars. Very rarely, endometrial growths have been found outside the abdomen, in the thigh, arm, or lung. Physicians may use stages to describe the severity of endometriosis. Endometrial implants that are small and not widespread are considered minimal or mild endometriosis. Moderate endometriosis means that larger implants or more extensive scar tissue is present. Severe endometriosis is used to describe large implants and extensive scar tissue. “Staging endometriosis is vitally important because all women with endometriosis are not the same.”8

What Are the Symptoms? Most commonly, the symptoms of endometriosis start years after menstrual periods begin. Over the years, the symptoms tend to gradually increase as the endometriosis areas increase in size. After menopause, the abnormal implants shrink away and the symptoms subside. The most common symptom is pain, especially excessive menstrual cramps (dysmenorrhea) which may be felt in the abdomen or lower back or pain during or after sexual activity (dyspareunia). Infertility occurs in about 30 to 40 percent of women with endometriosis. Rarely, the irritation caused by endometrial implants may progress into infection or abscesses causing pain independent of the menstrual cycle. Endometrial patches may also be tender to touch or pressure, and intestinal pain may also result from endometrial patches on the walls of the colon or intestine. The amount of pain is not always related to the severity of the disease-some women with severe endometriosis have no pain; while others with just a few small growths have incapacitating pain.

8

NICHD Researcher

Guidelines 13

Endometrial cancer is very rarely associated with endometriosis, occurring in less than 1 percent of women who have the disease. When it does occur, it is usually found in more advanced patches of endometriosis in older women and the long-term outlook in these unusual cases is reasonably good. While endometriosis is not a malignant disease, it does cause a lot of suffering and pain.9

How Is Endometriosis Related to Fertility Problems? Severe endometriosis with extensive scarring and organ damage may affect fertility. It is considered one of the three major causes of female infertility. However, unsuspected or mild endometriosis is a common finding among infertile women and how this type of endometriosis affects fertility is still not clear. While the pregnancy rates for patients with endometriosis remain lower than those of the general population, most patients with endometriosis do not experience fertility problems. “We do not have a clear understanding of the cause-effect relationship of endometriosis and infertility.”10

What Is the Cause of Endometriosis? The cause of endometriosis is still unknown. One theory is that during menstruation some of the menstrual tissue backs up through the fallopian tubes into the abdomen, where it implants and grows. Another theory suggests that endometriosis may be a genetic process or that certain families may have predisposing factors to endometriosis. In the latter view, endometriosis is seen as the tissue development process gone awry. Whatever the cause of endometriosis, its progression is influenced by various stimulating factors such as hormones or growth factors. In this regard, NICHD investigators are study- ing the role of the immune system in activating cells that may secrete factors which, in turn, stimulate endometriosis. In addition to these new hypotheses, investigators are continuing to look into previous theories that endometriosis is a disease influenced by delayed childbearing. Since the hormones made by the placenta during pregnancy 9

NICHD Researcher NICHD Researcher

10

14 Endometriosis

prevent ovulation, the progress of endometriosis is slowed or stopped during pregnancy and the total number of lifetime cycles is reduced for a woman who had multiple pregnancies.

How Is Endometriosis Diagnosed? Diagnosis of endometriosis begins with a gynecologist evaluating the patient's medical history. A complete physical exam, including a pelvic examination, is also necessary. However, diagnosis of endometriosis is only complete when proven by a laparoscopy, a minor surgical procedure in which a laparoscope (a tube with a light in it) is inserted into a small incision in the abdomen. The laparoscope is moved around the abdomen, which has been distended with carbon dioxide gas to make the organs easier to see. The surgeon can then check the condition of the abdominal organs and see the endometrial implants. The laparoscopy will show the locations, extent, and size of the growths and will help the patient and her doctor make better-informed decisions about treatment. “Endometriosis is a long-standing disease that often develops slowly.”11

What Is the Treatment? While the treatment for endometriosis has varied over the years, doctors now agree that if the symptoms are mild, no further treatment other than medication for pain may be needed. For those patients with mild or minimal endometriosis who wish to become pregnant, doctors are advising that, depending on the age of the patient and the amount of pain associated with the disease, the best course of action is to have a trial period of unprotected intercourse for 6 months to 1 year. If pregnancy does not occur within that time, then further treatment may be needed. For patients not seeking a pregnancy where treatment specific for the management of endometriosis is required and a definitive diagnosis of endometriosis by laparoscopy has been made, a physician may suggest hormone suppression treatment. Since this therapy shuts off ovulation, women being treated for endometriosis will not get pregnant during such 11

NICHD Researcher

Guidelines 15

therapy, although some may elect to become pregnant shortly after therapy is stopped. Hormone treatment is most effective when the implants are small. The doctor may prescribe a weak synthetic male hormone called Danazol, a synthetic progestin alone, or a combination of estrogen and progestin such as oral contraceptives. “We are finding good medical options without surgery.”12 Danazol has become a more common treatment choice than either progestin or the birth control pill. Disease symptoms are improved for 80 to 90 percent of the patients taking Danazol, and the size and the extent of implants are also reduced. While side effects with Danazol treatment are not uncommon (e.g., acne, hot flashes, or fluid retention), most of them are relatively mild and stop when treatment is stopped. Overall, pregnancy rates following this therapy depend on the severity of the disease. However, some recent studies have shown that with mild to minimal endometriosis, Danazol alone does not improve pregnancy rates. It is important to remember that Danazol treatment is unsafe if there is any chance that a woman is pregnant. A fetus accidentally exposed to this drug may develop abnormally. For this same reason, although pregnancy is not likely while a woman is taking this drug, careful use of a barrier birth control method such as a diaphragm or condom is essential during this treatment. Another type of hormone treatment is a synthetic pituitary hormone blocker called gonadotropin-releasing hormone agonist, or GnRH agonist. This treatment stops ovarian hormone production by blocking pituitary gland hormones that normally stimulate ovarian cycles. These hormones are currently being tested using different methods of administration. One such treatment involves a drug that is administered as a nasal spray twice daily for 6 months and works by suppressing production of estrogen, which controls the growth of the endometrial tissue. Other treatments being developed in this category include daily or monthly hormone injections. One concern is the loss of bone mineral which occurs with this type of hormone therapy. This may limit the duration and frequency of this type of treatment.

12

NICHD Researcher

16 Endometriosis

While pregnancy rates for women with fertility problems resulting from endometriosis are fairly good with no therapy and with only a trial waiting period, there may be women who need more aggressive treatment. Those women who are older and who feel the need to become pregnant more quickly or those women who have severe physical changes due to the disease, may consider surgical treatment. Also, women who are not interested in pregnancy, but who have severe, debilitating pain, may also consider surgery. Conservative surgery attempts to remove the diseased tissue without risking damage to healthy surrounding tissue. This surgery is called laparotomy and is performed in a hospital under anesthesia. Pregnancy rates are highest during the first year after surgery, as recurrences of endometriosis are fairly common. The specifics of the surgery should be discussed with a doctor. Some patients may need more radical surgery to correct the damage caused by untreated endometriosis. Hysterectomy and removal of the ovaries may be the only treatment possible if the ovaries are badly damaged. In some cases, hysterectomy alone without the removal of the ovaries may be reasonable. New surgical treatments are being developed that further utilize the laparoscope instead of full abdominal surgery. During routine laparoscopy, the surgeon can cauterize small areas of endometriosis. Other evolving techniques include using a laser during laparoscopy to vaporize abnormal tissue. This involves a shorter recovery time. Laparoscopy treatment is possible, however, only if the surgeon can see pelvic structures clearly through the laparoscope. These newer techniques should be performed by surgeons specializing in such delicate procedures. Although these techniques are promising, more study is needed to determine if they yield results comparable to conventional surgical management.

Additional Resources Because endometriosis affects each woman differently, it is essential that the patient maintains a good, clear, honest communication with her doctor. For the single truth about endometriosis is that there are no clear-cut, universal answers.

Guidelines 17

If pregnancy is an issue, then age may affect the treatment plan. If it is not an issue, then treatment decisions will depend primarily on the severity of symptoms. A number of organizations provide information about the diagnosis and treatment of endometriosis and offer support to women affected by this disease and their families. Please note that while the groups listed below are valuable resources for information about endometriosis, they were not consulted in the writing of this publication. The information presented here does not necessarily reflect the views of these organizations. Endometriosis Association 8585 North 76th Place Milwaukee, Wisconsin 53223 (414) 355-2200 The American College of Obstetricians and Gynecologists 409 12th Street, SW Washington, DC 20024-2188 (202) 638-5577 American Fertility Society 2140-llth Avenue South Suite 200 Birmingham, Alabama 35205-2800 (205) 933-8494

More Guideline Sources The guideline above on endometriosis is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to endometriosis. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with endometriosis. 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.

18 Endometriosis

Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. 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.

If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material 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 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 their site located at http://www.guideline.gov by using the keyword “endometriosis” or synonyms. The following was recently posted: ·

A decision tree for the use of estrogen replacement therapy or hormone replacement therapy in postmenopausal women: consensus opinion of The North American Menopause Society. Source: The North American Menopause Society.; 2000 March; 11 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1791&sSearch_string=endometriosis

·

Guideline for determining the route and method of hysterectomy for benign conditions. Source: Society of Pelvic Reconstructive Surgeons.; 1999; 3 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1379&sSearch_string=endometriosis

Guidelines 19

·

Hormone replacement therapy: collaborative decision making and management. Source: Institute for Clinical Systems Improvement.; 1999 August (revised 2001 Jul); 64 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2210&sSearch_string=endometriosis

·

Hysterectomy. Source: Optimed Medical Systems Clinical Development Group.; 1997 (recommendations revised 1999); The software includes over 100 menus and requires user to spend 2 to 5 minutes, depending on the clinical information. http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1350&sSearch_string=endometriosis

·

Low back pain or sciatica in the primary care setting. Source: Department of Defense/Veterans Health Administration.; 1999 May; Various pagings http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1804&sSearch_string=endometriosis

·

Management of initial abnormal Pap smear. Source: Institute for Clinical Systems Improvement.; 1999 May (revised 2001 Jul); 32 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1984&sSearch_string=endometriosis

·

National guideline for the management of pelvic infection and perihepatitis. Source: Association for Genitourinary Medicine/Medical Society for the Study of Venereal Diseases.; 1999 August; 3 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1443&sSearch_string=endometriosis

20 Endometriosis

·

Recommendations for the treatment of dysmenorrhea. Source: University of Texas at Austin School of Nursing, Family Nurse Practitioner Program.; 2001 February; 8 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1963&sSearch_string=endometriosis

·

The management of infertility in secondary care. Source: Royal College of Obstetricians and Gynaecologists.; 1998 October; 147 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1778&sSearch_string=endometriosis

·

The management of menorrhagia in secondary care. Source: Royal College of Obstetricians and Gynaecologists.; 1999 July; 77 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1782&sSearch_string=endometriosis Healthfinder™

Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which 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: ·

Facts About Endometriosis Summary: This fact sheet provides basic consumer information about endometriosis symptoms, diagnosis and treatment options and includes a list of resources where users can get additional information. Source: National Institute of Child Health and Human Development, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=742

Guidelines 21

·

Hysterectomy: Know Your Options Summary: Answers to women's concerns about this medical procedure that is frequently recommended as a solution to relieve chronic pain and/or heavy bleeding that is caused by fibroids, endometriosis, and other Source: National Women's Health Resource Center http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2596

·

On The Teen Scene: Endometriosis: Painful But Treatable Summary: The symptoms and physiological explanation of endometriosis are reviewed. Surgery and drug therapy as well as consequences of failure to treat the disease are explained. Source: Office of Consumer Affairs, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=569

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. 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 endometriosis. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing, for a nominal fee, short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is www.rarediseases.org.

22 Endometriosis

To see if a recent fact sheet has been published on endometriosis, simply go to the following hyperlink: http://www.rarediseases.org/cgibin/nord/alphalist. A complete guide on endometriosis can be purchased from NORD for a nominal fee.

Additional Web Sources A number of Web sites that often link to government sites are available to the public. 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

·

drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

·

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

·

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

·

Med Help International: http://www.medhelp.org/HealthTopics/A.html

·

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

·

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

·

WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Pertaining to the abdomen. [EU] Acne: An inflammatory disease of the pilosebaceous unit, the specific type usually being indicated by a modifying term; frequently used alone to designate common acne, or acne vulgaris. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU]

Guidelines 23

Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]

Benign: An enlarged prostate not caused by cancer. BPH can cause problems with urination because the prostate squeezes the urethra at the opening of the bladder. [NIH] Bladder: The balloon-shaped organ inside the pelvis that holds urine. [NIH] Chronic: Lasting a long time. Chronic diseases develop slowly. Chronic renal failure may develop over many years and lead to end-stage renal disease. [NIH] Contraceptive: conception. [EU]

An agent that diminishes the likelihood of or prevents

Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [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] Dysmenorrhea: Painful menstruation. [NIH] Dyspareunia: Difficult or painful coitus. [EU] 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; called also adenomyosis externa and endometriosis externa. [EU] Genitals: Sex organs, including the penis and testicles in men and the vagina and vulva in women. [NIH] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Hormone: A natural chemical produced in one part of the body and released into the blood to trigger or regulate particular functions of the body. Antidiuretic hormone tells the kidneys to slow down urine production. [NIH] Hysterectomy: The operation of excising the uterus, performed either through the abdominal wall (abdominal h.) or through the vagina (vaginal h.) [EU] Incision: 1. cleft, cut, gash. 2. an act or action of incising. [EU]

24 Endometriosis

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. it includes the large intestine and small intestine. [nih] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Malignant: Tending to become progressively worse and to result in death. Having the properties of anaplasia, invasion, and metastasis; said of tumours. [EU] Menopause: Cessation of menstruation in the human female, occurring usually around the age of 50. [EU] Menorrhagia: Excessive uterine bleeding occurring at the regular intervals of menstruation, the period of flow being of greater than usual duration. [EU] Menstruation: The cyclic, physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus; it is under hormonal control and normally recurs, usually at approximately four-week intervals, in the absence of pregnancy during the reproductive period (puberty through menopause) of the female of the human and a few species of primates. It is the culmination of the menstrual cycle. [EU] Nasal: Pertaining to the nose. [EU] Oral: Pertaining to the mouth, taken through or applied in the mouth, as an oral medication or an oral thermometer. [EU] Ovulation: The discharge of a secondary oocyte from a vesicular follicle of the ovary. [EU] Pelvic: Muscles that support the bladder. [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] Postmenopausal: Occurring after the menopause. [EU]

Guidelines 25

Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Sciatica: A syndrome characterized by pain radiating from the back into the buttock and into the lower extremity along its posterior or lateral aspect, and most commonly caused by prolapse of the intervertebral disk; the term is also used to refer to pain anywhere along the course of the sciatic nerve. [EU] Uterus: The hollow muscular organ in female mammals in which the fertilized ovum normally becomes embedded and in which the developing embryo and fetus is nourished. In the nongravid human, it is a pear-shaped structure; about 3 inches in length, consisting of a body, fundus, isthmus, and cervix. Its cavity opens into the vagina below, and into the uterine tube on either side at the cornu. It is supported by direct attachment to the vagina and by indirect attachment to various other nearby pelvic structures. Called also metra. [EU] Vagina: The tube in a woman's body that runs beside the urethra and connects the womb (uterus) to the outside of the body. Sometimes called the birth canal. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU]

Seeking Guidance 27

CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with endometriosis. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.13 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with endometriosis. The chapter ends with a discussion on how to find a doctor that is right for you.

Associations and Endometriosis As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.14 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 14 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 13

28 Endometriosis

your expectations, and how well you cope with your condition can all influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·

Department of Obstetrics and Gynecology Vanderbilt Center for Reproductive Medicine Vanderbilt University Medical Center Address: B-1100 Medical Center North Nashville, TN 37232 Telephone: (615) 322-6576 Web Site: http://www.mc.vanderbilt.edu/ Background: The Vanderbilt Center for Reproductive Medicine (VCRM) provides comprehensive diagnostic evaluation and therapeutic care for the couple with infertility, and for the woman with various types of disorders involving reproductive endocrinology. All clinical activities are backed by basic research projects, with interdigitating teaching and training programs. Although VCRM receives research grants from the U.S. National Institutes of Health, client services are provided on a fee basis. Special interests include infertility; ovulation induction; endometriosis; endocrinology; polycystic ovarian disease; hirsutism; male infertility; fertilization; menopause; and pelvic surgery. Relevant area(s) of interest: Endometriosis; In vitro fertilization; Infertility

·

Endometriosis Association Address: Endometriosis Association International Headquarters, 8585 North 76th Place, Milwaukee, WI 53223 Telephone: (414) 355-2200 Toll-free: (800) 992-3636 Fax: (414) 355-6065 Email: [email protected] Web Site: http://www.endometriosisassn.org Background: The Endometriosis Association is a not-for-profit self-help organization dedicated to providing support and education to women affected by endometriosis and their families. Endometriosis is a prevalent

Seeking Guidance 29

gynecological condition characterized by an inability to shed the build-up of bloody tissue that normally forms on the lining of the uterus (endometrium) before menstruation. Established in 1980, the organization provides support for women with endometriosis and their families; educational materials for the public and medical professionals about the disease; and promotes and carries out research on the disease. As part of its Research Program, the Association conducts research on endometriosis, including special programs at Dartmouth Medical School and at Vanderbilt University School of Medicine, continuing work on the relationship between dioxin and endometriosis. Consisting of 10,000 members and 250 chapters worldwide, the organization produces educational materials including 'What is Endometriosis?' written in several languages; the 'Endometriosis Association Newsletter' published six times a year; and a book entitled 'The Endometriosis Sourcebook.' Program activities include 'The Support Program' with a wide range of services including support groups, formal and informal counseling, crisis call assistance, networking, and other forms of support. Relevant area(s) of interest: Endometrial Growths, Endometrial Implants, Endometriosis ·

National Institute of Child Health and Human Development Address: 31 Center Drive Bethesda, MD, 20892-2425 MSC-2425, Room 2A32 Telephone: 800-370-2943 Web Site: http://www.nichd.nih.gov Background: The National Institute of Child Health and Human Development (NICHD) seeks to assure that every individual is born healthy, is born wanted, and has the opportunity to fulfill his or her potential for a healthy and productive life unhampered by disease or disability. In pursuit of this mission, the NICHD conducts and supports laboratory, clinical, and epidemiological research on the reproductive, neurobiologic, developmental, and behavioral processes that determine and maintain the health of children, adults, families, and populations. The National Institute of Child Health and Human Development (NICHD) conducts and supports basic and clinical research in maternal and child health and the population sciences. General Notes Information on Sudden Infant DeathSyndrome (SIDS) (800) 505-CRIB. Relevant area(s) of interest: Birth; Child health; childbirth, Down syndrome, oral contraception, precocious; childhood hyperactivity, maternal health, and sudden infant death; Family health; Fetal development; genetics.; Holdings; Human development; infant death

30 Endometriosis

syndrome, developmental disabilities, pregnancy, and; Maternal health; Medical rehabilitation; Pregnancy; puberty, endometriosis, gestational diabetes, vasectomy,; Public health; syndrome. Materials for professionals cover such topics as sudden; Topics of consumer materials include anorexia nervosa, cesarean ·

National Women's Health Network Address: National Women's Health Network 514 10th Street NW, Suite 400, Washington, D.C. 20004 Telephone: (202) 628-7814 Fax: (202) 347-1168 Background: The National Women's Health Network is a national notfor-profit voluntary health organization that functions as an advocate for health issues that affect women. The Network also functions as a clearinghouse for information on women's health issues and lifetime wellness. The Women's Health Information Service distributes brochures on topics such as Breast and Ovarian Cancer, Fibrocystic Disease, Interstitial Cystitis, Pelvic Inflammatory Disease, Vulvodynia, Urinary Tract Infections, and Toxic Shock Syndrome. The Network also distributes a regular newsletter. Relevant area(s) of interest: Endometriosis

·

OBGYN.net: The Obstetrics and Gynecology Network Address: OBGYN.net: The Obstetrics and Gynecology Network Web Site on the Internet, Email: [email protected] Web Site: http://www.obgyn.net Background: OBGYN.net: The Obstetrics and Gynecology Network is a web site on the Internet that serves as a comprehensive international resource center for professionals in obstetrics and gynecology, the medical industry, and the women they serve. The site, which is designed by obstetricians and gynecologists, is divided into different sections for its three major audiences: women, medical professionals, and the medical industry. Each section offers current reference information on obstetrics, gynecology, and general women's health issues; electronic journals; regular columns and features on topics of interest; and information on new research projects and developments. Additional features include highlights on helpful, informative web sites; dynamic links and information concerning medical and women's health associations and support groups; news and press releases; a regular calendar of events; the

Seeking Guidance 31

ability to access Medline abstracts from the National Library of Medicine; and discussion forums and live chats that enable women and medical professionals in the areas of obstetrics and gynecology to interact online. Online visitors may also join the site's update service to receive regular email updates concerning current features in OBGYN.net. Relevant area(s) of interest: Endometriosis ·

Society for the Study of Reproduction Address: Society for the Study of Reproduction 1526 Jefferson Street, Madison, WI 53711-2106 Telephone: (608) 256-2777 Fax: (608) 256-4610 Email: [email protected] Web Site: http://www.ssr.org/ Background: The Society for the Study of Reproduction (SSR) is a professional society that was founded in 1967 to promote the study of reproduction by fostering interdisciplinary communication among scientists, conducting conferences, and publishing meritorious studies. The Society's membership consists of scientists, medical and veterinary physicians, trainees in graduate and professional schools, and others who are engaged in research, education, and training in fields relevant to reproductive biology. The SSR is affiliated with colleges and universities, medical and veterinary schools, medical centers, research institutes, government agencies, and industry in approximately 47 countries. The Society's research focuses on important problems in human and animal reproduction as it relates to medicine and agriculture and basic biology. Such research areas include female and male infertility including pathophysiology, diagnosis, and treatment; contraception; lactation; pregnancy-related disorders including pre-eclampsia and premature labor; diseases of the reproductive tract including endometriosis and cancers of the ovary, uterus, and prostate; reproductive toxicology; basic mechanisms controlling the function of organs involved in reproduction; mechanisms of cell differentiation and development; and reproduction and conservation of endangered species. Society members have contributed toward the development of tests for pregnancy diagnosis and fetal monitoring; the development of methods for in vitro fertilization in humans and animals; and the training of scientists working for academia, government, and industry. The SSR conducts an Annual Meeting that serves as a forum for the exchange of current information in the field of reproduction. The scientific gathering offers symposia, technical workshops, and presentations from Society members and nonmembers.

32 Endometriosis

In addition, outstanding contributions to the science of reproduction are recognized at the Society's Annual Meeting. In the Society's commitment to promoting the education and training of young people, the SSR has also established an endowment fund to enhance the Annual Meeting as a broad forum for reproductive biology. The fund provides travel fellowships for trainees and foreign scientists, endowed lectures from distinguished scientists, and educational programs on such topics as the ethics of reproductive technologies, reproductive strategies for endangered species, and animal use and care. The SSR also publishes the journal 'Biology of Reproduction,' which includes original, peer-refereed scientific papers.

Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations.

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 endometriosis. 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.

DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “endometriosis” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.

Seeking Guidance 33

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 “endometriosis”. 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.” By making these selections and typing in “endometriosis” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with endometriosis. You should check back periodically with this database since it is updated every 3 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 specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “endometriosis” (or a synonym) in the search box.

Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective.

Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with endometriosis

34 Endometriosis

must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:15 ·

If you are in a managed care plan, check the plan's list of doctors first.

·

Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.

·

Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.

·

Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.

Additional steps you can take to locate doctors include the following: ·

Check with the associations listed earlier in this chapter.

·

Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.

·

The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at 16 http://www.abms.org/newsearch.asp. You can also contact the ABMS by phone at 1-866-ASK-ABMS.

·

You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA's Web site: http://www.amaassn.org/aps/amahg.htm.

If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. While board certification is a good measure of a doctor's knowledge, it is possible to receive quality care from doctors who are not board certified. 15 16

Seeking Guidance 35

expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

Finding an Obstetrician-Gynecologist The American College of Obstetricians and Gynecologists (ACOG) provides a searchable Physician Directory at http://www.acog.org/memberlookup/disclaimer.cfm. The directory is provided as a public service to help women find obstetrician-gynecologists in their area. The ACOG’s database includes over 43,000 of its members who practice obstetrics and/or gynecology in the U.S., Canada, and internationally. The Physician Directory is searchable by physician name, state, country, or zip code. Some of the topics covered can include information about each physician’s practice, such as office hours, affiliated hospitals, and languages spoken. A green icon next to a physician’s name denotes that information about this practice is available. By clicking on a linked name, you will be redirected to the associated physician’s home page.

Selecting Your Doctor17 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·

Give me a chance to ask questions about endometriosis?

·

Really listen to my questions?

·

Answer in terms I understood?

·

Show respect for me?

·

Ask me questions?

·

Make me feel comfortable?

17 This

section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

36 Endometriosis

·

Address the health problem(s) I came with?

·

Ask me my preferences about different kinds of treatments for endometriosis?

·

Spend enough time with me?

Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.

Working with Your Doctor18 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·

You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.

·

It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.

·

Bring a “health history” list with you (and keep it up to date).

·

Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.

·

Tell your doctor about any natural or alternative medicines you are taking.

·

Bring other medical information, such as x-ray films, test results, and medical records.

·

Ask questions. If you don't, your doctor will assume that you understood everything that was said.

·

Write down your questions before your visit. List the most important ones first to make sure that they are addressed.

·

Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.

This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

18

Seeking Guidance 37

·

Ask your doctor to draw pictures if you think that this would help you understand.

·

Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.

·

Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.

·

After leaving the doctor's office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.

By following these steps, you will enhance the relationship you will have with your physician.

Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:19 ·

Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html

·

Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html

·

Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html

You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.

19

38 Endometriosis

Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Contraception: The prevention of conception or impregnation. [EU] Cystitis: Inflammation of the bladder, causing pain and a burning feeling in the pelvis or urethra. [NIH] Eclampsia: Convulsions and coma occurring in a pregnant or puerperal woman, associated with preeclampsia, i.e., with hypertension, edema, and/or proteinuria. [EU] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Hirsutism: Abnormal hairiness, especially an adult male pattern of hair distribution in women. [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] Interstitial: A disorder that causes the bladder wall to become swollen and irritated, leading to scarring and stiffening of the bladder, decreased bladder capacity, and, in rare cases, ulcers in the bladder lining. IC is also known as painful bladder syndrome. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [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] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] 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]

Seeking Guidance 39

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]

Clinical Trials 41

CHAPTER 3. CLINICAL TRIALS AND ENDOMETRIOSIS Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning endometriosis.

What Is a Clinical Trial?20 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for endometriosis is to try it on patients in a clinical trial.

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

20

42 Endometriosis

What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on endometriosis.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for endometriosis compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment. How Is a Clinical Trial Conducted?

Various organizations support clinical trials at medical centers, hospitals, universities, and doctors' offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on endometriosis carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on endometriosis. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.”

Clinical Trials 43

This treatment, like a placebo, has no effect on endometriosis and does not harm patients. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how endometriosis develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for endometriosis. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial's investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo

44 Endometriosis

surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Endometriosis The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to endometriosis.21 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·

The Safety and Effectiveness of Surgery with or without Raloxifene for the Treatment of Pelvic Pain Caused by Endometriosis Condition(s): Endometriosis; Pelvic Pain Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Many women with lower abdominal pain have endometriosis. Endometriosis is a condition in which the lining of the uterus (endometrium) is found outside of the uterus. The diagnosis of endometriosis is usually made at surgery. The treatment of endometriosis includes medical and surgical approaches alone or in combination. The hormone estrogen stimulates the growth of the endometrium and may also stimulate the growth of endometriosis. Medical therapies that act to decrease the level of estrogen can reduce the amount of endometriosis and pain. When therapies are discontinued, symptoms often return. In

21

These are listed at www.ClinicalTrials.gov.

Clinical Trials 45

addition, medical treatment for endometriosis is expensive and is often associated with weak bones (osteoporosis) and hot flashes as a result of low levels of estrogen. Surgical treatment is removal or destruction of the endometriosis tissue. Studies show the pain from endometriosis is relieved longer with tissue removal than with destruction. This study was developed to see if surgery followed by daily doses of Raloxifene (Evista) is effective in reducing pain, for a longer time than surgery in combination with a placebo (inactive "sugar pill") treatment. Raloxifene acts like estrogens in some tissues and not like estrogens in others. Postmenopausal women receiving Raloxifene for the prevention of osteoporosis had an increase in bone density and an improvement of their blood lipids (fat content in the blood). However, unlike estrogen, Raloxifene does not promote the growth of breast tissue or the uterus. If Raloxifene blocks estrogen action in the lining of the uterus (endometrium) of reproductive age women, as it does in postmenopausal women, it may also limit the growth of endometriosis and prevent the return of pain. Phase(s): Phase II Study Type: Interventional Contact(s): Maryland; National Institute of Child Health and Human Development (NICHD), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222 [email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00001848 ·

Endometriosis : Traditional Medicine vs Hormone Therapy Condition(s): Endometriosis-related pelvic pain Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: This 12-week study will determine whether traditional Chinese medicine (acupuncture and Chinese herbs) is as effective as hormone therapy for alleviating endometriosis-related pelvic pain. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00034047

46 Endometriosis

Benefits and Risks22 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·

A new treatment could be more effective than the current treatment for endometriosis. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

·

If the treatment is effective, then it may improve health or prevent diseases or disorders.

·

Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

·

People who take part in trials contribute to scientific discoveries that may help other people with endometriosis. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent

Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial's risks and benefits, the researcher’s expectations of you, and your rights as a patient.

What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you

This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f2 91. 22

Clinical Trials 47

receive may cause side effects that are serious enough to require medical attention.

How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital's Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent. What Are a Patient's Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·

Information on all known risks and benefits of the treatments in the study.

·

Know how the researchers plan to carry out the study, for how long, and where.

·

Know what is expected of you.

·

Know any costs involved for you or your insurance provider.

·

Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.

·

Talk openly with doctors and ask any questions.

After you join a clinical trial, you have the right to: ·

Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.

·

Receive any new information about the new treatment.

·

Continue to ask questions and get answers.

48 Endometriosis

·

Maintain your privacy. Your name will not appear in any reports based on the study.

·

Know whether you participated in the treatment group or the control group (once the study has been completed).

What about Costs? In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don't have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care. What Questions Should You Ask before Joining a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·

What is the purpose of the clinical trial?

·

What are the standard treatments for endometriosis? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?

·

What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?

·

How long will the treatment last? How often will I have to come back for follow-up exams?

·

What are the treatment's possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?

·

Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?

·

How will my health be monitored?

·

Where will I need to go for the clinical trial? How will I get there?

·

How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?

Clinical Trials 49

·

Will I be able to see my own doctor? Who will be in charge of my care?

·

Will taking part in the study affect my daily life? Do I have time to participate?

·

How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with 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 their Web site (www.clinicaltrials.gov) and search by “endometriosis” (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

General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be

50 Endometriosis

available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

A Guide to Patient Recruitment : Today's Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

·

A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

·

The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

·

The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

·

Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

·

Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

·

Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the

Clinical Trials 51

cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [NIH] Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU]

53

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on endometriosis. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on endometriosis. In Part II, as in Part I, our objective is not to interpret the latest advances on endometriosis or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with endometriosis is suggested.

Studies 55

CHAPTER 4. STUDIES ON ENDOMETRIOSIS Overview Every year, academic studies are published on endometriosis or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on endometriosis. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on endometriosis and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and endometriosis, 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

56 Endometriosis

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 in “endometriosis” (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 a sample of what you can expect from this type of search: ·

Imagine This!: Infinite Uses of Guided Imagery in Women's Health Source: Journal of Holistic Nursing. 17(4): 317-330. December 1999. Summary: This journal article examines the range of applications for guided imagery in women's health. First, it presents background information about the history of imagery, definitions, theoretical foundations, and guided imagery techniques. Then, it reviews research supporting the effectiveness of imagery in various applications such as reducing labor pain, promoting successful lactation, decreasing postpartum depression, and decreasing stress during cancer treatment. Next, it describes an approach to introducing the techniques of guided imagery during routine office procedures such as the pelvic examination, so women will be prepared for crisis situations such as the birth of a child or the diagnosis and treatment of cancer. Finally, it suggests additional applications for guided imagery in women's health care, including other stressful office procedures, endometriosis, premenstrual syndrome, chemotherapy, high risk pregnancy, labor, menopause, urinary incontinence, and chronic illness. The article has 2 tables and 34 references.

·

Gynecology for the Gastroenterologist: The Woman in Her Forties and Beyond Source: Practical Gastroenterology. 20(5): 29-30, 32, 34-36. May 1996. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. EMail: [email protected]. Summary: This article, one in a series on gastrointestinal (GI) diseases of the elderly, considers gynecology for the gastroenterologist. The authors review a number of gynecologic conditions that may produce signs or symptoms suggesting GI disease. Indeed, they stress that distinguishing GI disease from gynecologic pathology may be difficult. A thorough

Studies 57

understanding of pelvic anatomy, a careful history, and strong clinical suspicion will clarify the nature of the complaints. If doubt persists, expert consultation and a multidisciplinary approach are recommended. Benign conditions discussed include disorders of pelvic support, leiomyomata (uterine fibroids), endometriosis, and infections. Malignant conditions include ovarian cancer and uterine or cervical cancer. The article concludes with a discussion of anal incontinence and rectovaginal fistulas. 3 references. (AA-M). ·

Miscellaneous Colorectal Surgical Conditions Source: Current Opinion in Gastroenterology. 7(1): 36-41. February 1991. Summary: This review article covers the past year's literature on colorectal surgical conditions, including neoplastic conditions, ischemic colitis, and endometriosis of the colon and rectum. Also reviewed are various functional diseases, radiation injury, rectal hemorrhage, colorectal trauma, and infectious colorectal diseases. Reports on gastrocolic fistulas, collagenous colitis, and hemophilia are briefly considered. (AA).

·

How do Patients with Interstitial Cystitis Present? Source: Journal of Urology. 166(6): 2118-2120. December 2001. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: The typical patient with interstitial cystitis has symptoms for 4 to 7 years before the correct diagnosis is made. Because patients do not typically present with a full constellation of symptoms, it is worthwhile to understand how the earliest symptoms present. This article reports on a study undertaken to determine how interstitial cystitis (IC) progresses from initial symptoms to diagnosis. The authors retrospectively analyzed the records of 45 patients to determine the dates of symptom onset and diagnosis, and sequence of urgency or frequency, nocturia (urinating at night), and pain. The authors also documented alternate and previous diagnoses, and previous surgical treatments. Of the patients, 89 percent presented with only 1 symptom. Median time from the initial symptom to all symptoms was 2 years (mean 5.5 years). The most common previous diagnoses were urinary infection in 19 cases, a gynecologic diagnosis in 14, and urethral diagnoses in 6. A previous urinary infection was documented in only 1 of 19 patients, while 11 had undergone hysterectomy and 5 diagnosed with endometriosis had no pathological documentation available. The authors note that clinicians may fail to

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appreciate the symptoms of early interstitial cystitis, which leads to delayed diagnosis until the patient is more symptomatic. The authors stress that IC should be considered when laboratory documentation for alternate diagnoses is lacking or when patients fail to respond to therapy for alternate diagnoses. 1 table. 17 references. ·

Chronic Pelvic Pain Source: American Family Physician. 54(7): 2237. November 15, 1996. Summary: This brief patient education fact sheet provides information about chronic pelvic pain, defined as pelvic pain that has lasted for at least 6 months. Four sections cover the possible causes of chronic pelvic pain, including endometriosis, irritable bowel syndrome, urethritis, or sexual abuse; diagnostic issues, including the patient's medical history, activities that seem to contribute to or lessen the pain, and diagnostic tests used; and treatment options for chronic pelvic pain, including drug therapy to stop ovulation, use of nonsteroidal anti-inflammatory pain relievers, relaxation exercises, biofeedback, physical therapy, abdominal trigger point injections, and antibiotics. The fact sheet is designed to be photocopied and distributed to patients.

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Rate of Hospitalization for Gynecologic Disorders Among Reproductive-Age Women in the United States Source: Obstetrics and Gynecology. 86(5): 764-769, November 1995. Summary: Researchers analyzed reproductive tract disorders that resulted in hospitalization of reproductive-age women in the United States. The researchers used data from the National Hospital Discharge Survey for 1988, 1989, and 1990 to study women 15 to 44 years old who had any gynecologic diagnoses noted in their discharge summaries. Data analysis indicated that based on average annual discharge rates per 10,000 women, the five most frequently diagnosed conditions were (1) pelvic inflammatory disease (PID), (2) benign cysts of the ovary, (3) endometriosis, (4) menstrual disorders, and (5) uterine leiomyomas. Results also showed that (1) the highest rates of PID were for women 25 to 39 years old and for minority women, (2) the highest rates of uterine leiomyomas were for women 40 to 44 years old and for minority women, (3) the highest rates of endometriosis were for white women 40 to 44 years old, (4) racial differences existed among all ages in the uterine leiomyoma and endometriosis groups, and (5) average annual rates of benign cysts and menstrual disorders increased with age. The researchers concluded that these findings (1) confirmed the importance of PID as a common cause of hospitalization among reproductive-age women; (2) identified additional gynecologic conditions as causes for hospitalization;

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and (3) found significant age and racial differences among women with discharge diagnoses of PID, uterine leiomyomas, and endometriosis. 7 tables, 6 references. ·

Bladder Endometriosis: Conservative Management Source: Journal of Urology. 163(6): 1814-1817. June 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: This article reports on a study undertaken to evaluate the characteristics of women with bladder endometriosis who are successfully treated with hormonal therapy. Endometriosis is the deposition of endometrial glands and uterine tissue outside the uterine cavity; in approximately 1 to 2 percent the urinary tract (notably the bladder) is a site for endometrial implantation. The records of 14 patients (mean age of 48.6 years, range 26 to 71 years) diagnosed with bladder endometriosis were reviewed for presenting complaints, findings and response to therapy. The most frequent presenting complaints were urgency (78 percent), frequency (71 percent), suprapubic pain (43 percent), urge incontinence (21 percent), and dyspareunia (painful intercourse, in 21 percent). Of the patients, 86 percent did not have a history of recurrent urinary tract infections, 6 (42 percent) had a history of endometriosis, including 3 who were previously treated with hysterectomy or oophorectomy (removal of the uterus or ovaries), and 8 (57 percent) were on some form of therapy for estrogen deficiency. In all patients, endometrial implants were identified on cystoscopic examination. Of the patients, 13 were treated either with low dose oral contraceptives, decrease or elimination of the estrogen component of the present regimen, or addition of progesterone to therapy; and 12 (92 percent) reported sustained improvement of symptoms at a mean of 18.6 months (range 8 to 24 months). The authors conclude that in more than 70 percent of cases the presenting symptoms of bladder endometriosis are identical to those of interstitial cystitis. Therefore, endometriosis should always be considered in the patient referred for frequency, urgency, and pain with no documented infection. Hormonal therapy is reasonable and effective management for bladder endometriosis. This option preserves fertility, making it especially attractive to younger women. 2 figures. 1 table. 25 references.

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Federally-Funded Research on Endometriosis The U.S. Government supports a variety of research studies relating to endometriosis and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.23 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. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to endometriosis and related conditions. 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 endometriosis and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for endometriosis: ·

Project Title: Antiprogestins in Endometrium Principal Investigator & Institution: Wiehle, Ronald D.; Zonagen, Inc. 2408 Timberloch Pl, B-4 the Woodlands, Tx 77380 Timing: Fiscal Year 2000; Project Start 5-JUL-2000; Project End 4-JAN2001 Summary: In May 1999, a Licensing Agreement between Zonagen, Inc., and the NICHD was finalized to develop new 19-substitutednorprogestins. New antiprogestins (APs) discovered by NICHD and realized as drugs through this SBIR, would bring the results of government-sponsored science into the public domain. We expect that the new generation of compounds will be used for a number of indications where the etiology is dominated by progesterone. Tissues of the reproductive system such as pituitary, breast, myometrium, cervix, and endometrium remain obvious target organs for treatment with APs. Other indications could include oral contraception, postcoital contraception, labor induction, cervical ripening, hormone replacement

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).

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therapy and treatment of breast cancer. The following document outlines experiments to be performed under a SBIR that would clarify the properties of these new APs and enhance their utility for the treatment of endometriosis. It is the intention of Phase I of this proposed SBIR program to determine effects on the eutopic endometrium of cynomolgus monkeys (Macaca fascicularis). We do not believe the antiprogestins could affect ectopic lesion (endometriosis) if there was no effect on eutopic endometrium. We intend to expand this program in Phase II to determine whether the same compound will reduce the size of endometriosis-like lesions in the same species. This animal model has been shown to respond to both GnRH agonists and to RU 486 with a decrease in lesion size. The use of GnRH agonists in women for the amelioration of endometriosis, although far from ideal, is one of the few medical therapies currently available. The primary outcome parameters will be alterations in the growth of eutopic/ectopic endometrium and effects on serum hormones with our lead antiprogestin compound. The secondary outcome parameter will be the effects on markers of endometriosis in peritoneal fluid. PROPOSED COMMERCIAL APPLICATIONS: Our preliminary evidence indicates that one or more of this new class of antiprogestins may be the ideal drug for treatment of endometriosis and uterine fibroids. Such compounds could fill Zonagen's developmental pipeline with drugs for those diseases and, potentially, other indications. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Chemokine Regulation in Models of Endometriosis Principal Investigator & Institution: Taylor, Robert N.; Vanderbilt University Nashville, Tn 37240 Timing: Fiscal Year 2000 Summary: Endometriosis is a common human gynecologic disorder associated with dysmenorrhea, pelvic pain and reduced fertility. Prevalence estimates range from 2-50%, although most scholars of endometriosis believe that it occurs in approximately 10% of reproductive aged American women. The annual United States health costs attributable to endometriosis exceed $1 billion. Recent studies suggest that endometriosis implants activate local peritoneal inflammatory responses that mediate the clinical symptoms. We hypothesize that the recruitment and subsequent accumulation of activated macrophages in the peritoneal cavity was an early and requisite step in the establishment of endometriosis implants and identified elevated concentrations of inflammatory and angiogenic cytokines (RANTES, IL-6, IL-8, VEGF) in peritoneal fluid of women with

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endometriosis. We propose to investigate the regulation of synthesis and secretion of one representative chemokine, RANTES, a potent chemoattractant for monocytes and T cells. We demonstrated that RANTES is localized in the stromal compartment of normal endometrium and endometriosis implants and that both mRNA and protein are expressed in endometrial stromal but not epithelial cells in vitro. In Specific Aim #1 we will use highly purified (>95%) primary stromal cell cultures to compare RANTES production in eutopic and ectopic cells from normal subjects, women with endometriosis and women with unexplained infertility. Our preliminary data indicate that RANTES protein secretion differs in the former two conditions. In Specific Aim #2, we will study the ability the natural ovarian steroid hormones (estradiol, progesterone), antagonists (tamoxifen, RU486, danazol) and other cytokines (TNF-alpha), IL-1alpha and beta, interferongamma) to modulate RANTES expression in vitro at the mRNA and protein levels. An expression vector containing 477 base pairs of the human RANTES gene promoter cloned upstream of a luciferase reporter will be used to map the transcriptional regulatory motifs in transiently transfected endometrial and endometriosis stromal cells. Specific Aim #3 will be executed in collaboration with Dr. Osteen using his in vivo model of human endometrium transplanted into the nude mouse peritoneal cavity. Hormones and cytokines that up- and down-regulate immunoreactive RANTES in vitro will be administered to mice bearing human endometrial implants to determine if these compounds regulate human RANTES in intact tissues in vivo. Cognate anti-hormones or cytokine neutralizing antibodies will be administered to confirm that the RANTES modulating effects are specific. It is likely that RANTES and other chemokines play early, requisite play early, requisite roles in the inflammatory process that accompanies this syndrome. These molecules should provide ideal targets for the future development of novel therapeutic antagonists for the medical treatment of endometriosis. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Cooperative Multicenter Reproductive Medicine Network Principal Investigator & Institution: Carr, Bruce R.; Dir, Div of Reproductive Endocrinology; Obstetrics and Gynecology; University of Texas Sw Med Ctr/Dallas Southwestern Medical Ctr/Dallas Dallas, Tx 75390 Timing: Fiscal Year 2000; Project Start 0-JUN-2000; Project End 1-MAR2005 Summary: This research proposal describes the qualifications and experience of the Division of Reproductive Endocrinology faculty and

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research team at the University of Texas Southwestern Medical Center at Dallas, the facilities, and patient population available to them for carrying out clinical protocols to be designed by the NICHD Reproductive Medicine Unit (RMU) Network. The UT Southwestern Division of Reproductive Endocrinology includes 6 clinicians, 4 of whom are board certified in Reproductive Endocrinology. Within the division is the Women's Research Center which includes 3 research nurses led by a research nurse coordinator with 20 years experience in protocol development and implementation are available for participation in RMU network protocols. This research team has successfully completed an extensive number of randomized trials, some of which were supported by NIH grant support as well as multi-center randomized trials supported by pharmaceutical companies. These investigations included infertility, andrology, endometriosis, uterine leiomyomata, androgen excess, contraception, and menopause. In order to develop an interdisciplinary approach to the study of reproductive disorders we have brought to the RMU network support of UT Southwestern's NIH General Clinical Research Center, Department of Urology, Psychiatry, Radiology, and Internal Medicine. A concept protocol is included which proposes to investigate pain relief in women suffering from endometriosis. This trial compares the effect of the medical treatment standard with gonadotropin releasing-hormone agonist versus continuous low-dose combined oral contraceptive pills. It is proposed that if continuous oral contraceptive pills are close in efficacy of relieving pain in women with endometriosis as are gonadotropin releasing hormone agonists, this mode of treatment would benefit a significant number of women wishing to save their reproductive organs for later reproduction. In summary, the reproductive endocrinology research team is experienced in multi- center clinical trials and is committed to collaborative participation consistent with the goals of the RMU network. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Endometriosis: Traditional Medicine vs Hormone Therapy Principal Investigator & Institution: Hammerschlag, Richard; Research Director; None; Oregon College of Oriental Medicine 10525 Se Cherry Blossom Dr, Portland, or 97216 Timing: Fiscal Year 2001; Project Start 0-SEP-2001; Project End 1-AUG2003 Summary: Endometriosis is a significant public health problem affecting 10-15% of women of childbearing age, many of whom suffer persistent pelvic pain and infertility. Therapeutic options include surgery and

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hormone therapy that are often temporarily effective but produce unwanted side-effects. The present proposal, based on case series reports of the effectiveness of Traditional Chinese Medicine (TCM: acupuncture and Chinese herbs) for this condition, aims to evaluate whether TCM is as effective as hormone therapy for alleviating endometriosis-related chronic pain. The study is designed as a prospective trial of 66 women, with laparoscopy-diagnosed endometriosis, randomized to TCM or hormone therapy. Women assigned to TCM will be divided into four sub-groups on the basis of the diagnostic categories of endometriosis recognized by TCM. A pre-established acupuncture protocol and herbal formula specific for each sub-group will be followed. This aspect of the research design permits an important feature of the clinical practice of TCM (matching treatment to sub-group diagnosis) to be adopted in a clinical trial. Women assigned to hormone therapy will be treated with the gonadotropin releasing hormone agonist (GnRHa), nafarelin, chosen for this study on the basis of its clinical trial-established efficacy, ease of patient usage via intranasal spray and milder side-effect profile relative to other GnRHa's. Pelvic pain symptoms (patient-scored) and signs (physician-scored) will be assessed at baseline, after 12 weeks of treatment, and at 12- and 24-week post-treatment follow-up. Pelvic examination scores will be determined by a physician blinded to the treatment group assignments. Side effects, including those of pseudomenopause known to result from GnRHa therapy, will be recorded in both groups at 4-week intervals during the 12-week treatment, and at each follow-up time. A further objective is to make a preliminary assessment of whether diagnostic sub-groups of endometriosis recognized by TCM serve as predictors of differential response to hormone therapy. Data obtained from this study, on treatment effectiveness, side effect profiles, recurrence of symptoms, compliance with therapy and drop-out rates, will be used to design a large-scale clinical trial. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Epidemiologic and Biologic Predictors of IVF Success Principal Investigator & Institution: Cramer, Daniel W.; Professor; Brigham and Women's Hospital 75 Francis St Boston, Ma 02115 Timing: Fiscal Year 2000; Project Start 1-AUG-1994; Project End 1-JUL2003 Summary: In 1994, more than 39,000 cycles involving ART were performed in the United States. Given the cost of approximately 8,000 per cycle, studies are needed which could improve the likelihood that ART will result in a successful pregnancy. In 1994, the investigators initiated a

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study of couples seeking ART that involved collect of baseline epidemiologic data, treatment variables, and biological specimens. The preliminary data collected on 927 couples, support published findings and suggest exciting new ones. Only 8 percent of women over the age of 39 years became pregnant other first ART cycle and the number of eggs retrieved during ART decline more rapidly after the age of 33 years. Key exposure examined in men and women included caffeine, alcohol, and tobacco. In women, smoking was the principal exposure that decreased number of eggs retrieved. The decrease occurred in both current and former smokers. In men, caffeine use decreased ART success. This association was not present if the ART cycle involved direct injection of sperm in eggs which suggests that caffeine (or tannins in coffee or tea) could be affecting ART success (or natural fertility) by interfering with sperm-egg penetration. Women with the primary diagnosis of endometriosis had fewer eggs retrieved, whereas diagnosis of hernia or varicocele was linked to decreased sperm concentration. Use of a gonadotropin releasing hormone agonist in a long or down regulation fashion prior to ovarian stimulation was associated with markedly better ART success and egg retrieval than used in the short or flare regimen. The joint effect of these female, male and treatment variables will be examined in discrete failure application, the investigators propose continuation of the study, anticipating that in increase in the sample size of 3,000 would allow them to examine important associations in diagnostic or treatment subgroups, as well as expand the power to study other intriguing preliminary findings. These include an association between endometriosis and a polymorphic variant, known as N314D, a key gene in galactose metabolism; evidence that acetaminophen use may lower follicle stimulating hormone levels; and evidence that alcohol use in men adversely affect sperm morphology. The investigators' ability to study male factor infertility will be enhanced by collection of a blood specimen from men and retrieval of residual semen after ART. The continued goal is to assess the effect of epidemiologic and biologic markers and treatment-related variables of ART success and to address broader aspects of reproductive physiology by examining gamete number and quality as outcomes. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Female Reproductive Outcomes and TCDD Exposure Principal Investigator & Institution: Eskenazi, Brenda; Professor; None; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2000; Project Start 1-JAN-1996; Project End 1-DEC2001

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Summary: (Adapted from applicant's abstract): The proposed project is a continuation of the Seveso Women's Health Study (SWHS), ongoing since 1996 (R01ES07171). The original purpose of the SWHS was to investigate the relationship of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and endometriosis in a nested case-control study embedded in a cohort of women exposed to extremely high levels of dioxin as a result of a chemical plant explosion in 1976 in Seveso, Italy. In order to identify cases and controls, the cohort of women aged 0 to 40 years at the time of accident, and who lived in Zone A (n=234) or Zone B (n=1,039) were interviewed extensively about their reproductive and pregnancy histories. Assessments included a blood draw, a pelvic examination, and transvaginal ultrasound. Participants were also asked to complete a menstrual diary. A unique strength of the study is that individual body burden TCDD levels can be measured in sera collected soon after the accident. More than 95% of the women were located twenty years after the accident and roughly 80% of the members of the cohort have participated. The current plan is to analyze the data collected in the SWHS to examine reproductive endpoints other than endometriosis, and to analyze the sera for TCDD necessary to examine these endpoints. In particular, the project will investigate the relationship of TCDD levels in sera with menstrual cycle characteristics (e.g. cycle length and flow), age of menarche, fetal loss, birthweight, clinical infertility, time to conception, and age at menopause. These endpoints were chosen, based on extensive rodent and rhesus monkey data, indicating that exposed animals experience higher rates of fetal mortality and resorption, smaller litter size, lower birthweight, lowered fecundity rates and, more recently, menstrual irregularities, reduced ovulation, delayed onset of puberty, and early onset of menopause. It is because of these animal data that the U.S. Environmental Protection Agency (EPA) is reassessing the allowable exposure levels of TCDD, which is ubiquitous in industrialized areas. There are also concerns that the non-cancer effects of this chemical may be the even more urgent threat to humans. The proposed investigation will be the first comprehensive reproductive health study conducted in human populations exposed to TCDD. If the findings in this highly exposed cohort with well-characterized individual exposure data do not confirm the animal findings, there can be less concern about human health effects, thereby having important policy implications for the regulation of TCDD. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Gene Expression in Endometriosis Principal Investigator & Institution: Warrington, Janet A.; Director; Affymetrix 3380 Central Expressway Santa Clara, Ca 95051

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Timing: Fiscal Year 2000; Project Start 1-SEP-2000; Project End 1-AUG2002 Summary: Genes drive the biological functions that characterize and distinguish tissue types. The levels and timing of gene expression govern cellular development, differentiation, function and physiology. In an effort to better understand the etiology of endometriosis, a disease affecting 10% of all women of child bearing age, we are studying the genes expressed in unaffected and endometriosis-affected women. Normal endometrium consists of proliferative, secretory and glandular epithelia, and stromal and vascular elements. The epithelial cells synchronously proliferate, then differentiate and disintegrate at 28 day intervals. Proliferation is the dominant activity during days 4-13 of the menstrual cycle. During the proliferative phase the endometrium thickens and is characterized by mitoses within the glandular epithelium and pseudostratification of nuclei. After ovulation occurs the secretory phase begins (days 14-28) characterized first by basal vacuolation and secretion in glandular epithelium and later stromal edema and predecidual reaction. Until recently it has not been possible to simultaneously and quantitatively measure the expression levels of the thousands of human genes that characterize endometrial tissue and that distinguish normally functioning tissue from disease affected tissue. Using GeneChip(R) probe array (chip) technology we are able to simultaneously measure the relative concentrations of thousands of mRNAs in a single experiment. In Phase 1 using chips containing probes for approximately 7200 human genes we will: 1) Identify genes expressed in normal endometrium during the proliferative phase of the human menstrual cycle. 2) Identify stage I-IV endometriosis associated gene expression differences in proliferative endometrium. 3) Identify expression differences associated with endometriosis stage II, III, and IV proliferative endometrium, peritoneal lesions and ovarian endometriomas using matched samples. Only recently, with the development of the oligonucleotide array technology for gene expression monitoring, has a project of this scope become feasible. PROPOSED COMMERCIAL APPLICATIONS: NONE AVAILABLE Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Macrophages, Oxidation, and Endometriosis Principal Investigator & Institution: Parthasarathy, Sampath; MccordCross Professor; Gynecology and Obstetrics; Emory University 1380 S Oxford Rd Atlanta, Ga 30322 Timing: Fiscal Year 2000; Project Start 1-DEC-1998; Project End 0-NOV2003

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Summary: Endometriosis is a common disorder that inflicts pain and suffering and is often the cause of infertility in women. There is a consensus that retrograde menstruation may account for the presence of endometrial cells in the peritoneal cavity. However, little is known regarding the etiology of the disease or why the disease occurs only in certain women despite the common occurrence of retrograde menstruation in most women. This program has five projects that propose novel hypotheses regarding the events that may lead to the establishment of endometriosis lesions. These ideas are extended as innovative specific aims that would be addressed using biochemical, immunological, and molecular biological techniques. Project 1 proposes that fundamental alterations in endometrial cell and macrophage scavenger functions to the peritoneal cavity of women with endometriosis are responsible for the survival and growth of the ectopic endometrium. Project 2 proposes an active mechanism by which intrinsic components of the peritoneal fluid may exacerbate an oxidative milieu that is conducive to the recruitment of mononuclear cells and the growth of the endometrial cells. This project suggests the presence of mildly oxidized lipoprotein components in the peritoneal fluid. Project 3 proposes that CSF-1 may play both autocrine and paracrine roles in promoting not only the growth of the endometrial cells but also in protecting macrophages from apoptotic death thereby increasing their survival in the peritoneal cavity. Project 4 will study the pharmacological regulation of macrophage scavenger function, production of cytokines, and endometrial cell growth. The effects of antioxidants, hormones, and retinoids on these functions will be determined. Project 5, the mini clinical project will establish the presence and differences in the markers of oxidative stress in the plasma of endometriosis subjects and controls. This project will also evaluate the efficacy of antioxidants to alter the levels of these markers. The program is supported by an administrative core and a tissue/cell culture core. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Mechanisms of Estrogen Biosynthesis in Endometriosis Principal Investigator & Institution: Bulun, Serdar E.; Associate Professor; Obstetrics and Gynecology; University of Illinois at Chicago at Chicago Chicago, Il 60612 Timing: Fiscal Year 2000; Project Start 5-JUL-1999; Project End 0-JUN2003 Summary: The long range goal is to characterize the molecular and cellular mechanisms that are responsible for local biosynthesis of estrogen in endometriosis. The findings of our preliminary studies

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include (i) significant levels of aromatase P450 (P450arom) mRNA, protein and activity in stromal cells of endometriotic tissue but not in eutopic endometrium; (ii) P450arom gene expression directed by promoter II and aromatase activity in endometriotic stromal cells are induced strikingly by PGE2 via EP2 receptors or by cAMP analogs; (iii) differential binding of stimulatory (SF-1) and inhibitory (COUP-TFs) transcription factors upstream of promoter II account for the difference in aromatase expression in endometriotic and eutopic endometrial stromal cells; (iv) an unusually severe case of recurrent postmenopausal endometriosis resolved after treatment with an aromatase inhibitor. Thus, molecular aberrations in endometriotic tissue in contrast to eutopic endometrium give rise to increased local concentration of estrogen that promotes the growth and development of pelvic endometriosis. To determine the molecular basis for estrogen and PGE2 formation and estrogen action in endometriosis, we propose the following studies: Initially, we will characterize regulatory elements and differential binding of nuclear proteins to these sequences upstream of P450arom promoter II in endometriotic and eutopic endometrial stromal cells using deletion mutations of this regulatory region, site-directed mutagenesis and electrophoretic mobility shift assays. Transcription factors that bind to these regulatory sequences will be defined and their roles will be characterized in the regulation of aromatase expression in endometriotic stromal cells. This will be accomplished by screening expression libraries using DNA binding sites as probes and determining the effects of these factors on promoter II activity and aromatase expression. We will define mechanisms whereby PGE2 action and production are regulated in endometriotic tissue. The regulation of expression of EP2 receptors and COX-2 will be evaluated in both endometriotic tissue and eutopic endometrium. Finally, the in vivo significance of local estrogen biosynthesis and estrogen (and progesterone) action will be determined in a mouse model of endometriosis. The rate of formation and the site of surgically transplanted endometriotic lesions will be quantified in transgenic mice with disrupted genes of P450arom, estrogen receptoralpha and progesterone receptor. The role of aromatase inhibitors in the treatment of endometriosis (in comparison with conventional treatments) will also be characterized in this model. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Mentoring in Research on Endometriosis Principal Investigator & Institution: Murphy, Ana A.; Associate Professor; Gynecology and Obstetrics; Emory University 1380 S Oxford Rd Atlanta, Ga 30322

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Timing: Fiscal Year 2001; Project Start 0-MAY-2001; Project End 0-APR2006 Summary: Dr. Ana A. Murphy is a professor in Gynecology and Obstetrics and Director of the Division of Reproductive Endocrinology and Infertility at Emory University School of Medicine. Dr. Murphy initiated, designed and implemented the Reproductive Endocrinology and Infertility Fellowship at Emory University that is currently approved by the American board of Obstetrics and Gynecology, Inc. Dr. Murphy became first Director in1997 and accepted her first fellow in 1998. The goal is to help the mentee became published and recognized and to achieve independent research support. The successful mentor must provide instruction on development of hypotheses that are original and worthwhile, the experimental tools to test the hypotheses, help the mentee identify a worthwhile field of investigation, and to remain focused. The line of research used to train the mentees will be the study of the pathophysiology of endometriosis and leiomyoma. She has demonstrated continued commitment to mentoring and training in patient-orientated research. The main focus of Dr. Murphy's research has been endometriosis, its pathophysiology as well as its surgical/medical treatment. Our hypothesis focuses on oxidative stress as the inciting agent that results in peritoneal fluid changes and activation of macrophages that mediate the infertility and pain seen in these patients. In the first year we have accumulated significant basic and clinical data in support of our hypothesis that a significant oxidative stress occurs in women with endometriosis. Recruitment for Aim 1 is complete and the data is being analyzed. Recruitment is underway for Aims 2,3. We have used RU486 as a biologic probe to study the in vivo regulation of endometrium and leiomyoma seen with low dose, in vivo. Preliminary data, has shown that leiomyoma and myometrium immunostain for glycodelin. In turn, glycodelin has been shown to decrease natural killer cell (NK cell) activity which is also decreased in women with leiomyoma. We hypothesize that RU486 has direct antiproliferative effect mediated by its antioxidant activity and an indirect immunomodulatory effect by decreasing glycodelin levels. Glycodelin may increase NK cell activity thus decreasing tumor growth. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Metalloproteinase/Disintegrin Function in Endometrium Principal Investigator & Institution: Hoffman, Loren H.; Vanderbilt University Nashville, Tn 37240 Timing: Fiscal Year 2000

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Summary: Endometrial epithelial cells undergo dramatic remodeling during the peri-implantation period. Such changes include alterations in cell-cell adhesions, in cell-matrix interactions, modified apical-basal polarity, and, in some species, cell-cell fusion. We have documented the expression of an mRNA encoding a transmembrane protein rbMDC9, a member of the ADAMs gene family with potential cell binding, cellmatrix interactions and fusogenic properties. RbMDC9 expression is upregulated in rabbit endometrium during hormonal preparation for implantation, and expression is further augmented by blastocysts. Preliminary evidence suggests a similar up-regulation in mouse and human uteri. We will test the hypothesis that MDC9 in rabbits serve as an integrin-binding adhesion molecule between epithelial cells and, in doing so, also functions in the redistribution of junction and cytoskeletal proteins. Furthermore, we hypothesize that ADAMs family proteins participate in cell-matrix interactions and in the fusions between adjacent epithelial cells and between trophoblast and epithelial cells during implantation, and in the ectopic attachment and invasion of endometrial tissue during endometriosis. Aim of the project will be 1) to determine if domain specific-targeting and post-translational processing regulate the function of epithelial cell rbMDC9 in peri-implantation-stage endometrium, 2) to determine if rbMDC9 ligand interactions are required for uterine epithelial junction or cytoskeletal protein modifications during implantation, 3) to define the function of rbMDC9 in implantation-specific cell-cell adhesion and/or fusion processes, and determine whether its expression of processing are regulated by blastocysts in vitro, and 4) to determine if MDC9 is expressed in a cyclespecific pattern in endometrium of women with and without endometriosis, and to analyze its regulation and potential roles in the adhesion and invasion of ectopic endometrium in an experimental model of endometriosis. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Molecular Pathogenesis of Ovarian Endometrioid Adenocarc Principal Investigator & Institution: Cho, Kathleen R.; Associate Professor; Pathology; University of Michigan at Ann Arbor Ann Arbor, Mi 48109 Timing: Fiscal Year 2002; Project Start 1-FEB-2002; Project End 1-JAN2007 Summary: Ovarian carcinoma (OvCa) is a major cause of cancerassociated morbidity and mortality for women, yet much remains to be learned about its pathogenesis. Like other cancers, OvCas are thought to

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arise through a multi-step process in which repeated cycles of somatic mutation and clonal selection produce variant progeny with increasingly aggressive growth properties. The genes mutated in cancer frequently encode proteins that function in conserved signaling pathways. Molecular genetic analyses suggest that the different histologic subtypes of OvCa (e.g., serous, clear cell, mucinous, and endometrioid) may represent distinct disease entities and that OvCa precursor lesions may be subtype specific. Hence, a clearer understanding of OvCa pathogenesis might be more readily attained by focusing molecular genetic studies on distinct OvCa types for defects in cell signaling pathways. The ovarian endometrioid adenocarcinomas (OEAs) share a number of molecular genetic features with uterine endometrioid adenocarcinomas, including frequent mutations of the CTNNB1 gene which encodes beta-catenin (beta-cat), a critical component of the highly conserved Wnt signaling pathway. Previous studies suggest that although the Wnt/beta-cat/Tcf pathway may be defective in a substantial percentage of OEAs, it is only rarely altered in other histologic subtypes of OvCa. This application describes studies that are focused on defining the molecular mechanisms by which Wnt pathway defects contribute to the development and behavior of a specific type of OvCa, namely endometrioid adenocarcinomas. Toward this end, four specific aims are proposed: 1) To complete a comprehensive mutational analysis of genes encoding proteins known to regulate the Wnt/betacat/Tcf signaling pathway in a large group of primary OEAs; 2) To characterize expression of candidate downstream genes transcriptionally activated by the beta-cat/Tcf signaling pathway in OEAs with known pathway defects; 3) To examine a spectrum of endometriosis lesions (putative OEA precursors) for defects in beta-cat/Tcf pathway genes, and to determine whether expression of mutant beta-cat results in malignant transformation of immortalized cells derived from endometriosis, and 4) To determine if selected beta-cat/Tcf- activated genes are necessary and/or sufficient for neoplastic transformation by mutant beta-cat in RK3E cells or human cells with relevance to ovarian cancer (immortalized ovarian surface epithelial cells expressing telomerase, or cell lines derived from endometriosis). Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Neural Mechanisms of Gynecological Pain Principal Investigator & Institution: Berkley, Karen J.; Mckenzie Professor; Psychology; Florida State University Tallahassee, Fl 32306 Timing: Fiscal Year 2000; Project Start 4-SEP-1977; Project End 0-JUN2002

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Summary: (adapted from applicants abstract): The long-range goal of the proposed research is to improve understanding of the neural mechanisms of gynecological pain. The studies use behavioral and electrophysiological methods to characterize escape behaviors and CNS activity elicited by pelvic organ stimulation in female rats under various normal and pathological conditions. Specific aims for the next 5 years focus on mechanisms of vaginal hyperalgesia (VAGH) and will test three hypotheses. (1) Reproductive senescence and VAGH: Vaginal sensitivity in women increases after menopause to produce VAGH. This VAGH is thought to be due to the effects of estrogen loss on vaginal tissue. The hypothesis that senescence-VAGH is associated with hypoestrogenicconditions and changes in physical properties of the vagina will be tested in rats by using behavioral methods in awake rats to study how escape responses to vaginal distension and how vaginal tone both changes as the rats age through senescence and following hormonal manipulations. (2) Endometriosis and VAGH: Viable endometrial tissue outside the uterus in women is associated with infertility and pelvic pain, including VAGH. Because estrogen is necessary for ectopic endometrial viability, behavioral methods and hormonal manipulations will be used on a rat model of endometriosis to test the hypothesis that endometriosis-VAGH, in contrast to senescence-VAGH, depends upon estrogen and is independent of vaginal tone. (3) CNS mechanisms: Despite the fact that sensory afferents of the rat female reproductive tract convey highly specific and topographically-organized information to the CNS, many neurons in the spinal cord and thalamus respond convergently to stimulation of pelvic organs and skin, and the responses can change depending on changing CNS control factors. Even more surprisingly, this situation appears also to apply to neurons in the two other ports-of-entry for pelvic information to the CNS, the gracile and solitary nuclei, suggesting that these two portal nuclei warrant inclusion, along with the spinal cord, in studies of CNS pain mechanisms. Accordingly, electrophysiological studies will compare how responses to stimulation of pelvic organs and skin by neurons in the gracile and solitary nuclei, as well as in the spinal cord, change as a consequence of estrous state, senescence-VAGH, and endometrious-VAGH. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Progesterone and the Pathophysiology of Endometriosis Principal Investigator & Institution: Osteen, Kevin G.; Professor; Vanderbilt University Nashville, Tn 37240 Timing: Fiscal Year 2000

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Summary: The disease endometriosis is defined as the growth of endometrial glandular epithelium and stroma at and extra-uterine or "ectopic" site. Ectopic implantation of endometrial tissue entering the peritoneal cavity via retrograde menstruation requires an invasive event and the biomolecules necessary for establishment of endometriosis include the matrix metalloproteinases (MMPs). The MMPs are expressed during estrogen associated growth and as component of menstrual breakdown and subsequent repair processes. The MMPs are not normally expressed during the progesterone-dominated secretory phase in vivo and are suppressed by progesterone in vitro. Our laboratory has linked MMP expression by human endometrial tissue to the establishment of experimental endometriosis. In this model, we find that suppressing that suppressing the secretion of MMPs or blocking their action with a natural inhibitor prevents formation of endometriotic-like lesions by human tissues injected into the peritoneal space of ovariectomized nude mice. The association of steroid-mediated MMP expression in the establishment of ectopic lesion in our experimental model appears to link the recognized role of estrogen to promoting the establishment of ectopic lesions in our experimental model appears to link the recognized role of estrogen to promoting the development of endometriosis in women and perhaps explains the protective effect ascribed to progesterone. Although local tissue production of transforming growth factor-beta (TGF-beta) acts in concert with progesterone via stromal epithelial communication to suppress MMPs in the normal endometrium, TGF-beta cannot sustain MMP suppression in the absence of progesterone. We have identified local retinoic acid (RA) synthesis in the endometrium and have found that RA may be necessary for formal suppression of MMP expression in concert with progesterone. In contrast, local production of interleukin1alpha (IL-1alpha) may work in opposition to progesterone to stimulate MMP expression. Clearly, alterations in the normal production of key cytokines, documented in endometriosis tissues, may cause aberrant MMP expression. To address these issues experimentally, our specific aims are 1) to define the progesterone-mediated cytokines relative to aberrant MMP expression in endometriosis tissues, 2) to determine the role that aberrant MMP expression plays in the establishment and progression of endometriotic lesions in an experimental model, 3) to examine the interactive roles progesterone and RA in MMP suppression in normal endometrium and in endometriosis tissues, and 4) to examine the interactive role of progesterone and IL-1 alpha in MMP regulation in normal endometrium and endometriosis tissues. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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·

Project Title: Risk Factors for Endometriosis Principal Investigator & Institution: Hunter, David; Epidemiology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 3-AUG-2001; Project End 1-JUL2003 Summary: (provided by applicant): Endometriosis, the third leading cause of gynecologic hospitalization in the United States, remains one of the most enigmatic gynecologic pathologies. Endometriosis is defined as the presence of endometrial tissue outside of the uterine cavity. These implants respond to the hormonal cues of the menstrual cycle and "bleed" as they would in the uterus. The consequence is the development of adhesions, scarring, and painful inflammation. Signs and symptoms include dysmenorrhea, dyspareunia, infertility, dysuria, and irritable bowel syndrome.The effects of the disease can be physically and mentally debilitating with frequent misdiagnoses and poor treatment options. Its prevalence among U.S. women has been estimated to be approximately 10%, [the] time from onset of symptoms to laparoscopically confirmed diagnosis is estimated to average between 6 and 11 years. To date, the etiology of endometriosis remains unknown and few epidemiologic studies exist. Using data on 2,690 laparoscopically confirmed incident cases of endometriosis collected from the Nurses' Health Study II, an ongoing, prospective cohort study that began in 1989, the applicant proposes a study to assess the following hypotheses: a) Women with menstrual characteristics of younger age at menarche, longer time to menstrual regularity, or shorter menstrual cycle length are at higher risk of endometriosis. b) Women with a low waist-to-hip ratio are a higher risk of endometriosis. c) Women with a higher body mass index at age 18 are at lower risk of endometriosis. d)Women who were born with a greater birthweight are at higher risk of endometriosis. All analyses will control for other known and suggested risk factors for endometriosis such as oral contraceptive use and cigarette smoking. The applicant will have more than 90% power to evaluate the above hypotheses. These analyses will be the first prospective data with adequate power to evaluate this important and understudied cause of morbidity among premenopausal women. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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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. 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 the public.24 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 endometriosis, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “endometriosis” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “endometriosis” (hyperlinks lead to article summaries): ·

Alternative medical treatment for endometriosis. Author(s): Taylor H, Guarnaccia M, Olive D. Source: Semin Reprod Endocrinol. 1997; 15(3): 285-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9383837&dopt=Abstract

Vocabulary Builder Abortion: 1. the premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. premature stoppage of a natural or a pathological process. [EU] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] 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.

24

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Adenocarcinoma: organization. [NIH]

A malignant epithelial tumor with a glandular

Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Anal: Pertaining to the anus. [EU] Antibiotic: A chemical substance produced by a microorganism which has the capacity, in dilute solutions, to inhibit the growth of or to kill other microorganisms. Antibiotics that are sufficiently nontoxic to the host are used as chemotherapeutic agents in the treatment of infectious diseases of man, animals and plants. [EU] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Antidepressant: An agent that stimulates the mood of a depressed patient, including tricyclic antidepressants and monoamine oxidase inhibitors. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antioxidant: One of many widely used synthetic or natural substances added to a product to prevent or delay its deterioration by action of oxygen in the air. Rubber, paints, vegetable oils, and prepared foods commonly contain antioxidants. [EU] Auricular: Pertaining to an auricle or to the ear, and, formerly, to an atrium of the heart. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] 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] Bursitis: Inflammation of a bursa, occasionally accompanied by a calcific deposit in the underlying supraspinatus tendon; the most common site is the subdeltoid bursa. [EU] Campylobacter: A genus of bacteria found in the reproductive organs, intestinal tract, and oral cavity of animals and man. Some species are pathogenic. [NIH] Carcinoma: A malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. [EU] Cervical: Pertaining to the neck, or to the neck of any organ or structure. [EU] Chemotherapy: The treatment of disease by means of chemicals that have a

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specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Colitis: Inflammation of the colon. [EU] Colorectal: Pertaining to or affecting the colon and rectum. [EU] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Dysuria: Painful or difficult urination. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Epithelium: The covering of internal and external surfaces of the body, including the lining of vessels and other small cavities. It consists of cells joined by small amounts of cementing substances. Epithelium is classified into types on the basis of the number of layers deep and the shape of the superficial cells. [EU] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Fistula: An abnormal passage or communication, usually between two internal organs, or leading from an internal organ to the surface of the body; frequently designated according to the organs or parts with which it communicates, as anovaginal, brochocutaneous, hepatopleural, pulmonoperitoneal, rectovaginal, urethrovaginal, and the like. Such passages are frequently created experimentally for the purpose of obtaining body secretions for physiologic study. [EU] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Gluten: The protein of wheat and other grains which gives to the dough its

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tough elastic character. [EU] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hernia: (he protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Incontinence: Loss of bladder or bowel control; the accidental loss of urine or feces. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Macaca: A genus of the subfamily cercopithecinae, family cercopithecidae, consisting of 16 species inhabiting forests of Africa, Asia, and the islands of Borneo, Philippines, and Celebes. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Menarche: The establishment or beginning of the menstrual function. [EU] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH]

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Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] 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] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nocturia: Excessive urination at night. [EU] Oophorectomy: ovariectomy. [EU]

The removal of an ovary or ovaries; called also

Osteoarthritis: Noninflammatory degenerative joint disease occurring chiefly in older persons, characterized by degeneration of the articular cartilage, hypertrophy of bone at the margins, and changes in the synovial membrane. It is accompanied by pain and stiffness, particularly after prolonged activity. [EU] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [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] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Parasitic: Pertaining to, of the nature of, or caused by a parasite. [EU] Pathologic: 1. indicative of or caused by a morbid condition. 2. pertaining to

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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] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] 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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] 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] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Premenstrual: Occurring before menstruation. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] 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] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Rantes: A chemokine that is a chemoattractant for eosinophils, monocytes, and lymphocytes. It is a potent and selective eosinophil chemotaxin that is stored in and released from platelets and activated T-cells. [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]

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Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrograde: 1. moving backward or against the usual direction of flow. 2. degenerating, deteriorating, or catabolic. [EU] Rheumatoid: Resembling rheumatism. [EU] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Somatic: 1. pertaining to or characteristic of the soma or body. 2. pertaining to the body wall in contrast to the viscera. [EU] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Stenosis: Narrowing or stricture of a duct or canal. [EU] 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] Symptomatic: 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. exhibiting the symptoms of a particular disease but having a different cause. 4. directed at the allying of symptoms, as symptomatic treatment. [EU] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer,

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and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Thalamus: Either of two large, ovoid masses, consisting chiefly of grey substance, situated one on each side of and forming part of the lateral wall of the third ventricle. It is divided into two major parts : dorsal and ventral, each of which contains many nuclei. [EU] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Urethritis: Inflammation of the urethra. [NIH] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU]

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CHAPTER 5. PATENTS ON ENDOMETRIOSIS Overview You can learn about innovations relating to endometriosis by reading recent patents and patent applications. 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.25 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 to patients with endometriosis 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 to patients with endometriosis. 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.

25Adapted

from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Patents on Endometriosis By performing a patent search focusing on endometriosis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on endometriosis: ·

Use of cathepsin S in the diagnosis and treatment of endometriosis Inventor(s): Schneider; Patrick (Irvine, CA), Yamamoto; Karen K. (San Clemente, CA), French; Cynthia K. (Irvine, CA) Assignee(s): Reprogen, Inc. (Costa Mesa, CA) Patent Number: 6,387,629 Date filed: March 26, 2001 Abstract: Cathepsin S expression is up-regulated in endometriotic tissue. This invention provides methods of diagnosing endometriosis by detecting up-regulation of a cathepsin S gene product, and methods of treating endometriosis by down-regulating expression of cathepsin S in ectopic or eutopic endometriotic tissue. Excerpt(s): This invention is directed to the field of medical diagnostics and treatment. More particularly, it is directed to methods of diagnosing and treating endometriosis based on the pathologic up-regulation of cathepsin S in endometriotic tissue. ... Endometriosis is a painful disorder that is characterized by the ectopic implantation of functioning endometrial tissue into the abdominal wall and the outer surface of various organs including, most commonly, the lower bowel, ovaries and fallopian tubes. P. Vigano et al. (1991) Fertility and Sterility 56:894. Currently, endometriosis-specific genes have not been identified and the events relating to the development of endometriosis are poorly understood. However, several reports suggest that retrograde menstruation linked with abnormal immune function may play a role in establishing ectopic endometriotic lesions. T. Ishimaru and H. Masuzaki (1991) Am. J. Obstet. Gynecol. 165:210-214. The identification of genes that are differentially expressed in endometriotic lesions compared to

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healthy endometrial tissue would provide markers for diagnosing endometriosis and targets for therapeutic intervention in endometriosis. ... Human endometrial tissue cultured in mice grows and mimics the progression to endometriosis. We have discovered that cathepsin S expression is up-regulated in such tissue. This invention provides methods and materials that take advantage of this fact. More particularly, this invention provides methods of diagnosing endometriosis by detecting up-regulation of cathepsin S in a sample from a patient suspected of having endometriosis. The methods involve detecting increased amounts of cathepsin S mRNA or cathepsin S protein in the sample compared to normal. This invention also provides methods of treating endometriosis by down-regulating the level of cathepsin S activity in ectopic or eutopic endometrial tissue. These methods include decreasing transcription, processing or translation of cathepsin S mRNA, as well as inhibiting biological activity of cathepsin S. Web site: http://www.delphion.com/details?pn=US06387629__ ·

Medicinal composition for treating dysmenorrhea and endometriosis industrial use Inventor(s): Suzuki; Nobutaka (Kanazawa, JP), Kohama; Takafumi (Nanao, JP) Assignee(s): Tradepia Co. Ltd. (Saitama, JP), Horphag Research Limited (St. Peter Port Guernsey, GB) Patent Number: 6,372,266 Date filed: May 19, 2000 Abstract: A medicinal composition for treating dysmenorrhea and endometriosis comprising a plant extract and containing proanthocyanidins as an effective component thereof. The composition is provided and administered in the form of soft capsules, tablets, or a powdery or liquid preparation to be used for treating dysmenorrhea and endometriosis. Excerpt(s): The present invention relates to a medicinal composition for treating dysmenorrhea and endometriosis, and more particularly to a medicinal composition comprising as its effective component a plant extract containing proanthocyanidins. ... Dysmenorrhea is characterized by spasmodic symptoms, such as severe lower abdominal pain, lumbago, headache and nausea, which develop at the onset of and during menstruation and which are not attributable to other gynecological diseases (adnexitis, endometriosis, uterine myoma, adenomyosis of the uterus, etc.). The causes include increased presence of prostaglandins in

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the menstrual fluid and an abrupt increase in the intrauterine pressure caused by the menstrual fluid held in the uterus due to the constriction of os uteri. Dysmenorrhea is treated by oral administration of Voltaren (generic name: dichlofenac sodium) or Sedes (generic name: pyrazolone analgesic, antiinflammatory and antipyretic composition). However, this treatment may temporality alleviate the symptoms but is generally ineffective. ... Endometriosis is a disease of ectopic occurrence, growth of endometrium (in the ovary, oviduct and Douglas' cul-de- sac) and the disease causing inflammation at the site and developing severe menstrual pain and lower abdominal pain at times other than the menstrual period. It is also one of the causes of sterility. Although still remaining to be clarified, a causal relation to dioxin has attracted attention in recent years. The disease is most prevalent in the reproductive ages (between ages of about 18 to about 42). Because of its dependence on follicular hormones (estrogens), the disease becomes gradually aggravated in menstruating women and conversely becomes alleviated and disappears postmenopausally with reduced production of estrogens. Web site: http://www.delphion.com/details?pn=US06372266__ ·

Prevention of endometriosis signs or symptons Inventor(s): Heinrichs; William LeRoy (8 Campbell La., Menlo Park, CA 94025) Assignee(s): none reported Patent Number: 6,265,393 Date filed: August 7, 1998 Abstract: Methods and articles of manufacture are provided for the longterm prevention of clinical symptoms and signs produced by endometriosis. Such methods and articles of manufacture involve the continuous coadministration of low doses of an estrogen agent and a progestin agent to maintain an induced state of oligomenorrhea or amenorrhea in an afflicted woman. Excerpt(s): The present invention relates to the coadministration of an estrogen agent and a progestin agent in low doses for the long-term prevention of endometriosis signs or symptoms. ... Many women, approximately 5-10 percent of those in their reproductive years, are afflicted with endometriosis and suffer progressive, disabling dysmenorrhea and pelvic pain around the time of their menses (Brosens, Endometriosis-A Disease Because it is Characterized by Bleeding, Am. J. Obstet. Gynecol. 176:263-7 (1997)). In addition, pelvic pain unassociated with menses may restrict afflicted women to measured participation in

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athletic and other physical activities, such as dancing and hiking. Through dyspareunia, they suffer not only the pain and often-missed orgasmic fulfillment, but also the doubts of sincerity and the cautious love of their sexual partners, perhaps even marital discord, separation, or infertility. Through relative infertility, they suffer further reductions in self-esteem from the pangs of guilt and failure engendered by struggles to conceive, suffering that adds personal, physical, and economic cost. Often, coital events or pelvic exams produce pelvic aching for hours or even days thereafter. ... The peri-menstrual pain experienced by afflicted women may be relieved in part by non-steroidal anti-inflanmmatory drugs (NSAID's). But those not benefitted adequately require ovulationsuppressing treatments, or finally laparoscopy, where the majority are discovered to have the findings typical of endometriosis, i.e., ectopic `implants` of endometrial tissue on the peritoneal surface of the pelvis or extra-genital areas. Others with unexplained infertility have similar findings. Web site: http://www.delphion.com/details?pn=US06265393__ ·

Anti-VEGF agents in the treatment of endometriosis Inventor(s): Charnock-Jones; David Stephen (Cambridge, GB), McLaren; John (Cambridge, GB), Prentice; Andrew (Milton, GB), Smith; Stephen Kevin (Cambridge, GB) Assignee(s): Metris Therapeutics Limited (London, GB) Patent Number: 6,121,230 Date filed: January 9, 1997 Abstract: Disclosed are: a composition for use in the treatment of endometriosis, comprising an agent capable of interfering with the production and/or activity of VEGF, and a physiologically acceptable carrier substance; a composition for the treatment of endometriosis comprising an agent which inhibits the activation and/or recruitment of peritoneal macrophages, and a physiologically acceptable carrier; and method of making the compositions and their use in the treatment of endometriosis. Excerpt(s): This invention relates to the discovery of expression of vascular endothelial growth factor (VEGF) and its associated receptors (Flt and KDR) in certain tissues and as a consequence demonstrates the potential for VEGF antagonists in the treatment/prevention of endometriosis and related conditions. ... Endometriosis is defined as the presence of endometrial cells outside of the uterine cavity. The disease affects women during their childbearing years with deleterious social,

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sexual and reproductive consequences. The development and maintenance of endometriosis involves the establishment and subsequent sustained growth of endometrial cells at ectopic sites, most commonly the pelvic peritoneum, following retrograde menstruation (Sampson 1927 Am. J. Obstet. Gynecol. 14, 422; Ridley & Edward 1958 Am. J. Obstet. Gynecol. 76, 783-790; Lieu & Hitchcock 1968 Br. J. Obstet. Gynecol. 93, 859-862; and Thomas & Prentice 1992 Repro. Med. Rev. 1, 21-36). Except for the influences of ovarian steroid hormones (Dizerega et al., 1980 Fertil. Steril. 33, 649-653; Bergqvist et al., 1985 Am. J. Pathol. 121, 337-341) little is known about the factors that control this disease. However, it may be that the growth of ectopic endometrial implants is influenced by angiogenic growth factors (angiogenesis being the name given to the formation of new blood vessels). ... Endometriotic lesions are characterised by hyper-vascularisation both within the endometriotic tissue and in the surrounding peritoneum (Shaw, p46-47 "An atlas of endometriosis" 1993, The Parthenon publishing group; and Folkman & Shing 1992 J. Biol. Chem. 267, 10931-10934). Vascular endothelial growth factor (VEGF) is a recently characterised angiogenic protein being a potent mitogen for endothelial cells and a mediator of vessel permeability (Ferrara et al., 1992 Endocrinol. Rev. 13, 18-32). VEGF and its receptors flt and KDR, which are expressed on endothelial cells, (De Vries et al., 1992 Science 255, 989-991) have been implicated in angiogenesis in the developing embryo (Breier et al., 1992 Development 114, 521-532; Jakeman et al., 1993 Endocrinology 133, 848-859; and Millauer et al., 1993 Cell 72, 835-846) and in adult tissue undergoing profound angiogenesis such as eutopic endometrium (Chamock-Jones et al., 1993 Biol. Repro. 48, 1120-1128) and the lutenised corpus luteum (Ravindranath et al., 1992 Endocrinology 13, 254-260). In addition, its role in tumour angiogenesis is becoming well established (Shweiki et al., 1992 Nature 359, 843-848; Kim et al., 1993 Nature 362, 841-844). Web site: http://www.delphion.com/details?pn=US06121230__ ·

Method for treating endometriosis or leiomyomata uteri with a competitive progesterone antagonist and a gestagen Inventor(s): Stockemann; Klaus (Berlin, DE), Chwalisz; Kristof (Berlin, DE) Assignee(s): Schering Aktiengesellschaft (Berlin, DE) Patent Number: 6,043,234 Date filed: June 10, 1997

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Abstract: This invention relates to the use of a product that contains in combination individual dosage units of a competitive progesterone antagonist and individual dosage units of a gestagen for its sequential, oral administration, in which each individual dosage unit that contains the competitive progesterone antagonist contains the latter in a nonabortion-inducing amount for the production of a pharmaceutical agent for treating endometriosis or leiomyomata uteri. Excerpt(s): This invention relates to the use of a combination product that consists of individual dosage units of a competitive progesterone antagonist and individual dosage units of a compound that are provided sequentially in it, having a gestagenic action for the production of a pharmaceutical agent for treating endometriosis or leiomyomata uteri. ... In addition, for gynecological applications, initial clinical studies have shown that AG's can be used for treating endometriosis and leiomyomata uteri (myoma) [10) Kettel, L. M. et al. (1991): Endocrine Responses to Long-Term Administration of the Antiprogesterone RU 486 in Patients with Pelvic Endometriosis. Fertility and Sterility, 56/3, 402-407; 11) Kettel, L. M. et al. (1993): Long-Term, Low-Dose RU486 in the Treatment of Endometriosis. Meeting of the Society of Gynecological Investigation 1993, Abstract p. 136; 12) Murphy, A. A. et al. (1993): Regression of Uterine Leiomyomata in Response to the Antiprogestin RU486, J. Clin. Endocrinol. Metab., 76/2, 513-517]. ... Despite the growth-inhibiting action of the progesterone antagonist on myoma [12)] and endometriosis [11)], an undesirable stimulation of the epithelium in the endometrium can occur [13)], possibly caused by the so-called "unopposed estrogen effect." Under certain circumstances this could pose a risk (chronic stimulation.fwdarw.risk or development of endometrial carcinoma) for long-term treatment with progesterone antagonists alone or prevent development of preparations. Web site: http://www.delphion.com/details?pn=US06043234__ ·

Methods of treating or preventing endometriosis with phytoestrogens Inventor(s): Hughes, Jr.; Claude L. (Simi Valley, CA), Cline; J. Mark (Winston-Salem, NC), Clarkson; Thomas B. (Clemmons, NC), Whitesides; Daniel B. (Charlotte, NC) Assignee(s): Wake Forest University (Winston-Salem, NC) Patent Number: 5,942,539 Date filed: October 3, 1997 Abstract: Methods of using phytoestrogens, in particular, isoflavones in the prevention and treatment of endometriosis and related disease

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conditions in females. One method comprises administering a therapeutically effective dosage of a phytoestrogen to females with endometriosis, females having symptoms related to endometriosis, or to females at risk of developing or suffering recurrence of endometriosis. In another method, at least one phytoestrogen may be administered singly or in combination with at least one hormonal therapeutic agent such as GnRH analogs, androgens, progestins, estrogens or any combination thereof. The therapeutically effective dosage of the phytoestrogen or the combination therapeutic ranges between about 25 and about 250 mg/day. Excerpt(s): The present invention relates to methods of treating and preventing endometriosis in adult females using phytoestrogens. More particularly, the present invention relates to methods of using phytoestrogens, in particular, isoflavones singly or in combination with other hormonal therapeutic agents to prevent endometriosis in females at risk for the disease as well as to treat those females with the disease or symptoms associated therewith. ... Endometriosis is a common and debilitating disease of adult women in their 20's and 30's in which functional endometrial tissue is present and growing in areas outside the uterus, in particular the peritoneal cavity. As a result, severe pain often occurs in response to the hormonal changes that take place during the female menstrual cycle. Even more devastating is the infertility that frequently occurs due to the abnormal growth and accumulation of endometrial tissue on organs outside of the uterus. ... At present, endometriosis is routinely treated with a variety of hormonal therapies, which include gonadotropin-releasing hormone analogs ("GnRH analogs"), danazol, progestins, and continuous high-dose oral contraceptives. Each of these therapies has similar response rates in terms of diminished pelvic pain and laparoscopically demonstrated extent of disease. However, the effectiveness of each current treatment option is compromised by severe side effects and/or major health concerns experienced by many women. Web site: http://www.delphion.com/details?pn=US05942539__ ·

Method for treating vaginitis and endometriosis Inventor(s): Ratcliff; Perry A. (Scottsdale, AZ) Assignee(s): Micropure, Inc. (Scottsdale, AZ) Patent Number: 5,935,592 Date filed: May 6, 1998

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Abstract: A stable solution, cream, salve, or spray composition containing activated chlorine dioxide and phosphates, such as disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, and sodium monofluorophosphate, is disclosed for the treatment of vaginitis and endometriosis by reducing any of Candida, Actinobacillus actinomycetemcomitans, Pseudomonades, and Porphyromonas gingivalis present in the vagina or the uterus. The preferred concentration ranges are in the range of about 0.005% to about 2.0% of chlorine dioxide, and in the range of about 0.02% to about 3.0% of phosphate. The phosphate compound retards escape of chlorine dioxide in the pH range of 6.0 to 7.4, at which pH chlorine dioxide becomes activated and releases sufficient chlorine dioxide to reduce motility and become lethal to the involved micro-organisms. Excerpt(s): Studies done in the mouth have demonstrated that the penetration of bacteria takes place in the presence of the volatile sulfur compounds, resulting in initiation of the inflammatory reaction including initiation of the complement cascade. I. Kleinberg and G. Westbay, J. Peridontol, 63(9): 768-774 (1992). Initiation of the inflammatory reaction and development of the complement leads to an eightfold increase in the cell division or mitosis of epithelial cells in the attachment apparatus of the gingiva. W. O. Engler, S. P. Ramfjiord and J. J. Hiniker, J. Periodont., 36:44-56 (1965). Because the epithelia of other orifices, and particularly vaginal epithelium, are very similar to the gingival epithelium, reactions similar to those described above for the gingival epithelium occur in all other parts of the body, as demonstrated by the occurence of vaOinitis and endometriosis of the vagina. Examples of such bacteria which may appear in any bodily orifice include Porphyromonas (formerly known as Bacteroides) gingivalis, Actinobacillus actinomycetemcomitans, and Pseudomonades. Web site: http://www.delphion.com/details?pn=US05935592__ ·

Antibody specific for an isolated chemotactic factor from patients with endometriosis Inventor(s): Lyttle; C. Richard (Bala Cynwyd, PA) Assignee(s): The Trustees of the University of Pennsylvania (Philadelphia, PA) Patent Number: 5,891,644 Date filed: May 5, 1998 Abstract: A composition comprising a soluble peptide of about 23 kD to about 29 kD, capable of causing neutrophil and macrophage chemotaxis,

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and which is substantially similar to chemotactic factor from peritoneal fluid of mammals with minimal or moderate endometriosis. Excerpt(s): The underlying mechanisms indicating an association between minimal to moderate endometriosis and infertility are not clearly understood. Recent investigations have focused on the presence of an aseptic inflammation of the peritoneal cavity, resulting in a distortion of the normal function of the pelvic organs, as an important contributory mechanism. Other proposed causes for reproductive failure in the less severe cases of endometriosis include oligoanovulation, luteal phase defects, and luteinized unruptured follicle syndrome. However, these suggestions need to be clearly substantiated and each one cannot be considered the sole cause of infertility in patients with endometriosis. Other factors, which include alterations in the sperm-egg interaction with possible phagocytosis of the sperm or interference with early embryo development, may be taken into consideration when studying the associated infertility of these patients. The biochemical modifications that have been described in endometriosis include an increase in the concentration of prostaglandins, cytokines and complement components in the peritoneal fluid and activation of resident macrophages. Halme J., et al., Am J Obstet Gynecol 1983 145:333 and Hill J. A., et al., Am J Obstet Gynecol 1989 161:861. The activation of leukocytes within the peritoneal cavity is evidenced by cytoskeletal rearrangement of the cells and by changes in the lipid metabolism with activation of protein kinases or release of lysosomal enzymes. ... The role of peritoneal fluid in the physiologic modifications of the peritoneal cavity of patients who otherwise would seem to have a normal pelvic environment has been studied. Endometriosis without severe anatomic distortion is associated with an increase in the peritoneal fluid volume, cell number, and concentration of lysosomic enzymes as compared with normal fertile controls. The peritoneal fluid arises primarily from two different sources: the plasma as a transudate and the ovary as an exudate; other sources are tubal fluid; retrograde menstruation, and secretions from the macrophages in the cavity. However, the exact source for the biochemical modifications observed in endometriosis is not clear. ... Normally the peritoneal fluid contains several types of blood cells, with macrophages and lymphocytes being the most abundant; desquamated endometrial and mesothelial cells are also present. This cellular composition is modified in patients with endometriosis. Badaway S. Z., et al., Fertil Steril 1984 42:704. Several theories exist regarding the mechanisms responsible for these alterations, one of which is considered by the present invention-the presence of a chemotactic stimulus that would attract more cells into the peritoneal cavity, or alternatively, activate and induce proliferation of resident macrophages in response to these unknown factors.

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Web site: http://www.delphion.com/details?pn=US05891644__ ·

Use of droloxifene for the treatment of protastic disease, endometriosis and obesity Inventor(s): Thompson; David D. (Gales Ferry, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 5,852,059 Date filed: January 6, 1997 Abstract: This invention provides a method for treating a condition or disease selected from endometriosis, obesity, benign prostatic hypertrophy and prostatic carcinoma in mammals which comprises administering to said mammal an amount of droloxifene or a pharmaceutically acceptable salt thereof which is effective in treating said condition or disease. Excerpt(s): This invention provides a method for treating a condition or disease selected from endometriosis, obesity, benign prostatic hypertrophy and prostatic carcinoma in mammals which comprises administering to said mammal an amount of droloxifene or a pharmaceutically acceptable salt thereof which is effective in treating said condition or disease. ... The remedies for the prostatic diseases, endometriosis and obesity of this invention comprise, as active ingredient, droloxifene or a salt thereof. The pharmaceutically acceptable salts of droloxifene are salts of non-toxic type commonly used, such as salts with organic acids (e.g., formic, acetic, citric, maleic, tartaric, methanesulfonic, benzenesulfonic or toluenesulfonic acids), inorganic acids (e.g. hydrochloric, hydrobromic, sulfuric or phosphoric acids), and amino acids (e.g., aspartic or glutamic acids). These salts may be prepared by the methods known to chemists of ordinary skill. ... The protocol for surgically inducing endometriosis is identical to that described by Jones, Acta Endocrinol (Copenh) 106: 282-8. Adult Charles River Sprague-Dawley CD.RTM. female rats (200-240 g) are used. An oblique ventral incision is made through the skin and musculature of the body wall. A segment of the right uterine horn is excised, the myometrium is separated from the endometrium, and the segment is cut longitudinally. A 5.times.5 mm section of the endometrium, with the epithelial lining apposed to the body wall, is sutured at its four corners to the muscle using polyester braid (Ethiflex, 7-0.RTM.). The criterion of a viable graft is the accumulation of fluid similar to that which occurs in the uterus as a result of oestrogen stimulation. Web site: http://www.delphion.com/details?pn=US05852059__

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Method of screening for endometriosis Inventor(s): Sharpe-Timms; Kathy Lynn (Columbia, MO) Assignee(s): Curators of the University of Missouri (Columbia, MO) Patent Number: 5,843,673 Date filed: June 7, 1995 Abstract: A glycoprotein having a molecular weight of 28,000 to 32,000 and an isoelectric point of 7.0 to 9.0, both as determined by twodimensional SDS polyacrylamide gel electrophoresis, is synthesized and secreted specifically by stromal cells of endometriotic origin. Amino acid residues in the region of the N-terminus of the glycoprotein share amino acid sequence identity with a region of tissue inhibitor of metalloproteinases-1 (TIMP-1). A method of screening for endometriosis is disclosed by detection of lower levels of the protein or TIMP-1 in peritoneal fluid or serum samples of women. Excerpt(s): The present invention relates to the field of fertility and more particularly, to means and methods for determining and diagnosing endometriosis in women. ... Endometriosis is defined as the ectopic presence of endometrial glands and stroma. Endometriotic tissue is comprised of tissue that is histologically similar yet biochemically and functionally different or out of phase from that of the uterine endometrium. ... For example, endometriosis differs from its uterine counterpart in steroid responsiveness and receptor content (Vierikko, et al., 1985; Lessey et al., 1989; Melega et al., 1991) and expression of epidermal growth factor and epidermal growth factor receptor (Melega et al., 1991; Haining et al., 1991). These altered characteristics, combined with an ectopic location, effect the physiological activity of the endometriotic tissue and thereby alter protein synthesis and secretion by the endometriotic tissue. Deviations in protein synthesis and secretion might be useful in developing unique markers for the nonsurgical diagnosis and management of endometriosis. Unfortunately, limited information is available concerning protein synthesis, secretion, regulation and expression in endometriotic tissue. Web site: http://www.delphion.com/details?pn=US05843673__

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Low dose androgenic compounds for prevention and treatment of endometriosis Inventor(s): Labrie; Fernand (Ste-Foy, CA) Assignee(s): Endorecherche Inc. (Quebec, CA) Patent Number: 5,753,639 Date filed: January 4, 1996 Abstract: A method of treatment or prevention of breast and endometrial cancer, osteoporosis and endometriosis in susceptible warm-blooded animals comprising administering a low dose of a progestin or other steroid derivative having androgenic activity and low masculinizing activity. Pharmaceutical compositions useful for such treatment and pharmaceutical kits containing such compositions are disclosed. An in vitro assay permitting specific measurements of androgenic activity of potentially useful compounds is also disclosed. Excerpt(s): This invention relates to a method for treating or preventing breast and endometrial cancer, bone loss, and for treating endometriosis in susceptible warm-blooded animals including humans involving administration of a compound possessing androgenic activity, and to kits containing active ingredients to be used in the therapy. ... Various investigators have been studying hormonal therapy for breast and endometrial cancer as well as for the prevention and treatment of bone loss and for treatment of endometriosis. The main approaches for the treatment of already developed breast cancer are related to the inhibition of estrogen action and/or formation. The role of estrogens in promoting the growth of estrogen-sensitive breast cancer is well recognized (Lippman, Semin. Oncol. 10 (suppl. 4): 11-19, 1983; Sledge and McGuire, Cancer Res. 38: 61-75, 1984; Wittliff, Cancer 53: 630-643, 1984; Poulin and Labrie, Cancer Res. 46: 4933-4937, 1986). ... The androgen methyltestosterone has been shown to relieve the symptoms of endometriosis (Hamblen, South Med. J. 50: 743, 1987; Preston, Obstet, Gynecol. 2: 152, 1965). Androgenic and masculinizing side effects (sometimes irreversible) are however important with potent androgenic compounds such as testosterone. Web site: http://www.delphion.com/details?pn=US05753639__

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.alpha..sub.v .beta..sub.3 integrin as a predictor of endometriosis Inventor(s): Lessey; Bruce A. (Hillsborough, NC) Assignee(s): University of Pennsylvania (Philadelphia, PA) Patent Number: 5,478,725 Date filed: November 19, 1993 Abstract: Methods of screening for endometriosis comprise obtaining a sample of endometrium selected from menstrual cycle day 20 to 24, identifying the endometrial sample as nulliparous, contacting the endometrium with a monoclonal antibody for .beta..sub.3 integrin, assaying for .beta..sub.3 integrin and correlating the absence of .beta..sub.3 integrin with endometriosis, wherein the endometrium is identified as mild/minimum endometriosis. A method of using monoclonal antibodies to screen for endometriosis is also within the scope of the invention. Methods for detecting receptivity of mammalian endometrium to embryo implantation comprising obtaining a sample of the endometrium, contacting the endometrium with a monoclonal antibody for .beta..sub.3 and detecting .beta..sub.3 in the endometrium. The invention also provides for methods of diagnosing infertility in a mammal and methods of detecting the window of embryo implantation in endometrium. Methods of in vitro fertilization, methods of preventing embryo implantation and a method of monitoring endometrial maturation are also within the scope of the present invention. Diagnostic kits useful in the practice of the methods of the invention are also provided. Excerpt(s): The relationship between minimal endometriosis and nulliparity and infertility remains controversial. While many cogent arguments exist to support this association, many clinicians today still do not believe that minimal or mild forms of the disease are detrimental to a couple's fertility. Several studies comparing women with normal endometrium to women with mild or minimal endometriosis have demonstrated a decrease in cycle fecundity, such as success rates in donor programs, IVF, or GIFT, supported by animal models. One reason for this lack of acceptance is the finding of many studies that expectant management yields pregnancy rates as high as most currently used treatments. ... Of the many mechanisms suggested to explain the decline in cycle fecundity of endometriosis patients, a defect in uterine receptivity has received perhaps the least attention. Fedele reported specific changes in the native endometrium in women with severe endometriosis, Fedele, L., et al., "Structural and Ultrastructural Defects in Preovulatory Endometrium of Normo-Ovulating Infertile Women with Minimal or Mild Endometriosis", Fertil. Steril. 1990, 53:989. Yovich

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suggested that severe endometriosis was associated with a defect in implantation, based on IVF-ET experience, see Yovich et al., "Hormonal Profiles and Embryo Quality in Women with Severe Endometriosis Treated by In Vitro Fertilization and Embryo Transfer", Fertil. Steril. 1988, 50:308. There is data from studies in the rabbit to suggest that implantation is adversely affected by surgically induced endometriosis, and that the effect is mediated by the peritoneal fluid, see Hahn et al., "Experimental Evidence for Failure to Implant as a Mechanism of Infertility Associated with Endometriosis", Am. J. Obstet. Gynecol. 1986, 155:1109. ... Endometriosis is a disorder that affects an estimated 2-5% of the general fertile female population, yet its prevalence in infertile women approaches 30-50%, Peterson et al., "Laparoscopy of the infertile Patient", Obstet. Gynecol. 1970, 36:667. While many affected women may have no symptoms, others suffer from dysmenorrhea (painful, difficult menstruation), dyspareunia (pain during intercourse), menstrual disturbances and infertility. That mild or minimal endometriosis is associated with infertility has been suggested by numerous studies, Hasson H. M., "Incidence of Endometriosis in Diagnostic Laparoscopy", J. Reprod. Med. 1976, 16:135 and has been recently reviewed, Bancroft, et al., "Minimal/Mild Endometriosis and Infertility. A Review", Br. J. Obstet. Gynaecol. 1989, 96:454. The mechanism by which minimal endometriosis causes infertility remains uncertain. Adverse effects on folliculogenesis, ovulation, ovum transport, fertilization, sperm quality, embryos, luteal phase function, and an increase in spontaneous abortion rates have all been postulated. These effects may be mediated by elaboration of peritoneal factors such as prostaglandins, cytokines, and growth factors; activation of peritoneal macrophages, or alterations in immune function such as decreased activity of natural killer cells. Kurzrock et al., "LIF: Not Just a Leukemia Inhibitory Factor", Endo. Rev. 1990, 12:208. A few authors have suggested that uterine receptivity to the embryo might be primarily affected by the presence of endometriosis, Muscato, et al., "Sperm Phagocytosis by Human Peritoneal Macrophages: A Possible Cause of Infertility in Endometriosis", Am. J. Obstet. Gynecol. 1982, 144:503 and Yovich et al., supra; and limited data from surgically induced endometriosis in animal models support this hypothesis, Hahn, et al., supra. Further, structural abnormalities have been described in the endometrium of women with endometriosis compared to normal fertile controls, Fedels, et al., supra. Web site: http://www.delphion.com/details?pn=US05478725__

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Method for treating endometriosis with topical preparations containing danazol Inventor(s): Igarashi; Masao (357-4, Hiyoshi-cho H-chome, Maebashi-shi, Gunma, JP) Assignee(s): none reported Patent Number: 4,997,653 Date filed: December 20, 1988 Abstract: A topical preparation of danazol comprising a matrix base, danazol retained therein, and optionally a release-promoting agent is provided.The topical preparation is more effective than oral administration of danazol in the shrinkage of endometriosis tissue, the induction of pregnancy, and the like. It does not show any side effects that have been encountered in the oral administration of danazol. Thus, the preparation is very useful remedy for endometriosis. Excerpt(s): This invention relates to danazol-containing topical preparations which are markedly effective in the treatment of pelvic endometriosis and uterine adenomyosis. More particularly, it relates to intrauterine and vaginal preparations comprising a matrix base having danazol retained therein. ... Endometriosis is a disease which occurs mostly in mature women and is frequently associated with infertility. According to the site of the focus, it is broadly divided into pelvic endometriosis (external endometriosis) and uterine adenomyosis (internal endometriosis). ... Danazol is a drug which is highly estimated and widely used as an oral remedy for endometriosis ("Gekkan Yakuji", Vol. 25, No. 4, p. 691, 1983), but its effectiveness as a topical remedy has been unknown not only in Japan but also throughout the world. This seems to be due to the fact that two theories are being widely supported in connection with the mode of action of orally administered danazol. One of them is the worldwide established theory that orally administered danazol suppresses the function of the hypothalamo-hypophysial system to decrease the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), resulting in decreased secretion of estrogens by the ovary and eventual shrinkage of endometriosis tissue (Fertility and Sterility, Vol. 29, p. 637, 1978). In other words, this theory insists that oral administration of danazol is the so-called pseudomenopausal therapy in which the functions of the ovary are suppressed completely. The other is a corrected theory which accepts the foregoing established theory in principle, but admits the presence of an appreciable direct effect on endometriosis cells (American Journal of Obstetrics and Gynecology, Vol. 140, p. 62, 1981).

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Web site: http://www.delphion.com/details?pn=US04997653__ ·

Method of treating or preventing endometriosis Inventor(s): Horrobin; David F. (Guildford, GB2), Casper; Robert A. (Ontario, CA) Assignee(s): Efamol Limited (Surrey, GB2) Patent Number: 4,758,592 Date filed: September 26, 1986 Abstract: Method of prevention or treatment of endometriosis wherein effective amounts of one or both of (i) gamma-linolenic acid and/or dihomo-gamma-linolenic acid and (ii) 18:4 n-3 and/or one or more of the metabolites of 18:4 n-3 (20:4 n-3, 20:5 n-3, 22:5 n-3 or 22:6 n-3) are administered against endometriosis as such or in the form of an ester, salt, amide or other derivative convertible in the body thereto, alone or in an acceptable pharmaceutical carrier or diluent. Excerpt(s): This invention relates to the prevent or treatment of endometriosis. ... Endometriosis is a common condition affecting women of reproductive age. For unknown reasons, endometrial tissue migrates from its normal position lining the uterus to other parts of the body, primarily within the abdominal cavity. The ovaries and gut wall are commonly affected. The endometrial tissue, like that in its normal position, grows and declines according to the menstrual cycle as a result of the actions of the ovarian hormones. Endometriosis causes many symptoms including abdominal and back pain, gastrointestinal upsets, infertility and menstrual disturbance. Since endometrial tissue requires ovarian hormones for growth, symptoms of endometriosis normally decline and disappear after the menopause. There is no satisfactory premenopausal treatment other than the use of drugs or other measures which suppress or remove ovarian functions or which antagonise the actions of ovarian hormones. Since such drugs interfere with fertility, they cannot be satisfactorily used in women whose main problem is infertility. Further, such drugs have many side effects and the suppression of normal reproductive function is unacceptable to many women. ... Some of the women with premenstrual syndrome also have endometriosis. Surprisingly, the inventors have found that in these women the administration of evening primrose oil (which contains GLA) produces a dramatic reduction in the symptoms of endometriosis, including the pain, gastrointestinal disturbances and menstrual distress. Combination of evening primrose oil with fish oil produces rather better results than the use of evening primrose oil alone, indicating that the

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fatty acids in the fish oil are making a contribution to the therapeutic effect. This treatment is a substantial development in the treatment of endometriosis, since the essential fatty acids do not interfere with fertility, so providing the first successful approach to this disease which does not even temporarily impair fertility. Web site: http://www.delphion.com/details?pn=US04758592__

Patent Applications on Endometriosis As of December 2000, U.S. patent applications are open to public viewing.26 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 endometriosis: ·

Endometriosis-Specific Secretory Protein Inventor(s): Timms, Kathy L. ; (Columbia, Mo) Correspondence: Kohn & Associates; Ilene N Montgomery; 30500 Northwestern Highway Suite 410; Farmington Hills; Mi; 48334 Patent Application Number: 20020009718 Date filed: March 19, 1998 Abstract: A method and kit of diagnosing endometriosis in a female patient suspected of having endometriosis is disclosed. The method includes obtaining a sample from the patient. The sample is analyzed to detect the presence of ENDO-I glycoprotein or its mRNA in the sample compared to non-endometriosis controls who do not express ENDO-I. The protein is characterized by (i) a molecular weight of 40,000 to 55,000 as determined by two-dimensional SDS-PAGE polyacrylamide gel electrophoresis; (ii) having an isoelectric point of 4.0 to 5.5; and (iii) being synthesized and secreted specifically by stromal cells of endometriotic tissue origin; and (iv) in humans having a cDNA as set forth in SEQ ID No:1. The present invention further discloses a cDNA for human ENDO-I (SEQ ID No:1) and antibody directed against ENDO-I. Excerpt(s): The present invention relates to the field of fertility and more particularly, to means and methods for determining and diagnosing endometriosis in women. ... Endometriosis is defined as the ectopic presence of endometrial glands and stroma. Endometriotic tissue is comprised of tissue that is histologically similar yet biochemically and

26

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

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functionally different or out of phase from that of the uterine endometrium. ... For example, endometriosis differs from its uterine counterpart in steroid responsiveness and receptor content [Vierikko, et al., 1985; Lessey et al., 1989; Melega et al., 1991] and expression of epidermal growth factor and epidermal growth factor receptor [Melega et al., 1991; Haining et a., 1991]. These altered characteristics, combined with an ectopic location, effect the physiological activity of the endometriotic tissue and thereby alter protein synthesis and secretion by the endometriotic tissue. Deviations in protein synthesis and secretion might be useful in developing unique markers for the nonsurgical diagnosis and management of endometriosis. Unfortunately, limited information is available concerning protein synthesis, secretion, regulation and expression in endometriotic tissue. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Diagnostic assay for endometriosis Inventor(s): Yeaman, Grant R. ; (Etna, NH) Correspondence: Leopold Presser; Scully, Scott, Murphy & Presser; 400 Garden City Plaza; Garden City; NY; 11530; US Patent Application Number: 20010044158 Date filed: April 19, 2001 Abstract: The present invention provides a method for detecting endometriosis in a patient and is an improvement over invasive and expensive surgical procedures. The method employs immunoassays which detect autoantibodies in a serum sample which react with Thomsen-Friedenreich antigen (Tf). Increased levels of autoantibodies in a serum sample from the patient which bind to Tf-like antigen is indicative of endometriosis in the patient. Excerpt(s): Endometriosis is a common disorder characterized by the growth of endometrial cells at extrauterine (ectopic) sites. It is a common disease which may affect up to 10% of reproductive age women (1). Although the etiology of endometriosis remains enigmatic, altered cellular and humoral immune function is clearly a feature of established disease (2-4). ... Autoantibodies to endometrial antigens and deposition of complement components have been described in a number of studies (reviewed in 2) and a number of serum, peritoneal fluid and endometrial antigens have been described. Perhaps the best characterized tissue antigens described, thus far, are the human chorionic gonadotropin receptor (5) and isoforms I and II of the enzyme carbonic anhydrase 6-8. Antibodies to transferrin and .alpha..sub.2-Heremans Schmidt

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glycoprotein (.alpha..sub.2-HSG) have also been described and proposed as diagnostic markers 9, 10. While considerable work has been carried out in terms of measuring the incidence of these antibodies in endometriosis, reproductive diseases, and other autoimmune diseases, the nature of the epitopes involved has received scant attention. The identified antigens are all glycoproteins. With only one apparent exception (5), carbohydrate antigens on these proteins have not been evaluated. ... The present invention provides diagnostic methods based on autoantibody reactivity with Tf-like antigen. The diagnostic methods are helpful in determining the presence of endometriosis in a patient and are an improvement over the current invasive methods of diagnosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Use of Ligands Specific to Major Histocompatibility Complex- Class I Antigens for Diagnosing Endometriosis Inventor(s): Miron, Pierre ; (Laval, Ca), Lachapelle, Marie-Helene ; (Laval, Ca), Roy, Denis-Claude ; (Laval, Ca) Correspondence: Merchant & Gould; P O Box 2903; Minneapolis; Mn; 55402-0903; US Patent Application Number: 20010006782 Date filed: March 2, 1999 Abstract: It is an object of the present invention to provide the clinicians with a new application for ligands specific to MHC-class I antigens, especially HLA-ABC antigens, this new application residing in the detection and diagnosis of endometriosis. It is also an object of the present invention to provide a method and a test kit for diagnosing endometriosis, preferably by immunohistochemistry, using a monoclonal anti-HLA-ABC antibody as a preferred ligand or diagnostic reagent. This new method is non-invasive and is more reliable as a screening test than the conventionally used laparoscopy. When the endometrium of a woman tests negatively with the claimed method, it prevents the use of laparoscopy which is an invasive method for detecting endometriosis. This method can be practised on a specimen obtained from the endometrium of a patient and does not require a specimen sampled directly from the endometriotic foci. Excerpt(s): This invention relates to the use of ligands specific to a Major Histocompatibility Complex (MHC)-class I antigen, especially an HLAABC surface antigen, which is normally exposed at the surface of cell membranes, and which is therefore present in or on endometrial cell, for the diagnosis of endometriosis. The detection of this antigen is carried

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out according to a process comprising the reaction of a ligand, preferably an antibody, which is normally used to detect the presence of a MHCclass I antigen at the surface of all cells expressing it. ... This invention also relates to a method for the diagnosis of endometriosis using the same ligand(s). ... Endometriosis is one of the most common disorders encountered in the field of gynaecology, affecting the health of an estimated 10 to 15% of women during their reproductive years. Although not life threatening, endometriosis is often associated with severe pelvic pain and infertility. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with endometriosis, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “endometriosis” (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 endometriosis. You can also use this procedure to view pending patent applications concerning endometriosis. Simply go back to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.

Vocabulary Builder Actinobacillus: A genus of pasteurellaceae described as gram-negative, nonsporeforming, nonmotile, facultative anaerobes. Most members are found both as pathogens and commensal organisms in the respiratory, alimentary, and genital tracts of animals. [NIH] Adnexitis: Inflammation of the adnexa uteri. [EU] Amenorrhea: amenia. [EU] Analgesic:

Absence or abnormal stoppage of the menses; called also An agent that alleviates pain without causing loss of

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consciousness. [EU] 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] Antibody: An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [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 Tlymphocytes, 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] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Aseptic: Free from infection or septic material; sterile. [EU] 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] Bacteroides: A genus of gram-negative, anaerobic, rod-shaped bacteria. Its organisms are normal inhabitants of the oral, respiratory, intestinal, and urogenital cavities of humans, animals, and insects. Some species may be pathogenic. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the

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influence of an electric current. [NIH] Embryo: In animals, those derivatives of the fertilized ovum that eventually become the offspring, during their period of most rapid development, i.e., after the long axis appears until all major structures are represented. In man, the developing organism is an embryo from about two weeks after fertilization to the end of seventh or eighth week. [EU] Enzyme: A protein molecule that catalyses chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions. Enzymes are classified according to the recommendations of the Nomenclature Committee of the International Union of Biochemistry. Each enzyme is assigned a recommended name and an Enzyme Commission (EC) number. They are divided into six main groups; oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] FSH: A gonadotropic hormone found in the pituitary tissues of mammals. It regulates the metabolic activity of ovarian granulosa cells and testicular Sertoli cells, induces maturation of Graafian follicles in the ovary, and promotes the development of the germinal cells in the testis. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Hydrogen: 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] Hypertrophy: Nutrition) the enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells. [EU] 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

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antibody by the test substance. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] LH: A small glycoprotein hormone secreted by the anterior pituitary. LH plays an important role in controlling ovulation and in controlling secretion of hormones by the ovaries and testes. [NIH] Lumbago: Pain in the lumbar region. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. [NIH] Metabolite: process. [EU]

Any substance produced by metabolism or by a metabolic

Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Motility: The ability to move spontaneously. [EU] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Neutrophil: Having an affinity for neutral dyes. [EU] Nulliparous: Having never given birth to a viable infant. [EU] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Pelvis: The bowl-shaped bone that supports the spine and holds up the digestive, urinary, and reproductive organs. The legs connect to the body at the pelvis. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs.

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The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Phagocytosis: Endocytosis of particulate material, such as microorganisms or cell fragments. The material is taken into the cell in membrane-bound vesicles (phagosomes) that originate as pinched off invaginations of the plasma membrane. Phagosomes fuse with lysosomes, forming phagolysosomes in which the engulfed material is killed and digested. [EU] Phosphates: Inorganic salts of phosphoric acid. [NIH] Porphyromonas: A genus of gram-negative, anaerobic, nonsporeforming, nonmotile rods or coccobacilli. Organisms in this genus had originally been classified as members of the bacteroides genus but overwhelming biochemical and chemical findings indicated the need to separate them from other Bacteroides species, and hence, this new genus was created. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Topical: Pertaining to a particular surface area, as a topical anti-infective applied to a certain area of the skin and affecting only the area to which it is applied. [EU] Trustees: Board members of an institution or organization who are entrusted with the administering of funds and the directing of policy. [NIH] Tumour: 1. swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. a new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Ventral: 1. pertaining to the belly or to any venter. 2. denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU]

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CHAPTER 6. BOOKS ON ENDOMETRIOSIS Overview This chapter provides bibliographic book references relating to endometriosis. You have many options to locate books on endometriosis. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some patients, however, feel uncomfortable approaching their local booksellers and prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on endometriosis include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is 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 “endometriosis” (or synonyms) into the “For these words:” box. You will only receive results on books. You should check back periodically with this database which is updated every 3 months. The following is a typical result when searching for books on endometriosis:

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·

Sick and Tired of Feeling Sick and Tired: Living With Invisible Chronic Illness Source: New York, NY: W.W. Norton and Company, Inc. 2000. 306 p. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Fax (301) 670-9486. Website: www.lupus.org/lupus. PRICE: $8.95 for 1-9 copies; $6.50 for 10-25 copies. ISBN 0393320650. Summary: This book offers hope and coping strategies to people who suffer from invisible chronic illnesses (ICIs) such as chronic fatigue and chronic pain. Part 1 focuses on the experience of having an ICI. Chapter 1 serves as an introduction to ICI. Chapter 2 describes some forms of ICI, including arthritis, Charcot-Marie-Tooth disease, chronic fatigue immune dysfunction syndrome, endometriosis, fibromyalgia, human immunodeficiency virus, inflammatory bowel disease, irritable bowel syndrome, lupus erythematosus, Lyme disease, migraine, multiple sclerosis, post polio syndrome, premenstrual syndrome, and thyroid illnesses. Chapter 3 explores the psychological consequences of ICI, focusing on self doubt, self dislike, uncertainty, fear of mental illness, fear of the course of illness, giving in to illness, interpersonal insecurity, loss of self esteem, guilt, and roller coaster feelings. Chapter 4 examines the dimensions of ICI and their psychological impact, focusing on the social acceptability of the illness, the clarity of diagnosis, and the potential severity of the illness. Chapters 5 through 8 deal with adjusting to and accepting a constant state of unwellness; seeking answers; consulting a doctor; and relating to family, friends, and colleagues. Part 2 focuses on coping with ICI. Chapters deal with living in the present, thinking clearly, handling irrational thinking, using imagery to confront irrational thinking, identifying one's life story and the role played in the story, getting and keeping the attention of the health care system, coping with ICI in the family, saying what one feels, hearing what is said, and managing the stress associated with ICI. The book includes a general reading list on illnesses and a list of illness associations. Numerous references.

·

The A-to-Z of pregnancy and childbirth: A concise encyclopedia Source: Alameda, CA: Hunter House. 1994. 336 pp. Contact: Available from Hunter House, P.O. Box 2914, Alameda, CA 94501. Telephone: (510) 865-5282. $16.95; $2.50 shipping for 1st book, $0.75 each additional book. Summary: This book for the consumer is presented in a dictionary format providing information on a variety of topics in pregnancy and childbirth.

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Entries are listed in alphabetical order, and have concise explanations. A short bibliography lists other general publications on women's health, pregnancy, and childbirth. Organizations and hotlines are listed for a few areas of women's health including childbirth education, DES, endometriosis, and breast cancer. A fold out, month-by-month chart of fetal and maternal development is also included.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes & Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ). The following have been recently listed with online booksellers as relating to endometriosis (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): · Medical Management of Endometriosis by Jean Pierre Raynaud (Editor) (1984); ISBN: 0881670405; http://www.amazon.com/exec/obidos/ASIN/0881670405/icongroupint erna · Endometriosis (1985); ISBN: 068418057X; http://www.amazon.com/exec/obidos/ASIN/068418057X/icongroupin terna · Living With Endometriosis : How to Cope With the Physical and Emotional Challenges by Kate Weinstein (1987); ISBN: 020119810X; http://www.amazon.com/exec/obidos/ASIN/020119810X/icongroupin terna · Overcoming Endometriosis : New Help from the Endometriosis Association by Mary Lou Ballweg (1987); ISBN: 0865531900; http://www.amazon.com/exec/obidos/ASIN/0865531900/icongroupint erna · Endometriosis (Current Reviews in Obstetrics and Gynaecology) by Daniel T. O'Connor (1987); ISBN: 0443029954; http://www.amazon.com/exec/obidos/ASIN/0443029954/icongroupint erna · Endometriosis (Contributions to Gynecology and Obstetrics, Vol 16) by M.A. Bruhat, M. Canis (Editor) (1987); ISBN: 3805546270;

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http://www.amazon.com/exec/obidos/ASIN/3805546270/icongroupint erna · Endometriosis Answer Book : New Hope, New Help by Niels Lauersen, Constance De Swaan (1988); ISBN: 0892563265; http://www.amazon.com/exec/obidos/ASIN/0892563265/icongroupint erna · Endometriosis : Contemporary Concepts in Clinical Management by Robert S. Schenken (Editor) (1988); ISBN: 0397508662; http://www.amazon.com/exec/obidos/ASIN/0397508662/icongroupint erna · Endometriosis and Infertility and Traditional Chinese Medicine : A Laywoman's Guide by Bob Flaws (1989); ISBN: 0936185147; http://www.amazon.com/exec/obidos/ASIN/0936185147/icongroupint erna · Endometriosis (Advances in Reproductive Endocrinology, Vol 1) by R.W. Shaw (Editor) (1990); ISBN: 0929858484; http://www.amazon.com/exec/obidos/ASIN/0929858484/icongroupint erna · Current Concepts in Endometriosis (1990); ISBN: 0845151738; http://www.amazon.com/exec/obidos/ASIN/0845151738/icongroupint erna · Current Concepts in Endometriosis : Proceedings of the Second International Symposium on Endometriosis Held in Houston, Texas, May 1-3, 1989 (Progres) by Dev R. Chadha, Veasy C. Buttram (Editor) (1990); ISBN: 0471566853; http://www.amazon.com/exec/obidos/ASIN/0471566853/icongroupint erna · Modern Approaches to Endometriosis by Eric J. Thomas, John A. Rock (Editor) (1991); ISBN: 0792389018; http://www.amazon.com/exec/obidos/ASIN/0792389018/icongroupint erna · The Treatment of Endometriosis-And Other Disorders and Infections (Recent Developments in Fertility and Sterility, Vol 4) by Morocco) World Congress on Fertility and Sterility 1989 Marrakech (1991); ISBN: 185070287X; http://www.amazon.com/exec/obidos/ASIN/185070287X/icongroupin terna · What Women Can Do About Chronic Endometriosis (The Dell Medical Library) by Judith Sachs (1991); ISBN: 0440206464;

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http://www.amazon.com/exec/obidos/ASIN/0440206464/icongroupint erna · The Current Status of Endometriosis : Research and Management : Proceedings of the 3rd World Congress on Endometriosis, Brussels, June 1992 (The Inte) by I. A. Brosens, J. Donnez (Editor) (1993); ISBN: 1850704546; http://www.amazon.com/exec/obidos/ASIN/1850704546/icongroupint erna · Atlas of Endometriosis by Dan C. Martin (1993); ISBN: 1563755475; http://www.amazon.com/exec/obidos/ASIN/1563755475/icongroupint erna · Modern Surgical Management of Endometriosis (1994); ISBN: 3540942432; http://www.amazon.com/exec/obidos/ASIN/3540942432/icongroupint erna · Alternatives for Women With Endometriosis : A Guide by Women for Women by Ruth Carol (Editor) (1994); ISBN: 1879427125; http://www.amazon.com/exec/obidos/ASIN/1879427125/icongroupint erna · Endometriosis : Advanced Management and Surgical Techniques by Camran R. Nezhat (Editor), et al (1995); ISBN: 0387942432; http://www.amazon.com/exec/obidos/ASIN/0387942432/icongroupint erna · Fibroid Tumor and Endometriosis Self Help Book by Susan M. Lark (1995); ISBN: 0890877734; http://www.amazon.com/exec/obidos/ASIN/0890877734/icongroupint erna · Endometriosis Today: Advances in Research and Practice by Japan)/ Sugimoto, World Congress on Endometriosis 1996 Yokohama-Shi, Hiroshi Minaguchi (Editor) (1997); ISBN: 1850709017; http://www.amazon.com/exec/obidos/ASIN/1850709017/icongroupint erna · Endometrium and Endometriosis by Michael P. Diamond, Kevin G., Ph.D. Osteen (Editor) (1997); ISBN: 0865425027; http://www.amazon.com/exec/obidos/ASIN/0865425027/icongroupint erna · Endometriosis-One Woman's Journey by Jennifer Marie Lewis (1998); ISBN: 1882180917; http://www.amazon.com/exec/obidos/ASIN/1882180917/icongroupint erna

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· Endometriosis : A Natural Approach by Jo Mears (1998); ISBN: 1569750882; http://www.amazon.com/exec/obidos/ASIN/1569750882/icongroupint erna · Endometriosis: Basic research and clinical practice by Eshre Campus Course on Endometriosis (Editor), et al (1999); ISBN: 1850700575; http://www.amazon.com/exec/obidos/ASIN/1850700575/icongroupint erna · Understanding and Managing Endometriosis: Advances in research and practiceThe Proceedings of the 6th World Congress of Endometriosis by Quebec)/ Lemay, A. World Congress on Endometriosis 1998 Quebec (Editor), et al (1999); ISBN: 1850700702; http://www.amazon.com/exec/obidos/ASIN/1850700702/icongroupint erna · Text and Atlas of Infertility Surgery by Robert B., Md Hunt (1999); ISBN: 0815147384; http://www.amazon.com/exec/obidos/ASIN/0815147384/icongroupint erna · Coping With Endometriosis : Sound, Compassionate Advice for Alleviating the Physical and Emotional Symptoms of This Frequently Misunderstood Illenss by Robert H., Ph.D. Phillips, Glenda Motta (2000); ISBN: 1583330747; http://www.amazon.com/exec/obidos/ASIN/1583330747/icongroupint erna · Endometriosis : Emerging Research and Intervention Strategies (Annals of the New York Academy of Sciences, V. 955) by Koji Yoshinaga (Editor), Estella C. Parrott (Editor) (2002); ISBN: 1573313807; http://www.amazon.com/exec/obidos/ASIN/1573313807/icongroupint erna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “endometriosis” (or synonyms) into the search box, and select “books only.”

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From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:27 ·

Atlas of endometriosis. Author: R.W. Shaw; Year: 1993; Carnforth, Lancs, UK; Pearl River, N.Y., USA: Parthenon Pub. Group, 1993; ISBN: 1850703906 http://www.amazon.com/exec/obidos/ASIN/1850703906/icongroupin terna

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Atlas of endometriosis. Author: [edited by] Dan C. Martin; Year: 1993; London; New York: Gower Medical Pub.; New York, N.Y., USA: Distributed in the USA and Canada by Raven Press, c1993; ISBN: 1563755475 http://www.amazon.com/exec/obidos/ASIN/1563755475/icongroupin terna

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Comparison of danazol and high-dose medroxyprogesterone acetate for the management of endometriosis genitals externa. Author: Sakari Telimaa; Year: 1988; Oulu: Dept. of Obstetrics and Gynaecology, University of Oulu, 1988; ISBN: 9514226933

·

Current concepts in endometriosis: proceedings of the Second International Symposium on Endometriosis, held in Houston, Texas, May 1-3, 1989. Author: editors, Dev R. Chadha, Veasy C. Buttram, Jr; Year: 1990; New York: Liss, c1990; ISBN: 0471566853 http://www.amazon.com/exec/obidos/ASIN/0471566853/icongroupin terna

·

Current status of endometriosis: research and management: the proceedings of the 3rd World Congress on Endometriosis, Brussels, June 1992. Author: edited by I. Brosens and J. Donnez; Year: 1993; Carnforth, Lancs, UK; Pearl River, N.Y.: Parthenon Pub. Group, c1993; ISBN: 1850704546 http://www.amazon.com/exec/obidos/ASIN/1850704546/icongroupin terna

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DATTA evaluation: gamete intrafallopian transfer. Author: C. Delance; Year: 1991; Chicago: AMA, 1991

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a “Books” button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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·

Endometriosis: advanced management and surgical techniques: Camran R. Nezhat ... [et al.], editors; managing editor, Gary S. Berger; foreword by Robert L. Barbieri; foreword by Mary Lake Polan. Author: World Congress on Endometriosis (4th: 1994: Salvador, Brazil); Year: 1995; New York: Springer-Verlag, c1995; ISBN: 0387942432 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0387942432/icongroupin terna

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Endometriosis: basic research and clinical practice: the proceedings of the ESHRE Campus Course on Endometriosis, Santa Margherita Ligure, Italy, 11-12 April 1997. Author: edited by P. L. Venturini and J.L.H. Evers; Year: 1998; New York: Parthenon Pub. Group, 1998; ISBN: 1850700575 http://www.amazon.com/exec/obidos/ASIN/1850700575/icongroupin terna

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Endometriosis: contemporary concepts in clinical management. Author: [edited by] Robert S. Schenken; with 12 contributors; Year: 1989; Philadelphia: Lippincott, c1989 [1988 printing]; ISBN: 0397508662 http://www.amazon.com/exec/obidos/ASIN/0397508662/icongroupin terna

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Endometriosis: current understanding and management. Author: edited by Robert W. Shaw; Year: 1995; Oxford; Cambridge, Mass., USA: Blackwell Science, 1995; ISBN: 0865428212 http://www.amazon.com/exec/obidos/ASIN/0865428212/icongroupin terna

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Endometriosis: the enigmatic disease. Author: by Stephen L. Corson; Year: 1992; Durant, OK: Essential Medical Information Systems, 1992; ISBN: 0929240421 http://www.amazon.com/exec/obidos/ASIN/0929240421/icongroupin terna

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Endometriosis and other disorders and infections: the proceedings of the 12th World Congress on Fertility and Sterility, Singapore, October 1986. Author: edited by Eng-Soon Teoh, S. Shan Ratnam, and KwangMeng Seng; Year: 1987; Carnforth, Lancs., U.K.; Park Ridge, N.J., U.S.A.: Parthenon Pub. Group, 1987; ISBN: 0940813203 (U.S.) http://www.amazon.com/exec/obidos/ASIN/0940813203/icongroupin terna

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Endometriosis answer: new hope, new help. Author: Niels H. Lauersen and Constance deSwaan; Year: 1988; New York: Rawson Associates, c1988; ISBN: 0892563265 http://www.amazon.com/exec/obidos/ASIN/0892563265/icongroupin terna

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Endometriosis today: advances in research and practice: the proceedings of the Vth World Congress on Endometriosis, Yokohama, Japan, October 1996. Author: edited by H. Minaguchi and O. Sugimoto; Year: 1997; New York: Parthenon Pub. Group, 1997; ISBN: 1850709017 http://www.amazon.com/exec/obidos/ASIN/1850709017/icongroupin terna

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Endometriosis. Author: edited by R.W. Shaw; Year: 1990; Carnforth, Lancs, UK: Park Ridge, N.J., USA: Parthenon Pub. Group, 1990; ISBN: 1850702977

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Endometrium and endometriosis. Author: edited by Michael P. Diamond, Kevin G. Osteen; Year: 1997; Malden, Mass.: Blackwell Science, c1997; ISBN: 0865425027 http://www.amazon.com/exec/obidos/ASIN/0865425027/icongroupin terna

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Fertility, sterility, and contraception. Author: edited by P. Belfort, J.A. Pinotti, and T.K.A.B. Eskes; Year: 1989; Carnforth, Lancs, UK; Park Ridge, N.J., USA: Parthenon Pub. Group, c1989; ISBN: 1850702322 http://www.amazon.com/exec/obidos/ASIN/1850702322/icongroupin terna

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Human endometrium. Author: edited by Carlo Bulletti, Erlio Gurpide, and Carlo Flamigni; Year: 1994; New York, N.Y.: New York Academy of Sciences, 1994; ISBN: 0897668707 (cloth: alk. paper) http://www.amazon.com/exec/obidos/ASIN/0897668707/icongroupin terna

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Hysterectomy. Ratings of appropriateness. Author: K. Hagenfeldt, B. Brorsson, S. J. Serstein; Year: 1995; Stockholm: Swedish Council on Technology Assessment in Health Care, 1995; ISBN: 9187890283

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Lasers in endoscopy. Author: edited by Dan C. Martin; Year: 1990; Santa Fe Springs: American Association of Gynecologic Laparoscopists, c1990; ISBN: 0961674776

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Modern approaches to endometriosis. Author: edited by Eric J. Thomas and John A. Rock; Year: 1991; Dordrecht; Boston: Kluwer Academic Publishers, c1991; ISBN: 0792389018 http://www.amazon.com/exec/obidos/ASIN/0792389018/icongroupin terna

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Overcoming endometriosis: new help from the Endometriosis Association. Author: Mary Lou Ballweg and the Endometriosis Association; foreword by Camran Nezhat; Year: 1987; Chicago: Congdon & Weed, 1987; ISBN: 0865531900 http://www.amazon.com/exec/obidos/ASIN/0865531900/icongroupin terna

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Peritoneal, ovarian and recto-vaginal endometriosis: the identification of three separate diseases. Author: by Michelle Nisolle and Jacques Donnez; Year: 1997; New York: Parthenon Pub. Group, c1997; ISBN: 1850709416 http://www.amazon.com/exec/obidos/ASIN/1850709416/icongroupin terna

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Proceedings of a Symposium on Endometriosis and EndometriosisRelated Infertility, Budapest, September 1987. Author: editors, K.-W. Schweppe, A.E. Schindler; Year: 1989; Budapest: Interpress, [1989]

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Progress in the management of endometriosis: the proceedings of the 4th World Congress on Endometriosis, 25-28 May 1994 Salvador, Bahia, Brazil. Author: edited by Elsimar M. Coutinho; co-edited by Paulo Spinola and Lesley Hanson de Moura; Year: 1995; New York: Parthenon Pub. Group, 1995; ISBN: 1850706514 http://www.amazon.com/exec/obidos/ASIN/1850706514/icongroupin terna

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Recent developments in fertility and sterility series: the proceedings of the XIIIth World Congress on Fertility and Sterility, Marrakesh, October 1989. Author: World Congress on Fertility and Sterility (13th: 1989: Marrakech, Morocco); Year: 1991; Carnforth, Lancs, UK; Park Ridge, N.J., USA: Parthenon Pub. Group, c1991; ISBN: 1850702845 (v. 1) http://www.amazon.com/exec/obidos/ASIN/1850702845/icongroupin terna

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Text and atlas of female infertility surgery. Author: [edited by] Robert B. Hunt; Year: 1999; St. Louis: Mosby, c1999; ISBN: 0815147384 http://www.amazon.com/exec/obidos/ASIN/0815147384/icongroupin terna

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Treatment of endometriosis and other disorders and infections. Author: edited by Y. Boutaleb and A. Gzouli; Year: 1991; Carnforth, Lancs, UK; Park Ridge, N.J., USA: Parthenon Pub. Group, c1991; ISBN: 185070287X http://www.amazon.com/exec/obidos/ASIN/185070287X/icongroupi nterna

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Tubal infertility. Author: Ivo A. Brosens, Alan G. Gordon; foreword by Howard W. Jones, Jr; Year: 1990; Philadelphia: Lippincott; London; New York: Gower Medical Pub., c1990; ISBN: 0397445725 (Lippincott/Gower)

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Understanding and managing endometriosis: advances in research and practice. Author: edited by A. Lemay and R. Maheux; Year: 1999; New York: Parthenon Pub. Group, c1999; ISBN: 1850700702 http://www.amazon.com/exec/obidos/ASIN/1850700702/icongroupin terna

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Chapters on Endometriosis Frequently, endometriosis will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with endometriosis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and endometriosis using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” By making these selections and typing in “endometriosis” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The following is a typical result when searching for book chapters on endometriosis: ·

Cancer and Other Chronic Diseases Source: in New Dimensions in Women's Health. Alexander, L.L.; LaRosa, J.H. London, England, Jones and Bartlett Publishers, pp. 353-384, 1994. Contact: Jones and Bartlett Publishers, One Exeter Plaza, Boston, MA 02116. (617) 859-3900; (800) 832-0034. Summary: Cancer and Other Chronic Diseases, a book chapter in New Dimensions in Women's Health, addresses (1) the major areas of a woman's body where cancer is most likely to occur and the factors that may influence carcinogenesis; (2) general trends in cancer death rates, breast cancer rates, and lung cancer rates for women; (3) differences in cancer incidence, survival, and death rates between minority and nonminority women; (4) differences in chronic disease incidence between minority and nonminority women; (5) common symptoms of fibrocystic breast disease; (6) usual treatment for fibroadenomas; (7) the five levels of classifying breast cancer and their relative survival rates; (8) the major risk factors for breast cancer and the three modalities for breast cancer screening; (9) the surgical procedures associated with breast cancer and the use of tamoxifen as a breast cancer treatment; (10) the purpose of a Papanicolaou (Pap) smear; (11) the classifications of cervical dysplasia, (12) major risk factors for cervical cancer; (13) cervical cancer screening guidelines; (14) the three primary treatment modalities for cervical dysplasia; (15) uterine fibroids; (16) endometriosis; (17) endometrial cancer; (18) ovarian cancer; (19) colorectal cancer; (20) melanoma; (21) skin cancer; (22) lung cancer, (23) arthritis; (24) osteoporosis; (25) lupus;

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(26) diabetes; (27) how pregnancy presents special risks to the diabetic mother; and (28) the seven warning signs of cancer. Knowledge, personal preventive practices, and lifestyle modifications are the best way for a woman to reduce her chances of acquiring cancer or a chronic disease, and they are the best measures to ensure early diagnosis if disease is present. ·

Endometriosis: A Gastroenterologist's Perspective Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 573-579. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 8746418 or (407) 352-3445. Price: $125.00. ISBN: 0721646700. Summary: This gastroenterology text chapter presents a gastroenterologist's perspective on endometriosis, defined as the presence of endometrial glands or stroma outside of the uterus. The authors first consider diagnostic issues, including the interplay between endometriosis and irritable bowel syndrome (IBS). They note that noncyclic symptoms are particularly common in cases of direct gastrointestinal (GI) involvement with endometriosis, and in such cases symptoms may also be influenced by GI activities such as eating or bowel movements. Those areas of the GI tract most contiguous to the uterus are most commonly involved. The authors explore the problem of rectosigmoid endometriosis (RSE), which presents with chronic 'colon' symptoms often indistinguishable from IBS. The authors describe the recommended diagnostic workup and present statistical information about the incidence of RSE; they also briefly discuss treatment options. 61 references.

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Heterotopias and Congenital Malformations Source: in Bork, K., et al. Diseases of the Oral Mucosa and the Lips. Orlando, FL: W.B. Saunders Company. 1993. p. 240-257. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522 (individuals) or (800) 782-4479 (schools); Fax (800) 874-6418 or (407) 3523445; http://www.wbsaunders.com. Price: $99.00 plus shipping and handling. ISBN: 0721640397. Summary: This chapter, from a textbook on diseases of the oral mucosa and the lips, discusses heterotopias and congenital malformations. Heterotopia refers to the presence of normal tissue in the wrong place (also known as ectopic tissue). Congenital malformations are anatomic

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defects, usually reflecting disturbed embryologic processes. Topics covered Fordyce's granules, oral hair, ectopic thyroid gland, hyperplastic foliate papillae (lingual tonsils), enlargement of the lymphoid tissue on the root of the tongue, endometriosis, double lip, Ascher syndrome, abnormalities of the frenulum, fissured tongue, median rhomboid glossitis, ankyloglossia, congenital fistulas (sinuses) of the lip, congenital cleft formation (lips, jaw, palate), facial clefts and related disorders, congenital cysts (epidermoid, dermoid, teratoid, lymphoepithelial, thyroglossal duct, gingival), eruption cyst, gingival cyst of the adult, nasopalatine duct cyst (incisive canal cyst), torus palatinus, torus mandibularis, multiple exostoses, symmetric peripheral fibromas of the jaw, and congenital crease of the lower lip. For each topic, the authors describe the clinical features and present brief therapeutic recommendations. Full-color photographs illustrate the chapter; references are provided for some sections. 35 figures. 79 references.

General Home References In addition to references for endometriosis, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Female Reproductive Health by N. Manassiev (Editor), M. Whitehead (Editor); Hardcover - 300 pages, 1st edition (May 15, 2002), CRC PressParthenon Publishers; ISBN: 1850704910; http://www.amazon.com/exec/obidos/ASIN/1850704910/icongroupinterna · Handbook of Women's Sexual and Reproductive Health by Gina M. Wingood (Editor), Ralph J. Diclemente (Editor); Hardcover - 472 pages (January 1, 2002), Plenum Publishing Corp.; ISBN: 0306466511; http://www.amazon.com/exec/obidos/ASIN/0306466511/icongroupinterna · Your Guy's Guide to Gynecology by Bruce Bekkar M.D., Udo Wahn M.D.; Hardcover - 288 pages (March 2000), North Star Publications Inc.; ISBN: 0965506746; http://www.amazon.com/exec/obidos/ASIN/0965506746/icongroupinterna

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Vocabulary Builder 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]

Calcium: A mineral that the body needs for strong bones and teeth. Calcium may form stones in the kidney. [NIH] Dysplasia: Abnormality of development; in pathology, alteration in size, shape, and organization of adult cells. [EU] Endoscopy: Visual inspection of any cavity of the body by means of an endoscope. [EU] Exostoses: Benign hypertrophy that projects outward from the surface of bone, often containing a cartilaginous component. [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] Glossitis: Inflammation of the tongue. [EU] Granule: A small pill made from sucrose. [EU] Incisive: 1. having the power or quality of cutting. 2. pertaining to the incisor teeth. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]

Malformation: A morphologic defect resulting from an intrinsically abnormal developmental process. [EU] Melanoma: A tumour arising from the melanocytic system of the skin and other organs. When used alone the term refers to malignant melanoma. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU]

Multimedia 125

CHAPTER 7. MULTIMEDIA ON ENDOMETRIOSIS Overview Information on endometriosis can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on endometriosis. 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. If you see an interesting item, visit your local medical library to check on the availability of the title.

Bibliography: Multimedia on Endometriosis The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in endometriosis (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on endometriosis. For more information, follow the hyperlink indicated: ·

Comprehensive review of endometriosis. Source: IMR, Interactive Medical Review; Year: 1996; Format: Electronic resource; Philadelphia, PA: Corporate Technology Ventures, c1996

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·

Contemporary laporoscopic surgery for endometriosis, hysterectomy, ovarian cyst, ectopic pregnancy. Source: by Camran Nezhat, Farr Nezhat, Ceana Nezhat; Year: 1993; Format: Videorecording; Pearl River, N.Y.: Parthenon Pub. Group, c1993

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Conventional and microscopic techniques in infertility surgery. Source: Alan H. DeCherney, Frederick Naftolin; Year: 1980; Format: Slide; [New York]: Medcom, c1980

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Diagnostic imaging in fertility disorders. Source: the Radiological Society of North America; Year: 1988; Format: Videorecording; Oak Brook, Ill.: The Society, c1988

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Endometriosis and adenomyosis. Source: Robert W. Kistner; Year: 1975; Format: Slide; New York: Medcom, c1975

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Endometriosis surgery. Source: produced by Advanced Medical Education, Inc. for the Learning Channel; Year: 1994; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c1994

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Endometriosis. Source: Time Life Medical; produced in association with Sonalysts Studios; Year: 1996; Format: Videorecording; New York, NY: Patient Education Media, c1996

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Endometriosis. Source: [presented by] the University of Texas Health Science Center at Houston; Year: 1990; Format: Videorecording; [Houston, Tex.]: UT/TV, Houston, c1990

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Endometriosis. Source: Loma Linda University School of Medicine; Year: 1964; Format: Filmstrip; Los Angeles: The University; [Thousand Oaks, Calif.: for loan or sale by Film Distributors International], c1964

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Estrogen replacement therapy in patients with previous endometrial and breast cancer. Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital, [and] Marshfield Medical Research Foundation; Year: 1992; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, [1992]

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Evaluation of the ovary : neoplasia, metaplasia, and functional cysts. Source: EduMed Corporation; Year: 1999; Format: Videorecording; Minnetonka, MN: EduMed Corp., c1999

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GnRH agonists. Source: endometriosis / the University of Texas Medical School at Houston; produced by UT-TV, Houston; Year: 1991; Format: Videorecording; [Houston, Tex.: UT/TV], c1991

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Gynecologic disorders. Source: [presented by] Journal of women's health; Year: 1993; Format: Videorecording; Bethesda, MD: BioConferences International, c1993

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·

Gynecological procedures and related injuries. Source: [presented by] Medi/Legal Institute; a VME production; Year: 1988; Format: Videorecording; [Sherman Oaks, Calif.]: The Institute, c1988

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Hysterectomy for diffuse ovarian endometriosis. Source: American College of Surgeons; produced by DG, Davis & Geck; Year: 1983; Format: Videorecording; Danbury, Conn.: American Cyanamid, c1983

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Infertility. Source: endometriosis / [authors, Michael P. Diamond ... [et al.]; Year: 1991; Format: Electronic resource; Baltimore: Williams & Wilkins, c1991

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Laparoscopically assisted transvaginal segmental bowel resection for endometriosis. Source: from the Film Library and the Clinical Congress of ACS; Year: 1995; Format: Videorecording; Woodbury, CT: Ciné-Med, [1995]

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Laparoscopy for endometriosis. Source: Celia E. Dominguez; Year: 2001; Format: Videorecording; Woodbury, CT: Cine-Med, 2001

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Malignant melanoma and its clinical simulators. Source: Darrell S. Rigel; Year: 1986; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1986

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Managing endometriosis today. Source: Marian Damewood; Year: 1986; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1986

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Safe laser endoscopic excision or vaporization of peritoneal endometriosis and removal of endometrioma by the technique of hydrodissection. Source: by Farr R. Nezhat, Camran Nezhat; produced by Video Tape Associates, Business Communications; Year: 1989; Format: Videorecording; Atlanta, Ga.: C. Nezhat, c1989

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Supravaginal hysterectomy for diffuse adenomyosis of the uterus. Source: by Arthur H. Curtis; from Department of Obstetrics and Gynecology, Northwestern University Medical School; Year: 1940; Format: Motion picture; [S.l.: s.n., 1940]

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Thoracic endometriosis. Source: James B. Williams, Jasper F. Williams, J. Winston Harper; produced by Davis & Geck; Year: 1972; Format: Motion picture; Danbury, Conn.: Davis & Geck, [1972]

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Treatment of extensive endometriosis. Source: [presented by] Camran Nezhat in association with LaserSonics; Year: 1986; Format: Videorecording; Santa Clara, CA: Cooper LaserSonics, [1986]

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Videolaseroscopy for the treatment of pelvic and abdominal adhesions. Source: [presented by] Camran Nezhat in association with LaserSonics; Year: 1986; Format: Videorecording; Santa Clara, CA: Cooper LaserSonics, [1986]

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·

Videolaserscopy of bowel endometriosis . Year: 1989; Format: Videorecording; Washington, DC: American College of Obstetricians and Gynecologists, [1989]

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Women's health series. Source: sponsored by U.S. Food and Drug Administration; Potomac Television/Communications, Inc; Year: 1991; Format: Videorecording; Capitol Heights, MD National Audiovisual Center, [1991]

Vocabulary Builder Curettage: The removal of growths or other material from the wall of a cavity or other surface, as with a curet; called also curettement. [EU] Metaplasia: The change in the type of adult cells in a tissue to a form which is not formal for that tissue. [EU] Resection: Excision of a portion or all of an organ or other structure. [EU]

Periodicals and News 129

CHAPTER 8. PERIODICALS AND NEWS ON ENDOMETRIOSIS Overview Keeping up on the news relating to endometriosis can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on endometriosis. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover endometriosis beyond and including those which are published by patient associations mentioned earlier. We will first focus on news services, and then on periodicals. News services, press releases, and newsletters generally use more accessible language, so if you do chose to subscribe to one of the more technical periodicals, make sure that it uses language you can easily follow.

News Services & Press Releases Well before articles show up in newsletters or the popular press, they may appear in the form of a press release or a public relations announcement. One of the simplest ways of tracking press releases on endometriosis is to search the news wires. News wires are used by professional journalists, and have existed since the invention of the telegraph. Today, there are several major “wires” that are used by companies, universities, and other organizations to announce new medical breakthroughs. 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.

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PR Newswire Perhaps the broadest of the wires is PR Newswire Association, Inc. To access this archive, simply go to http://www.prnewswire.com. Below the search box, select the option “The last 30 days.” In the search box, type “endometriosis” or synonyms. The search results are shown by order of relevance. When reading these press releases, do not forget that the sponsor of the release may be a company or organization that is trying to sell a particular product or therapy. Their views, therefore, may be biased. The following is typical of press releases that can be found on PR Newswire: ·

Symbollon Pharmaceuticals Announces First Quarter 2002 Results Summary: MORRIS PLAINS, N.J., April 30 /PRNewswire-FirstCall/ -Immunomedics, Inc. (Nasdaq: IMMU) today announced the issuance of two new patents covering therapeutics and diagnostic imaging agents and methods. U.S. Patent 6,331,175 involves a method and kit for treating organs and tissues that are abnormal or misplaced. The second patent, issued in Singapore as application 46446, provides a method and reagents for detecting cardiovascular lesions. The therapy patent provides a non-surgical method for ablating, or destroying, abnormal organs and tissues in the body by administering antibodies or antibody fragments specific to hormone receptors or growth factors, whereby the antibody or fragment is bound to a chemical or radiation ablation agent. Examples of tissues or organs that may require removal by non-surgical methods are ovaries, benign and malignant prostate cells, fibrocystic breast disease, and displaced (ectopic) endometrial cells, such as in endometriosis. The antibodies and fragments also include those specific for growth factor receptors, such as epidermal growth factor receptor, or EGFR. "Our prior patent on this subject covered only diagnostic imaging of these misplaced or diseased tissues, including even normal organ imaging, but this new patent now accomplishes non-invasive therapy of various conditions, including benign and malignant prostate cells, endometriosis, and premalignant breast disease," explained Immunomedics' President and Chief Executive Officer, Cynthia L. Sullivan.

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The second patent, covers cardiovascular imaging methods whereby myocardial infarction, atherosclerotic plaques, and clots can be imaged by radiolabeled antibodies and antibody fragments to white blood cell markers, as well as the use of antibody combinations against different targets such as fibrin, myosin, or platelets. Ms. Sullivan also commented on this patent by stating: "This Singapore counterpart to our U.S. and European patents opens opportunities for us to exploit this technology in Asia." "Antibody mixtures could enhance the potential sensitivity of the imaging agent for these cardiovascular diseases, which is not unlike our general approach to using antibody combinations in lymphoma and other cancer therapies," she commented further. Immunomedics is a biopharmaceutical company focused on the development, manufacture and commercialization of diagnostic imaging and therapeutic products for the detection and treatment of cancer and infectious diseases. Integral to these products are highly specific monoclonal antibodies and antibody fragments designed to deliver radioisotopes and chemotherapeutic agents to tumors and sites of infection. Immunomedics has five therapeutic products in clinical trials and has two marketed diagnostic imaging products. The most advanced therapeutic product candidates are LymphoCide(TM) (epratuzumab), which is in Phase II and Phase III clinical trials for the treatment of non-Hodgkin's lymphoma, and CEACide(TM) (labetuzumab), which is in Phase I/II clinical trials for the treatment of certain solid tumors. This release, in addition to historical information, contains forwardlooking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Such statements, including statements regarding clinical trials, involve significant risks and uncertainties and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, risks associated with new product development (including clinical trials outcome and regulatory requirements/actions), competitive risks to marketed products and availability of financing and other sources of capital, as well as the risks discussed in the Company's Quarterly Report on Form 10-Q for the quarter ended December 31, 2001.

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Company Contact: Rebecca Kinner, Investor Relations, (973) 605-8200, extension 263. Visit the company's web site at http://www.Immunomedics.

Reuters The Reuters' Medical News database can be very useful in exploring news archives relating to endometriosis. While some of the listed articles are free to view, others can be purchased for a nominal fee. To access this archive, go to http://www.reutershealth.com/frame2/arch.html and search by “endometriosis” (or synonyms). The following was recently listed in this archive for endometriosis: ·

Danazol use for endometriosis linked to ovarian cancer risk Source: Reuters Industry Breifing Date: March 18, 2002 http://www.reuters.gov/archive/2002/03/18/business/links/20020318 clin015.html

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Iceland study finds genetic link to endometriosis Source: Reuters Health eLine Date: February 28, 2002 http://www.reuters.gov/archive/2002/02/28/eline/links/20020228elin 024.html

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Autoimmune disease more likely with endometriosis Source: Reuters Health eLine Date: February 26, 2002 http://www.reuters.gov/archive/2002/02/26/eline/links/20020226elin 015.html

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Cyproterone or OCs effective for recurrent pelvic pain after endometriosis surgery Source: Reuters Industry Breifing Date: February 15, 2002 http://www.reuters.gov/archive/2002/02/15/business/links/20020215 clin002.html

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Endometriosis may be an autoimmune disease Source: Reuters Medical News Date: September 06, 2001 http://www.reuters.gov/archive/2001/09/06/professional/links/20010 906clin001.html

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Oxagen, Cerylid partner to study genetic causes of endometriosis Source: Reuters Industry Breifing Date: August 28, 2001 http://www.reuters.gov/archive/2001/08/28/business/links/20010828 inds006.html

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Zonagen hires Bridge Organics to produce new agents for endometriosis Source: Reuters Industry Breifing Date: June 15, 2001 http://www.reuters.gov/archive/2001/06/15/business/links/20010615 inds005.html

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Rise in leptin levels during endometriosis treatment points to adipogonadal axis Source: Reuters Medical News Date: August 10, 2000 http://www.reuters.gov/archive/2000/08/10/professional/links/20000 810clin004.html

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Inhibin B levels low during ovarian stimulation in women with endometriosis Source: Reuters Medical News Date: July 28, 2000 http://www.reuters.gov/archive/2000/07/28/professional/links/20000 728clin008.html

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Proteins may signal fertility in endometriosis patients Source: Reuters Health eLine Date: July 06, 2000 http://www.reuters.gov/archive/2000/07/06/eline/links/20000706elin 010.html

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Rare but there: endometriosis after C-section Source: Reuters Health eLine Date: April 13, 2000 http://www.reuters.gov/archive/2000/04/13/eline/links/20000413elin 013.html

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More awareness of incisional endometriosis needed among general surgeons Source: Reuters Medical News Date: April 11, 2000 http://www.reuters.gov/archive/2000/04/11/professional/links/20000 411prof009.html

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·

Goserelin slows endometriosis recurrence after conservative surgery Source: Reuters Medical News Date: July 16, 1999 http://www.reuters.gov/archive/1999/07/16/professional/links/19990 716clin002.html

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HRT recommended with Gn-RH agonist treatment of endometriosis Source: Reuters Medical News Date: July 05, 1999 http://www.reuters.gov/archive/1999/07/05/professional/links/19990 705clin010.html

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Endometriosis associated with estrogen receptor gene variability Source: Reuters Medical News Date: June 30, 1999 http://www.reuters.gov/archive/1999/06/30/professional/links/19990 630clin003.html

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Endometriosis described 300 years ago Source: Reuters Health eLine Date: June 28, 1999 http://www.reuters.gov/archive/1999/06/28/eline/links/19990628elin 003.html

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Endometriosis may increase cancer risk Source: Reuters Health eLine Date: April 21, 1999 http://www.reuters.gov/archive/1999/04/21/eline/links/19990421elin 018.html

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Depot leuprolide effective empiric treatment for suspected endometriosis Source: Reuters Medical News Date: January 20, 1999 http://www.reuters.gov/archive/1999/01/20/professional/links/19990 120clin006.html

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Age, parity and other characteristics predict minimal, mild endometriosis in infertile women Source: Reuters Medical News Date: August 27, 1998 http://www.reuters.gov/archive/1998/08/27/professional/links/19980 827epid002.html

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Pregnancy after surgery for endometriosis confers long-term protection against recurrence Source: Reuters Medical News Date: May 21, 1998 http://www.reuters.gov/archive/1998/05/21/professional/links/19980 521clin004.html

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Goserelin Plus Assisted Reproduction Effective For Infertile Women With Endometriosis Source: Reuters Medical News Date: March 20, 1998 http://www.reuters.gov/archive/1998/03/20/professional/links/19980 320clin003.html

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Leuprolide Plus Add-Back Hormones Suppresses Endometriosis Pain Source: Reuters Medical News Date: January 20, 1998 http://www.reuters.gov/archive/1998/01/20/professional/links/19980 120clin004.html

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Pelvic Irradiation Palliative In Recurrent Endometriosis Source: Reuters Medical News Date: November 17, 1997 http://www.reuters.gov/archive/1997/11/17/professional/links/19971 117clin006.html

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Progestins Effective First-Line Therapy For Symptomatic Endometriosis Source: Reuters Medical News Date: October 06, 1997 http://www.reuters.gov/archive/1997/10/06/professional/links/19971 006clin003.html

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Endometriosis Surgery Helps Symptoms Source: Reuters Health eLine Date: September 08, 1997 http://www.reuters.gov/archive/1997/09/08/eline/links/19970908elin 004.html

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Surgical Treatment Improves Fertility In Women With Mild Or Minimal Endometriosis Source: Reuters Medical News Date: July 24, 1997 http://www.reuters.gov/archive/1997/07/24/professional/links/19970 724clin001.html

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Surgery Helps Fertility in Mild Endometriosis Source: Reuters Health eLine Date: July 23, 1997 http://www.reuters.gov/archive/1997/07/23/eline/links/19970723elin 006.html

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Endometriosis Drug: Fewer Side Effects? Source: Reuters Health eLine Date: July 15, 1997 http://www.reuters.gov/archive/1997/07/15/eline/links/19970715elin 002.html

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Cancer Risk Elevated In Women With Endometriosis Source: Reuters Medical News Date: April 11, 1997 http://www.reuters.gov/archive/1997/04/11/professional/links/19970 411epid001.html

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Endometriosis Ups Cancer Risk Source: Reuters Health eLine Date: April 04, 1997 http://www.reuters.gov/archive/1997/04/04/eline/links/19970404elin 007.html

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Monocyte Chemotactic Protein-1 Elevated In Endometriosis Source: Reuters Medical News Date: January 28, 1997 http://www.reuters.gov/archive/1997/01/28/professional/links/19970 128clin006.html

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Depot Medroxyprogesterone Acetate Effective For Endometriosis Source: Reuters Medical News Date: September 13, 1996 http://www.reuters.gov/archive/1996/09/13/professional/links/19960 913clin009.html

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Endometriosis Adversely Affects Oocyte's Meiotic Ability Source: Reuters Medical News Date: April 18, 1996 http://www.reuters.gov/archive/1996/04/18/professional/links/19960 418clin006.html

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IVF-ET: Option For Couples With Endometriosis-Related Infertility Source: Reuters Medical News Date: April 03, 1996 http://www.reuters.gov/archive/1996/04/03/professional/links/19960 403clin003.html

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·

Reliable Test For Detecting Deep Endometriosis Described Source: Reuters Medical News Date: February 08, 1996 http://www.reuters.gov/archive/1996/02/08/professional/links/19960 208clin007.html

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RU486: Effective Against Endometriosis Source: Reuters Medical News Date: January 08, 1996 http://www.reuters.gov/archive/1996/01/08/professional/links/19960 108clin001.html

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Research Supports Theory Of Pathogenesis of Endometriosis Source: Reuters Medical News Date: December 01, 1995 http://www.reuters.gov/archive/1995/12/01/professional/links/19951 201scie003.html

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Endometriosis Therapy Refined Source: Reuters Medical News Date: November 20, 1995 http://www.reuters.gov/archive/1995/11/20/professional/links/19951 120clin006.html

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Hysterectomy Without Oophorectomy For Endometriosis Linked With Symptom Recurrence Source: Reuters Medical News Date: October 26, 1995 http://www.reuters.gov/archive/1995/10/26/professional/links/19951 026clin005.html

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Is Red Hair A Marker For Endometriosis? Source: Reuters Medical News Date: October 17, 1995 http://www.reuters.gov/archive/1995/10/17/professional/links/19951 017clin008.html

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Hormone Therapies Benefit Patients With Endometriosis Source: Reuters Medical News Date: September 18, 1995 http://www.reuters.gov/archive/1995/09/18/professional/links/19950 918clin005.html

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·

Depot Leuprolide Acetate Not Ideal Endometriosis Therapy Source: Reuters Medical News Date: June 16, 1995 http://www.reuters.gov/archive/1995/06/16/professional/links/19950 616clin004.html

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Causes Of Endometriosis In Parous Women Identified Source: Reuters Medical News Date: June 05, 1995 http://www.reuters.gov/archive/1995/06/05/professional/links/19950 605epid001.html 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 at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search at: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within their 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.

Internet Wire Internet Wire is more focused on technology than the other wires. To access this site, go to http://www.internetwire.com and use the “Search Archive” option. Type in “endometriosis” (or synonyms). As this service is oriented to technology, you may wish to search for press releases covering diagnostic procedures or tests that you may have read about.

Search Engines Free-to-view news can also be found in the news section of your favorite search engines (see the health news page at Yahoo:

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http://dir.yahoo.com/Health/News_and_Media/, or use this Web site’s general news search page http://news.yahoo.com/. Type in “endometriosis” (or synonyms). If you know the name of a company that is relevant to endometriosis, you can go to any stock trading Web site (such as www.etrade.com) and search for the company name there. News items across various news sources are reported on indicated hyperlinks.

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 “endometriosis” (or synonyms).

Newsletter Articles If you choose not to subscribe to a newsletter, you can nevertheless find references to newsletter articles. We recommend that you use the Combined Health Information Database, while limiting 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.” By making these selections, and typing in “endometriosis” (or synonyms) into the “For these words:” box, you will only receive results on newsletter articles. You should check back periodically with this database as it is updated every 3 months. The following is a typical result when searching for newsletter articles on endometriosis: ·

Pelvic Pain: IBS and Endometriosis Source: Intestinal Fortitude. 8(2): 3. 1997. Contact: Available from Intestinal Disease Foundation. 1323 Forbes Avenue, Suite 200, Pittsburgh, PA 15219. (412) 261-5888. Summary: This article, from a patient education newsletter, offers information on pelvic pain, and the role of irritable bowel syndrome (IBS) and endometriosis as causes of such pain. Because the nerves supplying the uterus, ovaries, bowel, bladder, and kidney all overlap, it can be very

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difficult to determine the cause of abdominal pain. The author notes that in women with chronic pelvic pain, about 15 percent have IBS and about 28 percent have endometriosis. Endometriosis is a disease in which the cells lining the uterus break out of the uterus and implant in other parts of the body, including the ovaries, tubes, bowel, and pelvis. Once these cells implant, they grow during the menstrual cycle and bleed during the woman's period. If the endometriosis cells are near the bowel, this can cause changes in bowel movements and pain similar to that caused by IBS. The author explores the symptoms, diagnosis, and treatment of these conditions. If a patient has chronic pelvic pain, the physician may try treating for IBS or endometriosis to see if the patient responds before making her undergo the risks of surgery. The author concludes that it is important to watch the symptoms and their relationship to different life events closely to help determine the cause of the pain. Fortunately, both diseases can usually be controlled. ·

IC and Sexuality: Communication Breakdown Source: ICA Update. 14(4): 1-4. 2000. Contact: Available from Interstitial Cystitis Association. 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Website: www.ichelp.org. Summary: This article explores the issue of sexuality for people with interstitial cystitis (IC), focusing on the importance of communication for coping with any sexual difficulties. With IC, painful sexual intercourse (dyspareunia) can occur for a number of reasons, many of which are still undefined. Theories about the causes of dyspareunia in IC include increased pelvic vascularity (blood flow to the pelvic region); increased nerve activation; pelvic floor dysfunction; sympathetic reflux dystrophy (which can cause diminished blood flow to the pelvic region and heighten pain); trauma to the bladder and surrounding areas during intercourse; irritating neurotransmitters; and related diseases, such as vulvodynia and or endometriosis. Regardless of cause, the pain is real and it can occur before, during, and after sexual activity. The author cautions that it may be difficult to find a physician or other health care provider who understands both the physical and emotional sides of sexual problems that are frequently associated with IC or who is comfortable discussing them with the patient. Having to contend with such a difficult disease as IC can amplify the difficulties that may develop within any intimate relationship. The key ingredient to better sexual expression and understanding, despite having IC, is communication. The author recommends talking openly, educating one's partner about IC, taking care of oneself, and experimenting with sexual alternatives. The

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author reports on information gleaned from a small group of patients with IC who discussed how they were working through their sexual intimacy issues.

Academic Periodicals covering Endometriosis Academic periodicals can be a highly technical yet valuable source of information on endometriosis. We have compiled the following list of periodicals known to publish articles relating to endometriosis and which are currently indexed within the National Library of Medicine's PubMed database (follow hyperlinks to view more information, summaries, etc., for each). In addition to these sources, to keep current on articles written on endometriosis published by any of the periodicals listed below, you can simply follow the hyperlink indicated or go to the following Web site: www.ncbi.nlm.nih.gov/pubmed. Type the periodical's name into the search box to find the latest studies published. If you want complete details about the historical contents of a periodical, go to: 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.” The following is a sample of periodicals which publish articles on endometriosis: ·

Alternative Therapies in Health and Medicine. (Altern Ther Health Med) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Alter native+Therapies+in+Health+and+Medicine&dispmax=20&dispstart=0

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Annals of Hematology. (Ann Hematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=An nals+of+Hematology&dispmax=20&dispstart=0

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Clinical Obstetrics and Gynecology. (Clin Obstet Gynecol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Cli nical+Obstetrics+and+Gynecology&dispmax=20&dispstart=0

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Fertility and Sterility. (Fertil Steril) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Fe rtility+and+Sterility&dispmax=20&dispstart=0

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Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. (Gynecol Endocrinol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Gy necological+Endocrinology+:+the+Official+Journal+of+the+International +Society+of+Gynecological+Endocrinology&dispmax=20&dispstart=0

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Planta Medica. (Planta Med) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Pl anta+Medica&dispmax=20&dispstart=0

Vocabulary Builder Cardiovascular: Pertaining to the heart and blood vessels. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Fibrin: The insoluble protein formed from fibrinogen by the proteolytic action of thrombin during normal clotting of blood. Fibrin forms the essential portion of the blood clot. [EU] Infarction: 1. the formation of an infarct. 2. an infarct. [EU] 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] Lymphoma: Any neoplastic disorder of the lymphoid tissue, the term lymphoma often is used alone to denote malignant lymphoma. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the

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properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Palliative: 1. affording relief, but not cure. 2. an alleviating medicine. [EU] Reflux: A backward or return flow. [EU]

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CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help patients with their conditions. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.

NIH Guidelines For the more common diseases, The National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·

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

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·

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

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.28 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:29 ·

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

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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

·

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

·

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,

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). 29 See http://www.nlm.nih.gov/databases/databases.html. 28

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fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html ·

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

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

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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

While all of the above references may be of interest to physicians who study and treat endometriosis, the following are particularly noteworthy.

The NLM Gateway30 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

30

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

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many of NLM's information resources or databases.31 One target audience for the Gateway is the Internet user who is new to NLM's online resources and does not know what information is available or how best to search for it. This audience may include physicians and other healthcare providers, researchers, librarians, students, and, increasingly, patients, their families, and the public.32 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “endometriosis” (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 Items Found Journal Articles 10532 Books / Periodicals / Audio Visual 283 Consumer Health 18 Meeting Abstracts 3 Other Collections 2 Total 10838

HSTAT33 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.34 HSTAT's audience includes healthcare providers, health service researchers, policy makers, insurance companies, consumers, and the information professionals who serve these groups. HSTAT provides access to a wide variety of publications, including clinical practice guidelines, quick-reference guides for clinicians, 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). 32 Other users may find the Gateway useful for an overall search of NLM's information resources. Some searchers may locate what they need immediately, while others will utilize the Gateway as an adjunct tool to other NLM search services such as PubMed® and MEDLINEplus®. The Gateway connects users with multiple NLM retrieval systems while also providing a search interface for its own collections. These collections include various types of information that do not logically belong in PubMed, LOCATORplus, or other established NLM retrieval systems (e.g., meeting announcements and pre-1966 journal citations). The Gateway will provide access to the information found in an increasing number of NLM retrieval systems in several phases. 33 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 34 The HSTAT URL is http://hstat.nlm.nih.gov/. 31

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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.35 Simply search by “endometriosis” (or synonyms) at the following Web site: http://text.nlm.nih.gov. Coffee Break: Tutorials for Biologists36 Some patients may wish to have access to 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. To this end, we recommend “Coffee Break,” 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.37 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.38 This site has new articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. You can access the Coffee Break Web site at http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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. 36 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 37 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. 38 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. 35

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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are a few 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/.

·

Image Engine: Multimedia electronic medical record system that integrates a wide range of digitized clinical images with textual data stored in the University of Pittsburgh Medical Center's MARS electronic medical record system; see the following Web site: http://www.cml.upmc.edu/cml/imageengine/imageEngine.html.

·

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

·

MedWeaver: Prototype system that allows users to search differential diagnoses for any list of signs and symptoms, to search medical literature, and to explore relevant Web sites; see http://www.med.virginia.edu/~wmd4n/medweaver.html.

·

Metaphrase: Middleware component intended for use by both caregivers and medical records personnel. It converts the informal language generally used by caregivers into terms from formal, controlled vocabularies; see the following Web site: http://www.lexical.com/Metaphrase.html.

The Genome Project and Endometriosis With all the discussion in the press about the Human Genome Project, it is only natural that physicians, researchers, and patients want to know about how human genes relate to endometriosis. In the following section, we will discuss databases and references used by physicians and scientists who work in this area.

Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for

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Biotechnology Information (NCBI).39 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI's Entrez database of MEDLINE articles and sequence information. Go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. to search the database. Type “endometriosis” (or synonyms) in the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. By following these links, especially the link titled “Database Links,” you will be exposed to numerous specialized databases that are largely used by the scientific community. These databases are overly technical and seldom used by the general public, but offer an abundance of information. The following is an example of the results you can obtain from the OMIM for endometriosis: ·

Endometriosis Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?131200

Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by the system of the body associated with it. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to re-visit it from time to time. The following systems and associated disorders are addressed: ·

Cancer: Uncontrolled cell division. Examples: Breast And Ovarian Cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von

Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

39

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Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html ·

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn's disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

·

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

·

Signals: Cellular messages. Examples: Ataxia telangiectasia, Baldness, Cockayne syndrome, Glaucoma, SRY: sex determination, Tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

·

Transporters: Pumps and channels. Examples: Cystic Fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson's disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html

Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

·

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

·

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

·

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

Physician Guidelines and Databases 153

·

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

·

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

·

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

·

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

·

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

·

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

·

NCBI's Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genom e, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” In the box next to “for,” enter “endometriosis” (or synonyms) and click “Go.”

Jablonski's Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database40 This online resource can be quite useful. It has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html you can also search across syndromes using an alphabetical index:. At Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.

40

154 Endometriosis

http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html search by keywords.

you

can

The Genome Database41 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB's mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “endometriosis” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms). This database is extremely technical as it was created for specialists. The articles are the results which are the most accessible to non-professionals and often listed under the heading “Citations.” The contact names are also accessible to non-professionals.

Specialized References The following books are specialized references written for professionals interested in endometriosis (sorted alphabetically by title, hyperlinks provide rankings, information, and reviews at Amazon.com): ·

Comprehensive Gynecology by Morton A. Stenchever, M.D. (Editor), et al; Hardcover - 1325 pages, 4th edition (April 27, 2001), Mosby, Inc.;

Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html#mission.

41

Physician Guidelines and Databases 155

ISBN: 032301402X; http://www.amazon.com/exec/obidos/ASIN/032301402X/icongroupinter na ·

Current Clinical Strategies: Gynecology and Obstetrics 2002: With ACOG Guidelines by Paul D. Chan, Christopher R. Winkle; Paperback 140 pages, 6th edition (January 15, 2002), Current Clinical Strategies; ISBN: 192962204X; http://www.amazon.com/exec/obidos/ASIN/192962204X/icongroupinter na

·

Danforth's Handbook of Obstetrics and Gynecology by James R. Scott, M.D., et al; Paperback, 2nd edition (April 15, 2003), Lippincott, Williams & Wilkins Publishers; ISBN: 0781723647; http://www.amazon.com/exec/obidos/ASIN/0781723647/icongroupinter na

·

Gynecologic Oncology; Hardcover, 1st edition (December 2002), Landes Bioscience; ISBN: 1570595828; http://www.amazon.com/exec/obidos/ASIN/1570595828/icongroupinter na

·

The Johns Hopkins Manual of Gynecology and Obstetrics (The Spiral Manual Series) by Brandon J. Bankowski (Editor); Paperback, 2nd edition (June 2002), Lippincott, Williams & Wilkins Publishers; ISBN: 0781735955; http://www.amazon.com/exec/obidos/ASIN/0781735955/icongroupinter na

·

Novak's Gynecology by Jonathan S. Berek, Paula A. Hillard; Hardcover, 13th edition (July 26, 2002), Lippincott, Williams & Wilkins Publishers; ISBN: 078173262X; http://www.amazon.com/exec/obidos/ASIN/078173262X/icongroupinter na

·

Obstetrics and Gynecology on Call by Horowitz; Paperback, 2nd edition (December 31, 2003), Appleton & Lange; ISBN: 0838571417; http://www.amazon.com/exec/obidos/ASIN/0838571417/icongroupinter na

·

Solving Patient Problems in Ob/Gyn: The Clerkship Series by Philippe H. Girerd, Tom Peng; Paperback, 1st edition (September 2002), Fence Creek Publishing; ISBN: 1889325082; http://www.amazon.com/exec/obidos/ASIN/1889325082/icongroupinter na

·

Textbook of Gynecology : An Evidence Based Approach by F. Sanfillipo; Hardcover (June 2002), CRC Press-Parthenon Publishers;

156 Endometriosis

ISBN: 184214040X; http://www.amazon.com/exec/obidos/ASIN/184214040X/icongroupinter na

Dissertations 157

CHAPTER 10. DISSERTATIONS ON ENDOMETRIOSIS Overview University researchers are active in studying almost all known diseases. The result of research is often published in the form of Doctoral or Master's dissertations. You should understand, therefore, that applied diagnostic procedures and/or therapies can take many years to develop after the thesis that proposed the new technique or approach was written. In this chapter, we will give you a bibliography on recent dissertations relating to endometriosis. You can read about these in more detail using the Internet or your local medical library. We will also provide you with information on how to use the Internet to stay current on dissertations.

Dissertations on Endometriosis ProQuest Digital Dissertations is the largest archive of academic dissertations available. From this archive, we have compiled the following list covering dissertations devoted to endometriosis. You will see that the information provided includes the dissertation’s title, its author, and the author’s institution. To read more about the following, simply use the Internet address indicated. The following covers recent dissertations dealing with endometriosis:

158 Endometriosis

·

From 'career Woman's' Disease to 'an Epidemic Ignored': Endometriosis in United States Culture since 1948 by Sanmiguel, Lisa Michelle; Phd from University of Illinois at Urbana-champaign, 2000, 474 pages http://wwwlib.umi.com/dissertations/fullcit/9955666

·

Living with Endometriosis: Women's Experiences with Disease Stressors, Coping, and Medical Support by Poulin, Elaine Marie; Phd from State University of New York at Buffalo, 2000, 125 pages http://wwwlib.umi.com/dissertations/fullcit/9958299

·

Matrix Metalloproteinase-3 in Uterus and Endometriosis by Cox, Kathryn Elizabeth; Phd from University of Missouri - Columbia, 2001, 200 pages http://wwwlib.umi.com/dissertations/fullcit/3012963

·

Persistent Organic Pollutants: Biomonitoring and Their Role in Endometriosis-related Infertility by Pauwels, An; Phd from Universitaire Instelling Antwerpen (belgium), 2000, 218 pages http://wwwlib.umi.com/dissertations/fullcit/9992667

·

Psychosocial Adjustment and Coping Strategies of Women with Endometriosis by Silverton, Rona Susan, Phd from New York University, 1990, 584 pages http://wwwlib.umi.com/dissertations/fullcit/9124707

·

The Use of Thermal Biofeedback in the Treatment of Pain Associated with Endometriosis: Preliminary Findings by Hawkins, Rebecca Sue; Phd from Fuller Theological Seminary, School of Psychology, 2000, 123 pages http://wwwlib.umi.com/dissertations/fullcit/9974146

·

'well Now, Who's the Doctor Here?': Boundary-work and Transgression in Patient and Expert Knowledges of Endometriosis by Whelan, Emma Christine; Phd from Carleton University (canada), 2001, 501 pages http://wwwlib.umi.com/dissertations/fullcit/NQ57638

Dissertations 159

Keeping Current As previously mentioned, an effective way to stay current on dissertations dedicated to endometriosis is to use the database called ProQuest Digital Dissertations via the Internet, located at the following Web address: http://wwwlib.umi.com/dissertations. The site allows you to freely access the last two years of citations and abstracts. Ask your medical librarian if the library has full and unlimited access to this database. From the library, you should be able to do more complete searches than with the limited 2-year access available to the general public.

161

PART III. APPENDICES

ABOUT PART III Part III is a collection of appendices on general medical topics which may be of interest to patients with endometriosis and related conditions.

Researching Your Medications 163

APPENDIX A. RESEARCHING YOUR MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to patients with endometriosis. While a number of hard copy or CD-Rom resources are available to patients and physicians for research purposes, a more flexible method is to use Internet-based databases. In this chapter, we will begin with a general overview of medications. We will then proceed to outline official recommendations on how you should view your medications. You may also want to research medications that you are currently taking for other conditions as they may interact with medications for endometriosis. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in the treatment of endometriosis. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

164 Endometriosis

Your Medications: The Basics42 The Agency for Health Care Research and Quality has published extremely useful guidelines on how you can best participate in the medication aspects of endometriosis. Taking medicines is not always as simple as swallowing a pill. It can involve many steps and decisions each day. The AHCRQ recommends that patients with endometriosis take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions early, you may avoid problems later. Here are some points to cover each time a new medicine is prescribed: ·

Ask about all parts of your treatment, including diet changes, exercise, and medicines.

·

Ask about the risks and benefits of each medicine or other treatment you might receive.

·

Ask how often you or your doctor will check for side effects from a given medication.

Do not hesitate to ask what is important to you about your medicines. You may want a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost, or how the medicine might affect how you live or work. Or, you may want the medicine your doctor believes will work the best. Telling your doctor will help him or her select the best treatment for you. Do not be afraid to “bother” your doctor with your concerns and questions about medications for endometriosis. You can also talk to a nurse or a pharmacist. They can help you better understand your treatment plan. Feel free to bring a friend or family member with you when you visit your doctor. Talking over your options with someone you trust can help you make better choices, especially if you are not feeling well. Specifically, ask your doctor the following: ·

The name of the medicine and what it is supposed to do.

·

How and when to take the medicine, how much to take, and for how long.

·

What food, drinks, other medicines, or activities you should avoid while taking the medicine.

·

What side effects the medicine may have, and what to do if they occur.

42

This section is adapted from AHCRQ: http://www.ahcpr.gov/consumer/ncpiebro.htm.

Researching Your Medications 165

·

If you can get a refill, and how often.

·

About any terms or directions you do not understand.

·

What to do if you miss a dose.

·

If there is written information you can take home (most pharmacies have information sheets on your prescription medicines; some even offer large-print or Spanish versions).

Do not forget to tell your doctor about all the medicines you are currently taking (not just those for endometriosis). This includes prescription medicines and the medicines that you buy over the counter. Then your doctor can avoid giving you a new medicine that may not work well with the medications you take now. When talking to your doctor, you may wish to prepare a list of medicines you currently take, the reason you take them, and how you take them. Be sure to include the following information for each: ·

Name of medicine

·

Reason taken

·

Dosage

·

Time(s) of day

Also include any over-the-counter medicines, such as: ·

Laxatives

·

Diet pills

·

Vitamins

·

Cold medicine

·

Aspirin or other pain, headache, or fever medicine

·

Cough medicine

·

Allergy relief medicine

·

Antacids

·

Sleeping pills

·

Others (include names)

166 Endometriosis

Learning More about Your Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications your doctor has recommended for endometriosis. 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 www.usp.org. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ 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.43 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 Pharmacopoeia (USP). It is important to read the disclaimer by the USP (http://www.nlm.nih.gov/medlineplus/drugdisclaimer.html) before using the information provided. Of course, we as editors cannot be certain as to what medications you are taking. Therefore, we have compiled a list of medications associated with the treatment of endometriosis. Once again, due to space limitations, we only list a sample of medications and provide hyperlinks to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to endometriosis:

Though cumbersome, the FDA database can be freely browsed at the following site: www.fda.gov/cder/da/da.htm.

43

Researching Your Medications 167

Clomiphene ·

Systemic - U.S. Brands: Clomid; Milophene; Serophene http://www.nlm.nih.gov/medlineplus/druginfo/clomiphenesyst emic202151.html

Danazol ·

Systemic - U.S. Brands: Danocrine http://www.nlm.nih.gov/medlineplus/druginfo/danazolsystemi c202180.html

Estrogens ·

Systemic - U.S. Brands: Alora; Aquest; Climara; Clinagen LA 40; Delestrogen; depGynogen; Depo-Estradiol; Depogen; Dioval 40; Dioval XX; Dura-Estrin; Duragen-20; E-Cypionate; Estinyl; Estrace; Estraderm; Estragyn 5; Estragyn LA 5; Estra-L 40; Estratab; Estro-A; Estro-Cyp; Estro http://www.nlm.nih.gov/medlineplus/druginfo/estrogenssystem ic202226.html

·

Vaginal - U.S. Brands: Estrace; Estring; Ogen; Ortho Dienestrol; Premarin http://www.nlm.nih.gov/medlineplus/druginfo/estrogensvagina l202227.html

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; Lo http://www.nlm.nih.gov/medlineplus/druginfo/estrogensandpr ogestinsoralcont202228.html

Goserelin ·

Systemic - U.S. Brands: Zoladex http://www.nlm.nih.gov/medlineplus/druginfo/goserelinsystem ic202267.html

Leuprolide ·

Systemic - U.S. Brands: Lupron; Viadur http://www.nlm.nih.gov/medlineplus/druginfo/leuprolidesyste mic202322.html

168 Endometriosis

Nafarelin ·

Systemic - U.S. Brands: Synarel http://www.nlm.nih.gov/medlineplus/druginfo/nafarelinsystem ic202646.html

Progestins for Noncontraceptive Use ·

Systemic - U.S. Brands: Amen; Aygestin; Crinone; Curretab; Cycrin; Depo-Provera; Gesterol 50; Gesterol LA 250; Hy/Gestrone; Hylutin; Megace; Prodrox; Prometrium; Pro-Span; Provera http://www.nlm.nih.gov/medlineplus/druginfo/progestinsforno ncontraceptiveu202758.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. You may be able to access these sources from your local medical library or your doctor's office.

Reuters Health Drug Database The Reuters Health Drug Database can be searched by keyword at the hyperlink: http://www.reutershealth.com/frame2/drug.html. The following medications are listed in the Reuters' database as associated with endometriosis (including those with contraindications):44 ·

Danazol http://www.reutershealth.com/atoz/html/Danazol.htm

·

Goserelin Acetate http://www.reutershealth.com/atoz/html/Goserelin_Acetate.htm

·

Leuprolide Acetate http://www.reutershealth.com/atoz/html/Leuprolide_Acetate.htm

·

Mifepristone http://www.reutershealth.com/atoz/html/Mifepristone.htm

·

Nafarelin Acetate http://www.reutershealth.com/atoz/html/Nafarelin_Acetate.htm

44

Adapted from A to Z Drug Facts by Facts and Comparisons.

Researching Your Medications 169

Mosby's GenRx Mosby's GenRx 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. Information can be obtained at the following hyperlink: http://www.genrx.com/Mosby/PhyGenRx/group.html.

Physicians Desk Reference The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink: http://physician.pdr.net/physician/templates/en/acl/psuser_t.htm.

Other Web Sites A number of additional Web sites discuss drug information. As an example, you may like to look at www.drugs.com which 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. which allows users to download articles on various drugs and therapeutics for a nominal fee: http://www.medletter.com/.

Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for patients with endometriosis--not because they are used in the treatment process, but because of contraindications, or side effects. Medications with contraindications are those that could react with drugs used to treat endometriosis or potentially create deleterious side effects in patients with endometriosis. You should ask your physician about any contraindications, especially as these might apply to other medications that you may be taking for common ailments. Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side

170 Endometriosis

effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it's especially important to read the label every time you use a medication. When your doctor prescribes a new drug, discuss all over-thecounter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals you take as well as the foods you eat. Ask your pharmacist for the package insert for each prescription drug you take. The package insert provides more information about potential drug interactions.

A Final Warning At some point, you may hear of alternative medications from friends, relatives, or in the news media. Advertisements may suggest that certain alternative drugs can produce positive results for patients with endometriosis. Exercise caution--some of these drugs may have fraudulent claims, and others may actually hurt you. The Food and Drug Administration (FDA) is the official U.S. agency charged with discovering which medications are likely to improve the health of patients with endometriosis. The FDA warns patients to watch out for45: ·

Secret formulas (real scientists share what they know)

·

Amazing breakthroughs or miracle cures (real breakthroughs don't happen very often; when they do, real scientists do not call them amazing or miracles)

·

Quick, painless, or guaranteed cures

This section has been adapted from http://www.fda.gov/opacom/lowlit/medfraud.html.

45

Researching Your Medications 171

·

If it sounds too good to be true, it probably isn't true.

If you have any questions about any kind of 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, 1888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

General References In addition to the resources provided earlier in this chapter, the following general references describe medications (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

New Pharmacological Approaches to Reproductive Health and Healthy Ageing : Symposium on the Occasion of the 80th Birthday of Professor Egon diczfalusy by Werner-Karl Raff (Editor), et al; Hardcover (December 2001), Springer Verlag; ISBN: 354042234X; http://www.amazon.com/exec/obidos/ASIN/354042234X/icongroupinterna

·

Complete Guide to Prescription and Nonprescription Drugs 2001 (Complete Guide to Prescription and Nonprescription Drugs, 2001) by H. Winter Griffith, Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/039952634X/icongroupinterna

·

The Essential Guide to Prescription Drugs, 2001 by James J. Rybacki, James W. Long; Paperback - 1274 pages (2001), Harper Resource; ISBN: 0060958162; http://www.amazon.com/exec/obidos/ASIN/0060958162/icongroupinterna

·

Handbook of Commonly Prescribed Drugs by G. John Digregorio, Edward J. Barbieri; Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/0942447417/icongroupinterna

·

Johns Hopkins Complete Home Encyclopedia of Drugs 2nd ed. by Simeon Margolis (Ed.), Johns Hopkins; Hardcover - 835 pages (2000), Rebus; ISBN: 0929661583; http://www.amazon.com/exec/obidos/ASIN/0929661583/icongroupinterna

·

Medical Pocket Reference: Drugs 2002 by Springhouse Paperback 1st edition (2001), Lippincott Williams & Wilkins Publishers; ISBN: 1582550964; http://www.amazon.com/exec/obidos/ASIN/1582550964/icongroupinterna

172 Endometriosis

·

PDR by Medical Economics Staff, Medical Economics Staff Hardcover 3506 pages 55th edition (2000), Medical Economics Company; ISBN: 1563633752; http://www.amazon.com/exec/obidos/ASIN/1563633752/icongroupinterna

·

Pharmacy Simplified: A Glossary of Terms by James Grogan; Paperback 432 pages, 1st edition (2001), Delmar Publishers; ISBN: 0766828581; http://www.amazon.com/exec/obidos/ASIN/0766828581/icongroupinterna

·

Physician Federal Desk Reference by Christine B. Fraizer; Paperback 2nd edition (2001), Medicode Inc; ISBN: 1563373971; http://www.amazon.com/exec/obidos/ASIN/1563373971/icongroupinterna

·

Physician's Desk Reference Supplements Paperback - 300 pages, 53 edition (1999), ISBN: 1563632950; http://www.amazon.com/exec/obidos/ASIN/1563632950/icongroupinterna

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Clomiphene: A stilbene derivative that functions both as a partial estrogen agonist and complete estrogen antagonist depending on the target tissue. It antagonizes the estrogen receptor thereby initiating or augmenting ovulation in anovulatory women. [NIH] Dienestrol: A synthetic, non-steroidal estrogen structurally related to stilbestrol. It is used, usually as the cream, in the treatment of menopausal and postmenopausal symptoms. [NIH] Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary cushing syndrome. [NIH]

Researching Alternative Medicine 173

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE Overview Complementary and alternative medicine (CAM) is one of the most contentious aspects of modern medical practice. You may have heard of these treatments on the radio or on television. Maybe you have seen articles written about these treatments in magazines, newspapers, or books. Perhaps your friends or doctor have mentioned alternatives. In this chapter, we will begin by giving you a broad perspective on complementary and alternative therapies. Next, we will introduce you to official information sources on CAM relating to endometriosis. Finally, at the conclusion of this chapter, we will provide a list of readings on endometriosis from various authors. We will begin, however, with the National Center for Complementary and Alternative Medicine's (NCCAM) overview of complementary and alternative medicine.

What Is CAM?46 Complementary and alternative medicine (CAM) covers a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as those treatments and healthcare practices which are not taught in medical schools, used in hospitals, or reimbursed by medical insurance companies. Many CAM therapies are termed “holistic,” which generally means that the healthcare practitioner considers the whole person, including physical, mental, emotional, and spiritual health. Some of these therapies are also known as “preventive,” which means that the practitioner educates and 46

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/faq/index.html#what-is.

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treats the person to prevent health problems from arising, rather than treating symptoms after problems have occurred. People use CAM treatments and therapies in a variety of ways. Therapies are used alone (often referred to as alternative), in combination with other alternative therapies, or in addition to conventional treatment (sometimes referred to as complementary). Complementary and alternative medicine, or “integrative medicine,” includes a broad range of healing philosophies, approaches, and therapies. Some approaches are consistent with physiological principles of Western medicine, while others constitute healing systems with non-Western origins. While some therapies are far outside the realm of accepted Western medical theory and practice, others are becoming established in mainstream medicine. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization and relaxation, manual healing including acupressure and massage, homeopathy, vitamins or herbal products, and acupuncture.

What Are the Domains of Alternative Medicine?47 The list of CAM practices changes continually. The reason being is that these new practices and therapies are often proved to be safe and effective, and therefore become generally accepted as “mainstream” healthcare practices. Today, CAM practices may be grouped within five major domains: (1) alternative medical systems, (2) mind-body interventions, (3) biologicallybased treatments, (4) manipulative and body-based methods, and (5) energy therapies. The individual systems and treatments comprising these categories are too numerous to list in this sourcebook. Thus, only limited examples are provided within each.

Alternative Medical Systems Alternative medical systems involve complete systems of theory and practice that have evolved independent of, and often prior to, conventional biomedical approaches. Many are traditional systems of medicine that are

47

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/classify/index.html.

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practiced by individual cultures throughout the world, including a number of venerable Asian approaches. Traditional oriental medicine emphasizes the balance or disturbances of qi (pronounced chi) or vital energy in health and disease, respectively. Traditional oriental medicine consists of a group of techniques and methods including acupuncture, herbal medicine, oriental massage, and qi gong (a form of energy therapy). Acupuncture involves stimulating specific anatomic points in the body for therapeutic purposes, usually by puncturing the skin with a thin needle. Ayurveda is India's traditional system of medicine. Ayurvedic medicine (meaning “science of life”) is a comprehensive system of medicine that places equal emphasis on body, mind, and spirit. Ayurveda strives to restore the innate harmony of the individual. Some of the primary Ayurvedic treatments include diet, exercise, meditation, herbs, massage, exposure to sunlight, and controlled breathing. Other traditional healing systems have been developed by the world’s indigenous populations. These populations include Native American, Aboriginal, African, Middle Eastern, Tibetan, and Central and South American cultures. Homeopathy and naturopathy are also examples of complete alternative medicine systems. Homeopathic medicine is an unconventional Western system that is based on the principle that “like cures like,” i.e., that the same substance that in large doses produces the symptoms of an illness, in very minute doses cures it. Homeopathic health practitioners believe that the more dilute the remedy, the greater its potency. Therefore, they use small doses of specially prepared plant extracts and minerals to stimulate the body's defense mechanisms and healing processes in order to treat illness. Naturopathic medicine is based on the theory that disease is a manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than disease treatment. Naturopathic physicians employ an array of healing practices, including the following: diet and clinical nutrition, homeopathy, acupuncture, herbal medicine, hydrotherapy (the use of water in a range of temperatures and methods of applications), spinal and soft-tissue manipulation, physical therapies (such as those involving electrical currents, ultrasound, and light), therapeutic counseling, and pharmacology.

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Mind-Body Interventions Mind-body interventions employ a variety of techniques designed to facilitate the mind's capacity to affect bodily function and symptoms. Only a select group of mind-body interventions having well-documented theoretical foundations are considered CAM. For example, patient education and cognitive-behavioral approaches are now considered “mainstream.” On the other hand, complementary and alternative medicine includes meditation, certain uses of hypnosis, dance, music, and art therapy, as well as prayer and mental healing.

Biological-Based Therapies This category of CAM includes natural and biological-based practices, interventions, and products, many of which overlap with conventional medicine's use of dietary supplements. This category includes herbal, special dietary, orthomolecular, and individual biological therapies. Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and/or control illness as well as promote health. Orthomolecular therapies aim to treat disease with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory diseases.

Manipulative and Body-Based Methods This category includes methods that are based on manipulation and/or movement of the body. For example, chiropractors focus on the relationship between structure and function, primarily pertaining to the spine, and how that relationship affects the preservation and restoration of health. Chiropractors use manipulative therapy as an integral treatment tool. In contrast, osteopaths place particular emphasis on the musculoskeletal system and practice osteopathic manipulation. Osteopaths believe that all of the body's systems work together and that disturbances in one system may have an impact upon function elsewhere in the body. Massage therapists manipulate the soft tissues of the body to normalize those tissues.

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Energy Therapies Energy therapies focus on energy fields originating within the body (biofields) or those from other sources (electromagnetic fields). Biofield therapies are intended to affect energy fields (the existence of which is not yet experimentally proven) that surround and penetrate the human body. Some forms of energy therapy manipulate biofields by applying pressure and/or manipulating the body by placing the hands in or through these fields. Examples include Qi gong, Reiki and Therapeutic Touch. Qi gong is a component of traditional oriental medicine that combines movement, meditation, and regulation of breathing to enhance the flow of vital energy (qi) in the body, improve blood circulation, and enhance immune function. Reiki, the Japanese word representing Universal Life Energy, is based on the belief that, by channeling spiritual energy through the practitioner, the spirit is healed and, in turn, heals the physical body. Therapeutic Touch is derived from the ancient technique of “laying-on of hands.” It is based on the premises that the therapist’s healing force affects the patient's recovery and that healing is promoted when the body's energies are in balance. By passing their hands over the patient, these healers identify energy imbalances. Bioelectromagnetic-based therapies involve the unconventional use of electromagnetic fields to treat illnesses or manage pain. These therapies are often used to treat asthma, cancer, and migraine headaches. Types of electromagnetic fields which are manipulated in these therapies include pulsed fields, magnetic fields, and alternating current or direct current fields.

Can Alternatives Affect My Treatment? A critical issue in pursuing complementary alternatives mentioned thus far is the risk that these might have undesirable interactions with your medical treatment. It becomes all the more important to speak with your doctor who can offer advice on the use of alternatives. Official sources confirm this view. Though written for women, we find that the National Women’s Health Information Center’s advice on pursuing alternative medicine is appropriate for patients of both genders and all ages.48

48

Adapted from http://www.4woman.gov/faq/alternative.htm.

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Is It Okay to Want Both Traditional and Alternative or Complementary Medicine? Should you wish to explore non-traditional types of treatment, be sure to discuss all issues concerning treatments and therapies with your healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires knowledge of both conventional and alternative therapies you are taking for the practitioner to have a complete picture of your treatment plan. The decision to use complementary and alternative treatments is an important one. Consider before selecting an alternative therapy, the safety and effectiveness of the therapy or treatment, the expertise and qualifications of the healthcare practitioner, and the quality of delivery. These topics should be considered when selecting any practitioner or therapy.

Finding CAM References on Endometriosis Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate for endometriosis. For the remainder of this chapter, we will direct you to a number of official sources which can assist you in researching studies and publications. Some of these articles are rather technical, so some patience may be required.

The Combined Health Information Database For a targeted search, The Combined Health Information Database is a bibliographic database produced by health-related agencies of the Federal Government (mostly from the National Institutes of Health). This database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “endometriosis” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique:

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·

Novel Approach to Treating Endometriosis: A Report on Two Cases Source: Alternative and Complementary Therapies. 5(5): 225-229. 1999. Summary: This journal article presents two case histories illustrating a novel approach to the treatment of severe endometriosis and infertility. Two women with laparoscopically diagnosed endometriosis, one aged 33 years and the other aged 25 years, had been unsuccessfully treated with conventional medical and surgical therapies. The patients were started on a new treatment program consisting of three phases: 1) diet modification to avoid allergy-provoking foods and sugar, 2) allergy desensitization using neutralizing-dose immunotherapy, and 3) antifungal drug therapy directed at Candida overgrowth. Both patients responded well to this treatment and subsequently became pregnant. The article has 1 table and 36 references.

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Finding the Healer Within Source: New York, NY: National League for Nursing. 1996. 219 p. Contact: National League for Nursing. 350 Hudson Street, New York, NY 10014. 212-989-9393, 800-669-1656, FAX: 212-989-3710. PRICE: $12.95. ISBN: 0887376819. Summary: This book, co-authored by a nurse practitioner and a free-lance writer/researcher, describes a holistic approach to women's health care. In Chapter 1, the first author provides background information about her philosophy of care and experience as a nurse practitioner. Chapter 2 presents an overview of psychoneuroimmunology (the mind/body connection) and immune system functioning. Chapter 3 explains how chronic stress affects the immune system and describes some of the tools that are available to help people handle stress more effectively. Chapter 4 examines the relationship between co-dependency and a variety of women's illnesses, including ovarian cysts, urinary tract infections, chronic pelvic pain, endometriosis, uterine fibroids, cancer, and irregular menses. Chapters 5 through 8 address specific women's health issues: illnesses of the breast, sexuality and sexually transmitted diseases, premenstrual syndrome, and perimenopause and menopause. Chapter 9 discusses the contributions of exercise, nutrition, and other lifestyle factors to wellness. Chapter 10 explores the importance of self-advocacy and assuming responsibility for one's own health. The book includes a bibliography, a list of resources, and an index.

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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 allow patients to search for articles that specifically relate to endometriosis and complementary medicine. To search the database, go to the following Web site: www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “endometriosis” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine (CAM) that are related to endometriosis: ·

Acute abdomen due to endometriosis as a diagnostic and therapeutic challenge in the treatment of acute myelocytic leukemia. Author(s): Karthaus M, Prahst A, Geissler RG, Hertenstein B, Degenhardt F, Ganser A. Source: Annals of Hematology. 1997 January; 74(1): 29-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9031612&dopt=Abstract

·

Altered sensitivity to anti-endometriosis medicines in an adenomyosis patient with thyroid dysfunction. Author(s): Tanaka T, Umesaki N, Ogita S. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 October; 14(5): 388-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11109979&dopt=Abstract

·

Alternative medical treatment for endometriosis. Author(s): Taylor H, Guarnaccia M, Olive D. Source: Semin Reprod Endocrinol. 1997; 15(3): 285-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9383837&dopt=Abstract

·

Considerations in selecting endometriosis. Author(s): Dawood MY.

appropriate

medical

therapy

for

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Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1993; 40 Suppl: S29-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8099023&dopt=Abstract ·

Conventional and alternative treatments for endometriosis. Author(s): Dog TL. Source: Alternative Therapies in Health and Medicine. 2001 NovemberDecember; 7(6): 50-6; Quiz 57. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11712471&dopt=Abstract

·

Endometriosis and infertility: new concepts. Author(s): Ryan IP, Taylor RN. Source: Obstetrical & Gynecological Survey. 1997 June; 52(6): 365-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9178310&dopt=Abstract

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Endometriosis and pain. Author(s): Martin DC, Ling FW. Source: Clinical Obstetrics and Gynecology. 1999 September; 42(3): 66486. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10451777&dopt=Abstract

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Endometriosis treated by the method of resolving blood stasis to eliminate obstruction in the lower-jiao. Author(s): Wang D, Wang Z, Yu C. Source: J Tradit Chin Med. 1998 March; 18(1): 7-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10437253&dopt=Abstract

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Heterologous transplantation of activated murine peritoneal macrophages inhibits gamete interaction in vivo: a paradigm for endometriosis-associated subfertility. Author(s): Steinleitner A, Lambert H, Lauredo I. Source: Fertility and Sterility. 1990 October; 54(4): 725-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2209896&dopt=Abstract

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Importance of lay organizations for coping with endometriosis. Author(s): Whitney ML. Source: J Reprod Med. 1998 March; 43(3 Suppl): 331-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9564669&dopt=Abstract

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Medroxyprogesterone acetate supplementation diminishes the hypoestrogenic side effects of gonadotropin-releasing hormone agonist without changing its efficacy in endometriosis. Author(s): Makarainen L, Ronnberg L, Kauppila A. Source: Fertility and Sterility. 1996 January; 65(1): 29-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8557151&dopt=Abstract

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Mistletoe therapy in endometriosis. Author(s): Lim YT. Source: Fertility and Sterility. 2002 February; 77 Suppl 1: S53. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11947886&dopt=Abstract

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RU486: pharmacology and potential use in the treatment of endometriosis and leiomyomata uteri. Author(s): Murphy AA, Castellano PZ. Source: Current Opinion in Obstetrics & Gynecology. 1994 June; 6(3): 26978. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8038415&dopt=Abstract

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Treatment of endometriosis involving a self-help group positively affects patients' perception of care. Author(s): Wingfield MB, Wood C, Henderson LS, Wood RM. Source: J Psychosom Obstet Gynaecol. 1997 December; 18(4): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9443134&dopt=Abstract

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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

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

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

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

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

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

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TPN.com: http://www.tnp.com/

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

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WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

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WellNet: http://www.wellnet.ca/herbsa-c.htm

The following is a specific Web list relating to endometriosis; 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 Endometriosis Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Endometriosis.htm Endometriosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html

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·

Alternative Therapy Osteopathy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,724, 00.html Traditional Chinese medicine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 85,00.html

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Herbs and Supplements Beta-Carotene Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Blue Flag Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Caffeine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Endometriosis.htm Caffeine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Chaste Tree Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html

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Chasteberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,767, 00.html Dong quai (angelica) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,774, 00.html Eicosapentaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Endometriosis.htm Estrogen Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Endometriosis.htm GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000111.html Grape seed extract Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,793, 00.html Gravel Root Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Hyperlink: http://www.wellnet.ca/herbsg-i.htm Ibuprofen Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html

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Leonurus Alternative names: Motherwort; Leonurus cardiaca Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Lipotropic combination Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,861, 00.html Methionine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 84,00.html Milk Thistle Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Motherwort Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Natural progesterone cream Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 99,00.html Oral Contraceptives Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Oral_Contraceptives.htm Progesterone Source: Healthnotes, Inc.; www.healthnotes.com

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Hyperlink: http://www.thedacare.org/healthnotes/Supp/Progesterone.htm Progesterone Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Endometriosis.htm Raspberry Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Red Raspberry Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Soy isoflavones Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 57,00.html Vervain Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Vitex Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Endometriosis.htm Vitex Alternative names: Vitex agnus-castus Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Herb/Vitex.htm

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Wild yam Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,100 70,00.html ·

Related Conditions Bone Loss Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Osteop orosiscc.html Dysmenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Dysmenorrhea.htm Dysmenorrhea Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Dysme norrheacc.html Dysmenorrhea Alternative names: Painful Menstruation Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000287.html Female Infertility Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000288.html Hair Growth, Excessive Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Hirsuti smcc.html Hirsuitism Source: Integrative Medicine Communications; www.onemedicine.com

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Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Hirsuti smcc.html Menstrual Pain Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Dysme norrheacc.html Osteoporosis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink:

http://www.drkoop.com/interactivemedicine/ConsConditions/Osteop orosiscc.html

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at: 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. The following additional references describe, in broad terms, alternative and complementary medicine (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): ·

Ayurveda for Women: A Guide to Vitality and Health by Robert E. Svoboda; Paperback - 176 pages (November 2000), Inner Traditions Int’l Ltd.; ISBN: 0892819391; http://www.amazon.com/exec/obidos/ASIN/0892819391/icongroupinterna

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The Path of Practice: A Woman's Book of Healing with Food, Breath, and Sound by Bri Maya Tiwari; Hardcover - 320 pages (October 31, 2000), Ballantine Books; ISBN: 0345430301; http://www.amazon.com/exec/obidos/ASIN/0345430301/icongroupinterna

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Reclaiming Our Health : Exploding the Medical Myth and Embracing the Sources of True Healing by John Robbins, Marianne Williamson; Paperback - 432 pages (February 1998), H J Kramer; ISBN: 0915811804; http://www.amazon.com/exec/obidos/ASIN/0915811804/icongroupinterna

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·

Taking Charge of Your Fertility: The Definitive Guide to Natural Birth Control, Pregnancy Achievement, and Reproductive Health (Revised Edition) by Toni Weschler; Paperback - 496 pages, Revised edition (November 13, 2001), Quill; ISBN: 0060937645; http://www.amazon.com/exec/obidos/ASIN/0060937645/icongroupinterna

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Women's Encyclopedia of Natural Medicine by Tori Hudson, Christiane Northrup; Paperback - 358 pages, 1st edition (April 11, 1999), McGraw Hill - NTC; ISBN: 0879837888; http://www.amazon.com/exec/obidos/ASIN/0879837888/icongroupinterna

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Woman Heal Thyself : An Ancient Healing System for Contemporary Women by Jeanne Elizabeth Blum; Paperback - 328 pages, Revised edition (September 1996), Charles Tuttle Co.; ISBN: 0804831017; http://www.amazon.com/exec/obidos/ASIN/0804831017/icongroupinterna

For additional information on complementary and alternative medicine, ask your doctor or write to: National Institutes of Health National Center for Complementary and Alternative Medicine Clearinghouse P. O. Box 8218 Silver Spring, MD 20907-8218

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Psychoneuroimmunology: The field concerned with the interrelationship between the brain, behavior and the immune system. Neuropsychologic, neuroanatomic and psychosocial studies have demonstrated their role in accentuating or diminishing immune/allergic responses. [NIH]

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APPENDIX C. RESEARCHING NUTRITION Overview Since the time of Hippocrates, doctors have understood the importance of diet and nutrition to patients’ health and well-being. Since then, they have accumulated an impressive archive of studies and knowledge dedicated to this subject. Based on their experience, doctors and healthcare providers may recommend particular dietary supplements to patients with endometriosis. Any dietary recommendation is based on a patient's age, body mass, gender, lifestyle, eating habits, food preferences, and health condition. It is therefore likely that different patients with endometriosis may be given different recommendations. Some recommendations may be directly related to endometriosis, while others may be more related to the patient's general health. These recommendations, themselves, may differ from what official sources recommend for the average person. In this chapter we will begin by briefly reviewing the essentials of diet and nutrition that will broadly frame more detailed discussions of endometriosis. We will then show you how to find studies dedicated specifically to nutrition and endometriosis.

Food and Nutrition: General Principles What Are Essential Foods? Food is generally viewed by official sources as consisting of six basic elements: (1) fluids, (2) carbohydrates, (3) protein, (4) fats, (5) vitamins, and

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(6) minerals. Consuming a combination of these elements is considered to be a healthy diet: ·

Fluids are essential to human life as 80-percent of the body is composed of water. Water is lost via urination, sweating, diarrhea, vomiting, diuretics (drugs that increase urination), caffeine, and physical exertion.

·

Carbohydrates are the main source for human energy (thermoregulation) and the bulk of typical diets. They are mostly classified as being either simple or complex. Simple carbohydrates include sugars which are often consumed in the form of cookies, candies, or cakes. Complex carbohydrates consist of starches and dietary fibers. Starches are consumed in the form of pastas, breads, potatoes, rice, and other foods. Soluble fibers can be eaten in the form of certain vegetables, fruits, oats, and legumes. Insoluble fibers include brown rice, whole grains, certain fruits, wheat bran and legumes.

·

Proteins are eaten to build and repair human tissues. Some foods that are high in protein are also high in fat and calories. Food sources for protein include nuts, meat, fish, cheese, and other dairy products.

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Fats are consumed for both energy and the absorption of certain vitamins. There are many types of fats, with many general publications recommending the intake of unsaturated fats or those low in cholesterol.

Vitamins and minerals are fundamental to human health, growth, and, in some cases, disease prevention. Most are consumed in your diet (exceptions being vitamins K and D which are produced by intestinal bacteria and sunlight on the skin, respectively). Each vitamin and mineral plays a different role in health. The following outlines essential vitamins: ·

Vitamin A is important to the health of your eyes, hair, bones, and skin; sources of vitamin A include foods such as eggs, carrots, and cantaloupe.

·

Vitamin B1, also known as thiamine, is important for your nervous system and energy production; food sources for thiamine include meat, peas, fortified cereals, bread, and whole grains.

·

Vitamin B2, also known as riboflavin, is important for your nervous system and muscles, but is also involved in the release of proteins from nutrients; food sources for riboflavin include dairy products, leafy vegetables, meat, and eggs.

·

Vitamin B3, also known as niacin, is important for healthy skin and helps the body use energy; food sources for niacin include peas, peanuts, fish, and whole grains

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·

Vitamin B6, also known as pyridoxine, is important for the regulation of cells in the nervous system and is vital for blood formation; food sources for pyridoxine include bananas, whole grains, meat, and fish.

·

Vitamin B12 is vital for a healthy nervous system and for the growth of red blood cells in bone marrow; food sources for vitamin B12 include yeast, milk, fish, eggs, and meat.

·

Vitamin C allows the body's immune system to fight various diseases, strengthens body tissue, and improves the body's use of iron; food sources for vitamin C include a wide variety of fruits and vegetables.

·

Vitamin D helps the body absorb calcium which strengthens bones and teeth; food sources for vitamin D include oily fish and dairy products.

·

Vitamin E can help protect certain organs and tissues from various degenerative diseases; food sources for vitamin E include margarine, vegetables, eggs, and fish.

·

Vitamin K is essential for bone formation and blood clotting; common food sources for vitamin K include leafy green vegetables.

·

Folic Acid maintains healthy cells and blood and, when taken by a pregnant woman, can prevent her fetus from developing neural tube defects; food sources for folic acid include nuts, fortified breads, leafy green vegetables, and whole grains.

It should be noted that one can overdose on certain vitamins which become toxic if consumed in excess (e.g. vitamin A, D, E and K). Like vitamins, minerals are chemicals that are required by the body to remain in good health. Because the human body does not manufacture these chemicals internally, we obtain them from food and other dietary sources. The more important minerals include: ·

Calcium is needed for healthy bones, teeth, and muscles, but also helps the nervous system function; food sources for calcium include dry beans, peas, eggs, and dairy products.

·

Chromium is helpful in regulating sugar levels in blood; food sources for chromium include egg yolks, raw sugar, cheese, nuts, beets, whole grains, and meat.

·

Fluoride is used by the body to help prevent tooth decay and to reinforce bone strength; sources of fluoride include drinking water and certain brands of toothpaste.

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·

Iodine helps regulate the body's use of energy by synthesizing into the hormone thyroxine; food sources include leafy green vegetables, nuts, egg yolks, and red meat.

·

Iron helps maintain muscles and the formation of red blood cells and certain proteins; food sources for iron include meat, dairy products, eggs, and leafy green vegetables.

·

Magnesium is important for the production of DNA, as well as for healthy teeth, bones, muscles, and nerves; food sources for magnesium include dried fruit, dark green vegetables, nuts, and seafood.

·

Phosphorous is used by the body to work with calcium to form bones and teeth; food sources for phosphorous include eggs, meat, cereals, and dairy products.

·

Selenium primarily helps maintain normal heart and liver functions; food sources for selenium include wholegrain cereals, fish, meat, and dairy products.

·

Zinc helps wounds heal, the formation of sperm, and encourage rapid growth and energy; food sources include dried beans, shellfish, eggs, and nuts.

The United States government periodically publishes recommended diets and consumption levels of the various elements of food. Again, your doctor may encourage deviations from the average official recommendation based on your specific condition. To learn more about basic dietary guidelines, visit the Web site: http://www.health.gov/dietaryguidelines/. Based on these guidelines, many foods are required to list the nutrition levels on the food’s packaging. Labeling Requirements are listed at the following site maintained by the Food and Drug Administration: http://www.cfsan.fda.gov/~dms/labcons.html. When interpreting these requirements, the government recommends that consumers become familiar with the following abbreviations before reading FDA literature:49 ·

DVs (Daily Values): A new dietary reference term that will appear on the food label. It is made up of two sets of references, DRVs and RDIs.

·

DRVs (Daily Reference Values): A set of dietary references that applies to fat, saturated fat, cholesterol, carbohydrate, protein, fiber, sodium, and potassium.

·

RDIs (Reference Daily Intakes): A set of dietary references based on the Recommended Dietary Allowances for essential vitamins and minerals

49

Adapted from the FDA: http://www.fda.gov/fdac/special/foodlabel/dvs.html.

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and, in selected groups, protein. The name “RDI” replaces the term “U.S. RDA.” ·

RDAs (Recommended Dietary Allowances): A set of estimated nutrient allowances established by the National Academy of Sciences. It is updated periodically to reflect current scientific knowledge. What Are Dietary Supplements?50

Dietary supplements are widely available through many commercial sources, including health food stores, grocery stores, pharmacies, and by mail. Dietary supplements are provided in many forms including tablets, capsules, powders, gel-tabs, extracts, and liquids. Historically in the United States, the most prevalent type of dietary supplement was a multivitamin/mineral tablet or capsule that was available in pharmacies, either by prescription or “over the counter.” Supplements containing strictly herbal preparations were less widely available. Currently in the United States, a wide array of supplement products are available, including vitamin, mineral, other nutrients, and botanical supplements as well as ingredients and extracts of animal and plant origin. The Office of Dietary Supplements (ODS) of the National Institutes of Health is the official agency of the United States which has the expressed goal of acquiring “new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold.”51 According to the ODS, dietary supplements can have an important impact on the prevention and management of disease and on the maintenance of health.52 The ODS notes that considerable research on the effects of dietary supplements has been conducted in Asia and Europe where the use of plant products, in particular, has a long tradition. However, the overwhelming majority of supplements have not been studied scientifically. To explore the role of dietary supplements in the improvement of health care, the ODS plans, organizes, and supports conferences, workshops, and This discussion has been adapted from the NIH: http://ods.od.nih.gov/whatare/whatare.html. 51 Contact: The Office of 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]. 52 Adapted from http://ods.od.nih.gov/about/about.html. The Dietary Supplement Health and Education Act defines dietary supplements as “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb or other botanical; or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above; and intended for ingestion in the form of a capsule, powder, softgel, or gelcap, and not represented as a conventional food or as a sole item of a meal or the diet.” 50

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symposia on scientific topics related to dietary supplements. The ODS often works in conjunction with other NIH Institutes and Centers, other government agencies, professional organizations, and public advocacy groups. To learn more about official information on dietary supplements, visit the ODS site at http://ods.od.nih.gov/whatare/whatare.html. Or contact: The Office of 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]

Finding Studies on Endometriosis The NIH maintains an office dedicated to patient nutrition and diet. 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). 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.53 IBIDS is available to the public free of charge through the ODS Internet page: 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. We recommend that you start with the Consumer Database. While you may not find references for the topics that are of most interest to you, check back periodically as this database is frequently updated. More studies can be found by searching the Full IBIDS Database. Healthcare professionals and researchers generally use the third option, which lists peer-reviewed 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.

53

Researching Nutrition 197

citations. In all cases, we suggest that you take advantage of the “Advanced Search” option that allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “endometriosis” (or synonyms) into the search box. To narrow the search, you can also select the “Title” field. The following information is typical of that found when using the “Full IBIDS Database” when searching using “endometriosis” (or a synonym): ·

A prospective randomized study comparing endocrinological and clinical effects of two types of GnRH agonists in cases of uterine leiomyomas or endometriosis. Author(s): Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan. Source: Takeuchi, H Kobori, H Kikuchi, I Sato, Y Mitsuhashi, N J-ObstetGynaecol-Res. 2000 October; 26(5): 325-31 1341-8076

·

Acute abdomen due to endometriosis as a diagnostic and therapeutic challenge in the treatment of acute myelocytic leukemia. Author(s): Department of Hematology and Oncology, Hannover Medical School, Germany. Source: Karthaus, M Prahst, A Geissler, R G Hertenstein, B Degenhardt, F Ganser, A Ann-Hematol. 1997 January; 74(1): 29-31 0939-5555

·

Adenocarcinoma from endometriosis causing urinary tract obstruction in a patient on oestrogen replacement therapy after hysterectomy. A case report. Author(s): Department of Obstetrics and Gynaecology, Johannesburg Hospital. Source: Frohlich, E P Koller, A B van Blerk, P J Margolius, K A S-AfrMed-J. 1988 December 17; 74(12): 638-9 0038-2469

·

Altered sensitivity to anti-endometriosis medicines in an adenomyosis patient with thyroid dysfunction. Author(s): Department of Obstetrics and Gynecology, Osaka City University Medical School, Japan. Source: Tanaka, T Umesaki, N Ogita, S Gynecol-Endocrinol. 2000 October; 14(5): 388-91 0951-3590

·

CA-125 monitored therapy with GnRH analogue of pelvic endometriosis. Author(s): Clinica Ostetrica e Ginecologica, Universita di Ferrara. Source: Negri, P Ricciardelli, M A Tomasi, A Grechi, E Fortini, R M ActaEur-Fertil. 1992 Jul-August; 23(4): 171-4 0587-2421

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·

Clinical experience in the treatment of endometriosis with GnRH agonist. Author(s): Division of Reproductive Endocrinology and Infertility, Vanderbilt University, Nashville, Tennessee. Source: Hill, G A Obstet-Gynecol-Survolume 1989 May; 44(5): 305-7 00297828

·

Comparison of the mechanisms of action of LHRH analogs and steroids in the treatment of endometriosis. Author(s): Service d'Endocrinologie et des Maladies de la Reproduction, Hopital Bicetre, Le Kremlin-Bicetre, France. Source: Bouchard, P Garcia, E Contrib-Gynecol-Obstet. 1987; 16260-5 0304-4246

·

Continuous exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibits the growth of surgically induced endometriosis in the ovariectomized mouse treated with high dose estradiol. Author(s): Reproductive Toxicology Section, Department of Health Ottawa, Ontario, Canada. Source: Yang, J Z Foster, W G Toxicol-Ind-Health. 1997 Jan-February; 13(1): 15-25 0748-2337

·

Delayed oral estradiol combined with leuprolide increases endometriosis-related pain. Author(s): Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver, USA. [email protected] Source: Hurst, B S Gardner, S C Tucker, K E Awoniyi, C A Schlaff, W D JSLS. 2000 Apr-June; 4(2): 97-101

·

Effects of an extended-interval dosing regimen of triptorelin depot on the hormonal profile of patients with endometriosis: prospective observational study. Author(s): Department of Obstetrics and Gynaecology, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong. Source: Tse, C Y Chow, A M Chan, S C Hong-Kong-Med-J. 2000 September; 6(3): 260-4 1024-2708

·

Endometriosis and infertility. Author(s): University of California, San Diego, School of Medicine, La Jolla. Source: el Roeiy, A Murphy, A A Curr-Opin-Obstet-Gynecol. 1990 April; 2(2): 166-72 1040-872X

·

Endometriosis of the lung. Author(s): Cattedra di Patologia Chirurgica, Istituto Scientifico S. Raffaele, Milano, Italy.

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Source: Di Palo, S Mari, G Castoldi, R Staudacher, C Taccagni, G Di Carlo, V Respir-Med. 1989 May; 83(3): 255-8 0954-6111 ·

Endometriosis of the rectum treated with a long term GnRH agonist and surgery. Author(s): Department of Obstetrics and Gynecology, David Grant United States Air Force Medical Center, Travis Air Force Base, Calif. Source: Markham, S M Welling, D R Larsen, K S Snell, M J N-Y-State-JMed. 1991 February; 91(2): 69-71 0028-7628

·

Endometriosis of the urinary tract. Author(s): Department of Urology, Medical University of South Carolina, Charleston. Source: Shook, T E Nyberg, L M Urology. 1988 January; 31(1): 1-6 00904295

·

Endometriosis therapy with gestrinone by oral, vaginal or parenteral administration. Author(s): Maternidade Climerio de Oliviera, Salvador Bahia, Brazil. Source: Coutinho, E Goncalves, M T Azadian Boulanger, G Silva, A R Contrib-Gynecol-Obstet. 1987; 16227-35 0304-4246

·

Estrogenic suppression by different administration schedules of goserelin depot for treatment of endometriosis. Author(s): Unita di Endocrinologia, University of Florence, Italy. Source: Magini, A Pellegrini, S Tavella, K Forti, G Massi, G B Serio, M JEndocrinol-Invest. 1993 November; 16(10): 775-80 0391-4097

·

Evaluation of combined endoscopic and pharmaceutical management of endometriosis during adolescence. Author(s): 2nd Department of Obstetrics and Gynecology, University of Athens, Areteion Hospital, Greece. Source: Hassan, E Kontoravdis, A Hassiakos, D Kalogirou, D Kontoravdis, N Creatsas, G Clin-Exp-Obstet-Gynecol. 1999; 26(2): 85-7 0390-6663

·

GnRH agonists in the treatment of endometriosis. Author(s): I Clinica Ostetrico-Ginecologica Universita di Milano, Italy. Source: Fedele, L Bianchi, S Arcaini, L Vercellini, P Candiani, G B ActaEur-Fertil. 1988 Jan-February; 19(1): 5-12 0587-2421

·

GnRH analogs in treating uterine leiomyomata and endometriosis. Author(s): 2nd Dept. of Obstetrics & Gynecology, Medical University of Gdansk, Poland. Source: Szczurowicz, A Wydra, D Clin-Exp-Obstet-Gynecol. 1996; 23(4): 214-9 0390-6663

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·

Gonadotropin releasing hormone analogues for endometriosis. Source: Anonymous Drug-Ther-Bull. 1993 March 15; 31(6): 21-2 0012-6543

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&pag e=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

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

·

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/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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·

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

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

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Healthnotes: http://www.thedacare.org/healthnotes/

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

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

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WebMDÒHealth: http://my.webmd.com/nutrition

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

The following is a specific Web list relating to endometriosis; 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 Pyridoxine Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Endometriosis.htm Vitamin C Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904, 00.html Vitamin E Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,906, 00.html

·

Minerals Calcium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884, 00.html

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Calcium/magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,937, 00.html Magnesium Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html ·

Food and Diet Apples Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Artichokes Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Beverages Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Endometriosis.htm Carrots Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Chocolate Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html

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Coffee Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Food_Guide/Coffee.htm Fats Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Fish Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Endometriosis.htm Garlic Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Grains Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Lemons Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Milk Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Omega-6 fatty acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,103 7,00.html Onions Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Poultry Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Rabbit Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Endometriosis.htm Saturated Fats Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Sugar Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Tea Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Vegetables Source: Integrative Medicine Communications; www.onemedicine.com

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Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html Water Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Endom etriosiscc.html

Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: 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] Gestrinone: A non-estrogenic contraceptive which is a weak progestin with strong anti-progesterone properties. It is effective if used once a week orally or can also be used in intravaginal devices. [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]

Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It

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occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Thermoregulation: Heat regulation. [EU] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Triptorelin: A long-acting gonadorelin analog agonist. It has been used in the treatment of prostatic cancer, ovarian cancer, precocious puberty, endometriosis, and to induce ovulation for in vitro fertilization. [NIH]

Finding Medical Libraries 207

APPENDIX D. FINDING MEDICAL LIBRARIES Overview At a medical library you can find medical texts and reference books, consumer health publications, specialty newspapers and magazines, as well as medical journals. In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Before going to the library, highlight the references mentioned in this sourcebook that you find interesting. Focus on those items that are not available via the Internet, and ask the reference librarian for help with your search. He or she may know of additional resources that could be helpful to you. Most importantly, 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. NLM's interlibrary loan services are only available to libraries. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.54

54

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

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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 Open to the Public In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries that are generally open to the public and have reference facilities. The following is the NLM’s list plus hyperlinks to each library Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of 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):55 ·

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), http://www.asmi.org/LIBRARY.HTM

·

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

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California: Kris Kelly Health Information Center (St. Joseph Health System), http://www.humboldt1.com/~kkhic/index.html

·

California: Community Health Library of Los Gatos (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)

55

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

Finding Medical Libraries 209

·

California: Health Library (Stanford University Medical Center), http://www-med.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

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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: San José PlaneTree Health Library, http://planetreesanjose.org/

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California: Sutter Resource Library (Sutter Hospitals Foundation), http://go.sutterhealth.org/comm/resc-library/sac-resources.html

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California: University of California, Davis. Health Sciences Libraries

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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System), http://www.valleycare.com/library.html

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California: Washington Community Health Resource Library (Washington Community Health Resource Library), http://www.healthlibrary.org/

·

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.exempla.org/conslib.htm

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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/

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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital), http://www.waterburyhospital.com/library/consumer.shtml

·

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute), http://www.christianacare.org/health_guide/health_guide_pmri_health _info.cfm

·

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine), http://www.delamed.org/chls.html

·

Georgia: Family Resource Library (Medical College of Georgia), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

·

Georgia: Health Resource Center (Medical Center of Central Georgia), http://www.mccg.org/hrc/hrchome.asp

210 Endometriosis

·

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library), http://hml.org/CHIS/

·

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center), http://www.nicon.org/DeArmond/index.htm

·

Illinois: Health Learning Center of Northwestern Memorial Hospital (Northwestern Memorial Hospital, Health Learning Center), http://www.nmh.org/health_info/hlc.html

·

Illinois: Medical Library (OSF Saint Francis Medical Center), http://www.osfsaintfrancis.org/general/library/

·

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital), http://www.centralbap.com/education/community/library.htm

·

Kentucky: University of Kentucky - Health Information Library (University of Kentucky, Chandler Medical Center, Health Information Library), http://www.mc.uky.edu/PatientEd/

·

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation), http://www.ochsner.org/library/

·

Louisiana: Louisiana State University Health Sciences Center Medical Library-Shreveport, http://lib-sh.lsuhsc.edu/

·

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital), http://www.fchn.org/fmh/lib.htm

·

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center), http://www.cmmc.org/library/library.html

·

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare), http://www.emh.org/hll/hpl/guide.htm

·

Maine: Maine Medical Center Library (Maine Medical Center), http://www.mmc.org/library/

·

Maine: Parkview Hospital, http://www.parkviewhospital.org/communit.htm#Library

·

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center), http://www.smmc.org/services/service.php3?choice=10

·

Maine: Stephens Memorial Hospital Health Information Library (Western Maine Health), http://www.wmhcc.com/hil_frame.html

·

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

Finding Medical Libraries 211

·

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre), http://www.deerlodge.mb.ca/library/libraryservices.shtml

·

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Md., 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://medlibwww.bu.edu/library/lib.html

·

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

·

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital), http://www.nebh.org/health_lib.asp

·

Massachusetts: St. Luke's Hospital Health Sciences Library (St. Luke's Hospital), 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), 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), http://www.cancer.med.umich.edu/learn/leares.htm

·

Michigan: Sladen Library & Center for Health Information Resources Consumer Health Information, http://www.sladen.hfhs.org/library/consumer/index.html

212 Endometriosis

·

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center), http://www.saintpatrick.org/chi/librarydetail.php3?ID=41

·

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/

·

Nevada: Health Science Library, West Charleston Library (Las Vegas Clark County Library District), http://www.lvccld.org/special_collections/medical/index.htm

·

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

·

New Jersey: Consumer Health Library (Rahway Hospital), http://www.rahwayhospital.com/library.htm

·

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center), http://www.englewoodhospital.com/links/index.htm

·

New Jersey: Meland Foundation (Englewood Hospital and Medical Center), 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), http://www.upstate.edu/library/hic/

·

New York: Health Sciences Library (Long Island Jewish Medical Center), 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

Finding Medical Libraries 213

·

Oklahoma: Saint Francis Health System Patient/Family Resource Center (Saint Francis Health System), http://www.sfhtulsa.com/patientfamilycenter/default.asp

·

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center), http://www.mcmc.net/phrc/

·

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center), http://www.hmc.psu.edu/commhealth/

·

Pennsylvania: Community Health Resource Library (Geisinger Medical Center), http://www.geisinger.edu/education/commlib.shtml

·

Pennsylvania: HealthInfo Library (Moses Taylor Hospital), http://www.mth.org/healthwellness.html

·

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System), http://www.hsls.pitt.edu/chi/hhrcinfo.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), http://www.shscares.org/services/lrc/index.asp

·

Pennsylvania: Medical Library (UPMC Health System), http://www.upmc.edu/passavant/library.htm

·

Quebec, Canada: Medical Library (Montreal General Hospital), http://ww2.mcgill.ca/mghlib/

·

South Dakota: Rapid City Regional Hospital - Health Information Center (Rapid City Regional Hospital, Health Information Center), http://www.rcrh.org/education/LibraryResourcesConsumers.htm

·

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

·

Texas: Matustik Family Resource Center (Cook Children's Health Care System), http://www.cookchildrens.com/Matustik_Library.html

·

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

·

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center), http://www.swmedctr.com/Home/

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APPENDIX E. YOUR RIGHTS AND INSURANCE Overview Any patient with endometriosis faces a series of issues related more to the healthcare industry than to the medical condition itself. This appendix covers two important topics in this regard: your rights and responsibilities as a patient, and how to get the most out of your medical insurance plan.

Your Rights as a Patient The President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has created the following summary of your rights as a patient.56

Information Disclosure Consumers have the right to receive accurate, easily understood information. Some consumers require assistance in making informed decisions about health plans, health professionals, and healthcare facilities. Such information includes: ·

Health plans. Covered benefits, cost-sharing, and procedures for resolving complaints, licensure, certification, and accreditation status, comparable measures of quality and consumer satisfaction, provider

56Adapted

from Consumer Bill of Rights and Responsibilities: http://www.hcqualitycommission.gov/press/cbor.html#head1.

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network composition, the procedures that govern access to specialists and emergency services, and care management information. ·

Health professionals. Education, board certification, and recertification, years of practice, experience performing certain procedures, and comparable measures of quality and consumer satisfaction.

·

Healthcare facilities. Experience in performing certain procedures and services, accreditation status, comparable measures of quality, worker, and consumer satisfaction, and procedures for resolving complaints.

·

Consumer assistance programs. Programs must be carefully structured to promote consumer confidence and to work cooperatively with health plans, providers, payers, and regulators. Desirable characteristics of such programs are sponsorship that ensures accountability to the interests of consumers and stable, adequate funding. Choice of Providers and Plans

Consumers have the right to a choice of healthcare providers that is sufficient to ensure access to appropriate high-quality healthcare. To ensure such choice, the Commission recommends the following: ·

Provider network adequacy. All health plan networks should provide access to sufficient numbers and types of providers to assure that all covered services will be accessible without unreasonable delay -including access to emergency services 24 hours a day and 7 days a week. If a health plan has an insufficient number or type of providers to provide a covered benefit with the appropriate degree of specialization, the plan should ensure that the consumer obtains the benefit outside the network at no greater cost than if the benefit were obtained from participating providers.

·

Women's health services. Women should be able to choose a qualified provider offered by a plan -- such as gynecologists, certified nurse midwives, and other qualified healthcare providers -- for the provision of covered care necessary to provide routine and preventative women's healthcare services.

·

Access to specialists. Consumers with complex or serious medical conditions who require frequent specialty care should have direct access to a qualified specialist of their choice within a plan's network of providers. Authorizations, when required, should be for an adequate number of direct access visits under an approved treatment plan.

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·

Transitional care. Consumers who are undergoing a course of treatment for a chronic or disabling condition (or who are in the second or third trimester of a pregnancy) at the time they involuntarily change health plans or at a time when a provider is terminated by a plan for other than cause should be able to continue seeing their current specialty providers for up to 90 days (or through completion of postpartum care) to allow for transition of care.

·

Choice of health plans. Public and private group purchasers should, wherever feasible, offer consumers a choice of high-quality health insurance plans.

Access to Emergency Services Consumers have the right to access emergency healthcare services when and where the need arises. Health plans should provide payment when a consumer presents to an emergency department with acute symptoms of sufficient severity--including severe pain--such that a “prudent layperson” could reasonably expect the absence of medical attention to result in placing that consumer's health in serious jeopardy, serious impairment to bodily functions, or serious dysfunction of any bodily organ or part. Participation in Treatment Decisions Consumers have the right and responsibility to fully participate in all decisions related to their healthcare. Consumers who are unable to fully participate in treatment decisions have the right to be represented by parents, guardians, family members, or other conservators. Physicians and other health professionals should: ·

Provide patients with sufficient information and opportunity to decide among treatment options consistent with the informed consent process.

·

Discuss all treatment options with a patient in a culturally competent manner, including the option of no treatment at all.

·

Ensure that persons with disabilities have effective communications with members of the health system in making such decisions.

·

Discuss all current treatments a consumer may be undergoing.

·

Discuss all risks, nontreatment.

benefits,

and

consequences

to

treatment

or

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·

Give patients the opportunity to refuse treatment and to express preferences about future treatment decisions.

·

Discuss the use of advance directives -- both living wills and durable powers of attorney for healthcare -- with patients and their designated family members.

·

Abide by the decisions made by their patients and/or their designated representatives consistent with the informed consent process.

Health plans, health providers, and healthcare facilities should: ·

Disclose to consumers factors -- such as methods of compensation, ownership of or interest in healthcare facilities, or matters of conscience -that could influence advice or treatment decisions.

·

Assure that provider contracts do not contain any so-called “gag clauses” or other contractual mechanisms that restrict healthcare providers' ability to communicate with and advise patients about medically necessary treatment options.

·

Be prohibited from penalizing or seeking retribution against healthcare professionals or other health workers for advocating on behalf of their patients.

Respect and Nondiscrimination Consumers have the right to considerate, respectful care from all members of the healthcare industry at all times and under all circumstances. An environment of mutual respect is essential to maintain a quality healthcare system. To assure that right, the Commission recommends the following: ·

Consumers must not be discriminated against in the delivery of healthcare services consistent with the benefits covered in their policy, or as required by law, based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment.

·

Consumers eligible for coverage under the terms and conditions of a health plan or program, or as required by law, must not be discriminated against in marketing and enrollment practices based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment.

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Confidentiality of Health Information Consumers have the right to communicate with healthcare providers in confidence and to have the confidentiality of their individually identifiable healthcare information protected. Consumers also have the right to review and copy their own medical records and request amendments to their records.

Complaints and Appeals Consumers have the right to a fair and efficient process for resolving differences with their health plans, healthcare providers, and the institutions that serve them, including a rigorous system of internal review and an independent system of external review. A free copy of the Patient's Bill of Rights is available from the American Hospital Association.57

Patient Responsibilities Treatment is a two-way street between you and your healthcare providers. To underscore the importance of finance in modern healthcare as well as your responsibility for the financial aspects of your care, the President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has proposed that patients understand the following “Consumer Responsibilities.”58 In a healthcare system that protects consumers' rights, it is reasonable to expect and encourage consumers to assume certain responsibilities. Greater individual involvement by the consumer in his or her care increases the likelihood of achieving the best outcome and helps support a quality-oriented, cost-conscious environment. Such responsibilities include: ·

Take responsibility for maximizing healthy habits such as exercising, not smoking, and eating a healthy diet.

·

Work collaboratively with healthcare providers in developing and carrying out agreed-upon treatment plans.

·

Disclose relevant information and clearly communicate wants and needs.

57 To order your free copy of the Patient's Bill of Rights, telephone 312-422-3000 or visit the American Hospital Association’s Web site: http://www.aha.org. Click on “Resource Center,” go to “Search” at bottom of page, and then type in “Patient's Bill of Rights.” The Patient’s Bill of Rights is also available from Fax on Demand, at 312-422-2020, document number 471124. 58 Adapted from http://www.hcqualitycommission.gov/press/cbor.html#head1.

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·

Use your health insurance plan's internal complaint and appeal processes to address your concerns.

·

Avoid knowingly spreading disease.

·

Recognize the reality of risks, the limits of the medical science, and the human fallibility of the healthcare professional.

·

Be aware of a healthcare provider's obligation to be reasonably efficient and equitable in providing care to other patients and the community.

·

Become knowledgeable about your health plan’s coverage and options (when available) including all covered benefits, limitations, and exclusions, rules regarding use of network providers, coverage and referral rules, appropriate processes to secure additional information, and the process to appeal coverage decisions.

·

Show respect for other patients and health workers.

·

Make a good-faith effort to meet financial obligations.

·

Abide by administrative and operational procedures of health plans, healthcare providers, and Government health benefit programs.

Choosing an Insurance Plan There are a number of official government agencies that help consumers understand their healthcare insurance choices.59 The U.S. Department of Labor, in particular, recommends ten ways to make your health benefits choices work best for you.60 1. Your options are important. There are many different types of health benefit plans. Find out which one your employer offers, then check out the plan, or plans, offered. Your employer's human resource office, the health plan administrator, or your union can provide information to help you match your needs and preferences with the available plans. The more information you have, the better your healthcare decisions will be. 2. Reviewing the benefits available. Do the plans offered cover preventive care, well-baby care, vision or dental care? Are there deductibles? Answers to these questions can help determine the out-of-pocket expenses you may More information about quality across programs is provided at the following AHRQ Web site: http://www.ahrq.gov/consumer/qntascii/qnthplan.htm. 60 Adapted from the Department of Labor: http://www.dol.gov/dol/pwba/public/pubs/health/top10-text.html. 59

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face. Matching your needs and those of your family members will result in the best possible benefits. Cheapest may not always be best. Your goal is high quality health benefits. 3. Look for quality. The quality of healthcare services varies, but quality can be measured. You should consider the quality of healthcare in deciding among the healthcare plans or options available to you. Not all health plans, doctors, hospitals and other providers give the highest quality care. Fortunately, there is quality information you can use right now to help you compare your healthcare choices. Find out how you can measure quality. Consult the U.S. Department of Health and Human Services publication “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer. 4. Your plan's summary plan description (SPD) provides a wealth of information. Your health plan administrator can provide you with a copy of your plan’s SPD. It outlines your benefits and your legal rights under the Employee Retirement Income Security Act (ERISA), the federal law that protects your health benefits. It should contain information about the coverage of dependents, what services will require a co-pay, and the circumstances under which your employer can change or terminate a health benefits plan. Save the SPD and all other health plan brochures and documents, along with memos or correspondence from your employer relating to health benefits. 5. Assess your benefit coverage as your family status changes. Marriage, divorce, childbirth or adoption, and the death of a spouse are all life events that may signal a need to change your health benefits. You, your spouse and dependent children may be eligible for a special enrollment period under provisions of the Health Insurance Portability and Accountability Act (HIPAA). Even without life-changing events, the information provided by your employer should tell you how you can change benefits or switch plans, if more than one plan is offered. If your spouse's employer also offers a health benefits package, consider coordinating both plans for maximum coverage. 6. Changing jobs and other life events can affect your health benefits. Under the Consolidated Omnibus Budget Reconciliation Act (COBRA), you, your covered spouse, and your dependent children may be eligible to purchase extended health coverage under your employer's plan if you lose your job, change employers, get divorced, or upon occurrence of certain other events. Coverage can range from 18 to 36 months depending on your situation. COBRA applies to most employers with 20 or more workers and

222

requires your plan to notify you of your rights. Most plans require eligible individuals to make their COBRA election within 60 days of the plan's notice. Be sure to follow up with your plan sponsor if you don't receive notice, and make sure you respond within the allotted time. 7. HIPAA can also help if you are changing jobs, particularly if you have a medical condition. HIPAA generally limits pre-existing condition exclusions to a maximum of 12 months (18 months for late enrollees). HIPAA also requires this maximum period to be reduced by the length of time you had prior “creditable coverage.” You should receive a certificate documenting your prior creditable coverage from your old plan when coverage ends. 8. Plan for retirement. Before you retire, find out what health benefits, if any, extend to you and your spouse during your retirement years. Consult with your employer's human resources office, your union, the plan administrator, and check your SPD. Make sure there is no conflicting information among these sources about the benefits you will receive or the circumstances under which they can change or be eliminated. With this information in hand, you can make other important choices, like finding out if you are eligible for Medicare and Medigap insurance coverage. 9. Know how to file an appeal if your health benefits claim is denied. Understand how your plan handles grievances and where to make appeals of the plan's decisions. Keep records and copies of correspondence. Check your health benefits package and your SPD to determine who is responsible for handling problems with benefit claims. Contact PWBA for customer service assistance if you are unable to obtain a response to your complaint. 10. You can take steps to improve the quality of the healthcare and the health benefits you receive. Look for and use things like Quality Reports and Accreditation Reports whenever you can. Quality reports may contain consumer ratings -- how satisfied consumers are with the doctors in their plan, for instance-- and clinical performance measures -- how well a healthcare organization prevents and treats illness. Accreditation reports provide information on how accredited organizations meet national standards, and often include clinical performance measures. Look for these quality measures whenever possible. Consult “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer.

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Medicare and Medicaid Illness strikes both rich and poor families. For low-income families, Medicaid is available to defer the costs of treatment. The Health Care Financing Administration (HCFA) administers Medicare, the nation's largest health insurance program, which covers 39 million Americans. In the following pages, you will learn the basics about Medicare insurance as well as useful contact information on how to find more in-depth information about Medicaid.61

Who is Eligible for Medicare? Generally, you are eligible for Medicare if you or your spouse worked for at least 10 years in Medicare-covered employment and you are 65 years old and a citizen or permanent resident of the United States. You might also qualify for coverage if you are under age 65 but have a disability or EndStage Renal disease (permanent kidney failure requiring dialysis or transplant). Here are some simple guidelines: You can get Part A at age 65 without having to pay premiums if: ·

You are already receiving retirement benefits from Social Security or the Railroad Retirement Board.

·

You are eligible to receive Social Security or Railroad benefits but have not yet filed for them.

·

You or your spouse had Medicare-covered government employment.

If you are under 65, you can get Part A without having to pay premiums if: ·

You have received Social Security or Railroad Retirement Board disability benefit for 24 months.

·

You are a kidney dialysis or kidney transplant patient.

Medicare has two parts: ·

Part A (Hospital Insurance). Most people do not have to pay for Part A.

·

Part B (Medical Insurance). Most people pay monthly for Part B.

This section has been adapted from the Official U.S. Site for Medicare Information: http://www.medicare.gov/Basics/Overview.asp.

61

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Part A (Hospital Insurance) Helps Pay For: Inpatient hospital care, care in critical access hospitals (small facilities that give limited outpatient and inpatient services to people in rural areas) and skilled nursing facilities, hospice care, and some home healthcare. Cost: Most people get Part A automatically when they turn age 65. You do not have to pay a monthly payment called a premium for Part A because you or a spouse paid Medicare taxes while you were working. If you (or your spouse) did not pay Medicare taxes while you were working and you are age 65 or older, you still may be able to buy Part A. If you are not sure you have Part A, look on your red, white, and blue Medicare card. It will show “Hospital Part A” on the lower left corner of the card. You can also call the Social Security Administration toll free at 1-800-772-1213 or call your local Social Security office for more information about buying Part A. If you get benefits from the Railroad Retirement Board, call your local RRB office or 1-800-808-0772. For more information, call your Fiscal Intermediary about Part A bills and services. The phone number for the Fiscal Intermediary office in your area can be obtained from the following Web site: http://www.medicare.gov/Contacts/home.asp. Part B (Medical Insurance) Helps Pay For: Doctors, services, outpatient hospital care, and some other medical services that Part A does not cover, such as the services of physical and occupational therapists, and some home healthcare. Part B helps pay for covered services and supplies when they are medically necessary. Cost: As of 2001, you pay the Medicare Part B premium of $50.00 per month. In some cases this amount may be higher if you did not choose Part B when you first became eligible at age 65. The cost of Part B may go up 10% for each 12-month period that you were eligible for Part B but declined coverage, except in special cases. You will have to pay the extra 10% cost for the rest of your life. Enrolling in Part B is your choice. You can sign up for Part B anytime during a 7-month period that begins 3 months before you turn 65. Visit your local Social Security office, or call the Social Security Administration at 1-800-7721213 to sign up. If you choose to enroll in Part B, the premium is usually taken out of your monthly Social Security, Railroad Retirement, or Civil

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Service Retirement payment. If you do not receive any of the above payments, Medicare sends you a bill for your part B premium every 3 months. You should receive your Medicare premium bill in the mail by the 10th of the month. If you do not, call the Social Security Administration at 1800-772-1213, or your local Social Security office. If you get benefits from the Railroad Retirement Board, call your local RRB office or 1-800-808-0772. For more information, call your Medicare carrier about bills and services. The phone number for the Medicare carrier in your area can be found at the following Web site: http://www.medicare.gov/Contacts/home.asp. You may have choices in how you get your healthcare including the Original Medicare Plan, Medicare Managed Care Plans (like HMOs), and Medicare Private Fee-for-Service Plans.

Medicaid Medicaid is a joint federal and state program that helps pay medical costs for some people with low incomes and limited resources. Medicaid programs vary from state to state. People on Medicaid may also get coverage for nursing home care and outpatient prescription drugs which are not covered by Medicare. You can find more information about Medicaid on the HCFA.gov Web site at http://www.hcfa.gov/medicaid/medicaid.htm. States also have programs that pay some or all of Medicare's premiums and may also pay Medicare deductibles and coinsurance for certain people who have Medicare and a low income. To qualify, you must have: ·

Part A (Hospital Insurance),

·

Assets, such as bank accounts, stocks, and bonds that are not more than $4,000 for a single person, or $6,000 for a couple, and

·

A monthly income that is below certain limits.

For more information on these programs, look at the Medicare Savings Programs brochure, http://www.medicare.gov/Library/PDFNavigation/PDFInterim.asp?Langua ge=English&Type=Pub&PubID=10126. There are also Prescription Drug Assistance Programs available. Find information on these programs which offer discounts or free medications to individuals in need at http://www.medicare.gov/Prescription/Home.asp.

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NORD’s Medication Assistance Programs Finally, the National Organization for Rare Disorders, Inc. (NORD) administers medication programs sponsored by humanitarian-minded pharmaceutical and biotechnology companies to help uninsured or underinsured individuals secure life-saving or life-sustaining drugs.62 NORD programs ensure that certain vital drugs are available “to those individuals whose income is too high to qualify for Medicaid but too low to pay for their prescribed medications.” The program has standards for fairness, equity, and unbiased eligibility. It currently covers some 14 programs for nine pharmaceutical companies. NORD also offers early access programs for investigational new drugs (IND) under the approved “Treatment INDs” programs of the Food and Drug Administration (FDA). In these programs, a limited number of individuals can receive investigational drugs that have yet to be approved by the FDA. These programs are generally designed for rare diseases or disorders. For more information, visit www.rarediseases.org.

Additional Resources In addition to the references already listed in this chapter, you may need more information on health insurance, hospitals, or the healthcare system in general. The NIH has set up an excellent guidance Web site that addresses these and other issues. Topics include:63 ·

Health Insurance: http://www.nlm.nih.gov/medlineplus/healthinsurance.html

·

Health Statistics: http://www.nlm.nih.gov/medlineplus/healthstatistics.html

·

HMO and Managed Care: http://www.nlm.nih.gov/medlineplus/managedcare.html

·

Hospice Care: http://www.nlm.nih.gov/medlineplus/hospicecare.html

·

Medicaid: http://www.nlm.nih.gov/medlineplus/medicaid.html

·

Medicare: http://www.nlm.nih.gov/medlineplus/medicare.html

·

Nursing Homes and Long-term Care: http://www.nlm.nih.gov/medlineplus/nursinghomes.html

Adapted from NORD: http://www.rarediseases.org/cgibin/nord/progserv#patient?id=rPIzL9oD&mv_pc=30. 63 You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html. 62

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·

Patient's Rights, Confidentiality, Informed Consent, Ombudsman Programs, Privacy and Patient Issues: http://www.nlm.nih.gov/medlineplus/patientissues.html

·

Veteran's Health, Persian Gulf War, Gulf War Syndrome, Agent Orange: http://www.nlm.nih.gov/medlineplus/veteranshealth.html

Vocabulary Builder Analgesics: Compounds capable of relieving pain without the loss of consciousness or without producing anesthesia. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Episiotomy: Surgical incision into the perineum and vagina to prevent traumatic tearing during delivery. [EU] Spotting: A slight discharge of blood via the vagina, especially as a sideeffect of oral contraceptives. [EU]

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APPENDIX F. MORE ON PAIN Overview You know it at once. It may be the fiery sensation of a burn moments after your finger touches the stove. Or it’s a dull ache above your brow after a day of stress and tension. Or you may recognize it as a sharp pierce in your back after you lift something heavy. It is pain. In its most benign form, it warns us that something isn’t quite right, that we should take medicine or see a doctor. At its worst, however, pain robs us of our productivity, our well-being, and, for many of us suffering from extended illness, our very lives. Pain is a complex perception that differs enormously among individual patients, even those who appear to have identical injuries or illnesses. In 1931, the French medical missionary Dr. Albert Schweitzer wrote, “Pain is a more terrible lord of mankind than even death itself.” Today, pain has become the universal disorder, a serious and costly public health issue, and a challenge for family, friends, and health care providers who must give support to the individual suffering from the physical as well as the emotional consequences of pain.

A Brief History of Pain Ancient civilizations recorded on stone tablets accounts of pain and the treatments used: pressure, heat, water, and sun. Early humans related pain to evil, magic, and demons. Relief of pain was the responsibility of sorcerers,

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shamans, priests, and priestesses, who used herbs, rites, and ceremonies as their treatments. The Greeks and Romans were the first to advance a theory of sensation, the idea that the brain and nervous system have a role in producing the perception of pain. But it was not until the Middle Ages and well into the Renaissance-the 1400s and 1500s-that evidence began to accumulate in support of these theories. Leonardo da Vinci and his contemporaries came to believe that the brain was the central organ responsible for sensation. Da Vinci also developed the idea that the spinal cord transmits sensations to the brain. In the 17th and 18th centuries, the study of the body-and the sensescontinued to be a source of wonder for the world’s philosophers. In 1664, the French philosopher René Descartes described what to this day is still called a “pain pathway.” Descartes illustrated how particles of fire, in contact with the foot, travel to the brain and he compared pain sensation to the ringing of a bell. In the 19th century, pain came to dwell under a new domain-science-paving the way for advances in pain therapy. Physician-scientists discovered that opium, morphine, codeine, and cocaine could be used to treat pain. These drugs led to the development of aspirin, to this day the most commonly used pain reliever. Before long, anesthesia-both general and regional-was refined and applied during surgery. “It has no future but itself,” wrote the 19th century American poet Emily Dickinson, speaking about pain. As the 21st century unfolds, however, advances in pain research are creating a less grim future than that portrayed in Dickinson’s verse, a future that includes a better understanding of pain, along with greatly improved treatments to keep it in check.

The Two Faces of Pain: Acute and Chronic What is pain? The International Association for the Study of Pain defines it as: An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. It is useful to distinguish between two basic types of pain, acute and chronic, and they differ greatly: ·

Acute pain, for the most part, results from disease, inflammation, or injury to tissues. This type of pain generally comes on suddenly, for

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example, after trauma or surgery, and may be accompanied by anxiety or emotional distress. The cause of acute pain can usually be diagnosed and treated, and the pain is self-limiting, that is, it is confined to a given period of time and severity. In some rare instances, it can become chronic. ·

Chronic pain is widely believed to represent disease itself. It can be made much worse by environmental and psychological factors. Chronic pain persists over a longer period of time than acute pain and is resistant to most medical treatments. It can—and often does—cause severe problems for patients.

The A to Z of Pain Hundreds of pain syndromes or disorders make up the spectrum of pain. There are the most benign, fleeting sensations of pain, such as a pin prick. There is the pain of childbirth, the pain of a heart attack, and the pain that sometimes follows amputation of a limb. There is also pain accompanying cancer and the pain that follows severe trauma, such as that associated with head and spinal cord injuries. A sampling of common pain syndromes follows, listed alphabetically. Arachnoiditis is a condition in which one of the three membranes covering the brain and spinal cord, called the arachnoid membrane, becomes inflamed. A number of causes, including infection or trauma, can result in inflammation of this membrane. Arachnoiditis can produce disabling, progressive, and even permanent pain. Arthritis. Millions of Americans suffer from arthritic conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and gout. These disorders are characterized by joint pain in the extremities. Many other inflammatory diseases affect the body’s soft tissues, including tendonitis and bursitis. Back pain has become the high price paid by our modern lifestyle and is a startlingly common cause of disability for many Americans, including both active and inactive people. Back pain that spreads to the leg is called sciatica and is a very common condition (see below). Another common type of back pain is associated with the discs of the spine, the soft, spongy padding between the vertebrae (bones) that form the spine. Discs protect the spine by absorbing shock, but they tend to degenerate over time and may sometimes rupture. Spondylolisthesis is a back condition that occurs when one vertebra extends over another, causing pressure on nerves and therefore pain. Also,

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damage to nerve roots (see “Spine Basics” in the Appendix) is a serious condition, called radiculopathy, that can be extremely painful. Treatment for a damaged disc includes drugs such as painkillers, muscle relaxants, and steroids; exercise or rest, depending on the patient’s condition; adequate support, such as a brace or better mattress and physical therapy. In some cases, surgery may be required to remove the damaged portion of the disc and return it to its previous condition, especially when it is pressing a nerve root. Surgical procedures include discectomy, laminectomy, or spinal fusion (see section on surgery in “How is Pain Treated?” for more information on these treatments). Burn pain can be profound and poses an extreme challenge to the medical community. First-degree burns are the least severe; with third-degree burns, the skin is lost. Depending on the injury, pain accompanying burns can be excruciating, and even after the wound has healed patients may have chronic pain at the burn site. Cancer pain can accompany the growth of a tumor, the treatment of cancer, or chronic problems related to cancer’s permanent effects on the body. Fortunately, most cancer pain can be treated to help minimize discomfort and stress to the patient. Headaches affect millions of Americans. The three most common types of chronic headache are migraines, cluster headaches, and tension headaches. Each comes with its own telltale brand of pain. ·

Migraines are characterized by throbbing pain and sometimes by other symptoms, such as nausea and visual disturbances. Migraines are more frequent in women than men. Stress can trigger a migraine headache, and migraines can also put the sufferer at risk for stroke.

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Cluster headaches are characterized by excruciating, piercing pain on one side of the head; they occur more frequently in men than women.

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Tension headaches are often described as a tight band around the head.

Head and facial pain can be agonizing, whether it results from dental problems or from disorders such as cranial neuralgia, in which one of the nerves in the face, head, or neck is inflamed. Another condition, trigeminal neuralgia (also called tic douloureux), affects the largest of the cranial nerves and is characterized by a stabbing, shooting pain. Muscle pain can range from an aching muscle, spasm, or strain, to the severe spasticity that accompanies paralysis. Another disabling syndrome is fibromyalgia, a disorder characterized by fatigue, stiffness, joint tenderness,

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and widespread muscle pain. Polymyositis, dermatomyositis, and inclusion body myositis are painful disorders characterized by muscle inflammation. They may be caused by infection or autoimmune dysfunction and are sometimes associated with connective tissue disorders, such as lupus and rheumatoid arthritis. Myofascial pain syndromes affect sensitive areas known as trigger points, located within the body’s muscles. Myofascial pain syndromes are sometimes misdiagnosed and can be debilitating. Fibromyalgia is a type of myofascial pain syndrome. Neuropathic pain is a type of pain that can result from injury to nerves, either in the peripheral or central nervous system (see “The Nervous Systems” in the Appendix). Neuropathic pain can occur in any part of the body and is frequently described as a hot, burning sensation, which can be devastating to the affected individual. It can result from diseases that affect nerves (such as diabetes) or from trauma, or, because chemotherapy drugs can affect nerves, it can be a consequence of cancer treatment. Among the many neuropathic pain conditions are diabetic neuropathy (which results from nerve damage secondary to vascular problems that occur with diabetes); reflex sympathetic dystrophy syndrome (see below), which can follow injury; phantom limb and post-amputation pain (see “Phantom Pain” in the Appendix), which can result from the surgical removal of a limb; postherpetic neuralgia, which can occur after an outbreak of shingles; and central pain syndrome, which can result from trauma to the brain or spinal cord. Reflex sympathetic dystrophy syndrome, or RSDS, is accompanied by burning pain and hypersensitivity to temperature. Often triggered by trauma or nerve damage, RSDS causes the skin of the affected area to become characteristically shiny. In recent years, RSDS has come to be called complex regional pain syndrome (CRPS); in the past it was often called causalgia. Repetitive stress injuries are muscular conditions that result from repeated motions performed in the course of normal work or other daily activities. They include: ·

Writer’s cramp, which affects musicians and writers and others

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Compression or entrapment neuropathies, including carpal tunnel syndrome, caused by chronic overextension of the wrist

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Tendonitis or tenosynovitis, affecting one or more tendons.

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Sciatica is a painful condition caused by pressure on the sciatic nerve, the main nerve that branches off the spinal cord and continues down into the thighs, legs, ankles, and feet. Sciatica is characterized by pain in the buttocks and can be caused by a number of factors. Exertion, obesity, and poor posture can all cause pressure on the sciatic nerve. One common cause of sciatica is a herniated disc. Shingles and other painful disorders affect the skin. Pain is a common symptom of many skin disorders, even the most common rashes. One of the most vexing neurological disorders is shingles or herpes zoster, an infection that often causes agonizing pain resistant to treatment. Prompt treatment with antiviral agents is important to arrest the infection, which if prolonged can result in an associated condition known as postherpetic neuralgia. Other painful disorders affecting the skin include: ·

Vasculitis, or inflammation of blood vessels

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Other infections, including herpes simplex

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Skin tumors and cysts

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Tumors associated with neurofibromatosis, a neurogenetic disorder

Sports injuries are common. Sprains, strains, bruises, dislocations, and fractures are all well-known words in the language of sports. Pain is another. In extreme cases, sports injuries can take the form of costly and painful spinal cord and head injuries, which cause severe suffering and disability. Spinal stenosis refers to a narrowing of the canal surrounding the spinal cord. The condition occurs naturally with aging. Spinal stenosis causes weakness in the legs and leg pain usually felt while the person is standing up and often relieved by sitting down. Surgical pain may require regional or general anesthesia during the procedure and medications to control discomfort following the operation. Control of pain associated with surgery includes presurgical preparation and careful monitoring of the patient during and after the procedure. Temporomandibular disorders are conditions in which the temporomandibular joint (the jaw) is damaged and/or the muscles used for chewing and talking become stressed, causing pain. The condition may be the result of a number of factors, such as an injury to the jaw or joint misalignment, and may give rise to a variety of symptoms, most commonly pain in the jaw, face, and/or neck muscles. Physicians reach a diagnosis by

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listening to the patient’s description of the symptoms and by performing a simple examination of the facial muscles and the temporomandibular joint. Trauma can occur after injuries in the home, at the workplace, during sports activities, or on the road. Any of these injuries can result in severe disability and pain. Some patients who have had an injury to the spinal cord experience intense pain ranging from tingling to burning and, commonly, both. Such patients are sensitive to hot and cold temperatures and touch. For these individuals, a touch can be perceived as intense burning, indicating abnormal signals relayed to and from the brain. This condition is called central pain syndrome or, if the damage is in the thalamus (the brain’s center for processing bodily sensations), thalamic pain syndrome. It affects as many as 100,000 Americans with multiple sclerosis, Parkinson’s disease, amputated limbs, spinal cord injuries, and stroke. Their pain is severe and is extremely difficult to treat effectively. A variety of medications, including analgesics, antidepressants, anticonvulsants, and electrical stimulation, are options available to central pain patients. Vascular disease or injury-such as vasculitis or inflammation of blood vessels, coronary artery disease, and circulatory problems-all have the potential to cause pain. Vascular pain affects millions of Americans and occurs when communication between blood vessels and nerves is interrupted. Ruptures, spasms, constriction, or obstruction of blood vessels, as well as a condition called ischemia in which blood supply to organs, tissues, or limbs is cut off, can also result in pain.

How Is Pain Diagnosed? There is no way to tell how much pain a person has. No test can measure the intensity of pain, no imaging device can show pain, and no instrument can locate pain precisely. Sometimes, as in the case of headaches, physicians find that the best aid to diagnosis is the patient’s own description of the type, duration, and location of pain. Defining pain as sharp or dull, constant or intermittent, burning or aching may give the best clues to the cause of pain. These descriptions are part of what is called the pain history, taken by the physician during the preliminary examination of a patient with pain. Physicians, however, do have a number of technologies they use to find the cause of pain. Primarily these include: ·

Electrodiagnostic procedures include electromyography (EMG), nerve conduction studies, and evoked potential (EP) studies. Information from

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EMG can help physicians tell precisely which muscles or nerves are affected by weakness or pain. Thin needles are inserted in muscles and a physician can see or listen to electrical signals displayed on an EMG machine. With nerve conduction studies the doctor uses two sets of electrodes (similar to those used during an electrocardiogram) that are placed on the skin over the muscles. The first set gives the patient a mild shock that stimulates the nerve that runs to that muscle. The second set of electrodes is used to make a recording of the nerve’s electrical signals, and from this information the doctor can determine if there is nerve damage. EP tests also involve two sets of electrodes-one set for stimulating a nerve (these electrodes are attached to a limb) and another set on the scalp for recording the speed of nerve signal transmission to the brain. ·

Imaging, especially magnetic resonance imaging or MRI, provides physicians with pictures of the body’s structures and tissues. MRI uses magnetic fields and radio waves to differentiate between healthy and diseased tissue.

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A neurological examination in which the physician tests movement, reflexes, sensation, balance, and coordination.

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X-rays produce pictures of the body’s structures, such as bones and joints.

How Is Pain Treated? The goal of pain management is to improve function, enabling individuals to work, attend school, or participate in other day-to-day activities. Patients and their physicians have a number of options for the treatment of pain; some are more effective than others. Sometimes, relaxation and the use of imagery as a distraction provide relief. These methods can be powerful and effective, according to those who advocate their use. Whatever the treatment regime, it is important to remember that pain is treatable. The following treatments are among the most common. Acetaminophen is the basic ingredient found in Tylenol® and its many generic equivalents. It is sold over the counter, in a prescription-strength preparation, and in combination with codeine (also by prescription). Acupuncture dates back 2,500 years and involves the application of needles to precise points on the body. It is part of a general category of healing called traditional Chinese or Oriental medicine. Acupuncture remains controversial but is quite popular and may one day prove to be useful for a variety of

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conditions as it continues to be explored by practitioners, patients, and investigators. Analgesic refers to the class of drugs that includes most painkillers, such as aspirin, acetaminophen, and ibuprofen. The word analgesic is derived from ancient Greek and means to reduce or stop pain. Nonprescription or overthe-counter pain relievers are generally used for mild to moderate pain. Prescription pain relievers, sold through a pharmacy under the direction of a physician, are used for more moderate to severe pain. Anticonvulsants are used for the treatment of seizure disorders but are also sometimes prescribed for the treatment of pain. Carbamazepine in particular is used to treat a number of painful conditions, including trigeminal neuralgia. Another antiepileptic drug, gabapentin, is being studied for its pain-relieving properties, especially as a treatment for neuropathic pain. Antidepressants are sometimes used for the treatment of pain and, along with neuroleptics and lithium, belong to a category of drugs called psychotropic drugs. In addition, anti-anxiety drugs called benzodiazepines also act as muscle relaxants and are sometimes used as pain relievers. Physicians usually try to treat the condition with analgesics before prescribing these drugs. Antimigraine drugs include the triptans- sumatriptan (Imitrex®), naratriptan (Amerge®), and zolmitriptan (Zomig®)-and are used specifically for migraine headaches. They can have serious side effects in some people and therefore, as with all prescription medicines, should be used only under a doctor’s care. Aspirin may be the most widely used pain-relief agent and has been sold over the counter since 1905 as a treatment for fever, headache, and muscle soreness. Biofeedback is used for the treatment of many common pain problems, most notably headache and back pain. Using a special electronic machine, the patient is trained to become aware of, to follow, and to gain control over certain bodily functions, including muscle tension, heart rate, and skin temperature. The individual can then learn to effect a change in his or her responses to pain, for example, by using relaxation techniques. Biofeedback is often used in combination with other treatment methods, generally without side effects. Similarly, the use of relaxation techniques in the treatment of pain can increase the patient’s feeling of well-being.

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Capsaicin is a chemical found in chili peppers that is also a primary ingredient in pain-relieving creams (see Chili Peppers, Capsaicin, and Pain in the Appendix). Chemonucleolysis is a treatment in which an enzyme, chymopapain, is injected directly into a herniated lumbar disc (see Spine Basics in the Appendix) in an effort to dissolve material around the disc, thus reducing pressure and pain. The procedure’s use is extremely limited, in part because some patients may have a life-threatening allergic reaction to chymopapain. Chiropractic refers to hand manipulation of the spine, usually for relief of back pain, and is a treatment option that continues to grow in popularity among many people who simply seek relief from back disorders. It has never been without controversy, however. Chiropractic’s usefulness as a treatment for back pain is, for the most part, restricted to a select group of individuals with uncomplicated acute low back pain who may derive relief from the massage component of the therapy. Cognitive-behavioral therapy involves a wide variety of coping skills and relaxation methods to help prepare for and cope with pain. It is used for postoperative pain, cancer pain, and the pain of childbirth. Counseling can give a patient suffering from pain much needed support, whether it is derived from family, group, or individual counseling. Support groups can provide an important adjunct to drug or surgical treatment. Psychological treatment can also help patients learn about the physiological changes produced by pain. COX-2 inhibitors (“superaspirins”) may be particularly effective for individuals with arthritis. For many years scientists have wanted to develop the ultimate drug-a drug that works as well as morphine but without its negative side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) work by blocking two enzymes, cyclooxygenase-1 and cyclooxygenase-2, both of which promote production of hormones called prostaglandins, which in turn cause inflammation, fever, and pain. Newer drugs, called COX-2 inhibitors, primarily block cyclooxygenase-2 and are less likely to have the gastrointestinal side effects sometimes produced by NSAIDs. On 1999, the Food and Drug Administration approved two COX-2 inhibitors-rofecoxib (Vioxx®) and celecoxib (Celebrex®). Although the long-term effects of COX2 inhibitors are still being evaluated, they appear to be safe. In addition, patients may be able to take COX-2 inhibitors in larger doses than aspirin and other drugs that have irritating side effects, earning them the nickname “superaspirins.”

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Electrical stimulation, including transcutaneous electrical stimulation (TENS), implanted electric nerve stimulation, and deep brain or spinal cord stimulation, is the modern-day extension of age-old practices in which the nerves of muscles are subjected to a variety of stimuli, including heat or massage. Electrical stimulation, no matter what form, involves a major surgical procedure and is not for everyone, nor is it 100 percent effective. The following techniques each require specialized equipment and personnel trained in the specific procedure being used: ·

TENS uses tiny electrical pulses, delivered through the skin to nerve fibers, to cause changes in muscles, such as numbness or contractions. This in turn produces temporary pain relief. There is also evidence that TENS can activate subsets of peripheral nerve fibers that can block pain transmission at the spinal cord level, in much the same way that shaking your hand can reduce pain.

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Peripheral nerve stimulation uses electrodes placed surgically on a carefully selected area of the body. The patient is then able to deliver an electrical current as needed to the affected area, using an antenna and transmitter.

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Spinal cord stimulation uses electrodes surgically inserted within the epidural space of the spinal cord. The patient is able to deliver a pulse of electricity to the spinal cord using a small box-like receiver and an antenna taped to the skin.

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Deep brain or intracerebral stimulation is considered an extreme treatment and involves surgical stimulation of the brain, usually the thalamus. It is used for a limited number of conditions, including severe pain, central pain syndrome, cancer pain, phantom limb pain, and other neuropathic pains.

Exercise has come to be a prescribed part of some doctors’ treatment regimes for patients with pain. Because there is a known link between many types of chronic pain and tense, weak muscles, exercise-even light to moderate exercise such as walking or swimming-can contribute to an overall sense of well-being by improving blood and oxygen flow to muscles. Just as we know that stress contributes to pain, we also know that exercise, sleep, and relaxation can all help reduce stress, thereby helping to alleviate pain. Exercise has been proven to help many people with low back pain. It is important, however, that patients carefully follow the routine laid out by their physicians.

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Hypnosis, first approved for medical use by the American Medical Association in 1958, continues to grow in popularity, especially as an adjunct to pain medication. In general, hypnosis is used to control physical function or response, that is, the amount of pain an individual can withstand. How hypnosis works is not fully understood. Some believe that hypnosis delivers the patient into a trance-like state, while others feel that the individual is simply better able to concentrate and relax or is more responsive to suggestion. Hypnosis may result in relief of pain by acting on chemicals in the nervous system, slowing impulses. Whether and how hypnosis works involves greater insight-and research-into the mechanisms underlying human consciousness. Ibuprofen is a member of the aspirin family of analgesics, the so-called nonsteroidal anti-inflammatory drugs (see below). It is sold over the counter and also comes in prescription-strength preparations. Low-power lasers have been used occasionally by some physical therapists as a treatment for pain, but like many other treatments, this method is not without controversy. Magnets are increasingly popular with athletes who swear by their effectiveness for the control of sports-related pain and other painful conditions. Usually worn as a collar or wristwatch, the use of magnets as a treatment dates back to the ancient Egyptians and Greeks. While it is often dismissed as quackery and pseudoscience by skeptics, proponents offer the theory that magnets may effect changes in cells or body chemistry, thus producing pain relief. Nerve blocks employ the use of drugs, chemical agents, or surgical techniques to interrupt the relay of pain messages between specific areas of the body and the brain. There are many different names for the procedure, depending on the technique or agent used. Types of surgical nerve blocks include neurectomy; spinal dorsal, cranial, and trigeminal rhizotomy; and sympathectomy, also called sympathetic blockade (see “Nerve Blocks” in the Appendix). Nonsteroidal anti-inflammatory drugs (NSAIDs) (including aspirin and ibuprofen) are widely prescribed and sometimes called non-narcotic or nonopioid analgesics. They work by reducing inflammatory responses in tissues. Many of these drugs irritate the stomach and for that reason are usually taken with food. Although acetaminophen may have some antiinflammatory effects, it is generally distinguished from the traditional NSAIDs.

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Opioids are derived from the poppy plant and are among the oldest drugs known to humankind. They include codeine and perhaps the most wellknown narcotic of all, morphine. Morphine can be administered in a variety of forms, including a pump for patient self-administration. Opioids have a narcotic effect, that is, they induce sedation as well as pain relief, and some patients may become physically dependent upon them. For these reasons, patients given opioids should be monitored carefully; in some cases stimulants may be prescribed to counteract the sedative side effects. In addition to drowsiness, other common side effects include constipation, nausea, and vomiting. Physical therapy and rehabilitation date back to the ancient practice of using physical techniques and methods, such as heat, cold, exercise, massage, and manipulation, in the treatment of certain conditions. These may be applied to increase function, control pain, and speed the patient toward full recovery. Placebos offer some individuals pain relief although whether and how they have an effect is mysterious and somewhat controversial. Placebos are inactive substances, such as sugar pills, or harmless procedures, such as saline injections or sham surgeries, generally used in clinical studies as control factors to help determine the efficacy of active treatments. Although placebos have no direct effect on the underlying causes of pain, evidence from clinical studies suggests that many pain conditions such as migraine headache, back pain, post-surgical pain, rheumatoid arthritis, angina, and depression sometimes respond well to them. This positive response is known as the placebo effect, which is defined as the observable or measurable change that can occur in patients after administration of a placebo. Some experts believe the effect is psychological and that placebos work because the patients believe or expect them to work. Others say placebos relieve pain by stimulating the brain’s own analgesics and setting the body’s self-healing forces in motion. A third theory suggests that the act of taking placebos relieves stress and anxiety-which are known to aggravate some painful conditions-and, thus, cause the patients to feel better. Still, placebos are considered controversial because by definition they are inactive and have no actual curative value. R.I.C.E.-Rest, Ice, Compression, and Elevation-are four components prescribed by many orthopedists, coaches, trainers, nurses, and other professionals for temporary muscle or joint conditions, such as sprains or strains. While many common orthopedic problems can be controlled with these four simple steps, especially when combined with over-the-counter

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pain relievers, more serious conditions may require surgery or physical therapy, including exercise, joint movement or manipulation, and stimulation of muscles. Surgery, although not always an option, may be required to relieve pain, especially pain caused by back problems or serious musculoskeletal injuries. Surgery may take the form of a nerve block (see “Nerve Blocks” in the Appendix) or it may involve an operation to relieve pain from a ruptured disc. Surgical procedures for back problems include discectomy or, when microsurgical techniques are used, microdiscectomy, in which the entire disc is removed; laminectomy, a procedure in which a surgeon removes only a disc fragment, gaining access by entering through the arched portion of a vertebra; and spinal fusion, a procedure where the entire disc is removed and replaced with a bone graft. In a spinal fusion, the two vertebrae are then fused together. Although the operation can cause the spine to stiffen, resulting in lost flexibility, the procedure serves one critical purpose: protection of the spinal cord. Other operations for pain include rhizotomy, in which a nerve close to the spinal cord is cut, and cordotomy, where bundles of nerves within the spinal cord are severed. Cordotomy is generally used only for the pain of terminal cancer that does not respond to other therapies. Another operation for pain is the dorsal root entry zone operation, or DREZ, in which spinal neurons corresponding to the patient’s pain are destroyed surgically. Because surgery can result in scar tissue formation that may cause additional problems, patients are well advised to seek a second opinion before proceeding. Occasionally, surgery is carried out with electrodes that selectively damage neurons in a targeted area of the brain. These procedures rarely result in long-term pain relief, but both physician and patient may decide that the surgical procedure will be effective enough that it justifies the expense and risk. In some cases, the results of an operation are remarkable. For example, many individuals suffering from trigeminal neuralgia who are not responsive to drug treatment have had great success with a procedure called microvascular decompression, in which tiny blood vessels are surgically separated from surrounding nerves.

What Is the Role of Age and Gender in Pain? Gender and Pain It is now widely believed that pain affects men and women differently. While the sex hormones estrogen and testosterone certainly play a role in this phenomenon, psychology and culture, too, may account at least in part for differences in how men and women receive pain signals. For example,

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young children may learn to respond to pain based on how they are treated when they experience pain. Some children may be cuddled and comforted, while others may be encouraged to tough it out and to dismiss their pain. Many investigators are turning their attention to the study of gender differences and pain. Women, many experts now agree, recover more quickly from pain, seek help more quickly for their pain, and are less likely to allow pain to control their lives. They also are more likely to marshal a variety of resources-coping skills, support, and distraction-with which to deal with their pain. Research in this area is yielding fascinating results. For example, male experimental animals injected with estrogen, a female sex hormone, appear to have a lower tolerance for pain-that is, the addition of estrogen appears to lower the pain threshold. Similarly, the presence of testosterone, a male hormone, appears to elevate tolerance for pain in female mice: the animals are simply able to withstand pain better. Female mice deprived of estrogen during experiments react to stress similarly to male animals. Estrogen, therefore, may act as a sort of pain switch, turning on the ability to recognize pain. Investigators know that males and females both have strong natural painkilling systems, but these systems operate differently. For example, a class of painkillers called kappa-opioids is named after one of several opioid receptors to which they bind, the kappa-opioid receptor, and they include the compounds nalbuphine (Nubain®) and butorphanol (Stadol®). Research suggests that kappa-opioids provide better pain relief in women. Though not prescribed widely, kappa-opioids are currently used for relief of labor pain and in general work best for short-term pain. Investigators are not certain why kappa-opioids work better in women than men. Is it because a woman’s estrogen makes them work, or because a man’s testosterone prevents them from working? Or is there another explanation, such as differences between men and women in their perception of pain? Continued research may result in a better understanding of how pain affects women differently from men, enabling new and better pain medications to be designed with gender in mind.

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Pain in Aging and Pediatric Populations: Special Needs and Concerns Pain is the number one complaint of older Americans, and one in five older Americans takes a painkiller regularly. In 1998, the American Geriatrics Society (AGS) issued guidelines for the management of pain in older people. The AGS panel addressed the incorporation of several non-drug approaches in patients’ treatment plans, including exercise.64 AGS panel members recommend that, whenever possible, patients use alternatives to aspirin, ibuprofen, and other NSAIDs because of the drugs’ side effects, including stomach irritation and gastrointestinal bleeding. For older adults, acetaminophen is the first-line treatment for mild-to-moderate pain, according to the guidelines. More serious chronic pain conditions may require opioid drugs (narcotics), including codeine or morphine, for relief of pain. Pain in younger patients also requires special attention, particularly because young children are not always able to describe the degree of pain they are experiencing. Although treating pain in pediatric patients poses a special challenge to physicians and parents alike, pediatric patients should never be undertreated. Recently, special tools for measuring pain in children have been developed that, when combined with cues used by parents, help physicians select the most effective treatments. Nonsteroidal agents, and especially acetaminophen, are most often prescribed for control of pain in children. In the case of severe pain or pain following surgery, acetaminophen may be combined with codeine.

A Pain Primer: What Do We Know about Pain? We may experience pain as a prick, tingle, sting, burn, or ache. Receptors on the skin trigger a series of events, beginning with an electrical impulse that travels from the skin to the spinal cord. The spinal cord acts as a sort of relay center where the pain signal can be blocked, enhanced, or otherwise modified before it is relayed to the brain. One area of the spinal cord in particular, called the dorsal horn (see section on “Spine Basics” in the Appendix), is important in the reception of pain signals. The most common destination in the brain for pain signals is the thalamus and from there to the cortex, the headquarters for complex thoughts. The 64

Journal of the American Geriatrics Society (1998; 46:635-651).

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thalamus also serves as the brain’s storage area for images of the body and plays a key role in relaying messages between the brain and various parts of the body. In people who undergo an amputation, the representation of the amputated limb is stored in the thalamus. (For a discussion of the thalamus and its role in this phenomenon, called phantom pain, see section on “Phantom Pain” in the Appendix.) Pain is a complicated process that involves an intricate interplay between a number of important chemicals found naturally in the brain and spinal cord. In general, these chemicals, called neurotransmitters, transmit nerve impulses from one cell to another. There are many different neurotransmitters in the human body; some play a role in human disease and, in the case of pain, act in various combinations to produce painful sensations in the body. Some chemicals govern mild pain sensations; others control intense or severe pain. The body’s chemicals act in the transmission of pain messages by stimulating neurotransmitter receptors found on the surface of cells; each receptor has a corresponding neurotransmitter. Receptors function much like gates or ports and enable pain messages to pass through and on to neighboring cells. One brain chemical of special interest to neuroscientists is glutamate. During experiments, mice with blocked glutamate receptors show a reduction in their responses to pain. Other important receptors in pain transmission are opiate-like receptors. Morphine and other opioid drugs work by locking on to these opioid receptors, switching on paininhibiting pathways or circuits, and thereby blocking pain. Another type of receptor that responds to painful stimuli is called a nociceptor. Nociceptors are thin nerve fibers in the skin, muscle, and other body tissues, that, when stimulated, carry pain signals to the spinal cord and brain. Normally, nociceptors only respond to strong stimuli such as a pinch. However, when tissues become injured or inflamed, as with a sunburn or infection, they release chemicals that make nociceptors much more sensitive and cause them to transmit pain signals in response to even gentle stimuli such as breeze or a caress. This condition is called allodynia -a state in which pain is produced by innocuous stimuli. The body’s natural painkillers may yet prove to be the most promising pain relievers, pointing to one of the most important new avenues in drug development. The brain may signal the release of painkillers found in the spinal cord, including serotonin, norepinephrine, and opioid-like chemicals.

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Many pharmaceutical companies are working to synthesize these substances in laboratories as future medications. Endorphins and enkephalins are other natural painkillers. Endorphins may be responsible for the “feel good” effects experienced by many people after rigorous exercise; they are also implicated in the pleasurable effects of smoking. Similarly, peptides, compounds that make up proteins in the body, play a role in pain responses. Mice bred experimentally to lack a gene for two peptides called tachykinins-neurokinin A and substance P-have a reduced response to severe pain. When exposed to mild pain, these mice react in the same way as mice that carry the missing gene. But when exposed to more severe pain, the mice exhibit a reduced pain response. This suggests that the two peptides are involved in the production of pain sensations, especially moderate-to-severe pain. Continued research on tachykinins, conducted with support from the NINDS, may pave the way for drugs tailored to treat different severities of pain. Scientists are working to develop potent pain-killing drugs that act on receptors for the chemical acetylcholine. For example, a type of frog native to Ecuador has been found to have a chemical in its skin called epibatidine, derived from the frog’s scientific name, Epipedobates tricolor. Although highly toxic, epibatidine is a potent analgesic and, surprisingly, resembles the chemical nicotine found in cigarettes. Also under development are other less toxic compounds that act on acetylcholine receptors and may prove to be more potent than morphine but without its addictive properties. The idea of using receptors as gateways for pain drugs is a novel idea, supported by experiments involving substance P. Investigators have been able to isolate a tiny population of neurons, located in the spinal cord, that together form a major portion of the pathway responsible for carrying persistent pain signals to the brain. When animals were given injections of a lethal cocktail containing substance P linked to the chemical saporin, this group of cells, whose sole function is to communicate pain, were killed. Receptors for substance P served as a portal or point of entry for the compound. Within days of the injections, the targeted neurons, located in the outer layer of the spinal cord along its entire length, absorbed the compound and were neutralized. The animals’ behavior was completely normal; they no longer exhibited signs of pain following injury or had an exaggerated pain response. Importantly, the animals still responded to acute, that is, normal, pain. This is a critical finding as it is important to retain the body’s ability to detect potentially injurious stimuli. The protective, early warning

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signal that pain provides is essential for normal functioning. If this work can be translated clinically, humans might be able to benefit from similar compounds introduced, for example, through lumbar (spinal) puncture. Another promising area of research using the body’s natural pain-killing abilities is the transplantation of chromaffin cells into the spinal cords of animals bred experimentally to develop arthritis. Chromaffin cells produce several of the body’s pain-killing substances and are part of the adrenal medulla, which sits on top of the kidney. Within a week or so, rats receiving these transplants cease to exhibit telltale signs of pain. Scientists, working with support from the NINDS, believe the transplants help the animals recover from pain-related cellular damage. Extensive animal studies will be required to learn if this technique might be of value to humans with severe pain. One way to control pain outside of the brain, that is, peripherally, is by inhibiting hormones called prostaglandins. Prostaglandins stimulate nerves at the site of injury and cause inflammation and fever. Certain drugs, including NSAIDs, act against such hormones by blocking the enzyme that is required for their synthesis. Blood vessel walls stretch or dilate during a migraine attack and it is thought that serotonin plays a complicated role in this process. For example, before a migraine headache, serotonin levels fall. Drugs for migraine include the triptans: sumatriptan (Imitrix®), naratriptan (Amerge®), and zolmitriptan (Zomig®). They are called serotonin agonists because they mimic the action of endogenous (natural) serotonin and bind to specific subtypes of serotonin receptors. Ongoing pain research, much of it supported by the NINDS, continues to reveal at an unprecedented pace fascinating insights into how genetics, the immune system, and the skin contribute to pain responses. The explosion of knowledge about human genetics is helping scientists who work in the field of drug development. We know, for example, that the painkilling properties of codeine rely heavily on a liver enzyme, CYP2D6, which helps convert codeine into morphine. A small number of people genetically lack the enzyme CYP2D6; when given codeine, these individuals do not get pain relief. CYP2D6 also helps break down certain other drugs. People who genetically lack CYP2D6 may not be able to cleanse their systems of these drugs and may be vulnerable to drug toxicity. CYP2D6 is currently under investigation for its role in pain.

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In his research, the late John C. Liebeskind, a renowned pain expert and a professor of psychology at UCLA, found that pain can kill by delaying healing and causing cancer to spread. In his pioneering research on the immune system and pain, Dr. Liebeskind studied the effects of stress-such as surgery-on the immune system and in particular on cells called natural killer or NK cells. These cells are thought to help protect the body against tumors. In one study conducted with rats, Dr. Liebeskind found that, following experimental surgery, NK cell activity was suppressed, causing the cancer to spread more rapidly. When the animals were treated with morphine, however, they were able to avoid this reaction to stress. The link between the nervous and immune systems is an important one. Cytokines, a type of protein found in the nervous system, are also part of the body’s immune system, the body’s shield for fighting off disease. Cytokines can trigger pain by promoting inflammation, even in the absence of injury or damage. Certain types of cytokines have been linked to nervous system injury. After trauma, cytokine levels rise in the brain and spinal cord and at the site in the peripheral nervous system where the injury occurred. Improvements in our understanding of the precise role of cytokines in producing pain, especially pain resulting from injury, may lead to new classes of drugs that can block the action of these substances.

What Is the Future of Pain Research? In the forefront of pain research are scientists supported by the National Institutes of Health (NIH), including the NINDS. Other institutes at NIH that support pain research include the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute of Nursing Research, the National Institute on Drug Abuse, and the National Institute of Mental Health. Developing better pain treatments is the primary goal of all pain research being conducted by these institutes. Some pain medications dull the patient’s perception of pain. Morphine is one such drug. It works through the body’s natural pain-killing machinery, preventing pain messages from reaching the brain. Scientists are working toward the development of a morphine-like drug that will have the paindeadening qualities of morphine but without the drug’s negative side effects, such as sedation and the potential for addiction. Patients receiving morphine also face the problem of morphine tolerance, meaning that over time they require higher doses of the drug to achieve the same pain relief. Studies have identified factors that contribute to the development of tolerance; continued

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progress in this line of research should eventually allow patients to take lower doses of morphine. One objective of investigators working to develop the future generation of pain medications is to take full advantage of the body’s pain “switching center” by formulating compounds that will prevent pain signals from being amplified or stop them altogether. Blocking or interrupting pain signals, especially when there is no injury or trauma to tissue, is an important goal in the development of pain medications. An increased understanding of the basic mechanisms of pain will have profound implications for the development of future medicines. The following areas of research are bringing us closer to an ideal pain drug. ·

Systems and Imaging: The idea of mapping cognitive functions to precise areas of the brain dates back to phrenology, the now archaic practice of studying bumps on the head. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and other imaging technologies offer a vivid picture of what is happening in the brain as it processes pain. Using imaging, investigators can now see that pain activates at least three or four key areas of the brain’s cortex-the layer of tissue that covers the brain. Interestingly, when patients undergo hypnosis so that the unpleasantness of a painful stimulus is not experienced, activity in some, but not all, brain areas is reduced. This emphasizes that the experience of pain involves a strong emotional component as well as the sensory experience, namely the intensity of the stimulus.

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Channels: The frontier in the search for new drug targets is represented by channels. Channels are gate-like passages found along the membranes of cells that allow electrically charged chemical particles called ions to pass into the cells. Ion channels are important for transmitting signals through the nerve’s membrane. The possibility now exists for developing new classes of drugs, including pain cocktails that would act at the site of channel activity.

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Trophic Factors: A class of “rescuer” or “restorer” drugs may emerge from our growing knowledge of trophic factors, natural chemical substances found in the human body that affect the survival and function of cells. Trophic factors also promote cell death, but little is known about how something beneficial can become harmful. Investigators have observed that an over-accumulation of certain trophic factors in the nerve cells of animals results in heightened pain sensitivity, and that some receptors found on cells respond to trophic factors and interact with each other. These receptors may provide targets for new pain therapies.

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Molecular Genetics: Certain genetic mutations can change pain sensitivity and behavioral responses to pain. People born genetically insensate to pain-that is, individuals who cannot feel pain-have a mutation in part of a gene that plays a role in cell survival. Using “knockout” animal models-animals genetically engineered to lack a certain gene-scientists are able to visualize how mutations in genes cause animals to become anxious, make noise, rear, freeze, or become hypervigilant. These genetic mutations cause a disruption or alteration in the processing of pain information as it leaves the spinal cord and travels to the brain. Knockout animals can be used to complement efforts aimed at developing new drugs.

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Plasticity: Following injury, the nervous system undergoes a tremendous reorganization. This phenomenon is known as plasticity. For example, the spinal cord is “rewired” following trauma as nerve cell axons make new contacts, a phenomenon known as “sprouting.” This in turn disrupts the cells’ supply of trophic factors. Scientists can now identify and study the changes that occur during the processing of pain. For example, using a technique called polymerase chain reaction, abbreviated PCR, scientists can study the genes that are induced by injury and persistent pain. There is evidence that the proteins that are ultimately synthesized by these genes may be targets for new therapies. The dramatic changes that occur with injury and persistent pain underscore that chronic pain should be considered a disease of the nervous system, not just prolonged acute pain or a symptom of an injury. Thus, scientists hope that therapies directed at preventing the long-term changes that occur in the nervous system will prevent the development of chronic pain conditions.

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Neurotransmitters: Just as mutations in genes may affect behavior, they may also affect a number of neurotransmitters involved in the control of pain. Using sophisticated imaging technologies, investigators can now visualize what is happening chemically in the spinal cord. From this work, new therapies may emerge, therapies that can help reduce or obliterate severe or chronic pain.

Hope for the Future Thousands of years ago, ancient peoples attributed pain to spirits and treated it with mysticism and incantations. Over the centuries, science has provided us with a remarkable ability to understand and control pain with medications, surgery, and other treatments. Today, scientists understand a great deal about the causes and mechanisms of pain, and research has produced dramatic improvements in the diagnosis and treatment of a

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number of painful disorders. For people who fight every day against the limitations imposed by pain, the work of NINDS-supported scientists holds the promise of an even greater understanding of pain in the coming years. Their research offers a powerful weapon in the battle to prolong and improve the lives of people with pain: hope.

Spine Basics: The Vertebrae, Discs, and Spinal Cord Stacked on top of one another in the spine are more than 30 bones, the vertebrae, which together form the spine. They are divided into four regions: ·

7 cervical or neck vertebrae (labeled C1-C7),

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12 thoracic or upper back vertebrae (labeled T1-T12),

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5 lumbar vertebrae (labeled L1-L5), which we know as the lower back, and

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Sacrum and coccyx, a group of bones fused together at the base of the spine.

The vertebrae are linked by ligaments, tendons, and muscles. Back pain can occur when, for example, someone lifts something too heavy, causing a sprain, pull, strain, or spasm in one of these muscles or ligaments in the back. Between the vertebrae are round, spongy pads of cartilage called discs that act much like shock absorbers. In many cases, degeneration or pressure from overexertion can cause a disc to shift or protrude and bulge, causing pressure on a nerve and resultant pain. When this happens, the condition is called a slipped, bulging, herniated, or ruptured disc, and it sometimes results in permanent nerve damage. The column-like spinal cord is divided into segments similar to the corresponding vertebrae: cervical, thoracic, lumbar, sacral, and coccygeal. The cord also has nerve roots and rootlets which form branch-like appendages leading from its ventral side (that is, the front of the body) and from its dorsal side (that is, the back of the body). Along the dorsal root are the cells of the dorsal root ganglia, which are critical in the transmission of “pain” messages from the cord to the brain. It is here where injury, damage, and trauma become pain.

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The Nervous Systems The central nervous system (CNS) refers to the brain and spinal cord together. The peripheral nervous system refers to the cervical, thoracic, lumbar, and sacral nerve trunks leading away from the spine to the limbs. Messages related to function (such as movement) or dysfunction (such as pain) travel from the brain to the spinal cord and from there to other regions in the body and back to the brain again. The autonomic nervous system controls involuntary functions in the body, like perspiration, blood pressure, heart rate, or heart beat. It is divided into the sympathetic and parasympathetic nervous systems. The sympathetic and parasympathetic nervous systems have links to important organs and systems in the body; for example, the sympathetic nervous system controls the heart, blood vessels, and respiratory system, while the parasympathetic nervous system controls our ability to sleep, eat, and digest food. The peripheral nervous system also includes 12 pairs of cranial nerves located on the underside of the brain. Most relay messages of a sensory nature. They include the olfactory (I), optic (II), oculomotor (III), trochlear (IV), trigeminal (V), abducens (VI), facial (VII), vestibulocochlear (VIII), glossopharyngeal (IX), vagus (X), accessory (XI), and hypoglossal (XII) nerves. Neuralgia, as in trigeminal neuralgia, is a term that refers to pain that arises from abnormal activity of a nerve trunk or its branches. The type and severity of pain associated with neuralgia vary widely.

Phantom Pain: How Does the Brain Feel? Sometimes, when a limb is removed during an amputation, an individual will continue to have an internal sense of the lost limb. This phenomenon is known as phantom limb and accounts describing it date back to the 1800s. Similarly, many amputees are frequently aware of severe pain in the absent limb. Their pain is real and is often accompanied by other health problems, such as depression. What causes this phenomenon? Scientists believe that following amputation, nerve cells “rewire” themselves and continue to receive messages, resulting in a remapping of the brain’s circuitry. The brain’s ability to restructure itself, to change and adapt following injury, is called plasticity (see section on Plasticity). Our understanding of phantom pain has improved tremendously in recent years. Investigators previously believed that brain cells affected by

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amputation simply died off. They attributed sensations of pain at the site of the amputation to irritation of nerves located near the limb stump. Now, using imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI), scientists can actually visualize increased activity in the brain’s cortex when an individual feels phantom pain. When study participants move the stump of an amputated limb, neurons in the brain remain dynamic and excitable. Surprisingly, the brain’s cells can be stimulated by other body parts, often those located closest to the missing limb. Treatments for phantom pain may include analgesics, anticonvulsants, and other types of drugs; nerve blocks; electrical stimulation; psychological counseling, biofeedback, hypnosis, and acupuncture; and, in rare instances, surgery.

Chili Peppers, Capsaicin, and Pain The hot feeling, red face, and watery eyes you experience when you bite into a red chili pepper may make you reach for a cold drink, but that reaction has also given scientists important information about pain. The chemical found in chili peppers that causes those feelings is capsaicin (pronounced cap-SAYsin), and it works its unique magic by grabbing onto receptors scattered along the surface of sensitive nerve cells in the mouth. In 1997, scientists at the University of California at San Francisco discovered a gene for a capsaicin receptor, called the vanilloid receptor. Once in contact with capsaicin, vanilloid receptors open and pain signals are sent from the peripheral nociceptor and through central nervous system circuits to the brain. Investigators have also learned that this receptor plays a role in the burning type of pain commonly associated with heat, such as the kind you experience when you touch your finger to a hot stove. The vanilloid receptor functions as a sort of “ouch gateway,” enabling us to detect burning hot pain, whether it originates from a 3-alarm habanera chili or from a stove burner. Capsaicin is currently available as a prescription or over-the-counter cream for the treatment of a number of pain conditions, such as shingles. It works by reducing the amount of substance P found in nerve endings and interferes with the transmission of pain signals to the brain. Individuals can become desensitized to the compound, however, perhaps because of longterm damage to nerve tissue. Some individuals find the burning sensation they experience when using capsaicin cream to be intolerable, especially

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when they are already suffering from a painful condition, such as postherpetic neuralgia. Soon, however, better treatments that relieve pain by blocking vanilloid receptors may arrive in drugstores. Marijuana As a painkiller, marijuana or, by its Latin name, cannabis, continues to remain highly controversial. In the eyes of many individuals campaigning on its behalf, marijuana rightfully belongs with other pain remedies. In fact, for many years, it was sold under highly controlled conditions in cigarette form by the Federal government for just that purpose. In 1997, the National Institutes of Health held a workshop to discuss research on the possible therapeutic uses for smoked marijuana. Panel members from a number of fields reviewed published research and heard presentations from pain experts. The panel members concluded that, because there are too few scientific studies to prove marijuana’s therapeutic utility for certain conditions, additional research is needed. There is evidence, however, that receptors to which marijuana binds are found in many brain regions that process information that can produce pain. Nerve Blocks Nerve blocks may involve local anesthesia, regional anesthesia or analgesia, or surgery; dentists routinely use them for traditional dental procedures. Nerve blocks can also be used to prevent or even diagnose pain. In the case of a local nerve block, any one of a number of local anesthetics may be used; the names of these compounds, such as lidocaine or novocaine, usually have an aine ending. Regional blocks affect a larger area of the body. Nerve blocks may also take the form of what is commonly called an epidural, in which a drug is administered into the space between the spine’s protective covering (the dura) and the spinal column. This procedure is most well known for its use during childbirth. Morphine and methadone are opioid narcotics (such drugs end in ine or one) that are sometimes used for regional analgesia and are administered as an injection. Neurolytic blocks employ injection of chemical agents such as alcohol, phenol, or glycerol to block pain messages and are most often used to treat cancer pain or to block pain in the cranial nerves (see “The Nervous

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Systems”). In some cases, a drug called guanethidine is administered intravenously in order to accomplish the block. Surgical blocks are performed on cranial, peripheral, or sympathetic nerves. They are most often done to relieve the pain of cancer and extreme facial pain, such as that experienced with trigeminal neuralgia. There are several different types of surgical nerve blocks and they are not without problems and complications. Nerve blocks can cause muscle paralysis and, in many cases, result in at least partial numbness. For that reason, the procedure should be reserved for a select group of patients and should only be performed by skilled surgeons. Types of surgical nerve blocks include: ·

Neurectomy (including peripheral neurectomy) in which a damaged peripheral nerve is destroyed.

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Spinal dorsal rhizotomy in which the surgeon cuts the root or rootlets of one or more of the nerves radiating from the spine. Other rhizotomy procedures include cranial rhizotomy and trigeminal rhizotomy, performed as a treatment for extreme facial pain or for the pain of cancer.

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Sympathectomy, also called sympathetic blockade, in which a drug or an agent such as guanethidine is used to eliminate pain in a specific area (a limb, for example). The procedure is also done for cardiac pain, vascular disease pain, the pain of reflex sympathetic dystrophy syndrome, and other conditions. The term takes its name from the sympathetic nervous system (see “The Nervous Systems”) and may involve, for example, cutting a nerve that controls contraction of one or more arteries.

Information Resources The National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health, is the leading federal supporter of research on brain and nervous system disorders. The Institute also sponsors an active public information program that offers information about diagnosis, treatment, and research on painful neurological disorders. For information on pain research supported by the Institute, or information on other neurological disorders, write to the Institute’s Brain Resources and Information Network (BRAIN) at:

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BRAIN P.O. Box 5801 Bethesda, MD 20824 301-496-5751 800-352-9424 http://www.ninds.nih.gov Additional information about pain research supported by the NIH may be obtained from: Public Information and Liaison Branch National Institute of Dental and Craniofacial Research National Institutes of Health Building 45, Room 4AS19 Bethesda, MD 20892-6400 301-496-4261 http://www.nidcr.nih.gov A number of private organizations offer a variety of services and information that can help those affected by pain. They include: American Chronic Pain Association P.O. Box 850 Rocklin, CA 95677-0850 916-632-0922 http://www.theacpa.org Self-help organization that offers educational materials and peer support groups. They emphasize positive approaches to coping with chronic pain. They will be launching a national pain awareness campaign in 2002. American Pain Foundation 201 North Charles Street, Suite 710 Baltimore, MD 21201 410-783-7292 888-615-PAIN (7246) http://www.painfoundation.org Independent non-profit information, education and advocacy organization serving people with pain. Raises public awareness, provides practical information, promotes research, and works to remove barriers and increase access to effective pain management.

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Arthritis Foundation 1330 West Peachtree Street P.O. Box 7669 Atlanta, GA 30309 404-965-7100 800-283-7800 http://www.arthritis.org Volunteer-driven organization that works to improve lives through leadership in the prevention, control, and cure of arthritis and related diseases. Offers free brochures on various types of arthritis, treatment options, and management of daily activities when affected. National Chronic Pain Outreach Association P.O. Box 274 Millboro, VA 24460 540-862-9437 [email protected] Non-profit organization which serves as a clearinghouse of information about chronic pain for pain sufferers, their physicians, other health care professionals, and the public. National Foundation for the Treatment of Pain 1330 Skyline Drive, Suite #21 Monterey, CA 93940 831-655-8812 http://www.paincare.org Not-for-profit organization dedicated to providing support for patients who are suffering from intractable pain, their families, friends, and the physicians who treat them. Offers a patient forum, advocacy programs, information, support resources, and direct medical intervention.

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries and glossaries. 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

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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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

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On-line Medical Dictionary (CancerWEB): http://www.graylab.ac.uk/omd/

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

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Terms and Definitions (Office of Rare Diseases): http://rarediseases.info.nih.gov/ord/glossary_a-e.html

Beyond these, MEDLINEplus contains a very user-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia Web site address is 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). Topics of interest can be researched by using keywords before continuing elsewhere, as these basic definitions and concepts will be useful in more advanced areas of research. You may choose to print various pages specifically relating to endometriosis and keep them on file. The NIH, in particular, suggests that patients with endometriosis visit the following Web sites in the ADAM Medical Encyclopedia:

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Basic Guidelines for Endometriosis Adenomyosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001513.htm Endometriosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000915.htm

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Signs & Symptoms for Endometriosis Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Back pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003108.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Dysmenorrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003150.htm Dyspareunia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003157.htm Heavy menstrual bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003263.htm

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Low back pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003108.htm Menstrual cramping Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003150.htm Menstruation, painful Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003150.htm Mood changes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Nodules Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003230.htm Spotting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003156.htm ·

Diagnostics and Tests for Endometriosis Abdominal MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003796.htm Abdominal X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003815.htm ADH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003702.htm Colonoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003886.htm

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Cyst Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003240.htm Cysts Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003240.htm Follicle stimulating hormone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003710.htm FSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003710.htm Laparoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003918.htm LH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003708.htm Luteinizing hormone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003708.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm

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Surgery and Procedures for Endometriosis Abdominal exploration Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002928.htm Abdominal hysterectomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002915.htm C-section Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002911.htm Episiotomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002920.htm Exploratory laparotomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002928.htm Hysterectomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002915.htm Removal of the uterus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002915.htm

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Background Topics for Endometriosis Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Analgesic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002123.htm

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Analgesics Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002123.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Hemorrhagic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002373.htm Pain medication Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002123.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries and glossaries: ·

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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ENDOMETRIOSIS GLOSSARY The following is a complete glossary of terms used in this sourcebook. The definitions are derived from official public sources including the National Institutes of Health [NIH] and the European Union [EU]. After this glossary, we list a number of additional hardbound and electronic glossaries and dictionaries that you may wish to consult. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Pertaining to the abdomen. [EU] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abortion: 1. the premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. premature stoppage of a natural or a pathological process. [EU] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acne: An inflammatory disease of the pilosebaceous unit, the specific type usually being indicated by a modifying term; frequently used alone to designate common acne, or acne vulgaris. [EU] Actinobacillus: A genus of pasteurellaceae described as gram-negative, nonsporeforming, nonmotile, facultative anaerobes. Most members are found both as pathogens and commensal organisms in the respiratory, alimentary, and genital tracts of animals. [NIH] Adenocarcinoma: organization. [NIH]

A malignant epithelial tumor with a glandular

Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adnexitis: Inflammation of the adnexa uteri. [EU] 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]

Adverse: Harmful. [EU]

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Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Amenorrhea: amenia. [EU]

Absence or abnormal stoppage of the menses; called also

Anal: Pertaining to the anus. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] 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] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]

Anorexia: Lack or loss of the appetite for food. [EU] Antibiotic: A chemical substance produced by a microorganism which has the capacity, in dilute solutions, to inhibit the growth of or to kill other microorganisms. Antibiotics that are sufficiently nontoxic to the host are used as chemotherapeutic agents in the treatment of infectious diseases of man, animals and plants. [EU] Antibody: An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [EU] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Antidepressant: An agent that stimulates the mood of a depressed patient, including tricyclic antidepressants and monoamine oxidase inhibitors. [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 Tlymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells;

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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] Antioxidant: One of many widely used synthetic or natural substances added to a product to prevent or delay its deterioration by action of oxygen in the air. Rubber, paints, vegetable oils, and prepared foods commonly contain antioxidants. [EU] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Aseptic: Free from infection or septic material; sterile. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Auricular: Pertaining to an auricle or to the ear, and, formerly, to an atrium of the heart. [EU] 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] Bacteroides: A genus of gram-negative, anaerobic, rod-shaped bacteria. Its organisms are normal inhabitants of the oral, respiratory, intestinal, and urogenital cavities of humans, animals, and insects. Some species may be pathogenic. [NIH] Benign: An enlarged prostate not caused by cancer. BPH can cause problems with urination because the prostate squeezes the urethra at the opening of the bladder. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Bladder: The balloon-shaped organ inside the pelvis that holds 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] Bursitis: Inflammation of a bursa, occasionally accompanied by a calcific deposit in the underlying supraspinatus tendon; the most common site is the subdeltoid bursa. [EU] Calcium: A mineral that the body needs for strong bones and teeth. Calcium may form stones in the kidney. [NIH]

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Campylobacter: A genus of bacteria found in the reproductive organs, intestinal tract, and oral cavity of animals and man. Some species are pathogenic. [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-, poly- and heterosaccharides. [EU] Carcinoma: A malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cervical: Pertaining to the neck, or to the neck of any organ or structure. [EU] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [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] Chronic: Lasting a long time. Chronic diseases develop slowly. Chronic renal failure may develop over many years and lead to end-stage renal disease. [NIH] Clomiphene: A stilbene derivative that functions both as a partial estrogen agonist and complete estrogen antagonist depending on the target tissue. It antagonizes the estrogen receptor thereby initiating or augmenting ovulation in anovulatory women. [NIH] Colitis: Inflammation of the colon. [EU] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH]

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Colorectal: Pertaining to or affecting the colon and rectum. [EU] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Constriction: The act of constricting. [NIH] Contraception: The prevention of conception or impregnation. [EU] Contraceptive: conception. [EU]

An agent that diminishes the likelihood of or prevents

Criterion: A standard by which something may be judged. [EU] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curettage: The removal of growths or other material from the wall of a cavity or other surface, as with a curet; called also curettement. [EU] Cystitis: Inflammation of the bladder, causing pain and a burning feeling in the pelvis or urethra. [NIH] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [NIH] Dancing: Rhythmic and patterned body movements which are usually performed to music. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] 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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Dienestrol: A synthetic, non-steroidal estrogen structurally related to stilbestrol. It is used, usually as the cream, in the treatment of menopausal and postmenopausal symptoms. [NIH]

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Dysmenorrhea: Painful menstruation. [NIH] Dyspareunia: Difficult or painful coitus. [EU] Dysplasia: Abnormality of development; in pathology, alteration in size, shape, and organization of adult cells. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Dysuria: Painful or difficult urination. [EU] Eclampsia: Convulsions and coma occurring in a pregnant or puerperal woman, associated with preeclampsia, i.e., with hypertension, edema, and/or proteinuria. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: In animals, those derivatives of the fertilized ovum that eventually become the offspring, during their period of most rapid development, i.e., after the long axis appears until all major structures are represented. In man, the developing organism is an embryo from about two weeks after fertilization to the end of seventh or eighth week. [EU] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [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; called also adenomyosis externa and endometriosis externa. [EU] Endoscopy: Visual inspection of any cavity of the body by means of an endoscope. [EU] Enzyme: A protein molecule that catalyses chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions. Enzymes are classified according to the recommendations of the Nomenclature Committee of the International Union of Biochemistry. Each

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enzyme is assigned a recommended name and an Enzyme Commission (EC) number. They are divided into six main groups; oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [EU] 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 health-related 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] Episiotomy: Surgical incision into the perineum and vagina to prevent traumatic tearing during delivery. [EU] Epithelium: The covering of internal and external surfaces of the body, including the lining of vessels and other small cavities. It consists of cells joined by small amounts of cementing substances. Epithelium is classified into types on the basis of the number of layers deep and the shape of the superficial cells. [EU] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [NIH] Exostoses: Benign hypertrophy that projects outward from the surface of bone, often containing a cartilaginous component. [NIH] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Facial: Of or pertaining to the face. [EU] 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] Femoral: Pertaining to the femur, or to the thigh. [EU] Fibrin: The insoluble protein formed from fibrinogen by the proteolytic action of thrombin during normal clotting of blood. Fibrin forms the essential portion of the blood clot. [EU]

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Fistula: An abnormal passage or communication, usually between two internal organs, or leading from an internal organ to the surface of the body; frequently designated according to the organs or parts with which it communicates, as anovaginal, brochocutaneous, hepatopleural, pulmonoperitoneal, rectovaginal, urethrovaginal, and the like. Such passages are frequently created experimentally for the purpose of obtaining body secretions for physiologic study. [EU] FSH: A gonadotropic hormone found in the pituitary tissues of mammals. It regulates the metabolic activity of ovarian granulosa cells and testicular Sertoli cells, induces maturation of Graafian follicles in the ovary, and promotes the development of the germinal cells in the testis. [NIH] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Genitals: Sex organs, including the penis and testicles in men and the vagina and vulva in women. [NIH] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Gestrinone: A non-estrogenic contraceptive which is a weak progestin with strong anti-progesterone properties. It is effective if used once a week orally or can also be used in intravaginal devices. [NIH] Glossitis: Inflammation of the tongue. [EU] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Granule: A small pill made from sucrose. [EU] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hernia: (he protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [EU] Hirsutism: Abnormal hairiness, especially an adult male pattern of hair distribution in women. [EU] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of

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allografts. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A natural chemical produced in one part of the body and released into the blood to trigger or regulate particular functions of the body. Antidiuretic hormone tells the kidneys to slow down urine production. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour now often used of endocrine factors as opposed to neural or somatic. [EU] Hydrogen: 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] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypertrophy: Nutrition) the enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells. [EU] Hysterectomy: The operation of excising the uterus, performed either through the abdominal wall (abdominal h.) or through the vagina (vaginal h.) [EU] 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] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Incision: 1. cleft, cut, gash. 2. an act or action of incising. [EU] Incisive: 1. having the power or quality of cutting. 2. pertaining to the incisor teeth. [EU] Incontinence: Loss of bladder or bowel control; the accidental loss of urine or feces. [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

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anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: 1. the formation of an infarct. 2. an infarct. [EU] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Interstitial: A disorder that causes the bladder wall to become swollen and irritated, leading to scarring and stiffening of the bladder, decreased bladder capacity, and, in rare cases, ulcers in the bladder lining. IC is also known as painful bladder syndrome. [NIH] Intestinal: Pertaining to the intestine. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] 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]

Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Lactation: The period of the secretion of milk. [EU] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [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: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Lethal: Deadly, fatal. [EU]

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LH: A small glycoprotein hormone secreted by the anterior pituitary. LH plays an important role in controlling ovulation and in controlling secretion of hormones by the ovaries and testes. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lumbago: Pain in the lumbar region. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]

Lymphoma: Any neoplastic disorder of the lymphoid tissue, the term lymphoma often is used alone to denote malignant lymphoma. [EU] Macaca: A genus of the subfamily cercopithecinae, family cercopithecidae, consisting of 16 species inhabiting forests of Africa, Asia, and the islands of Borneo, Philippines, and Celebes. [NIH] Malformation: A morphologic defect resulting from an intrinsically abnormal developmental process. [EU] Malignant: Tending to become progressively worse and to result in death. Having the properties of anaplasia, invasion, and metastasis; said of tumours. [EU] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU]

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Melanoma: A tumour arising from the melanocytic system of the skin and other organs. When used alone the term refers to malignant melanoma. [EU] Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Menopause: Cessation of menstruation in the human female, occurring usually around the age of 50. [EU] Menorrhagia: Excessive uterine bleeding occurring at the regular intervals of menstruation, the period of flow being of greater than usual duration. [EU] Menstruation: The cyclic, physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus; it is under hormonal control and normally recurs, usually at approximately four-week intervals, in the absence of pregnancy during the reproductive period (puberty through menopause) of the female of the human and a few species of primates. It is the culmination of the menstrual cycle. [EU] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Metabolite: process. [EU]

Any substance produced by metabolism or by a metabolic

Metaplasia: The change in the type of adult cells in a tissue to a form which is not formal for that tissue. [EU] Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary cushing syndrome. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Motility: The ability to move spontaneously. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU]

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Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Nasal: Pertaining to the nose. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] 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] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrophil: Having an affinity for neutral dyes. [EU] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nocturia: Excessive urination at night. [EU] Nulliparous: Having never given birth to a viable infant. [EU] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [NIH]

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Oophorectomy: ovariectomy. [EU]

The removal of an ovary or ovaries; called also

Oral: Pertaining to the mouth, taken through or applied in the mouth, as an oral medication or an oral thermometer. [EU] Osteoarthritis: Noninflammatory degenerative joint disease occurring chiefly in older persons, characterized by degeneration of the articular cartilage, hypertrophy of bone at the margins, and changes in the synovial membrane. It is accompanied by pain and stiffness, particularly after prolonged activity. [EU] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [NIH] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU] 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: 1. to administer an excessive dose. 2. an excessive dose. [EU] Ovulation: The discharge of a secondary oocyte from a vesicular follicle of the ovary. [EU] 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] Palliative: 1. affording relief, but not cure. 2. an alleviating medicine. [EU] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Parasitic: Pertaining to, of the nature of, or caused by a parasite. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] 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

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organs of the body caused by the disease). [EU] Pelvic: Muscles that support the bladder. [NIH] Pelvis: The bowl-shaped bone that supports the spine and holds up the digestive, urinary, and reproductive organs. The legs connect to the body at the pelvis. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] 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] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Phagocytosis: Endocytosis of particulate material, such as microorganisms or cell fragments. The material is taken into the cell in membrane-bound vesicles (phagosomes) that originate as pinched off invaginations of the plasma membrane. Phagosomes fuse with lysosomes, forming phagolysosomes in which the engulfed material is killed and digested. [EU] Phosphates: Inorganic salts of phosphoric acid. [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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Porphyromonas: A genus of gram-negative, anaerobic, nonsporeforming, nonmotile rods or coccobacilli. Organisms in this genus had originally been classified as members of the bacteroides genus but overwhelming biochemical and chemical findings indicated the need to separate them from other Bacteroides species, and hence, this new genus was created. [NIH] Postmenopausal: Occurring after the menopause. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Precursor: Something that precedes. In biological processes, a substance

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from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Premenstrual: Occurring before menstruation. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] 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] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prostaglandins: A group of compounds derived from unsaturated 20carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostate: In men, a walnut-shaped gland that surrounds the urethra at the neck of the bladder. The prostate supplies fluid that goes into semen. [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]

Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychoneuroimmunology: The field concerned with the interrelationship between the brain, behavior and the immune system. Neuropsychologic, neuroanatomic and psychosocial studies have demonstrated their role in accentuating or diminishing immune/allergic responses. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Rantes: A chemokine that is a chemoattractant for eosinophils, monocytes,

Glossary 281

and lymphocytes. It is a potent and selective eosinophil chemotaxin that is stored in and released from platelets and activated T-cells. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reflux: A backward or return flow. [EU] Resection: Excision of a portion or all of an organ or other structure. [EU] 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] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrograde: 1. moving backward or against the usual direction of flow. 2. degenerating, deteriorating, or catabolic. [EU] Rheumatoid: Resembling rheumatism. [EU] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Sciatica: A syndrome characterized by pain radiating from the back into the buttock and into the lower extremity along its posterior or lateral aspect, and most commonly caused by prolapse of the intervertebral disk; the term is also used to refer to pain anywhere along the course of the sciatic nerve. [EU] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any

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substance produced by secretion. [EU] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Somatic: 1. pertaining to or characteristic of the soma or body. 2. pertaining to the body wall in contrast to the viscera. [EU] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [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] Spotting: A slight discharge of blood via the vagina, especially as a sideeffect of oral contraceptives. [EU] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Stenosis: Narrowing or stricture of a duct or canal. [EU] 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] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Surgical: Of, pertaining to, or correctable by surgery. [EU]

Glossary 283

Sympathetic: 1. pertaining to, caused by, or exhibiting sympathy. 2. a sympathetic nerve or the sympathetic nervous system. [EU] Symptomatic: 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. exhibiting the symptoms of a particular disease but having a different cause. 4. directed at the allying of symptoms, as symptomatic treatment. [EU] Systemic: Pertaining to or affecting the body as a whole. [EU] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Thalamus: Either of two large, ovoid masses, consisting chiefly of grey substance, situated one on each side of and forming part of the lateral wall of the third ventricle. It is divided into two major parts : dorsal and ventral, each of which contains many nuclei. [EU] Thermal: Pertaining to or characterized by heat. [EU] Thermoregulation: Heat regulation. [EU] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Topical: Pertaining to a particular surface area, as a topical anti-infective applied to a certain area of the skin and affecting only the area to which it is applied. [EU] Toxic: Pertaining to, due to, or of the nature of a poison or toxin; manifesting the symptoms of severe infection. [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] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Triptorelin: A long-acting gonadorelin analog agonist. It has been used in the treatment of prostatic cancer, ovarian cancer, precocious puberty, endometriosis, and to induce ovulation for in vitro fertilization. [NIH] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Trustees: Board members of an institution or organization who are entrusted with the administering of funds and the directing of policy. [NIH] Tumour: 1. swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. a new growth of tissue in which the multiplication of cells is

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uncontrolled and progressive; called also neoplasm. [EU] Urethritis: Inflammation of the urethra. [NIH] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Uterus: The hollow muscular organ in female mammals in which the fertilized ovum normally becomes embedded and in which the developing embryo and fetus is nourished. In the nongravid human, it is a pear-shaped structure; about 3 inches in length, consisting of a body, fundus, isthmus, and cervix. Its cavity opens into the vagina below, and into the uterine tube on either side at the cornu. It is supported by direct attachment to the vagina and by indirect attachment to various other nearby pelvic structures. Called also metra. [EU] Vagina: The tube in a woman's body that runs beside the urethra and connects the womb (uterus) to the outside of the body. Sometimes called 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] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Ventral: 1. pertaining to the belly or to any venter. 2. denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU]

General Dictionaries and Glossaries While the above glossary is essentially complete, the dictionaries listed here cover virtually all aspects of medicine, from basic words and phrases to more advanced terms (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Dictionary of Medical Acronymns & Abbreviations by Stanley Jablonski (Editor), Paperback, 4th edition (2001), Lippincott Williams & Wilkins Publishers, ISBN: 1560534605, http://www.amazon.com/exec/obidos/ASIN/1560534605/icongroupinterna

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Dictionary of Medical Terms : For the Nonmedical Person (Dictionary of Medical Terms for the Nonmedical Person, Ed 4) by Mikel A. Rothenberg, M.D, et al, Paperback - 544 pages, 4th edition (2000), Barrons Educational

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Series, ISBN: 0764112015, http://www.amazon.com/exec/obidos/ASIN/0764112015/icongroupinterna ·

A Dictionary of the History of Medicine by A. Sebastian, CD-Rom edition (2001), CRC Press-Parthenon Publishers, ISBN: 185070368X, http://www.amazon.com/exec/obidos/ASIN/185070368X/icongroupinterna

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Dorland's Illustrated Medical Dictionary (Standard Version) by Dorland, et al, Hardcover - 2088 pages, 29th edition (2000), W B Saunders Co, ISBN: 0721662544, http://www.amazon.com/exec/obidos/ASIN/0721662544/icongroupinterna

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Dorland's Electronic Medical Dictionary by Dorland, et al, Software, 29th Book & CD-Rom edition (2000), Harcourt Health Sciences, ISBN: 0721694934, http://www.amazon.com/exec/obidos/ASIN/0721694934/icongroupinterna

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Dorland's Pocket Medical Dictionary (Dorland's Pocket Medical Dictionary, 26th Ed) Hardcover - 912 pages, 26th edition (2001), W B Saunders Co, ISBN: 0721682812, http://www.amazon.com/exec/obidos/ASIN/0721682812/icongroupinterna /103-4193558-7304618

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Melloni's Illustrated Medical Dictionary (Melloni's Illustrated Medical Dictionary, 4th Ed) by Melloni, Hardcover, 4th edition (2001), CRC PressParthenon Publishers, ISBN: 85070094X, http://www.amazon.com/exec/obidos/ASIN/85070094X/icongroupinterna

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Stedman's Electronic Medical Dictionary Version 5.0 (CD-ROM for Windows and Macintosh, Individual) by Stedmans, CD-ROM edition (2000), Lippincott Williams & Wilkins Publishers, ISBN: 0781726328, http://www.amazon.com/exec/obidos/ASIN/0781726328/icongroupinterna

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Stedman's Medical Dictionary by Thomas Lathrop Stedman, Hardcover 2098 pages, 27th edition (2000), Lippincott, Williams & Wilkins, ISBN: 068340007X, http://www.amazon.com/exec/obidos/ASIN/068340007X/icongroupinterna

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Tabers Cyclopedic Medical Dictionary (Thumb Index) by Donald Venes (Editor), et al, Hardcover - 2439 pages, 19th edition (2001), F A Davis Co, ISBN: 0803606540, http://www.amazon.com/exec/obidos/ASIN/0803606540/icongroupinterna

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INDEX A Abdomen ......12, 13, 14, 22, 24, 108, 180, 197, 265, 274, 277 Abdominal...11, 12, 14, 16, 23, 44, 58, 80, 86, 87, 101, 108, 127, 140, 269, 273, 278, 279 Aberrant.................................................74 Abortion .............................76, 91, 99, 265 Acetaminophen......................................65 Acne ..........................15, 22, 82, 265, 281 Adhesions................................71, 75, 127 Adnexitis ................................................87 Adolescence ........................124, 199, 265 Agonist..15, 63, 64, 65, 80, 134, 172, 182, 198, 199, 206, 268, 277, 283 Amenorrhea...........................................88 Anal .......................................................57 Analgesic .................................76, 88, 265 Androgenic ..............................23, 97, 269 Androgens .............................................92 Anesthesia.....................................16, 227 Anorexia ................................................30 Antibiotic ........................................82, 282 Antibody..78, 98, 102, 104, 105, 106, 107, 108, 130, 131, 266, 269, 273, 275 Antifungal.............................................179 Antigen .......103, 104, 106, 107, 108, 266, 271, 273, 275 Antioxidant.............................................70 Antiproliferative......................................70 Antipyretic ................................76, 88, 265 Aseptic .....................................82, 94, 282 Assay.............................97, 103, 107, 273 B Bacteria ....77, 82, 93, 106, 192, 266, 267, 268, 282 Benign .................18, 23, 58, 95, 130, 269 Biosynthesis ..........................................68 Bladder ...12, 23, 24, 38, 59, 79, 139, 140, 267, 269, 273, 274, 279, 280 Blastocyst ..........24, 78, 83, 269, 279, 283 C Calcium........................................193, 194 Capsules........................................87, 195 Carbohydrate...............104, 107, 194, 272 Carcinoma .................................71, 91, 95 Cardiovascular.............................130, 131 Causal ...................................................88 Cervical....................................57, 60, 121 Chemotaxis............................................93 Chemotherapy .......................................56

Chlorine................................................. 93 Cholesterol.................... 79, 192, 194, 275 Chronic... 21, 56, 58, 64, 80, 91, 112, 121, 122, 140, 151, 179, 217, 278 Colitis .................................................... 57 Colorectal...................................... 57, 121 Conception... 23, 38, 66, 76, 82, 265, 269, 282 Constriction ........................................... 88 Contraception ............. 29, 31, 60, 63, 119 Contraceptive.................. 63, 75, 205, 272 Criterion ................................................ 95 Cues...................................................... 75 Cystitis .................................... 57, 59, 140 Cytokines ...................... 61, 68, 74, 94, 99 D Danazol........................... 62, 92, 100, 117 Dancing................................................. 89 Degenerative ........................ 80, 193, 278 Desensitization ................................... 179 Diaphragm .............................. 15, 23, 269 Dysmenorrhea .. 12, 20, 61, 75, 87, 88, 99 Dyspareunia.......... 12, 59, 75, 89, 99, 140 Dysplasia .................................... 121, 152 Dystrophy.................................... 140, 152 Dysuria.................................................. 75 E Eclampsia ............................... 31, 81, 280 Ectopic . 61, 62, 68, 71, 73, 74, 86, 88, 89, 90, 96, 102, 103, 122, 126, 130 Edema....... 38, 67, 81, 106, 268, 270, 280 Electrophoresis ............................. 96, 102 Electrophysiological .............................. 73 Embryo....... 25, 38, 76, 77, 90, 94, 98, 99, 107, 265, 267, 270, 273, 284 Empiric ................................................ 134 Endocrinology ................... 28, 38, 63, 272 Endoscopy .......................................... 119 Enzyme ............................... 103, 107, 271 Epidemiological..................................... 29 Epidermal.............................. 96, 103, 130 Epithelium ........................... 67, 74, 91, 93 Epitopes .............................................. 104 Estradiol ........................................ 62, 198 Estrogens.................... 45, 88, 92, 97, 100 Exostoses ........................................... 123 Exudate................................. 94, 107, 271 F Facial .................................................. 123 Fatigue ................................................ 112 Fibrin ................................................... 131

Index 287

Fistula ............................................78, 272 G Gastrointestinal........56, 78, 101, 122, 272 Genitals .........................................12, 117 Gestrinone ...........................................199 Glossitis ...............................................123 Glycoproteins.......................104, 107, 272 Gynecology................................30, 35, 56 H Hemorrhage...........................................57 Hernia ....................................................65 Hirsutism................................................28 Hormonal ..24, 59, 71, 73, 75, 92, 97, 198, 276 Humoral ...............................................103 Hydrogen .........80, 93, 107, 268, 273, 278 Hyperalgesia..........................................73 Hypertrophy .............80, 95, 124, 271, 278 Hysterectomy......16, 18, 57, 59, 126, 127, 197, 263 I Immunohistochemistry ........................104 Immunotherapy......................78, 179, 269 Implantation 59, 71, 74, 78, 83, 86, 98, 99, 269, 283 Incision ..............14, 79, 95, 227, 271, 274 Incisive.................................................123 Incontinence ..............................56, 57, 59 Indicative ...80, 82, 83, 103, 278, 283, 284 Induction ..................28, 60, 100, 106, 266 Infarction..............................................131 Infertility 11, 13, 20, 28, 31, 62, 63, 65, 66, 68, 70, 73, 75, 83, 89, 92, 94, 98, 100, 101, 105, 120, 126, 179, 181, 198, 284 Inflammation .11, 75, 80, 88, 94, 107, 124, 271, 278, 281 Inorganic ................................................95 Interstitial .................57, 59, 124, 140, 281 Intestinal ..........12, 77, 106, 192, 267, 268 Intestines ...............................................12 Intrinsic ..................................................68 Isoflavones ......................................91, 92 L Lactation ..........................................31, 56 Laparoscopy ................14, 16, 64, 89, 104 Leptin ...................................................133 Lesion ..............................................61, 74 Lethal .....................................................93 Lipid .........................................79, 94, 275 Lipoprotein...............................68, 79, 275 Lumbago................................................87 Lupus ...........................................112, 121 Lymphoma...................131, 142, 151, 275 M Malignant ....13, 72, 77, 83, 124, 130, 142, 151, 265, 268, 275, 276, 283

Mediate ........................................... 61, 70 Mediator ................................................ 90 Melanoma ........... 121, 124, 127, 151, 276 Membranes ........................... 82, 104, 282 Menarche ........................................ 66, 75 Menopause ...... 12, 24, 28, 56, 63, 66, 73, 101, 179, 276, 279 Menorrhagia.......................................... 20 Menstruation .... 11, 13, 23, 24, 29, 68, 74, 81, 86, 87, 90, 94, 99, 108, 270, 276, 277, 280 Metabolite ........................................... 195 Metaplasia........................................... 126 Mitosis................................................... 93 Mobility.................................................. 69 Molecular . 68, 72, 96, 102, 146, 149, 151, 281 Monocytes............................... 62, 81, 280 Motility................................................... 93 Mucosa ....................... 122, 124, 275, 276 Mutagenesis ......................................... 69 Myometrium .............................. 60, 70, 95 Myosin................................................. 131 N Nasal..................................... 15, 124, 275 Nausea.................................................. 87 Neoplastic ....................... 57, 72, 142, 275 Neural ................................... 73, 193, 273 Neurons .................................. 73, 80, 277 Neurotransmitter ......................... 143, 277 Neutrophil.............................................. 93 Niacin .................................................. 192 Nocturia................................................. 57 Nulliparous ............................................ 98 O Obstetrics........................................ 30, 35 Oligomenorrhea .................................... 88 Oophorectomy ...................................... 59 Oral 15, 24, 29, 59, 60, 63, 75, 77, 88, 91, 92, 100, 106, 122, 198, 199, 227, 267, 268, 278, 282 Osteoporosis........................... 45, 97, 121 Ovary ... 4, 24, 31, 58, 78, 80, 88, 94, 100, 107, 126, 271, 272, 278 Overdose ............................................ 193 Ovulation.. 14, 28, 58, 66, 67, 89, 99, 108, 172, 206, 268, 275, 283 Ovum . 25, 81, 83, 99, 107, 270, 280, 283, 284 P Parenteral ........................................... 199 Pathologic ............................... 81, 86, 281 Pelvis . 22, 23, 38, 89, 108, 140, 265, 267, 269, 279 Phagocytosis ........................................ 94 Phosphates ........................................... 93

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Placenta.....................13, 78, 81, 271, 280 Polymorphic...........................................65 Postmenopausal..............18, 69, 172, 269 Potassium............................................194 Precursor ...............................................72 Preeclampsia.................................38, 270 Premenstrual .................56, 101, 112, 179 Prevalence.......................................75, 99 Progesterone ....59, 60, 62, 69, 74, 90, 91, 172, 205, 272, 276 Progressive............................88, 109, 284 Prostaglandins...........87, 94, 99, 172, 276 Prostate ...........23, 31, 130, 151, 267, 280 Proteins ......69, 71, 72, 78, 104, 106, 192, 194, 266, 269 Psychoneuroimmunology ....................179 Puberty ..............24, 30, 66, 206, 276, 283 R Reagent ...............................104, 106, 268 Receptor .69, 96, 103, 106, 130, 134, 172, 267, 268, 276 Recurrence ......................64, 92, 134, 135 Reflux ..................................................140 Resection.............................................127 Resorption .............................................66 Retinoids................................................68 Retrograde.....................68, 74, 86, 90, 94 Riboflavin.............................................192 S Sciatica ..................................................19 Sclerosis ......................................112, 152 Selenium..............................................194 Serum ........................61, 82, 96, 103, 282

Somatic .. 72, 82, 108, 124, 265, 273, 276, 283 Species .... 24, 31, 38, 61, 71, 77, 79, 106, 108, 109, 267, 268, 275, 276, 279, 282 Spectrum............................................... 72 Stasis .................................................. 181 Sterility .................... 24, 88, 119, 120, 274 Sulfur..................................................... 93 Surgical ...... 14, 16, 38, 44, 57, 70, 82, 83, 103, 118, 121, 130, 179, 272, 277, 282, 284 Sympathetic ................................ 140, 283 Symptomatic ............. 58, 80, 82, 278, 283 T Telomerase........................................... 72 Thalamus .............................................. 73 Thermoregulation................................ 192 Thyroxine ............................................ 194 Topical ................................ 100, 109, 283 Toxic .. 39, 78, 80, 95, 193, 206, 268, 277, 282, 283 Toxicology..................................... 31, 147 Transplantation ................................... 181 Triptorelin ............................................ 198 Trophoblast ............................. 71, 77, 267 Tumour.................................. 90, 124, 276 U Urethritis................................................ 58 V Vagina 4, 12, 23, 24, 25, 73, 93, 109, 227, 271, 272, 273, 276, 282, 284 Vaginitis .......................................... 92, 93 Vascular ............................ 24, 67, 89, 279

Index 289

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