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

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Endometriosis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83656-6 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. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

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

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

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ENDOMETRIOSIS........................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Endometriosis................................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 41 The National Library of Medicine: PubMed ................................................................................ 42 CHAPTER 2. NUTRITION AND ENDOMETRIOSIS ............................................................................ 129 Overview.................................................................................................................................... 129 Finding Nutrition Studies on Endometriosis ............................................................................ 129 Federal Resources on Nutrition ................................................................................................. 143 Additional Web Resources ......................................................................................................... 143 CHAPTER 3. ALTERNATIVE MEDICINE AND ENDOMETRIOSIS ..................................................... 147 Overview.................................................................................................................................... 147 The Combined Health Information Database............................................................................. 147 National Center for Complementary and Alternative Medicine................................................ 148 Additional Web Resources ......................................................................................................... 151 General References ..................................................................................................................... 155 CHAPTER 4. DISSERTATIONS ON ENDOMETRIOSIS ....................................................................... 157 Overview.................................................................................................................................... 157 Dissertations on Endometriosis ................................................................................................. 157 Keeping Current ........................................................................................................................ 158 CHAPTER 5. CLINICAL TRIALS AND ENDOMETRIOSIS .................................................................. 159 Overview.................................................................................................................................... 159 Recent Trials on Endometriosis ................................................................................................. 159 Keeping Current on Clinical Trials ........................................................................................... 173 CHAPTER 6. PATENTS ON ENDOMETRIOSIS .................................................................................. 175 Overview.................................................................................................................................... 175 Patents on Endometriosis........................................................................................................... 175 Patent Applications on Endometriosis....................................................................................... 196 Keeping Current ........................................................................................................................ 227 CHAPTER 7. BOOKS ON ENDOMETRIOSIS ...................................................................................... 229 Overview.................................................................................................................................... 229 Book Summaries: Federal Agencies............................................................................................ 229 Book Summaries: Online Booksellers......................................................................................... 231 The National Library of Medicine Book Index ........................................................................... 237 Chapters on Endometriosis ........................................................................................................ 238 CHAPTER 8. MULTIMEDIA ON ENDOMETRIOSIS ........................................................................... 239 Overview.................................................................................................................................... 239 Bibliography: Multimedia on Endometriosis ............................................................................. 239 CHAPTER 9. PERIODICALS AND NEWS ON ENDOMETRIOSIS ........................................................ 241 Overview.................................................................................................................................... 241 News Services and Press Releases.............................................................................................. 241 Newsletter Articles .................................................................................................................... 246 Academic Periodicals covering Endometriosis........................................................................... 246 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 249 Overview.................................................................................................................................... 249 U.S. Pharmacopeia..................................................................................................................... 249 Commercial Databases ............................................................................................................... 251 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 255 Overview.................................................................................................................................... 255

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NIH Guidelines.......................................................................................................................... 255 NIH Databases........................................................................................................................... 257 Other Commercial Databases..................................................................................................... 259 The Genome Project and Endometriosis .................................................................................... 259 APPENDIX B. PATIENT RESOURCES ............................................................................................... 263 Overview.................................................................................................................................... 263 Patient Guideline Sources.......................................................................................................... 263 Associations and Endometriosis................................................................................................. 269 Finding Associations.................................................................................................................. 269 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 271 Overview.................................................................................................................................... 271 Preparation................................................................................................................................. 271 Finding a Local Medical Library................................................................................................ 271 Medical Libraries in the U.S. and Canada ................................................................................. 271 ONLINE GLOSSARIES................................................................................................................ 277 Online Dictionary Directories ................................................................................................... 280 ENDOMETRIOSIS DICTIONARY............................................................................................ 283 INDEX .............................................................................................................................................. 365

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

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

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

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 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 “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 what you can expect from this type of search: •

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

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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.

Federally Funded Research on Endometriosis The U.S. Government supports a variety of research studies relating to endometriosis. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to endometriosis. 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. The following is typical of the type of information found when searching the CRISP database for endometriosis: •

Project Title: ANTIPROGESTINS IN CYNOMOLGUS ENDOMETRIOSIS Principal Investigator & Institution: Wiehle, Ronald D.; Zonagen, Inc. 2408 Timberloch Pl, B-4 the Woodlands, Tx 77380 Timing: Fiscal Year 2002; Project Start 05-JUL-2000; Project End 30-SEP-2003 Summary: (provided by applicant): In May 1999, a Licensing Agreement between Zonagen, Inc. and the NICHD was finalized to develop new 19-substitutednorprogestins. If the new antiprogestins behave as tissue-specific modulators in the manner of selective estrogen response modulators (SERMs), they may be recognized as an analogous class of drugs, i.e., as SPRMs. Such SPRMs discovered by NICHD and realized as drugs through this SBIR, would bring the results of government-sponsored

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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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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. Their potential for use in labor and delivery and in breast cancer remains high. The following document outlines experiments to be performed under Phase II of an SBIR that would clarify the properties of these new SPRMs and enhance their utility for the treatment of endometriosis. It was the intention of Phase I of this SBIR program to determine effects on the eutopic endometrium of cynomolgus monkeys (Macaca fascicularis) following short-term administration, of our lead compound, CDB-4124. We did not believe SPRMs could affect ectopic lesions (endometriosis) if there was no effect on eutopic endometrium. We found that our lead compound had effects on the endometrium similar to RU 486 but without evidence of effects on ovulation and without raising cortisol. We established methods and the baseline levels of markers of inflammation in the peritoneal cavity of the monkey. 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 ectopic endometrium and effects on hormones with our lead antiprogestin compound, CDB4124. The secondary outcome parameter will be the effects on markers of endometriosis in peritoneal fluid and bone mineral density. The tertiary outcome parameters will be the assessment of the impact of our compound on inflammation markers, on cycling and on liver function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CD1 AND BCR/FC RECEPTOR TARGETED LIGAND Principal Investigator & Institution: Yeaman, Grant R.; Research Assistant Professor; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Non-classical MHC molecules such as CD ld or CD1b have evolved in parallel to classical class II molecules and I. They are however more specialized in the type of ligand they present to T cells. Typically, CD1 molecules present lipids or glycolipids to T cells. CD1 ligands are associated with T cells specific for M. tuberculosis. The studies in this project are based on a unique collaboration. The expertise of Dr. Grant Yeaman an assistant professor at Dartmouth Medical School (DMS) studies the role of carbohydrate antigens in endometriosis and HIV infection will be combined with that of Drs. William Wade and Bruce Reinhold. Dr. Wade is an associate professor whose research interests center on antigen presentation. Dr. Reinhold is an assistant professor of chemistry at the University of New Hampshire who studies CD1 ligands using mass spectrum analysis. This combination of expertise will be used to design synthetic peptide and carbohydrate/lipid antigens to investigate how BCR or Fc receptors internalizes and initiate the processing of these antigens to their effective form that induces T cell activation. Aim 1: To determine if BCR can internalize and target CDlb ligands for presentation to CDlb-restricted T cells. CDlb molecules can bind mycobacterial lipids. We will track internalization of CDlb ligands in the endocytic pathway by confocal microscopy, mass spectral analysis and activation T cells. Aim 2: To demonstrate that BCR can internalize and target CDld ligands for presentation to CDld-restricted T cells. The OVA hydrophobic peptide (IINFEKLTEWTSS) that binds

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CDld will be modified to contain class II, I-Ad OVA peptide and a B cell epitope for the V5 specific Ab. The construct will be linked to an anti-IgG2a (BCR) F(ab)2, and used to treat A20 B cells transfected with murine CDlda; galactosyl ceramide will also be examined in this system. The complexes will be followed functionally through the early endosome (EE), the MIIC and the lysosome by confocal microscopy, biochemical analysis and by T cell activation. Aim 3: Determine the trafficking of CDId/b ligands targeted to FcyRl on DCs and demonstrate that the distribution of CD1 differs with antigen internalization or maturation of the DC. DCs are likely the first cell to acquire mycobaterial antigens for priming T cells. Antigen is acquired through macropinocytosis or receptor-mediated endocytosis. We will use ex vivo DC and target immune complexes or particulate antigen such as bacteria to CD64 as a means of following the intracellular traffic of the complexes (antigen) biochemically and functionally. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL GROWTH INHIBITON AND ESTROGEN ACTION Principal Investigator & Institution: Markaverich, Barry M.; Associate Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-1983; Project End 31-JUL-2005 Summary: (provided by the applicant) A long-range goal of this research is to define the role of MeHPLA and nuclear type II sites in normal and malignant cell proliferation. The identification of MeHPLA as a ligand for type II sites which controls cell growth led to the development of MeHPLA-related compounds with antiproliferative activities and potential for the treatment of benign prostatic hyperplasia, endometriosis, breast and prostatic cancer. We recently identified the nuclear type II binding site as histone H4. This exciting discovery targets very specific genomic pathways for regulation by MeHPLA and related-compounds including bioflavonoids and phytoestrogens. These compounds bind to type II sites (histone H4) with high affinity and have classically been defined as antioxidants that scavage free radicals. Our recent data indicate very specific regulation of gene transcription at the level of chromatin structure and function by type II site (histone H4) ligands. Histone acetylation is temporally and functionally coupled to DNA replication and gene expression in experimental systems including uterus and cancer cells. We propose that MeHPLA and related compounds control normal and malignant cell proliferation by modulating chromatin acetylation patterns and core nucleosome unwinding by binding to histone H4. We will assess hormonal (estrogen, progesterone) modulation of histone H4 gene expression (mRNA and protein), ligand binding activity and cell proliferation in rat uterus and in ER-dependent (MCF-7 cells) and ER-independent (MDA-MD-231) breast cancer cells in vitro and when grown in nude mice (Specific Aim 1). Potential involvement of histones H1, H2A, H2B and H3 in ligand binding to histone H4 will be studied (Specific Aim 2). The identity of the ligand binding domain(s) on histone H4 by will be determined by protein sequencing and site directed mutagenesis studies (Specific Aim 3). Effects of MeHPLA and related histone H4 ligands on chromatin structure, histone acetylation, and steroid hormone-dependent chromatin remodeling and gene transcription in a cell free system (Specific Aim 4) will be assessed. Estrogen, antiestrogen and MeHPLArelated compound effect on the acetylation of histone H4 (or other histones), specific gene (cyclin Dl and p21) transcription and expression and cell proliferation (cell cycle transcition, etc.) in estrogen-dependent and estrogen-independent breast cancer cells in vitro and in vivo (Specific Aim 5) will be evaluated. The proposed studies should precisely define specific

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effects of MeHPLA and bioflavonoids on chromatin structure and function, growth related gene transcription and cellular proliferation in normal and malignant cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOKINE REGULATION IN MODELS OF ENDOMETRIOSIS Principal Investigator & Institution: Taylor, Robert N.; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001 Summary: Endometriosis is a common human gynecologic disorder associated with dysmenorrhea, pelvic pain and reduced fertility. Prevalence estimates range from 250%, 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 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, interferon-gamma) 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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COOPERATIVE MULTI CENTER REPRODUCTIVE MEDICINE NETWORK Principal Investigator & Institution: Myers, Evan R.; Associate Professor; Obstetrics and Gynecology; Duke University Durham, Nc 27706

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Timing: Fiscal Year 2001; Project Start 10-MAR-2000; Project End 28-FEB-2005 Summary: Disorders of the reproductive system, such as male and female infertility, leiomyomata, endometriosis, polycystic ovarian syndrome, and sexual dysfunction, have a major public health and economic impact. For some conditions, such as infertility, many patients are responsible for all costs associated with therapy, and unintended consequences, such as multiple gestations, are relatively common. For other conditions, such as endometriosis or leiomyomata, definitive therapy may result in the loss of childbearing potential, and long-term evidence about alternatives is scant. Relatively few interventions for these disorders have subjected to rigorous scientific evaluation. The long-term objective of this project is to improve the care of men and women with disorders affecting the reproductive system by conducting controlled trials of selected diagnostic and therapeutic interventions. The specific aims of the Data Coordinating Center (DCC) for the Cooperative Reproductive Medicine Network are (A) to develop trial protocols that address important clinical problems using scientifically valid, clinically feasible, and economically reasonable approaches through collaboration with participating Reproductive Medicine Units (RMUs) and NICHD staff, (B) to provide leadership in defining and measuring a range of important outcomes, including physiological measurements, clinical outcomes, and economic and quality of life measures, (C) to coordinate and/or provide all services necessary for conducting trials, including recruiting services, and quality control, and (D) to coordinate the analysis, reporting, and dissemination of trial results to the Data Safety and Monitoring Committee, the RMUs, NICHD, peer-reviewed journals, and the public. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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

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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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--TISSUE AND CELL CULTURE Principal Investigator & Institution: Morales, Arlene J.; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--TISSUE PROCUREMENT AND CELL CULTURE Principal Investigator & Institution: Jaffe, Randal C.; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: The objective of the Tissue Procurement and Cell Culture Core is to strengthen and support the research of the U54 investigators by establishing an efficient, cost-effective facility for procuring and storing tissue samples, cell lines and for isolating and providing well characterized primary cells. To achieve this goal, the Core proposes to: Serve as a central purchasing and storage facility for common tissue culture reagents where savings will be manifested in terms of either cost or consistency. Coordinate the collection of endometriotic and eutopic endometrial tissues and serve as a tissue bank that provides well documented endometriotic and normal tissue. Prepare primary stromal and epithelial cell cultures from normal and endometriotic tissues. Provide a single source for cell lines used by multiple U54 investigators. Serve as a training center for cell culture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENT OF KETOROLAC DRUG DELIVERY DEVICE Principal Investigator & Institution: Wilson, Michelle L.; Umd, Inc. 3130 Highland Ave, 3Rd Fl Cincinnati, Oh 45219 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: (provided by applicant): The treatment of uterine pain during menses (dysmenorrhea), a disorder that seriously afflicts 5 million women in the U.S., with prostaglandin synthetase inhibitors (PSIs), has not been optimal because of significant systemic side effects. Using a rabbit model, we have developed a novel vaginal drug delivery system that takes advantage of the unique vaginal-to-uterine circulation to achieve therapeutic concentrations of PSIs in the uterine musculature without high concentrations in the systemic circulation. This patented delivery system consists of a drug reservoir/carrier assembly that can be incorporated into a series of unique, tampon-containing platforms or a vaginal ring and is designed to carry the PSI through the vaginal mucosa into uterine circulation during menstruation. This innovative approach will provide effective relief during menses to women who still experience

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disabling dysmenorrhea, miss work, or are hampered in their daily activities, as well as absorb the menses. In addition, this drug delivery platform can be modified for delivery of other compounds to treat preterm labor and endometriosis. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT CONTRACEPTION

OF

CONTINUOUS

VS.

SEQUENTIAL

ORAL

Principal Investigator & Institution: Legro, Richard S.; Associate Professor; ObstetricsGynecology; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Withdrawal bleeding that occurs during the placebo period of the traditional OCP regimen is unnecessary and unwanted, and contributes to substantial method discontinuation rates. In U.S. women this contributes to one of the highest unwanted pregnancy rates in the world. In this proposal we will test the hypothesis that a long-term (6 month) continuous combined oral contraceptive pill (CCOCP) regimen (20 mug ethinyl estradiol/1 mg norethindrone acetate) will result in more profound endometrial and ovarian suppression than a traditional 21 day active pill/7 day placebo OCP regimen (21/70CP) with a randomized double blind trial. Currently CCOCP is commonly used by clinicians for a variety of indications, with little data of its safety and efficacy. As the clinical marker of endometrial and ovarian activity, we will be using number of bleeding days as the primary outcome in this study. We will secondarily monitor endometrial thickness and ovarian follicle formation by ultrasound, endometrial histology by biopsy, ovarian steroid production by monthly serum and daily urinary measurements, and patient satisfaction by questionnaire. We believe that a reduction in days of bleeding that will occur on a CCOCP regimen will improve patient satisfaction and compliance with this contraceptive regimen. We theorize that a tong-term CCOCP regimen may more effectively suppress ovarian follicular development and endometrial growth, because there are fewer rebounds in hormone levels due to loss of suppression during placebo periods. This regimen may therefore provide both effective contraception (with greater leeway for skipped pills) as well as more effective treatment of multiple gynecological conditions such as dysmenorrhea, dysfunctional uterine bleeding, endometriosis, and peripheral androgen disorders such as acne and hirsutism, as well as a greater reduction in risk for endometrial and ovarian cancer. Therefore, the risks and benefits of a CCOCP regimen are an important women's health issue that warrant investigation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF DEHYDROEPIANDROSTERONE ON BONE DENSITY IN PREMENOPAUSAL WOMEN Principal Investigator & Institution: Leboff, Meryl S.; Associate Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001 Summary: We will test two hypothesis. First, that DHEA therapy reduces elevated markers of bone turnover. Second, that DHEA prevents the accelerated bone loss in women treated with GnRH agonists for endometriosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EMMPRIN ENDOMETRIUM

REGULATES

METALLOPROTEINASES

11

IN

Principal Investigator & Institution: Nowak, Romana A.; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: The human endometrium undergoes a highly regulated sequence of proliferation, differentiation, and ultimately proteolytic breakdown and shedding of tissue with each menstrual cycle. Metalloproteinases *MMPs) are intimately involved in the breakdown of endometrial tissue at the time of menstruation and also play a critical role during the process of implantation. Attachment and invasion of the implanting conceptus requires the participation of MMPs produced by both the embryo and endometrial cells. Pathological conditions such as endometriosis and adenomyosis are examples of inappropriate invasion by endometrium. An essential component of endometriosis is the attachment and invasion of endometrial fragments through the mesothelial cell layer into the underlying stroma. This process is dependent on expression of specific MMPs by the endometrial tissue. Recent studies have demonstrated that attachment and invasion of endometrial tissue can only occur with intact endometrial tissue fragments containing both epithelial and stromal components. This suggests that an important interaction between the two cell types is needed to allow this invasive event to occur. We have recently identified a protein in human endometrium and endometriotic lesions called extracellular and matrix metalloproteinase inducer (EMMPRIN). EMMPRIN is also expressed by uterine epithelial cells and trophoblast cells in the mouse and appears to play an important role in implantation since the EMMPRIN knockout mouse is infertile due to an implantation defect. We hypothesize that EMMPRIN produced the uterine epithelial cells regulates production of MMPs by uterine stromal cells and localization of MMPs within the endometrium. The specific aims of this proposal are: 1. To determine the role of EMMPRIN in regulating MMP production and cellular adhesion by the mouse embryo. 2. To determine whether the failure of implantation in EMMPRIN knockout mice is due to impaired adhesion and MMP production by trophoblast or endometrial stromal cells. 3. To determine whether EMMPRIN regulates the expression of MMPs by eutopic and endometriotic uterine stromal cells and/or serves as a docking protein for specific MMPs produced by these cells. The results of these studies will provide important insights into epithelial-stromal cell communication in the uterus that may clarify the mechanisms involved in implantation as well as pathogenic events such as endometriosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOMETRIAL INFECTION BY NEISSERIA GONORRHOEAE Principal Investigator & Institution: Timmerman, Michelle M.; Microbiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 31-OCT-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The pathogenesis of gonococcal infection of human endometrium is relatively undescribed even though the endometrium is a site of bacterial persistence. Endometrial infection can progress to pelvic inflammatory disease. The human and bacterial factors involved in initial interactions are uncertain. Whether gonococci invade, traverse, or merely attach to endometrial cells is unknown. The types of endometrial cells infected have not been delineated. In this proposal, I plan to elucidate the nature of the molecular interactions between the gonococcus and human

12 Endometriosis

endometrial epithelia. Based on my preliminary studies, I hypothesize that gonococci are internalized by both receptor-mediated endocytosis and macropinocytosis. In order to resolve this hypothesis I propose the following specific aims: 1. Development of a primary human endometrial epithelial cell culture system. 2. Characterization of initial interactions between N. gonorrhoeae and primary endometrial epithelial cells. 3. Characterization of the endometrial receptor(s) for N. ganorrhoeae and the gonococcal ligand for these receptor(s). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOMETRIAL INTEGRINS AND UTERINE RECEPTIVITY Principal Investigator & Institution: Lessey, Bruce A.; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001 Summary: The endometrium undergoes a period of receptivity towards the embryo, defined by both morphological and biochemical changes. We hypothesize that both endocrine and paracrine regulatory components maintain a "receptive" endometrium. Acquisition of uterine receptivity appears to be associated with disappearance of the progesterone receptor on cycle day 19 to 20. Inadequate progesterone leading to persistent PR results in histological and biochemical immaturity of the endometrium. EGF and EGF-like molecules are important to implantation in both human and rodent species. One endometrial integrin, the alpha v beta vitronectin receptor, appears in the glandular and luminal epithelium at or near the time of embryo attachment, and later in the decidua, when invasion occurs. This integrin is inhibited by estrogen and progesterone and stimulated by EGF. Further, certain conditions associated with infertility exhibit aberrant alpha v beta 3 expression. The purpose os this proposal is to 1)document the use of the alpha v beta 3 integrin marker of uterine receptivity for diagnosis of defects in uterine receptivity in women with infertility, 2) discover shared attributes of women with these defects, 3) identify other proteins or endometrial products aberrantly expressed in the setting of defective uterine receptivity, and 4) clarify the molecular mechanisms regulating endometrial cycle-specific integrin expression. We hypothesize that inflammatory cytokines and androgens contribute to these deficits. To accomplish this we plan to prospectively examine alpha v beta 3 in women with infertility during their initial evaluation and to randomize those with endometriosis to two treatment regimens. Secondly, we will investigate the expression of the alpha v beta 3 integrin in women with polycystic ovarian disease associated with hyperandrogenism and anovulation. RIA will be used to compare concentrations of sex steroids, peptide hormones and selected cytokines between groups, in serum and in peritoneal fluid. The expression of androgen receptors in endometrium of normal and hyperandrogenic women will be examined. Regulation of the beta 3 integrin subunit gene will be investigated using an in vitro model of endometrial epithelium, the well characterized Ishikawa cell line, we will determine the effects of hormones, paracrines factors, and peritoneal fluid on the regulation of the alpha v beta integrin. With the beta 3 promoter in a CAT reporter gene construct, the regulatory sequences involved in control of this integrin subunit will be defined. It is expected that a better understanding of the mediators of normal cycle fecundity will improve our ability to diagnosis and treat couples with infertility as well as to aid in developing new methods of contraception. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 30-SEP-2001; Project End 31-AUG-2003 Summary: (APPLICANT'S ABSTRACT): 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 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 sideeffect 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 12and 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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENDOMETRIOSIS ASSOCIATED SECRETORY PROTEINS Principal Investigator & Institution: Timms, Kathy L.; Mellon Pitts Corporation (Mpc Corp) Pittsburgh, Pa 152133890 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ENDOMETRIOSIS IN BABOON--ESTABLISHMENT /FERTILITY Principal Investigator & Institution: Fazleabas, Asgerally T.; Professor; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: Endometriosis is defined as the presence of endometrium-like tissue outside of the uterine cavity. It is one of the most common causes of infertility and chronic

14 Endometriosis

pelvic pain and affects 1 in 10 women in the reproductive age group. It is inherited in a polygenic manner with a complex and multifactorial etiology. Although existence of this disease has been known for over 100 years, our current knowledge of its pathogenesis, the pathophysiology of related infertility and its spontaneous evolution is limited. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long term studies in women. Therefore, we have developed an appropriate non-human primate to study the etiology of this disease. We propose that endometriosis develops in two distinct phases. Phase I is invasive and dependent on ovarian steroids. Phase II, which is the active phase of the disease, is characterized by endogenous estrogen biosynthesis. Using the baboon model for endometriosis we will; 1) explore the role of paracrine factors produced by the endometrial tissue itself in endometriosis; 2) determine the role of endocrine factors on the ectopic establishment of endometrial tissue; and 3) investigate the physiological consequences of endometriosis on reproduction. Specifically, in Specific Aim 1, we will use the in vivo model system to characterize changes in estrogen receptor and aromatase gene expression during disease progression. These changes will establish the role for estrogen to directly or indirectly regulate metalloproteinases (MMP-3 and MMP-7) and vascular endothelial growth factor (VEGF) to enable menstrual tissues to implant in an ectopic site. In Specific Aim 2 we will determine the role of ovarian steroids, particularly estradiol, in the establishment of endometriotic lesions. We propose to use three treatment modalities following introduction of menstrual effluent into the peritoneal cavity: a) suppression of ovarian function following menses with GnRH agonists; b) addition of low doses of exogenous progesterone during the follicular phases; c) ovariectomy and steroid replacement following menstruation. In Specific Aim 3 we will determine the effects of endometriotic lesions on uterine receptivity. Using a simulated pregnant baboon model we will determine if the hCG-induced, functional changes in both epithelial and stromal cells are affected in baboons with endometriosis during the period of uterine receptivity. In addition, we will determine if treatment with an aromatase inhibitor suppresses the disease and reverses the deleterious effects on endometriosis on uterine receptivity. These studies will provide significant information on the establishment and progression of endometriosis and its potential effects on fertility. These studies have direct relevance for the diagnosis and treatment of this disease in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOMETRIOTIC HAPTOGLOBIN ALTERS MACROPHAGE FUNCTION Principal Investigator & Institution: Sharpe-Timms, Kathy L.; Professor; Obstetrics and Gynecology; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Endometriosis affects 5 1/2 million reproductive age women and girls in the USA and Canada, and millions more worldwide, causing pelvic pain and infertility. Diagnosis and treatment require costly, invasive surgery to identify and ablate ectopic endometrial tissue. Endometriosis is one of the three top reasons for hysterectomy in the USA; over 1/2 million hysterectomies are performed annually at an estimated cost of more than $5 billion. Yet, the pathogenesis of endometriosis remains poorly defined. The long-term objectives of this research are to develop novel methods of medical management by characterizing endometriotic secretory proteins that correlate with the cellular and molecular pathogenic mechanisms of endometriosis. This research evolves from the discovery that endometriotic lesions actually synthesize and secrete haptoglobin (Hp). Intriguingly, endometriotic

Studies

15

haptoglobin (eHp) is differentially glycosylated compared to hepatic Hp. Preliminary data support a pathologically relevant role for eHp in the aberrant immunological phenomena that support the disease process in women with endometriosis. The hypothesis to be tested is that by expressing eHp, endometriotic tissues from women with endometriosis avoid phagocytic eradication while stimulating peritoneal macrophage inflammatory cytokine secretion. In turn, the macrophage cytokines increase endometriotic tissue eHp production, creating a local, feed-forward loop between ectopic endometrium and macrophages favoring the establishment of endometriosis. To test this hypothesis, peritoneal macrophages, and endometriotic lesions when present, will be collected from women without and with endometriosis. These immune cells and tissues will be used to investigate three specific aims: 1) Identify the effects of eHp on peritoneal macrophage phagocytosis by analyzing the five steps of macrophage function in vitro including chemotaxis, adherence, ingestion, oxidative metabolism and activation. 2) Characterize a ligand/receptor mechanism whereby eHp causes aberrant macrophage function, by selectively altering eHp glycans and/or blocking peritoneal macrophage integrins. 3) Quantify the effects of macrophage inflammatory cytokines and growth factors on eHp synthesis and secretion. These experiments will provide insight into the pathogenesis of endometriosis by determining if endometriotic tissues, peritoneal macrophages or both are responsible for this pathology, if this mechanism is unique to women with endometriosis and confirm our feedforward hypothesis. As a result, novel non-invasive strategies for early detection and innovative treatment of endometriosis may be developed that markedly reduce the health burden of this malady. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGIC AND BIOLOGIC PREDICTORS OF IVF SUCCESS Principal Investigator & Institution: Cramer, Daniel W.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-AUG-1994; Project End 31-JUL-2003 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 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

16 Endometriosis

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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FEMALE REPRODUCTIVE OUTCOMES AND TCDD EXPOSURE Principal Investigator & Institution: Eskenazi, Brenda; Professor; None; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2001; Project Start 01-JAN-1996; Project End 30-APR-2002 Summary: (Adapted from applicant's abstract): The proposed project is a continuation of the Seveso Women's Health Study (SWHS), ongoing since 1996 (R01ES07171). The original purpose of the SWHS was to investigate the relationship of 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and endometriosis in a nested casecontrol study embedded in a cohort of women exposed to extremely high levels of dioxin as a result of a chemical plant explosion in 1976 in Seveso, Italy. In order to identify cases and controls, the cohort of women aged 0 to 40 years at the time of accident, and who lived in Zone A (n=234) or Zone B (n=1,039) were interviewed extensively about their reproductive and pregnancy histories. Assessments included a blood draw, a pelvic examination, and transvaginal ultrasound. Participants were also asked to complete a menstrual diary. A unique strength of the study is that individual body burden TCDD levels can be measured in sera collected soon after the accident. More than 95% of the women were located twenty years after the accident and roughly 80% of the members of the cohort have participated. The current plan is to analyze the data collected in the SWHS to examine reproductive endpoints other than endometriosis, and to analyze the sera for TCDD necessary to examine these endpoints. In particular, the project will investigate the relationship of TCDD levels in sera with menstrual cycle characteristics (e.g. cycle length and flow), age of menarche, fetal loss, birthweight, clinical infertility, time to conception, and age at menopause. These endpoints were chosen, based on extensive rodent and rhesus monkey data, indicating that exposed animals experience higher rates of fetal mortality and resorption, smaller litter size, lower birthweight, lowered fecundity rates and, more recently, menstrual irregularities, reduced ovulation, delayed onset of puberty, and early onset of menopause. It is because of these animal data that the U.S. Environmental Protection Agency (EPA) is reassessing the allowable exposure levels of TCDD, which is ubiquitous in industrialized areas. There are also concerns that the non-cancer effects of this chemical may be the even more urgent threat to humans. The proposed investigation will be the first comprehensive reproductive health study conducted in human populations exposed to TCDD. If the findings in this highly exposed cohort with well-characterized individual exposure data do not confirm the animal findings, there can be less concern about human health effects, thereby having important policy implications for the regulation of TCDD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FETAL ENDOMETRIOSIS

DIOXIN

EXPOSURE

AND

THE

Studies

17

PATHOLOGY

OF

Principal Investigator & Institution: Osteen, Kevin G.; Professor; Obstetrics and Gynecology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 05-MAY-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Endometriosis is a complex and persistent disease, which most often develops following retrograde menstruation and ectopic establishment of endometrial fragments. Ectopic growth is an invasive event, which mimics cancer metastasis, and women with endometriosis appear to have an increased risk for the development of certain neoplasms. Estrogen exposure predisposes development of endometriosis, while progesterone exposure, either therapeutically or during pregnancy, may lower a woman's risk of the disease. Exposure to dioxin (TCDD:2,3,7,8 tetrachlorodibenzo-p-dioxin), an endocrine and immune disrupting toxin increased the rate of spontaneous endometriosis in an exposed primate colony and, at autopsy revealed aggressive endometriosis in exposed animals. Although an association between TCDD and the development of endometriosis in women remains speculative, our studies using a mouse model of endometriosis has revealed TCDD treatment is associated with increased expression of matrix metalloproteinases (MMPs) and a more aggressive disease. A potential mechanism of TCDD action associated with endometriosis is as an inhibitor of transforming growth factor-132, an essential tissue factor for normal embryonic development as well as MMP regulation in adult tissues. In order to assess the possibility that in utero or neonatal exposure to TCDD may permanently alter steroid-mediated regulation of MMPs later in life, we propose the development of in vivo and in vitro murine (mouse) models in which to explore MMP regulation. Although mice do not spontaneously develop endometriosis, recent data suggest the disease may have an origin in defective steroid sensitivity in the uterus. Identifying the mechanisms by which fetal/neonatal TCDD disrupts steroid-mediated MMP regulation in the adult mouse uterus will provide insight into the potential role of toxin exposure in the development of endometriosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GONADOTROPIN RELEASING HORMONE ACTION Principal Investigator & Institution: Conn, P M.; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001 Summary: Studies dealing with the biochemical and molecular mechanism of gonadotropin releasing hormone (GnRH) action have served to (a) identify new human and veterinary uses for GnRH and its analogs, (b) bring these uses to fruition through a rational process based on understanding of the mechanism of hormone action, and (c) provide the means for anticipating, understanding, and ameliorating side-effects of the agents. FDA approvals of GnRH agonists for the treatment of prostate cancer, endometriosis, and precocious puberty, as well as for the use of natural sequence GnRH to induce ovulation and to test the hypothalamic-pituitary-gonadal axis, are examples of the clinical usefulness derived from these fundamental observations. There are multiple advantages to the study of GnRH-stimulation of the gonadotrope that make it facile to collect interpretable data (a) GnRH stimulation of the gonadotrope cell has clearly defined, specific and measurable endpoints release of endocr ine (a nd potentially endocrine) substances (LH, FSH, secretogranin II, ?-subunit of gonadotropin), regulation of target cell sensitivity, regulation of the GnRH receptor, and biosynthesis of released

18 Endometriosis

substances. (b) The releasing hormone itself (as well as its agonists and antagonists) can be radioiodinated to high specific activity. (c) Many (>3,000) analogs exist that can be chemically derivatized without loss of biological activity. Antagonists and agonists which bind the receptor with greater affinities than the natural sequence GnRH are available. (d) Virtually all known agonists and antagonists are Apure@ in action and metabolically stable agonists are available. The present project is divided into areas of focus that form the basis of organization of the work. The first will provide information on the structure of the GnRH receptor and early actions following the interaction of the receptor with GnRH and its analogs and should advance our understanding of the receptor in the mec hanism of GnRH action. The second area will provide information on the relationship between the multiple effector mechanisms already implicated in GnRH action with the multiple actions stimulated by the releasing hormone (release of multiple endocrine substances, regulation of target cell responsiveness, biosynthesis, and regulation of receptor number). This is important since considerable confusion remains regarding these relations. The third area involves understanding the molecular sites of action of activin and inhibin in relation to GnRH action and are significant to understand the actions of these agents in vivo. The approaches will take advantage of newly available genetic probes, antisera, and cell lines. FUNDING NIH HD19899 PUBLICATIONS Conn PM, Parker JV. Animal rights reaching the public. Science 282:1417, 1998. Conn PM (editor-in-chief). Clinical Management of Diabetic Neuropathy. Contemporary Endocrinology Vol 7 (A Veves, ed). Totowa, NJ Humana, 347 pp, 1998. Conn PM (editor-in-chief). G Proteins, Receptors, and Disease. Contemporary Endocrinology Vol 6 (A Spiegel, ed). Totowa, NJ Humana, 324 pp, 1998. Conn PM, Jennes J, Janovick JA. GnRH (Gonadotropin-Releasing Hormone). In Encyclopedia of Reproduction (E Knobil, JD Neill, eds). New York, NY Academic Press, pp 464-477, 1998. Conn PM. Make science relevant, human and clear. The Scientist 12:9, 1998. Cornea A, Janovick JA, Stanislaus D, Conn PM. Redistribution of Gq/11? in pituitary gonadotrope in response to a GnRH agonist. Endocrinology 1:397-402, 1998. Lin X, Janovick JA, Brothers S, Blomenrvhr J, Bogerd J, Conn PM. Addition of catfish gonadotropin-releasing hormone (GnRH) receptor intracellular carboxyl-terminal tail to rat GnRH receptor alters receptor expression and regulation. Mol Endocrinol 12:161-171, 1998. Lin X, Janovick JA, Conn PM. Mutations at the consensus phosphorylation sites in the third intracellular loop of the rat GnRH receptor effects on receptor ligand binding and signal transduction. Biol Reprod 59:1470-1476, 1998. Lin X, Conn PM. Transcriptional activation of gonadotropin-releasing hormone (GnRH) receptor gene by GnRH and cyclic AMP. Endocrinology 139:3896-3902, 1998. Lin X, Cornea A, Janovick JA, Conn PM. Visualization of unoccupied and occupied gonadotropin-releasing hormone receptor in living cells. Mol Cell Endocrinol 146:27-37, 1998. Stanislaus D, Ponder S, Ji T, Conn PM. GnRH receptor couples to multiple G-proteins in gonadotropes and in GGH3 cells evidence from palmitoylation and overexpression of G-proteins. Biol Reprod 59:579-586, 1998. Stanislaus D, Janovick JA, Ji T, Wilkie T, Offermanns S, Conn PM. Gonadotropin and gonadal steroid release in response to a GnRH agonist in Gq? and G11? knockout mice. Endocrinology 139:2710-2717, 1998. Stanislaus D, Pinter J, Janovick JA, Conn PM. Mechanisms mediating multiple physiological responses to gonadotropin-releasing hormone. Mol Cell Endocrinol 144:110, 1998. Ulloa-Aguirre A, Stanislaus D, Arora V, Vddndnen J, Brothers S, Janovick JA, Conn PM. The third intracellular loop of the rat gonadotropin-releasing hormone (GnRH) receptor couples the receptor to Gs- and Gq/11-mediated signal transduction pathways evidence from loop fragment transfection in GGH3 cells. Endocrinology 5:2472-2478, 1998. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GONADOTROPIN-RELEASING HORMONE ACTION Principal Investigator & Institution: Conn, Paul M.; Professor & Chairman of Pharmacology; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-APR-1984; Project End 30-NOV-2003 Summary: Studies dealing with the biochemical and molecular mechanism of gonadotropin releasing hormone (GnRH) action have served to: (a) identify new clinical and veterinary uses for GnRH and its analogs, (b) bring these uses to fruition through a rational process based on understanding of the mechanism of hormone action, and (c) provide the means for anticipating, understanding, and ameliorating side-effects of the agents. FDA approvals of GnRH agonists for the treatment of prostate cancer, endometriosis, and precocious puberty, as well as for the use of natural sequence GnRH to induce ovulation, and to test the hypothalamic-pituitary-gonadal axis, are examples of the clinical usefulness derived from these fundamental observations. There are multiple advantages to the study of GnRH- stimulation of the gonadotrope that make it facile to collect interpretable data: (a) GnRH stimulation of the gonadotrope cell has clearly defined, specific and measurable endpoints: release of endocrine (and potentially endocrine) substances (LH, FSH, secretogranin II, alpha- subunit of gonadotropin), regulation of target cell sensitivity, regulation of the GnRH receptor, and biosynthesis of released substances. (b)The releasing hormone itself (as well as its agonists and antagonists) can be radioiodinated to high specific activity. (c) Many (>3,000) analogs exist that can be chemically derivatized without loss of biological activity. Antagonists and agonists which bind the receptor with greater affinities than the natural sequence GnRH are available. (d) Virtually all known agonists and antagonists are "pure" in action and metabolically stable agonists are available. The present project is divided into three areas of focus that are detailed in the "Specific Aims" section and form the basis of organization of the "Research Design and Methods" section. The first area will provide information on the structure of the GnRH receptor and early actions following the interaction of the receptor with GnRH and its analogs. At the present time, due to technical difficulties in dealing with the receptor itself, it has not been possible to use standard techniques to purify or even solubilize the receptor for a protracted period. Accordingly, these studies should advance our understanding of the receptor in the mechanism of GnRH action. The second area will provide information on the relationship between the multiple effector mechanisms already implicated in GnRH action with the multiple actions stimulated by the releasing hormone (release of multiple endocrine substances, regulation of target cell responsiveness, biosynthesis, and regulation of receptor number). This is important since considerable confusion remains regarding these relationships. The third area involves understanding the molecular sites of action of activin and inhibin in relation to GnRH action and are significant to understand the actions of these agent in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONAL REGULATION OF INFLAMMATORY RESPONSES & CELL GROWTH IN ENDOMETRIOSIS Principal Investigator & Institution: Sidell, Neil; Professor; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

20 Endometriosis

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Project Title: HORMONE-ACTION AND CYTOKINE REGULATION OF DECIDUA CELLS Principal Investigator & Institution: Chaffin, Charles L.; Associate Professor; Phys Med and Rehabilitation; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2001; Project Start 01-MAY-2000; Project End 30-APR-2004 Summary: Our objectives are to demonstrate with morphological and biochemical evidence that progesterone actions modulate positive and negative growth factors, cell cycle regulators, and cytokines which in turn regulate the stromal cell cycle and cell survival/death during pregnancy in the rat. We hypothesize that protein kinase C plays a pivotal role in mediating these actions. The experimental designs take advantage of the in vivo change in the threshold of stromal cells for PKC-stimulated apoptosis in decidual basalis of the rat at day 10 of pregnancy when the threshold is high and at day 14 when the threshold is low. Our goal is to lower the threshold for apoptosis by ovariectomy (Ovx), administration of anti-progestins and phorbol esters by enhancing PKC activity. We hypothesize the down- stream effects include enhanced expression of cell cycle arrest proteins and effectors of apoptosis. The threshold for apoptosis will be increased by administering progesterone to Ovx pregnant rats and drugs that inhibit PKC activity. We will examine stromal cells for changes in progesterone receptor isoform expression (PR-A, -B, -C), regulators of cell cycle progression (D-cyclins, PCNA) and arrest (p21, p27). Signaling pathways leading to cell death are monitored by expression of Bcl2, Bax, PKC, caspase-3 by Western blot analysis and enzyme assay. The cell-types involved and the distribution of cytokine expression are evaluated by immunochemistry. The role of progesterone and downstream bioactive signals that confer cell cycle progression and resistance to cell death, thus, will be distinguished from anti-progestin/PKC mediated pathways that lead to apoptosis and cell death in a relatively natural context. We hypothesize that each element in the network functions as an active and reactive link in the highly integrated scheme of protein signals that regulate the stromal cell cycle and that the effects of regulatory agents depend upon the cellular context for modulation and interpretation of cytokine signals. The results from this project will lead to a better understanding of the role of progesterone in maintenance of pregnancy and stromal cell function. The results will also provide a physiologic basis for the clinical manipulation of apoptotic thresholds to change the natural progression of related proliferative diseases such as uterine leiomyomatas and endometriosis and aid in the design of cytotoxic chemotherapies and immunotherapeutic strategies for treatment of gynecologic cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HYALURONAN/CD44 AND THE EARLY ENDOMETRIOTIC LESION Principal Investigator & Institution: Schenken, Robert S.; Professor; Obstetrics and Gynecology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Endometriosis is a common gynecologic disease affecting up to 10% of reproductive-age women. Despite this high prevalence and the severe symptoms associated with the disease, little is known about the pathogenesis of endometriosis. One theory, known as Sampson's theory, proposes that fragments of menstrual endometrium pass retrograde through the fallopian tubes into the peritoneal cavity where they attach and grow on peritoneal surfaces. We recently developed a novel in vitro model of endometriosis using explants of human peritoneum or

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mesothelial cell monolayers and mechanically dispersed endometrial cells. Our studies demonstrate that endometrial fragments rapidly adhere to intact cultured peritoneal mesothelium. Both ESC and EEC adhere to peritoneal mesothelium within one hour of plating. Recent studies suggest that hyaluronan, a linear disaccharides polymer produced by mesothelium, and CD44, a multifunctional type 1 transmembrane glycoprotein that regulates cell-cell interactions, are involved in the binding of ovarian cancer and gastric cancer cells to mesothelium. Using our model, we demonstrated that hyaluronidase inhibits attachment of endometrial cells to mesothelial cells suggesting that hyaluronan/CD44 is also involved in the pathogenesis of endometriosis. A significant body of evidence using cell types other than endometrial suggests that the CD44 isoform expression, CD44 cell surface density, and CD44 glycosylation/glycosaminoglycanation pattern differentially affect a cells ability to adhere to hyaluronan. Our preliminary data demonstrate that endometrial epithelial cells from women with endometriosis have a greater ability to bind to mesothelial cells and that binding to mesothelial cells is dependent on the cell surface density of CD44. These observations coupled with the variable expression of CD44 isoforms in human endometrium lead us to hypothesize that the qualitative and quantitative expression of CD44 regulates the ability of endometrial cells to adhere to peritoneal mesothelium. The novel experiments described herein will characterize CD44 cell isoform expression, cell surface density and glycosylation/glycosaminoglycanation patterns in endometrial cells of women with and without endometriosis. This will enhance our understanding of the development of the early endometriotic lesion. The findings should enable us to predict a woman's risk of developing endometriosis based on endometrial cell CD44 characteristics and suggest new approaches to prevent the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN UTERO PCB EXPOSURE & MENSTRUAL DISORDERS Principal Investigator & Institution: Hauser, Russ B.; Assistant Professor; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001 Summary: (Taken from application) Currently, there is scientific and public concern about whether exposure to putative endocrine disruptors, such as polychlorinated biphenyls (PCBs), are associated with adverse reproductive health effects. This concern stems from studies showing that PCB residues are found in a large proportion in a large proportion of the general population, as well as animal and some human studies suggesting possible associations of exposure to PCBs with altered reproductive function. The proposed study will investigate the relationship between PCBs and endometriosis, which is an important public health issue because it affects more than five million women in the United States and has large social and economic impacts. Endometriosis is a relatively common disease (prevalence estimated at 5 to 10%) that can affect fertility as well as other aspects of a woman's general health and well-being. Animal and human data suggest that the critical exposure window for endocrine disruptors may be in utero because the developing fetus is extremely sensitive to endocrine hormones during reproductive development. Therefore, the proposed epidemiologic study is designed to investigate the relationship between in utero exposure, the hypothesized critical exposure window, and endometriosis and menstrual cycle dysfunction. The proposed project, a case-control study nested in the National Collaborative Perinatal Project (NCPP) cohort, will extend follow-up through the reproductive years of the daughters of the pregnant women recruited in the NCPP (1959-1966). During pregnancy, one or more blood samples were taken from the pregnant women and archived. The daughters

22 Endometriosis

will be traced and will complete a question on endometriosis and menstrual cycle characteristics. Cases are daughters with laparoscopy-confirmed endometriosis. The NCPP cohort provides a unique opportunity to study in utero exposure to PTCBs and female reproductive to PCBs and female reproductive health without having to initiate an expensive prospective study and follow individuals for 20 or more years. In addition, in the proposed, a current blood sample will be analyzed to reflect adult PCB levels that may confound the relationship between endometriosis and in utero PCB exposure, and will serve as a source of additional information on cumulative exposure. The area of human reproductive health effects of endocrine disrupting chemicals, such as PCBs, was identified as a current topic for special emphasis by the NIEHS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFLAMMATION AND OVARIAN CANCER Principal Investigator & Institution: Ness, Roberta B.; Professor and Chair; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 12-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): The cause of ovarian cancer is unclear. We have suggested that inflammation may be involved. Ovulation, endometriosis, and talc use all promote inflammation, and all increase the risk of ovarian cancer; tubal ligation and hysterectomy prevent the ovaries from being exposed to inflammants, and reduce risk. Furthermore, inflammation entails DNA damage and repair, oxidative stress, and elevations in prostaglandins and cytokines, all of which may be mutagenic. Building on our track record of success with conducting ovarian cancer case-control studies, we propose a population-based study to examine the role of inflammation in the risk for ovarian cancer. We will enroll 900 women with incident ovarian cancer (cases) from hospitals in Western Pennsylvania, Northern Ohio, and Western New York. One thousand eight hundred controls, ascertained via random digit dialing, will be frequency matched to cases on age, race, and residence. Using in-person standardized interviews and blood draws, we propose to: 1) evaluate whether non-steroidal antiinflammatory drugs (NSAIDs) protect against ovarian cancer; 2) compare in cases and controls allelic variants in inflammatory and antinflammatory cytokines and growth factors including IL-1, TNF-a, IL-10, IGF-1 and TGF-b; 3) evaluate whether markers of past PID, i.e. higher antibody titers to chlamydia and its related heat shock protein (HSP)-60, relate to ovarian cancer; 4) in a secondary aim, explore whether allelic variants in the NSAID metabolizing enzymes CYP2C9 and UGT1A6 interact with NSAID use to reduce the risk of ovarian cancer. Exploring the relationships among inflammatory predisposition, inflammatory exposures, anti-inflammatory medications, and ovarian cancer represents a novel avenue of research. In particular, NSAID use may prove to be a potentially important chemopreventative for this often-fatal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERMEDIATE ALTERNATIVES

OUTCOMES

OF

HYSTERECTOMY

AND

Principal Investigator & Institution: Kuppermann, Miriam; Ob, Gyn and Reproductive Scis; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2007 Summary: (TAKEN FROM APPLICANT): The proposed application expands on our existing prospective longitudinal study of 811 women with non-cancerous uterine

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conditions for which hysterectomy is a reasonable treatment option: abnormal uterine bleeding, symptomatic uterine leiomyomata, and pelvic pain/endometriosis. The principal aims of the proposed study are to 1) determine whether and how intermediate-term (4-8 year) clinical and qualityof- life outcomes differ by treatment group (hysterectomy, uterus-preserving surgery, or non-surgical treatments) for their uterine conditions; and 2) develop predictive models of treatment choice and satisfaction from a broad array of domains. The proposed expansion of the existing study is motivated by two main factors. First, by increasing the size of our cohort by an additional 700 we will extend the mean duration of follow-up from 1.7 to 4.1 years, and we will obtain at least four years of follow-up data on over 976 women. The increased sample at four years will allow us to accrue an adequate number of women undergoing hysterectomy and non-surgical treatments to support a statistically meaningful comparison. Because symptoms for women with noncancerous uterine conditions typically extend from the early 40?s to menopause, including intermediate-term, face this decision, providing useful information will help equip women and their physicians to make informed, shared decisions. Second, we will enhance our measures of sexual functioning, depression, and incontinence, and include assessments of newly available alternative treatments. These additions reflect changes in the understanding of the role of these factors in the management of non-cancerous uterine conditions since the inception of the original study. The results of this study are central to our long-term goal of improving decision making in the management of non-cancerous uterine conditions. The findings that emerge from the proposed study will be relevant to the development of evidence-based guidelines and the creation of decision-assisting tools to help women with non-cancerous uterine conditions make informed choices regarding their treatment during their decade of risk for hysterectomy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LHRH SYNTHETIC PEPTIDE VACCINE FOR PROSTATE CANCER Principal Investigator & Institution: Finstad, Connie L.; United Biomedical, Inc. 25 Davids Dr Hauppauge, Ny 11788 Timing: Fiscal Year 2002; Project Start 10-SEP-1999; Project End 31-MAY-2004 Summary: United Biomedical, Inc, (UBI) has developed an alternative approach to injectable LHRH agonists and other androgen-ablation therapies for the treatment of prostate cancer through development of an anti-LHRH immune response. The LHRH synthetic peptide vaccine comprises the LHRH decapeptide covalently linked to helper T cell epitopes and to an additional peptide that provides specific immune adjuvanting activities. This molecular conformation produces a potent B cell response and antiLHRH antibodies in sufficiently high titer to neutralize circulating LHRH and thereby suppress androgen production. Studies in rodents have demonstrated that the LHRH peptide vaccine can rouse a specific immune response that inhibits and androgendependent tumor growth in the host by blocking synthesis of testosterone. The goal is to evaluate the efficacy and safety of the LHRH peptide vaccine prepared in several adjuvant formulations to induce antibody adult male baboons. If successful, these preclinical studies will provide supporting data for an IND application and the testing of the LHRH peptide vaccine formulation as an alternative hormonal ablative therapy for prostate cancer. PROPOSED COMMERCIAL APPLICATIONS: The LHRH synthetic peptide vaccine is an immunotherapy for the treatment of androgen-responsive, advanced prostate cancer. This vaccine is predicted to be effective because its mode of action is analogous to the LHRH agonist-androgen-ablation therapies currently used to treat prostate cancer as well as other hormone-responsive benign conditions and tumors

24 Endometriosis

(e.g., endometriosis, leiomyoma). Commercial advantages of the LHRH vaccine therapy over agonists include improved patient compliance and less costly treatment option. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIVING WITH CHRONIC PELVIC PAIN: PERSONAL/SOCIAL IMPACT Principal Investigator & Institution: Strzempko, Fran M.; Dean's Office; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 15-MAR-2003; Project End 30-NOV-2004 Summary: (provided by applicant): Chronic pelvic pain (CPP) is an ambiguous and disabling condition, affecting 10-15% of U.S. women of reproductive age. Endometriosis, a condition for which there is no effective treatment, is the most common diagnosis of CPP. Common symptoms include pelvic pain, and dyspareunia. Relationship and role disruptions in endometriosis are reported, but the woman and couple's symptom experiences and responses have not been documented. The purpose of this study is to articulate the woman and her partner's illness understanding, symptom experience, and relationship responses to living with CPP. The larger aim is to develop knowledge to support the holistic care for women with CPP, so we may provide humanistic and effective nursing interventions for women and their partners. The proposed study is a mixed-method design, with qualitative methodology as primary. Interpretive phenomenology guides the design and conduct of the study. A measurement of distress and affective response is the adjunct quantitative method. Specific aims are: 1) articulate the commonalities and differences of the lived experience of women who have CPP with a diagnosis of endometriosis, and their partners; 2) describe the symptom experience from the woman and her intimate partner's perspective; 3) compare dyadic versus individual constructions of living with endometriosis; and 4) describe the relationship between the woman and her partner's symptom experience. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MACROPHAGES, OXIDATION, AND ENDOMETRIOSIS Principal Investigator & Institution: Parthasarathy, Sampath; Professor and Director; Gynecology and Obstetrics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2003 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

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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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MBRS SCORE PROGRAM AT THE PONCE SCHOOL OF MEDICINE Principal Investigator & Institution: Torres-Ruiz, Jose A.; Associate Professor; Biochemistry; Ponce School of Medicine G.P.O. Box 7004 Ponce, Pr 00731 Timing: Fiscal Year 2002; Project Start 30-SEP-1986; Project End 31-MAY-2005 Summary: (provided by applicant): In this supplemental application we are requesting funds to support three additional subprojects in the MBRS-SCORE Program at the Ponce School of Medicine. The goals of our MBRS-SCORE Program are to: 1) increase the biomedical research productivity, 2) the scientific competitiveness and recognition of the faculty, 3) by providing first rate research and development opportunities, and 4) in creating a stimulating research atmosphere at the institution. The present supplemental application contains three (3) new MBRS subprojects. These initiatives include both basic and clinical research activities from faculty in the departments of Biochemistry, Microbiology, and Physiology. The diverse projects include such areas as endometriosis, gastric human physiology, retrovirology, molecular biology, and bacterial genetics. These research projects will be sustained by an administrative component and by technical and personnel support that includes collaborators, consultants, and laboratory technicians. In addition, some of the activities will be complementary to other minority targeted programs in the institution such as the RCMI Program, the Howard Hughes Medical Institute Science Education Initiative for Biomedical Research Institutions Program, the Health Careers Opportunity Program (HCOP) and, eventually the MBRS RISE Program. Progress in the Specific Aims of each project and in the overall aims of the Program will be evaluated yearly in a formative report and at the end in a summative document. Progress and achievements of the Program will be assessed continuously through an ongoing formative evaluation intended to provide information to improve the performance in the various program subprojects and though a summative evaluation that will finally assess the Program's success and the extent to which the completed project has met its goals. Both the evaluation of the implementation to assess whether the Program is being conducted as planned and of the process, the assessment, and the progress being made by the participant in meeting the individual subprojects and the program goals will be performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS FOR RACIAL DISPARITY IN PRETERM BIRTH Principal Investigator & Institution: Hitti, Jane E.; Obstetrics and Gynecology; University of Washington Seattle, Wa 98195

26 Endometriosis

Timing: Fiscal Year 2001; Project Start 24-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): We propose a five year population-based prospective cohort study to evaluate the relative contributions to pre term birth of 10 genital tract infection, maternal stress and a genetic predisposition to an enhanced immune response among African American and white women resident in King County, Washington. Potential subjects will be identified through birth certificate data, with appropriate measures to protect confidentiality. We will enroll 100 African American and 100 white women with a prior early preterm birth at 20-34 weeks gestation and a comparison group of 100 African American and 100 white women with prior term birth at >36 weeks. The initial assessment will be performed at least 6 months after the index delivery and will include evaluation of vaginal flora and endometritis, maternal stress by qualitative and quantitative measures, periodontitis, and genetic variability in cytokine production. We will offer participants treatment or referral for any modifiable risk factors for preterm birth that are identified in the initial evaluation. We will then follow subjects prospectively and anticipate that 30-40% of the cohort will have a subsequent pregnancy during follow-up. Women with a subsequent pregnancy will be offered evaluation of vaginal flora, cervical length, and maternal stress with treatment or referral offered for modifiable risk factors. Outcomes for second pregnancies will be ascertained. This study design will allow us to examine the following specific aims: 1. Study the role of increased antigenic stimulation from lower genital tract infection as a determinant of endometritis, chorioamnionitis and preterm birth among African American and white women. 2. Examine the correlation of maternal stress with inflammatory arousal, stratified by race and prior pregnancy history. 3. Assess maternal and fetal genetic contributions to the pro-inflammatory response and correlate these with preterm birth and neonatal outcome. In combination, these inter-related aims will address the most plausible mechanisms by which African American women continue to be at least twice as likely as white women to deliver prematurely. We also plan to explore the synergy between genetic predisposition, maternal stress, inflammatory arousal, lower genital tract infection, and preterm birth. We hypothesize that women with more than one predisposing factor are at a markedly increased risk for preterm birth, and that African American women are more likely than white women to have multiple predisposing factors. We hope that these studies may eventually lead to the development of more effective strategies to prevent preterm birth and to reduce the disparity in preterm birth, low birthweight and infant mortality between African American and white women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS ENDOMETRIOSIS

OF

ESTROGEN

BIOSYNTHESIS

IN

Principal Investigator & Institution: Bulun, Serdar E.; Professor; Obstetrics and Gynecology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 05-JUL-1999; Project End 30-JUN-2003 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 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

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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 receptor-alpha 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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENTORING IN RESEARCH ON ENDOMETRIOSIS Principal Investigator & Institution: Murphy, Ana A.; Professor; Gynecology and Obstetrics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 10-MAY-2001; Project End 30-APR-2006 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

28 Endometriosis

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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOMETRIUM

METALLOPROTEINASE/DISINTEGRIN

FUNCTION

IN

Principal Investigator & Institution: Hoffman, Loren H.; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001 Summary: Endometrial epithelial cells undergo dramatic remodeling during the periimplantation period. Such changes include alterations in cell-cell adhesions, in cellmatrix 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, cell-matrix interactions and fusogenic properties. RbMDC9 expression is up-regulated 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 specifictargeting 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 implantationspecific 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 cycle-specific 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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METRONIDAZOLE PRETERM BIRTH IN WOMEN

PLUS

ERYTHROMYCIN

TO

PREVENT

Principal Investigator & Institution: Caritis, Steve N.; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001 Summary: Aims of the study are to 1)determine whether or not the administration of antimicrobial therapy in women with elevated cervical oncofetal fibronectin will reduce the risk of spontaneous preterm birth, reduce the risk of early neonatal sepsis, clinical chorioamnionitis, and early postpartum endometritis, and 2)determine the effect of

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antimicrobial therapy on fetal fibronectin positivity and its ability to prevent preterm delivery. Patients are screened at the time of a vaginal exam for the presence of cervical oncofetal fibronectin by obtaining two swabs. If the dipstick test for these swabs is positive, the specimen is sent to a central lab for an ELISA assay for the presence of fetal fibronectin. If the assay is positive, the patient is randomized into the double-blind, placebo-controlled trial of metronidazole 250mg vs. placebo/placebo. Patients take the study drug for 10 days and return for an exam similar to the screening exam. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MINORITY PREDOCTORAL FELLOWSHIP PROGRAM Principal Investigator & Institution: Rojas-Cartagena, Carmencita; Microbiology; Ponce School of Medicine G.P.O. Box 7004 Ponce, Pr 00731 Timing: Fiscal Year 2002; Project Start 20-MAR-2003 Summary: (provided by applicant): Endometriosis is a disorder characterized by the presence of histologically normal endometrial tissue outside the uterus. Endometriosis often presents with symptoms that mimic gastrointestinal disorders such as Crohn's disease, which makes it's diagnosis extremely difficult. Both disease produce similar symptoms, and their pathogenesis still remains to be elucidated. The objective of this study is to elucidate the the role of TNF/TNFR expression in rats models of intestinal endometriosis and Crohn's disease. The proposed rat model of Crohn's disease has been extensively used to study the pathophysiology of this disease. The rat model of intestinal endometriosis wil specfically address the pathopysiological role of TNF/TNFR expression in the implantation of ectopic endometrium in the intestine. The specific aims of the proposed plan are to: 1)determine the TNF'-aipha mRNA and protein expression in the implants, intestine, and peritoneal fluid in a rat model of intestinal endometriosis and compare with the rat model of Crohn's disease 2) determine the expression on TNF receptors (TNFR1/TNFR2) in the endometrial implants and associated intestine in a rat model of intestinal endometriosis and compare with the rat model of Crohn's disease 3) determine the expression of tumor necrosis factor receptor-associated factors (TRAFs) in both animals models and, 4) establish a specific pathophysiological role of TNF/TNFR signaling for the rat model of intestinal endometriosis and the rat model of Crohn's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR PATHOGENESIS OF OVARIAN ENDOMETRIOID ADENOCARC Principal Investigator & Institution: Cho, Kathleen R.; Professor; Pathology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: Ovarian carcinoma (OvCa) is a major cause of cancer- associated morbidity and mortality for women, yet much remains to be learned about its pathogenesis. Like other cancers, OvCas are thought to 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

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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/beta-cat/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://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NESA-HARVARD ACCUPUNCTURE RESEARCH COLLABORATIVE Principal Investigator & Institution: Wayne, Peter M.; None; New England School of Acupuncture 30 Common St Watertown, Ma 02472 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-MAY-2006 Summary: As a Developmental Center for Research in Complementary and Alternative Medicine (DCRC), the New England School of Acupuncture (NESA)-Harvard Acupuncture Research Collaborative will bring together leaders from the oriental medicine (OM) and conventional medicine communities to critically evaluate the efficacy and safety of acupuncture, and develop sound methodologies and feasible study designs required for acupuncture research. Our DCRC will strengthen and build upon already ongoing collaborations between NESA, the Harvard Medical School's (HMS) Osher Institute, and two other HMS-affiliated institutions, the Dana Farber Cancer Institute and Children's Hospital Boston. The DCRC will support three developmental/exploratory studies and two infrastructure cores (Administrative and Clinical Trials) that will be synergistically integrated by three themes. The first theme centers around diversifying OM research to evaluate the plurality of approaches employed in clinical practice which will be addressed through the evaluation of both Japanese- and Chinese-style acupuncture. The second theme emphasizes the development and implementation of novel research methods that are required to meet the unique challenges posed in clinical trials of acupuncture and OM. One of our three studies will develop, validate, and test the reliability of an instrument used to derive OM diagnoses in the context of clinical trials. Other methodological issues related to individualization of acupuncture treatments, appropriate controls in acupuncture trials, and the development of outcome measures that reflect the treatment philosophy of OM will also be addressed. The third theme addresses the benefits of acupuncture as an adjunct therapy in the treatment of women's health conditions. Specifically, we will study the application of acupuncture to two conditions for which the current evidence

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evaluating its efficacy and safety is limited-- chemotherapy-induced neutropenia in women with ovarian cancer, and chronic pelvic pain in adolescent and young women with endometriosis. Integral to our DCRC are a number of academic and administrative mentoring programs through which HMS faculty, staff, and training programs will assist NESA in developing its clinical research infrastructure and capacity to autonomously sustain a productive research program that combines the highest standards of science and the integrity of traditional OM practices. The ultimate goal of our DCRC will be for NESA to play the lead role in the future submission of R01 and R21 proposals that build upon our developmental studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL NON-PEPTIDE ANTAGONISTS OF THE GNRH RECEPTOR Principal Investigator & Institution: Struthers, Richard S.; Neurocrine Biosciences, Inc. 10555 Science Center Dr San Diego, Ca 921211100 Timing: Fiscal Year 2001; Project Start 05-APR-2000; Project End 31-AUG-2003 Summary: (provided by applicant): Prostate cancer, breast cancer, endometriosis and uterine fibroids are fairly common and serious diseases in men and women. Their etiology is not fully understood, but all can be treated by removal of endogenous gonadal steroid hormones, testosterone and estrogen. This has led to the discovery of several successful pharmaceutical products based on blocking the actions of the hypothalamic peptide, gonadotropin-releasing hormone (GnRH). Down-regulation of the GnRH receptor by peptide superagonists, or blockade by peptide antagonists, prevents pituitary gonadotropin secretion and leads to dramatic reductions in gonadal steroid production. GnRH-based drugs are now used extensively in these patients, as well as for hormonal manipulation as part of assisted reproductive therapy or for treatment of precocious puberty. Here we propose to develop orally active small molecule antagonists of the GnRH receptor, in order to overcome many of the limitations of these injectable peptide drugs and expand the clinical utility of GnRHbased strategies. In Phase I we have used high-throughput parallel organic synthesis to design multiple chemical series of highly potent, nonpeptide GnRH antagonists. We have also established a series of in vitro and in vivo assays to evaluate absorption, distribution and metabolism of these compounds. In Phase II we propose a combination of parallel synthetic chemistry and assay strategies to optimize pharmacokinetic and pharmacodynamic properties of compounds from three of these series in order to produce compounds suitable for clinical development. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORGANIZATION OF THE IMMUNE SYSTEM IN THE HUMAN FEMALE REPRODUCTIVE TRACT Principal Investigator & Institution: Fanger, Michael W.; Professor of Microbiology & Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001 Summary: The tissues of the human female reproductive tract (FRT) exhibit defined and organized microenvironments that influence immune cell function. Furthermore, the sex steroid hormones, estradiol and progesterone, have a controlling influence on both the afferent and the efferent arms of the immune system. To date, studies of the human mucosal immune system have largely relied on the study of isolated cells, an approach which does not allow evaluation of the influence of tissue architecture and

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microenvironment. Moreover, relatively few studies of the immune system of the human FRT have been carried out. Thus, our current understanding of the organization and function of the immune system in this critically important organ system is clearly inadequate, as is our understanding of the endocrine influences on immunity in these tissues. The proposed studies will use novel in situ techniques, which utilize viable tissue sections, to test the hypothesis that sex hormones regulate immune cell organization and function in the different microenvironments of the uterine endometrium (EM) of the FRT. In particular, we postulate that during the menstrual cycle, sex hormones and cytokines act in concern to regulate the organization and function of immune cells within the EM of the FRT. More specifically, we will: 1) Determine the organization of T and B lymphocytes and myeloid cells within the different microenvironments of the EM of the FRT and how this varies with stage of the menstrual cycle. 2) Identify the mechanisms responsible for the regulation of architectural remodeling in the EM with regard to the role of cell proliferation, apoptosis, cytokines and adhesion molecules. 3) Determine the role of sex hormones and cytokines on cytotoxic T cell and myeloid cell function in the different microenvironments of the EM. The results of these studies should provide valuable insights into the organization and function of the immune system of the FRT, which in turn will enhance our understanding of the susceptibility of the FRT to sexually transmitted diseases, and be of value in the rational design of regimens for immunization against these diseases. These studies will also contribute important information useful for the evaluation of the mechanisms leading to gynecological malignancies and other diseases of the FRT, including endometriosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT PROJECTS Principal Investigator & Institution: Page, Roy C.; Professor; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROGESTERONE, CELL CYCLE AND CANCER Principal Investigator & Institution: Pollard, Jeffrey W.; Professor; Developmtl & Molecular Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 05-JAN-2001; Project End 31-DEC-2005 Summary: Estrogens are the major carcinogen in the environment of most females with exposure to unopposed estrogen increasing the risk of breast and endometrial cancer. Conversely, it has become increasingly apparent that estrogens are essential for the well being of women (and men) throughout life. Progesterone acts to oppose the effects of estrogen on cell proliferation and, consequently, it is used in the treatment of endometrial cancer and it is an essential component of hormone replacement therapy designed to alleviate post-menopausal symptoms in women. It is, therefore, of fundamental importance to understand the mechanism of action of these hormones on cell proliferation. In adult ovariectomized mice, a single injection of estradiol-17beta (E2) results in the stimulation of a wave of DNA synthesis and cell proliferation that is restricted to the uterine epithelium. This proliferation is completely inhibited by pretreatment with progesterone (P4). The uterine epithelium can be isolated with great purity in a state suitable for biochemical analysis. This method together with defined

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hormonal regimens provides a controllable model in which to study the mechanism of action of these hormones in vivo. In tissue culture cells the cell cycle is regulated by the orderly activation of cyclins and their dependent kinases (Cdk). These include the cyclin D-Cdk4 and cyclin D-Cdk6 complexes acting early in G1 and the cyclin E-Cdk2 complex acting at the G1 to S-phase boundary. Our studies in the uterine epithelium have shown that E2 induces the re-localization of cyclin D1 and Cdk-4 to the nucleus and, results in orderly activation of cyclin-E and cyclin ACdk-2 activities and hyper-phosphorylation of pRb and p107. Progesterone pre- treatment prohibited the cyclin D1/Cdk-4 relocalization to the nucleus with a consequent inhibition of pRb and p107 phosphorylation. In addition, P4 abrogated the E2 induced cyclin E and cyclin A-Cdk2 activities. The specific aims of this grant are: 1) To determine the mechanism whereby P4 prohibits cyclin D1/Cdk4 nuclear accumulation following E2 treatment; 2) To determine the mechanism of action of P4-inhibition of Cdk-2 activation; 3) identify differentially regulated genes in the uterine epithelium following E2 treatment in the presence and absence of P4; 4) to develop methods to interfere with signaling pathways in the uterine epithelium in vivo. It is expected that by the end of the grant that the mechanisms of cyclin D1/Cdk4 exclusion can be identified and novel proteins associated with this process isolated. Furthermore, novel E2 and P4-regulated genes that play important roles in the control of epithelial cell proliferation should be identified. These studies will define specific mechanisms that may result in the development of therapeutics that would inhibit estrogen's mitogenic effects in tumors as well as in benign proliferative diseases such as endometrial polyps and endometriosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF ANGIOGENESIS Principal Investigator & Institution: Folkman, M Judah.; Director; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 01-SEP-1987; Project End 31-AUG-2007 Summary: (provided by applicant): In this competitive renewal, five principal investigators, who have a strong track record in making novel contributions to angiogenesis research, propose to continue their collaborative efforts which are focused on analysis of the molecular mechanisms responsible for control of normal and tumor angiogenesis and on identification of novel angiogenesis inhibitors. M. Klagsbrun, will analyze the function of neuropilins (VEGF and semaphorin receptors) and their ligands in a zebra- model of developmental angiogenesis and in mouse models of tumor angiogenesis and metastasis. D. lngber, will analyze the biomechanical mechanisms by which extracellular matrix acts locally to regulate capillary cell sensitivity to soluble angiogenic factors and thereby controls capillary morphogenesis. He will explore how local changes in matrix mechanics alter cytoskeleton tension generation and focal adhesion formation, how these alterations impact on cell migration and whether cell tension contributes to capillary pattern formation. P. D'Amore, has generated mice that express single VEGF isoforms (120, 164, and 188) and will analyze the role of VEGF isoforms in tumor angiogenesis and their interaction with neuropilin. Additionally, she will investigate the role of VEGF in the adult vasculature. M. Moses, will analyze the transcriptional regulation of VEGF expres-sion during the initiation of angiogenesis. She will also determine whether urinary MMPs alone, or in combination with VEGF and bFGF, can predict the initiation of angiogenesis during tumor progression. J. Folkman, will further explore the mechanisms of inhibitors to be used for antiangiogenic therapy. New goals include identification of novel specific inhibitors of lymphangiogenesis, determining whether circulating endothelial cell precursors are predictive of intense

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tumor angiogenesis and whether endometriosis, which has an invasive component, is angiogenesis-dependent and therefore a target of anti-angiogenesis therapy in patients. Together, the five research programs in this application cover a broad range of investigation that should significantly enhance our understanding of how angiogenesis is regulated and how it can be inhibited. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF GNRH RECEPTOR GENE EXPRESSION Principal Investigator & Institution: Clay, Colin M.; Associate Professor; Physiology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2001; Project Start 01-JAN-1995; Project End 31-DEC-2004 Summary: The binding of gonadotropin-releasing hormone (GnRH) to specific, highaffinity receptors located on gonadotrope cells of the anterior pituitary gland is central to reproduction. In the absence of GnRH input, synthesis and secretion of luteinzing hormone and, consequently, normal gonadal function ceases. Thus, the GnRH receptor (GnRHR) is the site that receives and mediates the primary stimulatory input to gonadotropes. We have found that expression of the murine GnRHR in gonadotropederived alphaT3-1 cells is mediated by a complex enhancer whose components include a binding site for steroidogenic factor-1 (SF- 1), an AP-1 element, and an element we have termed the GnRH receptor activating sequence (GRAS). This complex enhancer also integrates multiple endocrine inputs. First, we have recently found that GRAS colocalizes with activin regulation of the GnRHR promoter. Unresolved, however, is the identity of the protein(s) that integrate functional activity at GRAS. In Specific Aim 1, we propose to identify the protein(s) that regulate the functional activity, and activin responsiveness of GRAS. Second, AP-1 appears to be the operative element that mediates GnRH regulation; however, important questions remain as to the signal transduction cascades and downstream targets that ultimately lead to GnRH activation at the GnRHR AP-1 site. In Specific Aim 2, our goal is to define the molecular mechanisms underlying GnRH regulation of GnRHR gene expression. We have also found that 1900 bp of proximal promoter is sufficient for tissue-specific expression and GnRH responsiveness in transgenic mice. In Specific Aim 3, we propose to expand these studies to further explore the requirements for tissue/cell-specific expression and hormonal regulation of the GnRHR gene. Finally, we have generated cell lines that express intrinsically fluorescent forms of the GnRHR. These molecules provide a unique opportunity to study the GnRHR as both an occupied and unoccupied receptor in living cells. In Specific Aim 4, we will use fluorescence resonance energy transfer to test the hypothesis that an early event in GnRH signaling is agonist induced receptor selfassociation. In terms of fertility regulation, the relevance of investigating GnRH and its cognate receptor is clear. However, the use of potent agonists and antagonists of GnRH in the treatment of fibroid tumors, endometriosis, and carcinomas of the breast, prostate, testes, and pituitary underscores the need for a full understanding of GnRH and the GnRHR in both health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF IGFBP-1 BY FKHR AND HOXA10 IN PREGNANCY Principal Investigator & Institution: Kim, Ji-Yong Julie.; Obstetrics and Gynecology; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 31-MAY-2007

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Summary: (provided by applicant): The long-term objective of this application is to better understand the dynamic interaction that occurs between the conceptus and the mother that allow for the establishment and maintenance of pregnancy. The major focus of our research is on the molecular events that occur in the endometrium in response to early embryonic signals and the invading trophoblast. Aberrant expression of genes in the endometrium during this time is detrimental to the maintenance of pregnancy and could lead to miscarriages, spontaneous abortions and infertility. In response to pregnancy hormones and conceptus factors, the endometrium undergoes a major transformation, termed decidualization. During this process, the stromal cells of the endometrium express important genes. This study focuses on the regulation of a major secretory product of the decidualizing stromal cells, insulin-like growth factor binding protein-1 (IGFBP-1). IGFBP-1 modulates the actions of insulin-like growth factors (IGFs) which are critical during early pregnancy and can act independently of IGFs to regulate trophoblast invasion. Recently, we demonstrated that two transcription factors, FKHR and HOXA10, which have been demonstrated to be important in reproductive processes, interact with one another and up regulate the IGFBP-1 promoter in a cooperative manner in endometrial stromal cells. Based on this novel data, studies have been designed to further delineate the mechanisms involved in the cooperative up regulation of the IGFBP-1 promoter by FKHR and HOXA10. In aim 1 the binding sites of FKHR and HOXA10 on the IGFBP-1 promoter are identified. With the use of a powerful new technique, chromatin immunoprecipitation (CHIP), the binding sites for endogenous FKHR and HOXA10 proteins on the endogenous IGFBP-1 gene within the chromatin in the decidualized stromal cells are determined. This technique allows one to study interaction of transcription factors with the chromatin as they occur in situ. In aim 2, characterization of FKHR and HOXA10 and determination of binding sequences on the IGFBP-1 gene in cells originating from non-pregnant and pregnant baboon endometrium will be performed by taking "snapshots" of the cells and tissue using formaldehyde cross linking. These studies will demonstrate the influence of the conceptus on FKHR and HOXA10 expression and their activation of the IGFBP-1 gene. In aim 3, FKHR and HOXA10 expression and activity in the endometrium of baboons with endometriosis will be studied. The objective of aim 3 is to determine why FKHR and HOXA10 do not significantly activate the IGFBP-1 promoter. The stromal cells from baboons with endometriosis are obviously different from that of a normal animal. These studies will give a better understanding of the molecular events that may be associated with increased implantation failure in women with endometriosis. The three aims in this application will provide valuable insights into the molecular dynamics of the endometrium in response to pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REPRODUCTIVE/CONTRACEPTIVE ENDOMETRIOSIS

RISK

FACTORS

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Principal Investigator & Institution: Holt, Victoria L.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 01-MAY-1997; Project End 30-APR-2003 Summary: Endometriosis affects up to 10% of women of reproductive age in the U.S. with chronic pelvic pain, dysmenorrhea, and probable increased risk of infertility. Although the disease has been identified as a top research priority by the National Institutes of Health, the etiology is still uncertain, and few modifiable risk factors have been identified. Past epidemiologic research has been inconclusive about the impact of reproductive or contraceptive history on the development of endometriosis. Most

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studies of these risk factors have been limited by using cases identified at infertility surgery, as these women may be atypical of all endometriosis cases in terms of reproductive and contraceptive history. We propose a population-based case-control study of endometriosis among the entire population of reproductive-age women enrolled in an HMO in western Washington State to test the hypothesis that spontaneous abortion and induced abortion may increase risk of endometriosis, taking into account possible hormonal and immunological influences. The associations between endometriosis and delayed childbearing and various types of contraception will be investigated as well. All 18-44 year old enrollees of Group Health Cooperative of Puget Sound (GHC) diagnosed with endometriosis by surgery, and a portion of those diagnosed by physical examination or ultrasound examination alone between August l, 1996 and April 30, 2001 will be identified and invited to participate (approximately 750 women of all races). Cases will be selected using computerized records, and eligibility verified by medical records. Controls randomly selected from computerized enrollment files will be frequency matched to cases on age and primary care clinic region. Data will be obtained from cases and controls by in-person interview, and anthropometric measurement; and linked with the GHC computerized pharmacy database. Subjects will be interviewed regarding their reproductive and contraceptive histories; including spontaneous and induced abortions, stillbirths, livebirths, use of hormonal contraceptives, intrauterine devices, and sterilization procedures; menstrual history; infertility history; and other risk factors for endometriosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RISK FACTORS FOR ENDOMETRIOSIS Principal Investigator & Institution: Hunter, David J.; Director; Epidemiology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 03-AUG-2001; Project End 31-JUL-2003 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

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first prospective data with adequate power to evaluate this important and understudied cause of morbidity among premenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RISK FACTORS FOR HIP FRACTURES AMONG THE ELDERLY Principal Investigator & Institution: Melton, Joseph L.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001 Summary: This project complements studies of pathophysiology by addressing fractures, the principle clinical manifestation of osteoporosis. Through the unique data resources of the Rochester Epidemiology Project, we can identify large inception cohorts of Rochester and/or Olmsted County, Minnesota., residents with specific medical and surgical conditions and conduct a series of retrospective (=historical) cohort studies to estimate the long-term risk of age-related fractures associated with secondary osteoporosis, an important contributor to bone loss in the elderly. Secondary, osteoporosis is an important area of research because new therapies are being developed for affected men and older women who are not candidates for estrogen replacement. We previously determined the risk of fracture among cohorts with diabetes mellitus, hyperparathryoidism, thyroidectomy, gastrectomy, pernicious anemia, oophorectomy, urolithiasis, anticoagulant therapy, anorexia nervosa, dementia, parkinsonism, epilepsy, poliomyelitis, rheumatoid arthritis, ankylosing spondylitis and breast cancer. We now proposed to extend this work by quantifying the fracture risk associated with conditions that might impair peak bone mass (endometriosis, infertility), induce hypogonadism (orchiectomy), disturb extraskeletal bone metabolism in the kidney (chronic renal failure) and gut (inflammatory bowel disease) or cause a generalized increase in bone resorbing cytokine (multiple myeloma). Each condition represents a natural experiment with respect to the pathogenesis of osteoporosis, several of which parallel the concerns of other projects. These will be the first assessments of fracture risk among cohorts of unselected patients from the community, and the results should be more valid and more precise than any previous estimates. Our overall goal is to develop new information that will lead to effective strategies for preventing osteoporosis-related fractures among the elderly. This project contributes by demonstrating the public health importance of specific risk factors and, by identifying high risk groups within each cohort, allowing future control programs to be designed and conducted more efficiently. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF CSF1 AND ITS RECEPTOR IN ENDOMETRIOSIS Principal Investigator & Institution: Tekmal, Rajeshwar R.; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SEX HORMONE REGULATION OF INNATE IMMUNITY Principal Investigator & Institution: Wira, Charles R.; Professor of Physiology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007

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Description (provided by applicant): The overall objective of Project 1 is to define the role of sex hormones in regulating the innate immune system of the FRT. Epithelial cells within the fallopian tube, uterus, cervix and vagina are the first line of defense against potentially pathogenic microbes and are individually responsive to estradiol and progesterone. In studies proposed in this application, we will test the hypothesis that epithelial cells represent the front line of the innate immune system throughout the human FRT and that innate immune protection by these cells is precisely regulated by female sex hormones. These studies will define the mechanisms whereby sex hormones influence phenotype, innate function, and communication between the innate and adaptive immune systems. We postulate that the innate immune responses of epithelial cells are under hormone control and that, in addition to conferring protection, these cells are capable of initiating an adaptive immune response. More specifically, we will: 1) Define the processes by which sex hormones modulate anti-bacterial activity, defensins and Secretory Leukocyte Protease Inhibitor (SLPI) produced by epithelial cells throughout the FRT; 2) Determine if exposure to specific PAMP (antigens) enhances or limits continued expression/production of anti-bacterial activity, defensins and SLPI in a way which is mediated through TLRs, and is precisely controlled by sex hormones; 3) Examine the role of sex hormones in regulating cytokine expression by reproductive tract epithelial cells in the presence and/or absence of PAMP; and 4) Define the role of sex hormone environment in modulating the interactions between reproductive tract epithelial cells and immune cells and determine if sex hormones directly influence links between the innate and adaptive immune systems. Understanding how the immune system in the reproductive tract can respond to bacterial and viral challenges requires that we understand the unique characteristics of the immune system in the female reproductive tract and the ways in which the innate and adaptive immune system are either enhanced and/or suppressed at particular times in a woman?s life. These studies should provide the basis of knowledge essential for understanding the role of hormones in autoimmune diseases such as Multiple Sclerosis, the prevention of local infection in the genital mucosa, and the management of sexually transmitted diseases as well as the treatment of gynecological cancers and endometriosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNTHETIC SUBSTANCES CONTROLLING REPRODUCTION Principal Investigator & Institution: Rivier, Jean E.; Professor; Salk Institute for Biological Studies 10010 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: Gonadotropin releasing hormone (GnRH) is a key regulator of reproductive functions. Repeated administration of potent and long acting GnRH agonists inhibits gonadal functions through desensitization of the GnRH receptor. This property is used clinically for t he treatment of prostate cancers, managed of endometriosis and in vitro fertilization for example. Potent peptide antagonists of GnRH have also been identified recently that have the advantage of intermediate and more profound inhibition of gonadotropins than the agonists thus opening the door to the use of the former for male contraception. None of these peptides are potent orally, Peptide GnRH agonists and antagonists are very different structurally. Whereas nothing is known of the conformation of GnRH agonists at the receptor, we have shown that several covalent constraints [cyclo(4-10), cyclo(5-8) and cyclo(1-5)] in GnRH antagonists are compatible with high affinity and in vivo potency. The NMR structures of these analogs led to the determination of a GnRH antagonist consensus model that was used for the successful design of a bioactive tri-aminoglycine-based library. Additionally, this model was

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helpful in identifying a putative one-to-one correspondence with elements of a potent non-peptide ligand (T-98475). We have also successfully introduced urea function in several GnRH antagonist structures that resulted in high affinity and extended duration of action, suggesting an important role for inter/intramolecular hydrogen bonding interactions in peptide stability, solubility and distribution. One the basis of these results, we propose to test four hypotheses: A. Strategically placed positive and negative charges on residues (1-5), (4-10) and (5-8) will stabilize the GnRH bioactive conformation with retention of biological activity, B. The GnRH antagonist consensus model will be used for the design of small GnRH peptidomimetic ligands containing aminoglycine scaffolds (betide), C. Functional groups found in GnRH rather than in GnRH antagonists will be introduces in betides to field the first peptidomimetic GnRH agonist and structural insights on the process of receptor activation, D. Optimization of hydrogen bonding interactions using urea functionalities will yield safe and long activating GnRH antagonists that display immediate onset of action in short- and longterm indications. Such molecules are not presently available to academic researchers. As in the past twenty years, collaborations with academic colleagues will be initiated, to maximize the impact of this research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF TIMP-1 IN UTERINE PHYSIOLOGY Principal Investigator & Institution: Nothnick, Warren B.; Assistant Professor and Director; Gynecology and Obstetrics; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2006 Summary: Tissue inhibitors of metalloproteinase-1 (TIMP-1) is expressed in the uteri of both menstruating and non-menstruating species. In menstruating species, TIMP-1 is postulated to control the extent of tissue breakdown that occurs during menses. However, as TIMP-1 is expressed beyond the period of menses as well as within the uterus of non-menstruating species, the role of this TIMP within the uterus beyond the regulation of tissue breakdown is uncertain. We have previously demonstrated and present strong supportive evidence in this application, which suggest that TIMP-1 plays a role in uterine development, growth and function. The goal of the proposed application is to expand these preliminary observations and further examine the role of TIMP-1 within the uterus during post-natal uterine development and growth. The hypothesis to be tested is that TIMP-1 controls steroid-regulated uterine development and cell proliferation via a MMP-dependent mechanism which involves modulation of steroid receptor expression within the uterus. We will use TIMP-1 deficient mice and a variety of molecular, cellular and biochemical approaches to test this hypothesis by: 1) examining the spatio-temporal pattern of TIMPs and the function of TIMP-1 during uterine growth and development, 2) determining the mechanisms by which TIMP-1 regulates uterine cell proliferation, and 3) delineating the processes by which TIMP-1 regulates uterine progesterone receptor expression. The proposed experiments will provide new insight into the control of uterine cell proliferation as well as steroid action thereby defining a novel role for TIMP-1 within the uterus. These studies will broaden our understanding on the role of TIMP-1 in uterine physiology and may help to develop new strategies to treat uterine disorders such as infertility, endometriosis and uterine cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATMENT OF ENDOMETRIOSIS-ASSOCIATED PELVIC PAIN Principal Investigator & Institution: Guzick, David S.; Professor and Chair; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Approximately one-third of women with chronic pelvic pain have endometriosis. Surgical treatment of endometriosis with laparoscopic excision of implants and lysis of adhesions is often successful in reducing pain in the short term. Furthermore, several postoperative medical treatments have been shown to be efficacious in maintaining pain reduction for as long as the medication is continued. After stopping the medication, however, the level of pain tends to trend upwards towards pre-treatment levels. The desired postoperative treatment is one that is can be used for a long period of time, so as to minimize the chance of pain recurrence. Simplicity of administration and cost-effectiveness are other desirable characteristics of an ideal postoperative regimen. The only FDA approved 12-month treatment for endometriosis-associated pain is a combination of leuprolide acetate (a GnRH analog), 11.25 mg IM q 12 weeks, and norethindrone acetate, 5 mg PO daily. Use of this regimen has been constrained by its complexity and cost. As an alternative, the continuous use of oral contraceptives has been advocated as a practical, inexpensive strategy for long-term medical treatment of endometriosis-associated pain. Although such an approach is frequently used in clinical practice, there has been no clinical trial of its efficacy. The goal of this project is to compare the efficacy and cost-effectiveness of continuous oral contraceptives and leuprolide+norethindrone in the postoperative treatment of endometriosis-associated pelvic pain. Investigators at the University of Rochester School of Medicine and Harvard Medical School will recruit 194 women for randomization to one of the two treatments, each of which will continue for 48 weeks. Randomization will occur after biopsy-proven endometriosis is established. Pelvic pain and quality-of-life assessments will be obtained at regular intervals. The recruitment goal is 88 subjects per arm after a 10% drop-our rate. Change scores for these measures will be compared between the two treatments. The study has 80% power to test non-inferiority of oral contraceptives at the 5% level of significance, using a 1-point difference in the change scores for pain as the threshold. In addition, a cost-effectiveness analysis will be performed by calculating the cost per unit reduction in pain score for each treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VITAMIN A AND REPRODUCTION Principal Investigator & Institution: Ong, David E.; Professor; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 30-SEP-1989; Project End 31-MAR-2005 Summary: Vitamin A, retinol, is an essential nutrient that serves as precursor to the important hormone, retinoic acid (RA). Relatively little is known of the control of synthesis of RA from retinol in the normal, fully-developed animal and sites of action of RA are inferred, rather than demonstrated. Previous work has identified estrogen as a physiological signal which induces the synthesis of RA in the rat uterus and that coordinately directs cell-specific expression of the three cellular retinoid-binding proteins present in the uterus during the estrous cycle. Proposed studies will: l) Identify uterine genes that are under estrogen control indirectly, via RA stimulation. The techniques of differential display or subtractive hybridization followed by library screening or will be used to identify these genes. Candidate genes will be followed during the estrous cycle to confirm their physiological significance. 2) Demonstrate the

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site(s) of expression of the estrogen-stimulated RA responsive genes by in situ hybridization and immunolocalization during the estrous cycle. Demonstration of expression/non-expression of candidate genes in cells expressing cellular retinoic acidbinding protein will test the competing hypotheses that this protein either blocks or enhances the RA responsiveness of cells. 3) Establish the mechanism by which estrogen directly regulates cellular retinoic-acid binding protein (II) expression in the uterus. The promoter region of the rat gene will be cloned, dissected and tested using CAT reporter constructs in an estrogen responsive cell line. 4) Demonstrate the mechanism by which estrogen induces RA synthesis in the uterus. Specifically, is this induction a direct effect of estrogen on pre-existing enzymes, does it require transcription, or is it indirect? A novel radioreceptor assay capable of detecting small amounts of RA has been developed for this aim. In summary, the work to be accomplished here will allow dissection of the effects of the demonstrated estrogen-stimulated synthesis of RA signal that is part of a normal physiological process. This will provide important information on retinoic acid action in the unmanipulated, intact animal. Regulation of retinoic acid production by estrogen has direct importance for understanding/treating conditions such as endometriosis, breast cancer, and cancers of the female reproductive system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “endometriosis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for endometriosis in the PubMed Central database: •

A case of sigmoid endometriosis difficult to differentiate from colon cancer. by Dimoulios P, Koutroubakis IE, Tzardi M, Antoniou P, Matalliotakis IM, Kouroumalis EA.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=184504

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The public health toll of endometriosis. by Weir E.; 2001 Apr 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80996

3 4

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

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

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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.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with endometriosis, simply go to the PubMed Web site at http://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): •

A case of inguinal endometriosis with difficulty in preoperative diagnosis. Author(s): Hagiwara Y, Hatori M, Katoh H, Kokubun S. Source: Upsala Journal of Medical Sciences. 2002; 107(3): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696574&dopt=Abstract

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A case of persistent endometriosis after total hysterectomy with both salpingooophorectomy managed by radiation therapy. Author(s): Kim KS, Moon WS, Song HW, Kim JH, Cho SN. Source: Archives of Gynecology and Obstetrics. 2001 November; 265(4): 225-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789754&dopt=Abstract

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A comparative study of the acceptability and effect of goserelin and nafarelin on endometriosis. Author(s): Bergqvist A; SCANDET Group. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 December; 14(6): 425-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228063&dopt=Abstract

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A defective expression of ICAM-1 (CD54) on secretory endometrial cells is associated with endometriosis. Author(s): Prefumo F, Semino C, Melioli G, Venturini PL. Source: Immunology Letters. 2002 January 1; 80(1): 49-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716965&dopt=Abstract

6

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

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A long-term follow-up study of women with asymptomatic endometriosis diagnosed incidentally at sterilization. Author(s): Moen MH, Stokstad T. Source: Fertility and Sterility. 2002 October; 78(4): 773-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372455&dopt=Abstract

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A prospective randomized study comparing endocrinological and clinical effects of two types of GnRH agonists in cases of uterine leiomyomas or endometriosis. Author(s): Takeuchi H, Kobori H, Kikuchi I, Sato Y, Mitsuhashi N. Source: The Journal of Obstetrics and Gynaecology Research. 2000 October; 26(5): 32531. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11147718&dopt=Abstract

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A systematic review of the accuracy of ultrasound in the diagnosis of endometriosis. Author(s): Moore J, Copley S, Morris J, Lindsell D, Golding S, Kennedy S. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2002 December; 20(6): 630-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493057&dopt=Abstract

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Aberrant expression of intercellular adhesion molecule-1 and killer inhibitory receptors induces immune tolerance in women with pelvic endometriosis. Author(s): Maeda N, Izumiya C, Oguri H, Kusume T, Yamamoto Y, Fukaya T. Source: Fertility and Sterility. 2002 April; 77(4): 679-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937115&dopt=Abstract

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Abnormal cervicovaginal smears due to endometriosis: a continuing problem. Author(s): Lundeen SJ, Horwitz CA, Larson CJ, Stanley MW. Source: Diagnostic Cytopathology. 2002 January; 26(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782085&dopt=Abstract

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Abnormal interleukin-1 receptor type II gene expression in the endometrium of women with endometriosis. Author(s): Kharfi A, Boucher A, Akoum A. Source: Biology of Reproduction. 2002 February; 66(2): 401-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11804955&dopt=Abstract

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Accuracy of laparoscopic diagnosis of endometriosis. Author(s): Mettler L, Schollmeyer T, Lehmann-Willenbrock E, Schuppler U, Schmutzler A, Shukla D, Zavala A, Lewin A. Source: Jsls. 2003 January-March; 7(1): 15-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722993&dopt=Abstract

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ACOG practice bulletin. Medical management of endometriosis. Number 11, December 1999 (replaces Technical Bulletin Number 184, September 1993).Clinical management guidelines for obstetrician-gynecologists. Author(s): ACOG Committee on Practice Bulletins--Gynecology. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2000 November; 71(2): 183-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11186465&dopt=Abstract

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Adhesion of endometrial cells labeled with 111Indium-tropolonate to peritoneum: a novel in vitro model to study endometriosis. Author(s): Beliard A, Noel A, Goffin F, Frankenne F, Foidart JM. Source: Fertility and Sterility. 2003 March; 79 Suppl 1: 724-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620483&dopt=Abstract

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Adolescent endometriosis. Author(s): Attaran M, Gidwani GP. Source: Obstetrics and Gynecology Clinics of North America. 2003 June; 30(2): 379-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836726&dopt=Abstract

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Adolescent endometriosis: diagnosis and treatment approaches. Author(s): Laufer MR, Sanfilippo J, Rose G. Source: Journal of Pediatric and Adolescent Gynecology. 2003 June; 16(3 Suppl): S3-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742180&dopt=Abstract

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Aggressive endometriosis. Author(s): Zardawi I. Source: International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. 2003 January-February; 13(1): 98-99; Author Reply 100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631230&dopt=Abstract

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Alterations in expression of endometrial endothelial nitric oxide synthase and alpha(v)beta(3) integrin in women with endometriosis. Author(s): Khorram O, Lessey BA. Source: Fertility and Sterility. 2002 October; 78(4): 860-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372469&dopt=Abstract

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An association of IgG anti-laminin-1 autoantibodies with endometriosis in infertile patients. Author(s): Inagaki J, Sugiura-Ogasawara M, Nomizu M, Nakatsuka M, Ikuta K, Suzuki N, Kaihara K, Kobayashi K, Yasuda T, Shoenfeld Y, Aoki K, Matsuura E. Source: Human Reproduction (Oxford, England). 2003 March; 18(3): 544-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615822&dopt=Abstract

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An evidence-based evaluation of endometriosis-associated infertility. Author(s): Pritts EA, Taylor RN. Source: Endocrinology and Metabolism Clinics of North America. 2003 September; 32(3): 653-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14560892&dopt=Abstract

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An improved mouse model for endometriosis allows noninvasive assessment of lesion implantation and development. Author(s): Fortin M, Lepine M, Page M, Osteen K, Massie B, Hugo P, Steff AM. Source: Fertility and Sterility. 2003 September; 80 Suppl 2: 832-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505761&dopt=Abstract

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An in vitro model to study the pathogenesis of the early endometriosis lesion. Author(s): Witz CA, Dechaud H, Montoya-Rodriguez IA, Thomas MR, Nair AS, Centonze VE, Schenken RS. Source: Annals of the New York Academy of Sciences. 2002 March; 955: 296-307; Discussion 340-2, 396-406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949956&dopt=Abstract

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Analysis of an interleukin-6 gene promoter polymorphism in women with endometriosis by pyrosequencing. Author(s): Wieser F, Fabjani G, Tempfer C, Schneeberger C, Sator M, Huber J, Wenzl R. Source: Journal of the Society for Gynecologic Investigation. 2003 January; 10(1): 32-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517591&dopt=Abstract

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Analysis of p53 and c-erbB-2 expression in ovarian endometrioid carcinomas arising in endometriosis. Author(s): Prefumo F, Venturini PL, Fulcheri E. Source: International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists. 2003 January; 22(1): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496703&dopt=Abstract

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Anasarca and small bowel obstruction secondary to endometriosis. Author(s): Mussa FF, Younes Z, Tihan T, Lacy BE. Source: Journal of Clinical Gastroenterology. 2001 February; 32(2): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205657&dopt=Abstract

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Anatomical distribution of deeply infiltrating endometriosis: surgical implications and proposition for a classification. Author(s): Chapron C, Fauconnier A, Vieira M, Barakat H, Dousset B, Pansini V, VacherLavenu MC, Dubuisson JB. Source: Human Reproduction (Oxford, England). 2003 January; 18(1): 157-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525459&dopt=Abstract

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Anatomopathological lesions of bladder endometriosis are heterogeneous. Author(s): Chapron C, Boucher E, Fauconnier A, Vieira M, Dubuisson JB, VacherLavenu MC. Source: Fertility and Sterility. 2002 October; 78(4): 740-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372449&dopt=Abstract

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Anesthetic implications of thoracic endometriosis. Author(s): Gamaleldin H, Tetzlaff JE, Whalley D. Source: Journal of Clinical Anesthesia. 2002 February; 14(1): 36-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880020&dopt=Abstract

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Angiogenic activity and IL-8 concentrations in peritoneal fluid and sera in endometriosis. Author(s): Barcz E, Rozewska ES, Kaminski P, Demkow U, Bobrowska K, Marianowski L. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 December; 79(3): 229-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445988&dopt=Abstract

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Angiogenic factors in endometriosis. Author(s): Taylor RN, Lebovic DI, Mueller MD. Source: Annals of the New York Academy of Sciences. 2002 March; 955: 89-100; Discussion 118, 396-406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949968&dopt=Abstract

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Antiangiogenic agents are effective inhibitors of endometriosis. Author(s): Hull ML, Charnock-Jones DS, Chan CL, Bruner-Tran KL, Osteen KG, Tom BD, Fan TP, Smith SK. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2889-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788903&dopt=Abstract

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Antizona and antisperm antibodies in women with endometriosis and/or infertility. Author(s): Szczepanska M, Skrzypczak J, Kamieniczna M, Kurpisz M. Source: Fertility and Sterility. 2001 January; 75(1): 97-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11163823&dopt=Abstract

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Are the basic assumptions correct--is endometriosis a progressive, self-destructive disease? Author(s): Brosens IA. Source: Fertility and Sterility. 2001 January; 75(1): 229; Author Reply 230. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229335&dopt=Abstract

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Are the basic assumptions correct--is endometriosis a progressive, self-destructive disease? Author(s): Redwine DB. Source: Fertility and Sterility. 2001 January; 75(1): 229-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229334&dopt=Abstract

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Aromatase P450 messenger RNA expression in eutopic endometrium is not a specific marker for pelvic endometriosis. Author(s): Dheenadayalu K, Mak I, Gordts S, Campo R, Higham J, Puttemans P, White J, Christian M, Fusi L, Brosens J. Source: Fertility and Sterility. 2002 October; 78(4): 825-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372463&dopt=Abstract

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Assessment of fallopian tube cytology for the diagnosis of endometriosis and hydrosalpinx. Author(s): Matsushima T, Kaseki H, Ishihara K, Araki T. Source: Journal of Nippon Medical School = Nihon Ika Daigaku Zasshi. 2002 October; 69(5): 445-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382004&dopt=Abstract

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Association of interleukin-6 and estradiol with hepatocyte growth factor in peritoneal fluid of women with endometriosis. Author(s): Khan KN, Masuzaki H, Fujishita A, Hamasaki T, Kitajima M, Hasuo A, Miyamura Y, Ishimaru T. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 August; 81(8): 764-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174163&dopt=Abstract

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Association of the CYP17 gene and CYP19 gene polymorphisms with risk of endometriosis in Japanese women. Author(s): Kado N, Kitawaki J, Obayashi H, Ishihara H, Koshiba H, Kusuki I, Tsukamoto K, Hasegawa G, Nakamura N, Yoshikawa T, Honjo H. Source: Human Reproduction (Oxford, England). 2002 April; 17(4): 897-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11925378&dopt=Abstract

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Atherosclerosis, oxidation and endometriosis. Author(s): Santanam N, Song M, Rong R, Murphy AA, Parthasarathy S. Source: Free Radical Research. 2002 December; 36(12): 1315-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607823&dopt=Abstract

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Autoantibodies in endometriosis sera recognize a Thomsen-Friedenreich-like carbohydrate antigen. Author(s): Lang GA, Yeaman GR. Source: Journal of Autoimmunity. 2001 March; 16(2): 151-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11247641&dopt=Abstract

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Autoantibody responses to carbohydrate epitopes in endometriosis. Author(s): Yeaman GR, Collins JE, Lang GA. Source: Annals of the New York Academy of Sciences. 2002 March; 955: 174-82; Discussion 199-200, 396-406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949946&dopt=Abstract

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Basal and stimulated secretion of cytokines by peritoneal macrophages in women with endometriosis. Author(s): Rana N, Braun DP, House R, Gebel H, Rotman C, Dmowski WP. Source: Fertility and Sterility. 1996 May; 65(5): 925-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8612850&dopt=Abstract

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Basic research in endometriosis. Author(s): Sharpe-Timms KL. Source: Obstetrics and Gynecology Clinics of North America. 1997 June; 24(2): 269-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9163767&dopt=Abstract

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Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Author(s): Pizzo A, Salmeri FM, Ardita FV, Sofo V, Tripepi M, Marsico S. Source: Gynecologic and Obstetric Investigation. 2002; 54(2): 82-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566749&dopt=Abstract

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Benefit of in vitro fertilization treatment for endometriosis-associated infertility. Author(s): Kodama H, Fukuda J, Karube H, Matsui T, Shimizu Y, Tanaka T. Source: Fertility and Sterility. 1996 December; 66(6): 974-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8941064&dopt=Abstract

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Benign, borderline, and malignant endometrioid neoplasia arising in endometriosis in association with tamoxifen therapy. Author(s): McCluggage WG, Bryson C, Lamki H, Boyle DD. Source: International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists. 2000 July; 19(3): 276-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10907178&dopt=Abstract

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Biases in the endometriosis literature. Illustrated by 20 years of endometriosis research in Leuven. Author(s): Koninckx PR. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1998 December; 81(2): 259-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9989875&dopt=Abstract

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Big picture of endometriosis helps provide guidance on approach to teens: comparative historical data show endo starting younger, is more severe. Author(s): Ballweg ML. Source: Journal of Pediatric and Adolescent Gynecology. 2003 June; 16(3 Suppl): S21-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742183&dopt=Abstract

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Bilateral ureteral obstruction secondary to ovarian remnants with endometriosis. Author(s): Hoffman MS, Durfee JK. Source: Obstetrics and Gynecology. 2000 November; 96(5 Pt 2): 845. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11094237&dopt=Abstract

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Bladder detrusor endometriosis: clinical and pathogenetic implications. Author(s): Vercellini P, Meschia M, De Giorgi O, Panazza S, Cortesi I, Crosignani PG. Source: The Journal of Urology. 1996 January; 155(1): 84-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7490905&dopt=Abstract

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Bladder endometriosis must be considered as bladder adenomyosis. Author(s): Donnez J, Spada F, Squifflet J, Nisolle M. Source: Fertility and Sterility. 2000 December; 74(6): 1175-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119746&dopt=Abstract

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Bladder endometriosis: conservative management. Author(s): Westney OL, Amundsen CL, McGuire EJ. Source: The Journal of Urology. 2000 June; 163(6): 1814-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10799189&dopt=Abstract

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Bladder endometriosis: deep infiltrating endometriosis or adenomyosis? Author(s): Fedele L, Piazzola E, Raffaelli R, Bianchi S. Source: Fertility and Sterility. 1998 May; 69(5): 972-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9591511&dopt=Abstract

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Bladder endometriosis: pertinent clinical images. Author(s): Batler RA, Kim SC, Nadler RB. Source: Urology. 2001 April; 57(4): 798-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306413&dopt=Abstract

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Blaming the victim. The psychologizing of endometriosis. Author(s): Ballweg ML. Source: Obstetrics and Gynecology Clinics of North America. 1997 June; 24(2): 441-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9163775&dopt=Abstract

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Blood leukocyte subsets are modulated in patients with endometriosis. Author(s): Gagne D, Rivard M, Page M, Shazand K, Hugo P, Gosselin D. Source: Fertility and Sterility. 2003 July; 80(1): 43-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849800&dopt=Abstract

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Bone density in women with endometriosis. Author(s): Colacurci N, De Seta L, Passaro M, Scala P, De Franciscis P, Zarcone R. Source: Panminerva Medica. 1998 June; 40(2): 126-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9689833&dopt=Abstract

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Bowel resection for intestinal endometriosis. Author(s): Urbach DR, Reedijk M, Richard CS, Lie KI, Ross TM. Source: Diseases of the Colon and Rectum. 1998 September; 41(9): 1158-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9749501&dopt=Abstract

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Breast-fed infants, possibly exposed to dioxins in milk, have unexpectedly lower incidence of endometriosis in adult life. Author(s): Tsutsumi O, Momoeda M, Takai Y, Ono M, Taketani Y. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2000 February; 68(2): 151-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10717822&dopt=Abstract

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Breast-feeding and endometriosis. Author(s): Thylan S. Source: Journal of Paediatrics and Child Health. 1996 June; 32(3): 271-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8827554&dopt=Abstract

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Bronchoscopic and angiographic findings in tracheobronchial endometriosis. Author(s): Kuo PH, Wang HC, Liaw YS, Kuo SH. Source: Thorax. 1996 October; 51(10): 1060-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8977610&dopt=Abstract

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Buserelin acetate implants in the treatment of pain in endometriosis. Author(s): Choktanasiri W, Rojanasakul A. Source: J Med Assoc Thai. 2001 May; 84(5): 656-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560214&dopt=Abstract

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Caesarean section scar endometriosis: two cases of recurrent disease and a literature review. Author(s): Kaloo P, Reid G, Wong F. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 May; 42(2): 218-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12069156&dopt=Abstract

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Can we decrease breakthrough bleeding in patients with endometriosis on norethindrone acetate? Author(s): Muneyyirci-Delale O, Jalou S, Rahman M, Nacharaju V. Source: Int J Fertil Womens Med. 2003 January-February; 48(1): 32-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643518&dopt=Abstract

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Case 4. Umbilical endometriosis. Author(s): Rubegni P, Sbano P, Santopietro R, Fimiani M. Source: Clinical and Experimental Dermatology. 2003 September; 28(5): 571-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950365&dopt=Abstract

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Catamenial hemoptysis and pulmonary endometriosis: a case report. Author(s): Yu Z, Fleischman JK, Rahman HM, Mesia AF, Rosner F. Source: The Mount Sinai Journal of Medicine, New York. 2002 September; 69(4): 261-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357268&dopt=Abstract

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Catamenial pneumothorax caused by endometriosis in the visceral pleura. Author(s): Sakamoto K, Ohmori T, Takei H. Source: The Annals of Thoracic Surgery. 2003 July; 76(1): 290-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842566&dopt=Abstract

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Catechol-O-methyltransferase polymorphism and endometriosis. Author(s): Wieser F, Wenzl R, Tempfer C, Worda C, Huber J, Schneeberger C. Source: Journal of Assisted Reproduction and Genetics. 2002 July; 19(7): 343-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12168735&dopt=Abstract

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CD10 is helpful in detecting occult or inconspicuous endometrial stromal cells in cases of presumptive endometriosis. Author(s): Groisman GM, Meir A. Source: Archives of Pathology & Laboratory Medicine. 2003 August; 127(8): 1003-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873175&dopt=Abstract

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CD10 is useful in demonstrating endometrial stroma at ectopic sites and in confirming a diagnosis of endometriosis. Author(s): Onda T, Ban S, Shimizu M. Source: Journal of Clinical Pathology. 2003 January; 56(1): 79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499444&dopt=Abstract

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Cervical endometriosis presented as a polypoid mass of portio cervix uteri. Author(s): Kano H, Kanda H. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 January; 23(1): 84-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647713&dopt=Abstract

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Cesarean scar endometriosis. A report of two cases. Author(s): Taff L, Jones S. Source: J Reprod Med. 2002 January; 47(1): 50-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838312&dopt=Abstract

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Cesarean section scar endometriosis: a case report and review of the literature. Author(s): Phupong V, Triratanachat S. Source: J Med Assoc Thai. 2002 June; 85(6): 733-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12322849&dopt=Abstract

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Characteristics of patients with endometriosis in the United States and the United Kingdom. Author(s): Kuohung W, Jones GL, Vitonis AF, Cramer DW, Kennedy SH, Thomas D, Hornstein MD. Source: Fertility and Sterility. 2002 October; 78(4): 767-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372454&dopt=Abstract

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Characteristics of uterine contractility during menses in women with mild to moderate endometriosis. Author(s): Bulletti C, De Ziegler D, Polli V, Del Ferro E, Palini S, Flamigni C. Source: Fertility and Sterility. 2002 June; 77(6): 1156-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12057721&dopt=Abstract

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Clear cell carcinoma arising in endometriosis of the rectum following progestin therapy. Author(s): Pokieser W, Schmerker R, Kisser M, Peters-Engl C, Muhlbauer H, Ulrich W. Source: Pathology, Research and Practice. 2002; 198(2): 121-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11928865&dopt=Abstract

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Clear cells carcinoma of fallopian tubes associated with tubal endometriosis. Case report and review. Author(s): de la Torre FJ, Rojo F, Garcia A. Source: Archives of Gynecology and Obstetrics. 2002 July; 266(3): 172-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197560&dopt=Abstract

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Clinical aspects of endometriosis. Author(s): Murphy AA. Source: Annals of the New York Academy of Sciences. 2002 March; 955: 1-10; Discussion 34-6, 396-406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949938&dopt=Abstract

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Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases, Axl and Sky, in human uterine endometrium and ovarian endometriosis. Author(s): Sun WS, Misao R, Iwagaki S, Fujimoto J, Tamaya T. Source: Molecular Human Reproduction. 2002 June; 8(6): 552-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12029073&dopt=Abstract

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Colonic endometriosis or adenoma? Author(s): McCullough TK, Cohen P, Vlavianos T, Sutton CJ, Allen-Mersh TG. Source: Journal of the Royal Society of Medicine. 2002 April; 95(4): 202-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934914&dopt=Abstract

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Colorectal endometriosis: aggressive surgical management and practical considerations in a patient with advanced disease. Author(s): Succi L, Urrico GS, Politi A, Scollo P, Prumeri S, Campione S, Latteri F. Source: Chir Ital. 2001 September-October; 53(5): 713-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723904&dopt=Abstract

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Comparative immunohistochemical studies of endometriosis lesions and endometriotic cysts. Author(s): Nezhat FR, Kalir T. Source: Fertility and Sterility. 2002 October; 78(4): 820-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372462&dopt=Abstract

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Comparison of a levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study. Author(s): Vercellini P, Frontino G, De Giorgi O, Aimi G, Zaina B, Crosignani PG. Source: Fertility and Sterility. 2003 August; 80(2): 305-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909492&dopt=Abstract

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Comparison of clinical and laparascopic features of infertile women suffering from genital tuberculosis (TB) or pelvic inflammatory disease (PID) or endometriosis. Author(s): Avan BI, Fatmi Z, Rashid S. Source: J Pak Med Assoc. 2001 November; 51(11): 393-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840606&dopt=Abstract

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Comparison of magnetic resonance imaging and transvaginal ultrasonography in diagnosing bladder endometriosis. Author(s): Balleyguier C, Chapron C, Dubuisson JB, Kinkel K, Fauconnier A, Vieira M, Helenon O, Menu Y. Source: The Journal of the American Association of Gynecologic Laparoscopists. 2002 February; 9(1): 15-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821601&dopt=Abstract

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Complete removal of endometriosis improves fecundity. Author(s): Suginami H, Tokushige M, Taniguchi F, Kitaoka Y. Source: Gynecologic and Obstetric Investigation. 2002; 53 Suppl 1: 12-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834863&dopt=Abstract

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Concentration of interleukin-12 in the peritoneal fluid is not influenced by the presence of endometriosis, its stage or the phase of the menstrual cycle. Author(s): Gazvani R, Bates M, Vince G, Christmas S, Lewis-Jones I, Kingsland C. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2001 February; 80(2): 175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11167215&dopt=Abstract

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Concerning the article by Meaddough et al: Sexual activity, orgasm and tampon use are associated with a decreased risk for endometriosis. Author(s): Guidone HC, Marvel ME. Source: Gynecologic and Obstetric Investigation. 2002; 54(2): 64-5; Author Reply 65-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566744&dopt=Abstract

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Concerning the article by Meaddough et al: Sexual activity, orgasm and tampon use are associated with a decreased risk for endometriosis. Author(s): Ballweg ML, Quinn BW. Source: Gynecologic and Obstetric Investigation. 2002; 54(2): 63; Author Reply 65-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566743&dopt=Abstract

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Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill regimen. Author(s): Vercellini P, Frontino G, De Giorgi O, Pietropaolo G, Pasin R, Crosignani PG. Source: Fertility and Sterility. 2003 September; 80(3): 560-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969698&dopt=Abstract

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Contribution of diminished ovarian reserve to hypofertility associated with endometriosis. Author(s): Hock DL, Sharafi K, Dagostino L, Kemmann E, Seifer DB. Source: J Reprod Med. 2001 January; 46(1): 7-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11209637&dopt=Abstract

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Conventional medical therapies for endometriosis. Author(s): Rice VM. Source: Annals of the New York Academy of Sciences. 2002 March; 955: 343-52; Discussion 389-93, 396-406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949960&dopt=Abstract

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Coordinated but depressed expression of human leukocyte antigen-DR, intercellular adhesion molecule-1, and CD14 on peritoneal macrophages in women with pelvic endometriosis. Author(s): Izumiya C, Maeda N, Kusume T, Masumoto T, Yamashita C, Yamamoto Y, Oguri H, Fukaya T. Source: Fertility and Sterility. 2003 September; 80 Suppl 2: 768-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505752&dopt=Abstract

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Critical appraisal of endometriosis management for pain and subfertility. Author(s): Zuberi NF, Rizvi JH. Source: J Pak Med Assoc. 2003 April; 53(4): 152-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776900&dopt=Abstract

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Current thinking on the pathogenesis of endometriosis. Author(s): Donnez J, Van Langendonckt A, Casanas-Roux F, Van Gossum JP, Pirard C, Jadoul P, Squifflet J, Smets M. Source: Gynecologic and Obstetric Investigation. 2002; 54 Suppl 1: 52-8; Discussion 5962. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441661&dopt=Abstract

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Cutaneous endometriosis and its association with caesarean section and gynaecological procedures. Author(s): Scholefield HJ, Sajjad Y, Morgan PR. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2002 September; 22(5): 553-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521430&dopt=Abstract

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Cutaneous endometriosis: non-invasive analysis by epiluminescence microscopy. Author(s): De Giorgi V, Massi D, Mannone F, Stante M, Carli P. Source: Clinical and Experimental Dermatology. 2003 May; 28(3): 315-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780722&dopt=Abstract

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Cycle-specific and cumulative fecundity in patients with endometriosis who are undergoing controlled ovarian hyperstimulation-intrauterine insemination or in vitro fertilization-embryo transfer. Author(s): Dmowski WP, Pry M, Ding J, Rana N. Source: Fertility and Sterility. 2002 October; 78(4): 750-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372451&dopt=Abstract

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CYP1A1, CYP19, and GSTM1 polymorphisms increase the risk of endometriosis. Author(s): Arvanitis DA, Koumantakis GE, Goumenou AG, Matalliotakis IM, Koumantakis EE, Spandidos DA. Source: Fertility and Sterility. 2003 March; 79 Suppl 1: 702-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620480&dopt=Abstract

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Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis. Author(s): Vercellini P, De Giorgi O, Mosconi P, Stellato G, Vicentini S, Crosignani PG. Source: Fertility and Sterility. 2002 January; 77(1): 52-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779591&dopt=Abstract

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Cystoscopy-assisted laparoscopic resection of extramucosal bladder endometriosis. Author(s): Seracchioli R, Mannini D, Colombo FM, Vianello F, Reggiani A, Venturoli S. Source: Journal of Endourology / Endourological Society. 2002 November; 16(9): 663-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490020&dopt=Abstract

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Danazol for pelvic pain associated with endometriosis. Author(s): Selak V, Farquhar C, Prentice A, Singla A. Source: Cochrane Database Syst Rev. 2001; (4): Cd000068. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687066&dopt=Abstract

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Danazol for pelvic pain associated with endometriosis. Author(s): Selak V, Farquhar C, Prentice A, Singla A. Source: Cochrane Database Syst Rev. 2000; (2): Cd000068. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796483&dopt=Abstract

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De novo formation of adhesions in endometriosis: the role of iron and free radical reactions. Author(s): Arumugam K, Yip YC. Source: Fertility and Sterility. 1995 July; 64(1): 62-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7789581&dopt=Abstract

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Decrease in peripheral blood polymorphonuclear leukocyte chemotactic index in endometriosis: role of prostaglandin E2 release. Author(s): Garzetti GG, Ciavattini A, Provinciali M, Amati M, Muzzioli M, Governa M. Source: Obstetrics and Gynecology. 1998 January; 91(1): 25-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9464715&dopt=Abstract

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Decreased apoptosis and sensitivity to macrophage mediated cytolysis of endometrial cells in endometriosis. Author(s): Dmowski WP, Gebel H, Braun DP. Source: Human Reproduction Update. 1998 September-October; 4(5): 696-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10027622&dopt=Abstract

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Decreased expression of the decoy interleukin-1 receptor type II in human endometriosis. Author(s): Akoum A, Jolicoeur C, Kharfi A, Aube M. Source: American Journal of Pathology. 2001 February; 158(2): 481-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159185&dopt=Abstract

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Deep endometriosis conundrum: evidence in favor of a peritoneal origin. Author(s): Vercellini P, Aimi G, Panazza S, Vicentini S, Pisacreta A, Crosignani PG. Source: Fertility and Sterility. 2000 May; 73(5): 1043-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10785236&dopt=Abstract

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Deeply infiltrating endometriosis: implications, diagnosis, and management. Author(s): Kwok A, Lam A, Ford R. Source: Obstetrical & Gynecological Survey. 2001 March; 56(3): 168-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254153&dopt=Abstract

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Degranulating eosinophils in human endometriosis. Author(s): Cochrane Database Syst Rev. 2001;(4):CD000068 Source: American Journal of Pathology. 2000 May; 156(5): 1581-8. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11687066

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Delayed oral estradiol combined with leuprolide increases endometriosis-related pain. Author(s): Hurst BS, Gardner SC, Tucker KE, Awoniyi CA, Schlaff WD. Source: Jsls. 2000 April-June; 4(2): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917114&dopt=Abstract

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Delineation of a new syndrome: clustering of pyloric stenosis, endometriosis, and breast cancer in two families. Author(s): Liede A, Pal T, Mitchell M, Narod SA. Source: Journal of Medical Genetics. 2000 October; 37(10): 794-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11183186&dopt=Abstract

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Depot leuprorelin acetate versus danazol in the treatment of infertile women with symptomatic endometriosis. Author(s): Rotondi M, Labriola D, Rotondi M, Ammaturo FP, Amato G, Carella C, Izzo A, Panariello S. Source: Eur J Gynaecol Oncol. 2002; 23(6): 523-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556096&dopt=Abstract

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Detection of aromatase cytochrome P-450 in endometrial biopsy specimens as a diagnostic test for endometriosis. Author(s): Kitawaki J, Kusuki I, Koshiba H, Tsukamoto K, Fushiki S, Honjo H. Source: Fertility and Sterility. 1999 December; 72(6): 1100-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10593388&dopt=Abstract

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Detection of DNA copy number changes in human endometriosis by comparative genomic hybridization. Author(s): Gogusev J, Bouquet de Joliniere J, Telvi L, Doussau M, du Manoir S, Stojkoski A, Levardon M. Source: Human Genetics. 1999 November; 105(5): 444-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10598811&dopt=Abstract

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Development of a Web site for the genetic epidemiology of endometriosis. Author(s): Zondervan K, Cardon L, Kennedy S. Source: Fertility and Sterility. 2002 October; 78(4): 777-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372456&dopt=Abstract

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Development of an endometriosis quality-of-life instrument: The Endometriosis Health Profile-30. Author(s): Jones G, Kennedy S, Barnard A, Wong J, Jenkinson C. Source: Obstetrics and Gynecology. 2001 August; 98(2): 258-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506842&dopt=Abstract

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Development of dysplastic mucinous epithelium from endometriosis of the appendix. Author(s): Mai KT, Burns BF. Source: Histopathology. 1999 October; 35(4): 368-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10564392&dopt=Abstract

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Development of endometriosis-like lesions after transplantation of human endometrial fragments onto the chick embryo chorioallantoic membrane. Author(s): Maas JW, Groothuis PG, Dunselman GA, de Goeij AF, Struijker-Boudier HA, Evers JL. Source: Human Reproduction (Oxford, England). 2001 April; 16(4): 627-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11278208&dopt=Abstract

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Diagnosis and treatment of endometriosis. Author(s): Wellbery C. Source: American Family Physician. 1999 October 15; 60(6): 1753-62, 1767-8. Review. Erratum In: Am Fam Physician 2000 May 1; 61(9): 2614. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10537390&dopt=Abstract

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Diagnosis and treatment of sigmoidal endometriosis--a case report. Author(s): Bartkowiak R, Zieniewicz K, Kaminski P, Krawczyk M, Marianowski L, Szymanska K. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 July-August; 6(4): 787-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208411&dopt=Abstract

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Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis. Author(s): Stratton P, Winkel C, Premkumar A, Chow C, Wilson J, Hearns-Stokes R, Heo S, Merino M, Nieman LK. Source: Fertility and Sterility. 2003 May; 79(5): 1078-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738499&dopt=Abstract

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Diagnostic delay in women with pain and endometriosis. Author(s): Husby GK, Haugen RS, Moen MH. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2003 July; 82(7): 649-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790847&dopt=Abstract

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Diaphragmatic endometriosis. Author(s): Cooper MJ, Russell P, Gallagher PJ. Source: The Medical Journal of Australia. 1999 August 2; 171(3): 142-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474606&dopt=Abstract

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Diaphragmatic endometriosis: diagnosis, surgical management, and long-term results of treatment. Author(s): Redwine DB. Source: Fertility and Sterility. 2002 February; 77(2): 288-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821085&dopt=Abstract

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Dienogest is as effective as triptorelin in the treatment of endometriosis after laparoscopic surgery: results of a prospective, multicenter, randomized study. Author(s): Cosson M, Querleu D, Donnez J, Madelenat P, Konincks P, Audebert A, Manhes H. Source: Fertility and Sterility. 2002 April; 77(4): 684-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937116&dopt=Abstract

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Different aetiological mechanisms for unexplained and endometriosis-associated infertility cannot be inferred from unstimulated IVF cycles using HCG to induce ovulation. Author(s): Keay SD, Cahill DJ. Source: Human Reproduction (Oxford, England). 2002 July; 17(7): 1926-7; Author Reply 1927. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093863&dopt=Abstract

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Different basic fibroblast growth factor and fibroblast growth factor-antisense expression in eutopic endometrial stromal cells derived from women with and without endometriosis. Author(s): Mihalich A, Reina M, Mangioni S, Ponti E, Alberti L, Vigano P, Vignali M, Di Blasio AM. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2853-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788899&dopt=Abstract

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Differential expression of IGF-I and IGF-II in eutopic and ectopic endometria of women with endometriosis and in women without endometriosis. Author(s): Sbracia M, Zupi E, Alo P, Manna C, Marconi D, Scarpellini F, Grasso JA, Di Tondo U, Romanini C. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 1997 April; 37(4): 326-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9161641&dopt=Abstract

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Differential expression of interleukins (IL)-13 and IL-15 in ectopic and eutopic endometrium of women with endometriosis and normal fertile women. Author(s): Chegini N, Roberts M, Ripps B. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2003 February; 49(2): 75-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765345&dopt=Abstract

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Dioxin stimulates RANTES expression in an in-vitro model of endometriosis. Author(s): Zhao D, Pritts EA, Chao VA, Savouret JF, Taylor RN. Source: Molecular Human Reproduction. 2002 September; 8(9): 849-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200463&dopt=Abstract

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Dioxins and endometriosis: a plausible hypothesis. Author(s): Birnbaum LS, Cummings AM. Source: Environmental Health Perspectives. 2002 January; 110(1): 15-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781160&dopt=Abstract

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Distinct mechanisms regulate cyclooxygenase-1 and -2 in peritoneal macrophages of women with and without endometriosis. Author(s): Wu MH, Sun HS, Lin CC, Hsiao KY, Chuang PC, Pan HA, Tsai SJ. Source: Molecular Human Reproduction. 2002 December; 8(12): 1103-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468643&dopt=Abstract

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Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis. Author(s): Ota H, Igarashi S, Sasaki M, Tanaka T. Source: Human Reproduction (Oxford, England). 2001 March; 16(3): 561-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228229&dopt=Abstract

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DNA microarray analysis of gene expression markers of endometriosis. Author(s): Eyster KM, Boles AL, Brannian JD, Hansen KA. Source: Fertility and Sterility. 2002 January; 77(1): 38-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779588&dopt=Abstract

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Do soluble cell adhesion molecules play a role in endometriosis? Author(s): Daniel Y, Geva E, Amit A, Eshed-Englender T, Baram A, Fait G, Lessing JB. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2000 March; 43(3): 160-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10735592&dopt=Abstract

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Does deep endometriosis infiltrating the uterosacral ligaments present an asymmetric lateral distribution? Author(s): Chapro C, Fauconnier A, Dubuisson JB, Vieira M, Bonte H, Vacher-Lavenu MC. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2001 October; 108(10): 1021-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11702831&dopt=Abstract

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Does endometriosis really have premalignant potential? A clonal analysis of lasermicrodissected tissue. Author(s): Mayr D, Amann G, Siefert C, Diebold J, Anderegg B. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 April; 17(6): 693-5. Epub 2003 February 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594178&dopt=Abstract

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Does ovulation induction affect the pregnancy rate after laparoscopic treatment of endometriosis? Author(s): Karabacak O, Kambic R, Gursoy R, Ozeren S. Source: Int J Fertil Womens Med. 1999 January-February; 44(1): 38-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10206198&dopt=Abstract

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Dominant expression of progesterone receptor form B mRNA in ovarian endometriosis. Author(s): Misao R, Iwagaki S, Fujimoto J, Sun W, Tamaya T. Source: Hormone Research. 1999; 52(1): 30-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10640897&dopt=Abstract

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Dynamic aspects of endometriosis in a mouse model through analysis of implantation and progression. Author(s): Rossi G, Somigliana E, Moschetta M, Santorsola R, Cozzolino S, Filardo P, Salmaso A, Zingrillo B. Source: Archives of Gynecology and Obstetrics. 2000 February; 263(3): 102-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10763836&dopt=Abstract

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Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Author(s): Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. Source: Fertility and Sterility. 2002 October; 78(4): 699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372443&dopt=Abstract

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Effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis who were treated with laparoscopic conservative surgery: a 1-year prospective randomized double-blind controlled trial. Author(s): Zullo F, Palomba S, Zupi E, Russo T, Morelli M, Cappiello F, Mastrantonio P. Source: American Journal of Obstetrics and Gynecology. 2003 July; 189(1): 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861130&dopt=Abstract

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Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis. Author(s): Garcia-Velasco JA, Mulayim N, Kayisli UA, Arici A. Source: Fertility and Sterility. 2002 October; 78(4): 855-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372468&dopt=Abstract

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Emerging role of genomics in endometriosis research. Author(s): Taylor RN, Lundeen SG, Giudice LC. Source: Fertility and Sterility. 2002 October; 78(4): 694-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372442&dopt=Abstract

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Endometrial adenocarcinoma arising from endometriosis of the rectosigmoid colon. Author(s): Jones KD, Owen E, Berresford A, Sutton C. Source: Gynecologic Oncology. 2002 August; 86(2): 220-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144831&dopt=Abstract

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Endometriosis and ovarian cancer: thoughts on shared pathophysiology. Author(s): Ness RB. Source: American Journal of Obstetrics and Gynecology. 2003 July; 189(1): 280-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861175&dopt=Abstract

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Endometriosis causing cyclic compression of the right external iliac vein with cyclic edema of the right leg and thigh. Author(s): Rosengarten AM, Wong J, Gibbons S. Source: J Obstet Gynaecol Can. 2002 January; 24(1): 33-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196886&dopt=Abstract

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Endometriosis causing extensive intestinal obstruction simulating carcinoma of the sigmoid colon: a case report and review of the literature. Author(s): Varras M, Kostopanagiotou E, Katis K, Farantos Ch, Angelidou-Manika Z, Antoniou S. Source: Eur J Gynaecol Oncol. 2002; 23(4): 353-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12214744&dopt=Abstract

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Endometriosis co-existing with bilateral dermoid cysts of the ovaries treated by laparoscopy. Author(s): Frederick J, DaCosta V, Wynter S, Tenant I, McKenzie C, McDonald Y. Source: The West Indian Medical Journal. 2003 June; 52(2): 179-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506771&dopt=Abstract

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Endometriosis in reproductive immunology. Author(s): Ulcova-Gallova Z, Bouse V, Svabek L, Turek J, Rokyta Z. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2002 May; 47(5): 269-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12148541&dopt=Abstract

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Endometriosis in the differential diagnosis of abdominal wall masses. Author(s): Divani S, Vardouli A, Exarhos N, Lioupis A. Source: Acta Cytol. 2003 September-October; 47(5): 944-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526686&dopt=Abstract

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Endometriosis is sustained by tumour necrosis factor-alpha. Author(s): Bullimore DW. Source: Medical Hypotheses. 2003 January; 60(1): 84-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450770&dopt=Abstract

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Endometriosis of the urinary tract. Author(s): Comiter CV. Source: The Urologic Clinics of North America. 2002 August; 29(3): 625-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476526&dopt=Abstract

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Endometriosis presenting as a groin tumour: case report. Author(s): Oyetunde O, Akang EE. Source: East Afr Med J. 2000 July; 77(7): 398-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862163&dopt=Abstract

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Endometriosis presenting as an obstructed femoral hernia: a case report. Author(s): Makunike R, Muronda C, Saburi SD. Source: Cent Afr J Med. 2001 July; 47(7): 184-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201030&dopt=Abstract

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Endometriosis results from the dislocation of basal endometrium. Author(s): Leyendecker G, Herbertz M, Kunz G, Mall G. Source: Human Reproduction (Oxford, England). 2002 October; 17(10): 2725-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351554&dopt=Abstract

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Endometriosis, tampons and orgasm during menstruation: science, press and patient organizations. Author(s): D'Hooghe TM, Yankowitz J. Source: Gynecologic and Obstetric Investigation. 2002; 54(2): 61-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566742&dopt=Abstract

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Endometriosis. Author(s): Gould D. Source: Nurs Stand. 2003 March 19-25; 17(27): 47-53; Quiz 54-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683119&dopt=Abstract

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Endometriosis. Author(s): Farquhar C. Source: Clin Evid. 2002 June; (7): 1654-62. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230778&dopt=Abstract

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Endometriosis: candidate genes. Author(s): Campbell IG, Thomas EJ. Source: Human Reproduction Update. 2001 January-February; 7(1): 15-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11212068&dopt=Abstract

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Endometriosis: correlation between histologic and visual findings at laparoscopy. Author(s): Martin DC. Source: American Journal of Obstetrics and Gynecology. 2003 June; 188(6): 1663; Author Reply 1663-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825014&dopt=Abstract

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Endometriosis: current concepts and therapy. Author(s): Cleve Clin J Med. 2002 Aug;69(8):654 Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 August; 78(2): 107-19. Review. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12184474

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Endometriosis: modern surgical management to improve fertility. Author(s): Gordts S, Campo R, Brosens I, Puttemans P. Source: Best Practice & Research. Clinical Obstetrics & Gynaecology. 2003 April; 17(2): 275-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12758100&dopt=Abstract

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Endometriosis: novel etiopathogenetic concepts and clinical perspectives. Author(s): Vignali M, Infantino M, Matrone R, Chiodo I, Somigliana E, Busacca M, Vigano P. Source: Fertility and Sterility. 2002 October; 78(4): 665-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372439&dopt=Abstract

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Endometriosis: preoperative and postoperative medical treatment. Author(s): Vercellini P, Frontino G, De Giorgi O, Pietropaolo G, Pasin R, Crosignani PG. Source: Obstetrics and Gynecology Clinics of North America. 2003 March; 30(1): 163-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699264&dopt=Abstract

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Endometriosis: radiologic-pathologic correlation. Author(s): Woodward PJ, Sohaey R, Mezzetti TP Jr. Source: Radiographics : a Review Publication of the Radiological Society of North America, Inc. 2001 January-February; 21(1): 193-216; Questionnaire 288-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158655&dopt=Abstract

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Endometriosis: still tough to diagnose and treat. Author(s): Attaran M, Falcone T, Goldberg J. Source: Cleve Clin J Med. 2002 August; 69(8): 647-53. Review. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184473&dopt=Abstract

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Endometriosis: the pathophysiology as an estrogen-dependent disease. Author(s): Kitawaki J, Kado N, Ishihara H, Koshiba H, Kitaoka Y, Honjo H. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 December; 83(1-5): 149-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650711&dopt=Abstract

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Endometriosis--a missed malady. Author(s): Taylor MM. Source: Aorn Journal. 2003 February; 77(2): 298, 301-9, 312-3; Quiz 314-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619848&dopt=Abstract

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Endometriosis-associated ovarian carcinoma: differential expression of vascular endothelial growth factor and estrogen/progesterone receptors. Author(s): Del Carmen MG, Smith Sehdev AE, Fader AN, Zahurak ML, Richardson M, Fruehauf JP, Montz FJ, Bristow RE. Source: Cancer. 2003 October 15; 98(8): 1658-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534882&dopt=Abstract

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Endometriotic haptoglobin binds to peritoneal macrophages and alters their function in women with endometriosis. Author(s): Sharpe-Timms KL, Zimmer RL, Ricke EA, Piva M, Horowitz GM. Source: Fertility and Sterility. 2002 October; 78(4): 810-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372461&dopt=Abstract

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Epithelial neutrophil-activating peptide 78 concentrations are elevated in the peritoneal fluid of women with endometriosis. Author(s): Mueller MD, Mazzucchelli L, Buri C, Lebovic DI, Dreher E, Taylor RN. Source: Fertility and Sterility. 2003 March; 79 Suppl 1: 815-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620496&dopt=Abstract

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Evaluation and management of women with endometriosis. Author(s): Winkel CA. Source: Obstetrics and Gynecology. 2003 August; 102(2): 397-408. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907119&dopt=Abstract

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Evidence for asymmetric distribution of sciatic nerve endometriosis. Author(s): Vercellini P, Chapron C, Fedele L, Frontino G, Zaina B, Crosignani PG. Source: Obstetrics and Gynecology. 2003 August; 102(2): 383-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907116&dopt=Abstract

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Evidence for local production of inhibin A and activin A in patients with ovarian endometriosis. Author(s): Reis FM, Di Blasio AM, Florio P, Ambrosini G, Di Loreto C, Petraglia F. Source: Fertility and Sterility. 2001 February; 75(2): 367-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172841&dopt=Abstract

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Exceptionally high levels of CA125 due to endometriosis. Author(s): Caroline C, Bashir T. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2002 May; 22(3): 329-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521524&dopt=Abstract

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Expression of erythropoietin and erythropoietin receptor in peritoneal endometriosis. Author(s): Matsuzaki S, Canis M, Yokomizo R, Yaegashi N, Bruhat MA, Okamura K. Source: Human Reproduction (Oxford, England). 2003 January; 18(1): 152-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525458&dopt=Abstract

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Expression of serum human leukocyte antigen and growth factor levels in a Greek family with familial endometriosis. Author(s): Matalliotakis IM, Goumenou AG, Koumantakis GE, Athanassakis I, Dionyssopoulou E, Neonaki MA, Vassiliadis S. Source: Journal of the Society for Gynecologic Investigation. 2003 February; 10(2): 11821. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594002&dopt=Abstract

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Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Author(s): Kao LC, Germeyer A, Tulac S, Lobo S, Yang JP, Taylor RN, Osteen K, Lessey BA, Giudice LC. Source: Endocrinology. 2003 July; 144(7): 2870-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810542&dopt=Abstract

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Extremely elevated serum CA125 due to endometriosis. Author(s): Kashyap RJ. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1999 May; 39(2): 269-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10755799&dopt=Abstract

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Familial risk among patients with endometriosis. Author(s): dos Reis RM, de Sa MF, de Moura MD, Nogueira AA, Ribeiro JU, Ramos ES, Ferriani RA. Source: Journal of Assisted Reproduction and Genetics. 1999 October; 16(9): 500-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10530406&dopt=Abstract

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Fatal acute hepatic failure induced by danazol in a patient with endometriosis and aplastic anemia. Author(s): Hayashi T, Takahashi T, Minami T, Akaike J, Kasahara K, Adachi M, Hinoda Y, Takahashi S, Hirayama T, Imai K. Source: Journal of Gastroenterology. 2001 November; 36(11): 783-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11757752&dopt=Abstract

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Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility. The Canadian Collaborative Group on Endometriosis. Author(s): Berube S, Marcoux S, Langevin M, Maheux R. Source: Fertility and Sterility. 1998 June; 69(6): 1034-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9627289&dopt=Abstract

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Fecundity of infertile women with minimal or mild endometriosis. A clinical study. Author(s): Milingos S, Mavrommatis C, Elsheikh A, Kallipolitis G, Loutradis D, Diakomanolis E, Michalas S. Source: Archives of Gynecology and Obstetrics. 2002 November; 267(1): 37-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410372&dopt=Abstract

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Fertility after laparoscopic management of deep endometriosis infiltrating the uterosacral ligaments. Author(s): Chapron C, Fritel X, Dubuisson JB. Source: Human Reproduction (Oxford, England). 1999 February; 14(2): 329-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10099973&dopt=Abstract

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Fertility drugs and ovarian epithelial cancer: the endometriosis hypothesis. Author(s): Paulson RJ. Source: Journal of Assisted Reproduction and Genetics. 1997 April; 14(4): 228-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9130072&dopt=Abstract

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Fibrinolysis in the peritoneal fluid during adhesions, endometriosis and ongoing pelvic inflammatory disease. Author(s): Edelstam G, Lecander I, Larsson B, Astedt B. Source: Inflammation. 1998 August; 22(4): 341-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9675606&dopt=Abstract

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Fibrinolytic factors in endometriotic tissue, endometrium, peritoneal fluid, and plasma from women with endometriosis and in endometrium and peritoneal fluid from healthy women. Author(s): Bruse C, Bergqvist A, Carlstrom K, Fianu-Jonasson A, Lecander I, Astedt B. Source: Fertility and Sterility. 1998 November; 70(5): 821-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9806560&dopt=Abstract

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Fibrogenesis in peritoneal endometriosis. A semi-quantitative analysis of type-I collagen. Author(s): Matsuzaki S, Canis M, Darcha C, Dechelotte P, Pouly JL, Bruhat MA. Source: Gynecologic and Obstetric Investigation. 1999; 47(3): 197-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10087417&dopt=Abstract

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Fine needle aspiration cytodiagnosis of endometriosis in an abdominal scar after caesarean section. Author(s): Gupta RK, Green C, Wood KP. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2000 February; 11(1): 67-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714379&dopt=Abstract

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Flare-up of endometriosis induced by gonadotropin-releasing hormone agonist leading to bowel obstruction. Author(s): Hall LL, Malone JM, Ginsburg KA. Source: Fertility and Sterility. 1995 December; 64(6): 1204-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7589678&dopt=Abstract

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Fluorescence diagnosis of endometriosis on the chorioallantoic membrane using 5aminolaevulinic acid. Author(s): Malik E, Meyhofer-Malik A, Berg C, Bohm W, Kunzi-Rapp K, Diedrich K, Ruck A. Source: Human Reproduction (Oxford, England). 2000 March; 15(3): 584-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10686200&dopt=Abstract

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Fluorescence diagnosis of endometriosis using 5-aminolevulinic acid. Author(s): Malik E, Berg C, Meyhofer-Malik A, Buchweitz O, Moubayed P, Diedrich K. Source: Surgical Endoscopy. 2000 May; 14(5): 452-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10858470&dopt=Abstract

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Focus group study of endometriosis: struggle, loss and the medical merry-go-round. Author(s): Cox H, Henderson L, Andersen N, Cagliarini G, Ski C. Source: International Journal of Nursing Practice. 2003 February; 9(1): 2-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588614&dopt=Abstract

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Follicular fluid of women with endometriosis stimulates the proliferation of endometrial stromal cells. Author(s): Bahtiyar MO, Seli E, Oral E, Senturk LM, Zreik TG, Arici A. Source: Human Reproduction (Oxford, England). 1998 December; 13(12): 3492-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9886538&dopt=Abstract

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Follicular hormonal environment and embryo quality in women with endometriosis. Author(s): Garrido N, Navarro J, Remohi J, Simon C, Pellicer A. Source: Human Reproduction Update. 2000 January-February; 6(1): 67-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711831&dopt=Abstract

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Follow-up of laparoscopic treatment of stage III-IV endometriosis. Author(s): Busacca M, Bianchi S, Agnoli B, Candiani M, Calia C, De Marinis S, Vignali M. Source: The Journal of the American Association of Gynecologic Laparoscopists. 1999 February; 6(1): 55-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9971852&dopt=Abstract

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Follow-up report on a randomized controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal to moderate endometriosis. Author(s): Sutton CJ, Pooley AS, Ewen SP, Haines P. Source: Fertility and Sterility. 1997 December; 68(6): 1070-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9418699&dopt=Abstract

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Functional and phenotypic alterations in peritoneal macrophages from patients with early and advanced endometriosis. Author(s): Raiter-Tenenbaum A, Baranao RI, Etchepareborda JJ, Meresman GF, Rumi LS. Source: Archives of Gynecology and Obstetrics. 1998; 261(3): 147-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9651659&dopt=Abstract

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Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis. Author(s): Ueda M, Yamashita Y, Takehara M, Terai Y, Kumagai K, Ueki K, Kanda K, Hung YC, Ueki M. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 October; 16(5): 391-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587534&dopt=Abstract

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Genetic abnormalities detected by comparative genomic hybridization in a human endometriosis-derived cell line. Author(s): Gogusev J, Bouquet de Joliniere J, Telvi L, Doussau M, du Manoir S, Stojkoski A, Levardon M. Source: Molecular Human Reproduction. 2000 September; 6(9): 821-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10956554&dopt=Abstract

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Genetic alterations in microsatellite marker sites among tumor suppressor genes in endometriosis. Author(s): Nakayama K, Toki T, Nikaido T, Zhai YL, Konishi I. Source: Gynecologic and Obstetric Investigation. 2001; 51(4): 240-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408734&dopt=Abstract

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Genetic contribution of the interleukin-10 promoter polymorphism in endometriosis susceptibility. Author(s): Kitawaki J, Obayashi H, Ohta M, Kado N, Ishihara H, Koshiba H, Kusuki I, Tsukamoto K, Hasegawa G, Nakamura N, Yoshikawa T, Honjo H. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2002 January; 47(1): 12-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883743&dopt=Abstract

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Genetic factors contribute to the risk of developing endometriosis. Author(s): Stefansson H, Geirsson RT, Steinthorsdottir V, Jonsson H, Manolescu A, Kong A, Ingadottir G, Gulcher J, Stefansson K. Source: Human Reproduction (Oxford, England). 2002 March; 17(3): 555-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870102&dopt=Abstract

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Genetic influences on endometriosis in an Australian twin sample. [email protected]. Author(s): Treloar SA, O'Connor DT, O'Connor VM, Martin NG. Source: Fertility and Sterility. 1999 April; 71(4): 701-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10202882&dopt=Abstract

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Genetics of endometriosis. Author(s): Simpson JL, Bischoff FZ, Kamat A, Buster JE, Carson SA. Source: Obstetrics and Gynecology Clinics of North America. 2003 March; 30(1): 21-40, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699256&dopt=Abstract

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Glutathione S-transferase M1 and T1 genotypes and endometriosis risk: a casecontrolled study. Author(s): Lin J, Zhang X, Qian Y, Ye Y, Shi Y, Xu K, Xu J. Source: Chin Med J (Engl). 2003 May; 116(5): 777-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875700&dopt=Abstract

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Glutathione S-transferase M1 gene polymorphism and susceptibility to endometriosis in a French population. Author(s): Baranova H, Bothorishvilli R, Canis M, Albuisson E, Perriot S, Glowaczower E, Bruhat MA, Baranov V, Malet P. Source: Molecular Human Reproduction. 1997 September; 3(9): 775-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9358003&dopt=Abstract

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Glycosidases in the peritoneal fluid from infertile women with and without endometriosis. Author(s): Brandelli A, Passos EP. Source: Clinical Biochemistry. 1998 April; 31(3): 181-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9629492&dopt=Abstract

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Glycosylation and over-expression of endometriosis-associated peritoneal haptoglobin. Author(s): Piva M, Moreno JI, Sharpe-Timms KL. Source: Glycoconjugate Journal. 2002 January; 19(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652078&dopt=Abstract

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Gn-RH agonists and ovarian endometriosis. Author(s): Descamps P, Lansac J. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1998 August; 79(2): 143-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9720831&dopt=Abstract

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GnRH analogs in treating uterine leiomyomata and endometriosis. Author(s): Szczurowicz A, Wydra D. Source: Clin Exp Obstet Gynecol. 1996; 23(4): 214-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9001782&dopt=Abstract

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GnRH analogues, transvaginal ultrasound-guided drainage and intracystic injection of recombinant interleukin-2 in the treatment of endometriosis. Author(s): Acien P, Quereda FJ, Gomez-Torres MJ, Bermejo R, Gutierrez M. Source: Gynecologic and Obstetric Investigation. 2003; 55(2): 96-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771456&dopt=Abstract

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Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Author(s): Cochrane Database Syst Rev. 2003;(3):CD000155 Source: Cochrane Database Syst Rev. 2000; (2): Cd000346. Review. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12917884

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Gonadotropin-releasing hormone agonist and danazol normalize aromatase cytochrome P450 expression in eutopic endometrium from women with endometriosis, adenomyosis, or leiomyomas. Author(s): Ishihara H, Kitawaki J, Kado N, Koshiba H, Fushiki S, Honjo H. Source: Fertility and Sterility. 2003 March; 79 Suppl 1: 735-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620485&dopt=Abstract

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Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis. Author(s): Meresman GF, Bilotas M, Buquet RA, Baranao RI, Sueldo C, Tesone M. Source: Fertility and Sterility. 2003 September; 80 Suppl 2: 702-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505742&dopt=Abstract

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Gonadotropin-releasing hormone agonist plus “add-back” hormone replacement therapy for treatment of endometriosis: a prospective, randomized, placebocontrolled, double-blind trial. Author(s): Franke HR, van de Weijer PH, Pennings TM, van der Mooren MJ. Source: Fertility and Sterility. 2000 September; 74(3): 534-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10973651&dopt=Abstract

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Gonadotropin-releasing hormone agonist treatment for endometriosis of the rectovaginal septum. Author(s): Fedele L, Bianchi S, Zanconato G, Tozzi L, Raffaelli R. Source: American Journal of Obstetrics and Gynecology. 2000 December; 183(6): 1462-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11120511&dopt=Abstract

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Gonadotropin-releasing hormone analog repairs reduced endometrial cell apoptosis in endometriosis in vitro. Author(s): Imai A, Takagi A, Tamaya T. Source: American Journal of Obstetrics and Gynecology. 2000 May; 182(5): 1142-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10819849&dopt=Abstract

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Gonadotropin-releasing hormone analogue (goserelin) plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. Author(s): Howell R, Edmonds DK, Dowsett M, Crook D, Lees B, Stevenson JC. Source: Fertility and Sterility. 1995 September; 64(3): 474-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7641897&dopt=Abstract

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Gonadotropin-releasing hormone analogue plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. Author(s): Gregoriou O, Konidaris S, Vitoratos N, Papadias C, Papoulias I, Chryssicopoulos A. Source: Int J Fertil Womens Med. 1997 November-December; 42(6): 406-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459084&dopt=Abstract

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Goserelin acetate (Zoladex) with or without hormone replacement therapy for the treatment of endometriosis. Author(s): Moghissi KS, Schlaff WD, Olive DL, Skinner MA, Yin H. Source: Fertility and Sterility. 1998 June; 69(6): 1056-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9627292&dopt=Abstract

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Goserelin followed by assisted reproduction: results in infertile women with endometriosis. Author(s): Ruiz-Velasco V, Allende S. Source: Int J Fertil Womens Med. 1998 January-February; 43(1): 18-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9532465&dopt=Abstract

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Granulomatous peritonitis after laparoscopic cholecystectomy mimicking pelvic endometriosis. Author(s): Merchant SH, Haghir S, Gordon GB. Source: Obstetrics and Gynecology. 2000 November; 96(5 Pt 2): 830-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11094226&dopt=Abstract

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Growth-regulated alpha expression in the peritoneal environment with endometriosis. Author(s): Oral E, Seli E, Bahtiyar MO, Olive DL, Arici A. Source: Obstetrics and Gynecology. 1996 December; 88(6): 1050-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8942852&dopt=Abstract

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GSTM1 null polymorphism and susceptibility to endometriosis and ovarian cancer. Author(s): Baxter SW, Thomas EJ, Campbell IG. Source: Carcinogenesis. 2001 January; 22(1): 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159742&dopt=Abstract

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Haemoperitoneum due to cornual endometriosis during pregnancy resulting in intrauterine death. Author(s): Leung WC, Leung TW, Lam YH. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1998 May; 38(2): 156-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9653849&dopt=Abstract

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Health and fertility outcomes among women surgically treated for endometriosis. Author(s): Batt RE, Buck GM, Smith RA. Source: The Journal of the American Association of Gynecologic Laparoscopists. 1997 August; 4(4): 435-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9224576&dopt=Abstract

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Healthy women and patients with endometriosis show high concentrations of inhibin A, inhibin B, and activin A in peritoneal fluid throughout the menstrual cycle. Author(s): Florio P, Luisi S, Vigano P, Busacca M, Fadalti M, Genazzani AR, Petraglia F. Source: Human Reproduction (Oxford, England). 1998 September; 13(9): 2606-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9806293&dopt=Abstract

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Hemoperitoneum secondary to pelvic endometriosis in pregnancy. Author(s): Ismail KM, Shervington J. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1999 November; 67(2): 107-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10636055&dopt=Abstract

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Hemorrhagic ascites associated with endometriosis. A case report. Author(s): Dias CC, Andrade JM, Ferriani RA, Villanova MG, Meirelles RS. Source: J Reprod Med. 2000 August; 45(8): 688-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10986691&dopt=Abstract

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Hemothorax after Lupron therapy of a patient with pleural endometriosis--a case report and literature review. Author(s): Margolis MT, Thoen LD, Mercer LJ, Keith LG. Source: Int J Fertil Menopausal Stud. 1996 January-February; 41(1): 53-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8673157&dopt=Abstract

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Hepatic endometriosis: a case report and review of the literature. Author(s): Reid GD, Kowalski D, Cooper MJ, Kaloo P. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2003 February; 43(1): 87-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755358&dopt=Abstract

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Hepatic endometriosis: a case report. Author(s): Cravello L, D'Ercole C, Le Treut YP, Blanc B. Source: Fertility and Sterility. 1996 October; 66(4): 657-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8816634&dopt=Abstract

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Hepatocyte growth factor concentrations are elevated in peritoneal fluid of women with endometriosis. Author(s): Osuga Y, Tsutsumi O, Okagaki R, Takai Y, Fujimoto A, Suenaga A, Maruyama M, Momoeda M, Yano T, Taketani Y. Source: Human Reproduction (Oxford, England). 1999 June; 14(6): 1611-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10357985&dopt=Abstract

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Heritability and molecular genetic studies of endometriosis. Author(s): Simpson JL, Bischoff FZ. Source: Annals of the New York Academy of Sciences. 2002 March; 955: 239-51; Discussion 293-5, 396-406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949952&dopt=Abstract

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Heritability and molecular genetic studies of endometriosis. Author(s): Bischoff FZ, Simpson JL. Source: Human Reproduction Update. 2000 January-February; 6(1): 37-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711828&dopt=Abstract

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High frequency of endometrial polyps in endometriosis. Author(s): Kim MR, Kim YA, Jo MY, Hwang KJ, Ryu HS. Source: The Journal of the American Association of Gynecologic Laparoscopists. 2003 February; 10(1): 46-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554993&dopt=Abstract

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High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Author(s): Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. Source: Human Reproduction (Oxford, England). 2002 October; 17(10): 2715-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351553&dopt=Abstract

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High resolution imaging of endometriosis and ovarian carcinoma with optical coherence tomography: feasibility for laparoscopic-based imaging. Author(s): Boppart SA, Goodman A, Libus J, Pitris C, Jesser CA, Brezinski ME, Fujimoto JG. Source: British Journal of Obstetrics and Gynaecology. 1999 October; 106(10): 1071-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10519434&dopt=Abstract

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High-frequency power Doppler angiographic appearance and microvascular flow velocity in recurrent scar endometriosis. Author(s): Wu YC, Tsui KH, Hung JH, Yuan CC, Ng HT. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2003 January; 21(1): 96-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528172&dopt=Abstract

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Histocompatibility leukocyte antigen-G is not expressed by endometriosis or endometrial tissue. Author(s): Hornung D, Fujii E, Lim KH, Vigne JL, McMaster MT, Taylor RN. Source: Fertility and Sterility. 2001 April; 75(4): 814-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11287041&dopt=Abstract

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Histologic appearance of endometriosis infiltrating uterosacral ligaments in women with painful symptoms. Author(s): Bonte H, Chapron C, Vieira M, Fauconnier A, Barakat H, Fritel X, VacherLavenu MC, Dubuisson JB. Source: The Journal of the American Association of Gynecologic Laparoscopists. 2002 November; 9(4): 519-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386367&dopt=Abstract

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Histologic transformation of benign endometriosis to early epithelial ovarian cancer. Author(s): Sainz de la Cuesta R, Eichhorn JH, Rice LW, Fuller AF Jr, Nikrui N, Goff BA. Source: Gynecologic Oncology. 1996 February; 60(2): 238-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8631545&dopt=Abstract

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Histological classification of endometriosis as a predictor of response to treatment. Author(s): Abrao MS, Neme RM, Carvalho FM, Aldrighi JM, Pinotti JA. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2003 July; 82(1): 31-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834939&dopt=Abstract

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How does endometriosis affect infertility? Author(s): Navarro J, Garrido N, Remohi J, Pellicer A. Source: Obstetrics and Gynecology Clinics of North America. 2003 March; 30(1): 181-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699265&dopt=Abstract

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How old is endometriosis? Late 17th- and 18th-century European descriptions of the disease. Author(s): Knapp VJ. Source: Fertility and Sterility. 1999 July; 72(1): 10-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10428141&dopt=Abstract

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HOX gene expression is altered in the endometrium of women with endometriosis. Author(s): Taylor HS, Bagot C, Kardana A, Olive D, Arici A. Source: Human Reproduction (Oxford, England). 1999 May; 14(5): 1328-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10325287&dopt=Abstract

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Human arylhydrocarbon receptor repressor (AHRR) gene: genomic structure and analysis of polymorphism in endometriosis. Author(s): Watanabe T, Imoto I, Kosugi Y, Fukuda Y, Mimura J, Fujii Y, Isaka K, Takayama M, Sato A, Inazawa J. Source: Journal of Human Genetics. 2001; 46(6): 342-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393538&dopt=Abstract

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Human endometriosis-derived permanent cell line (FbEM-1): establishment and characterization. Author(s): Bouquet de Joliniere J, Validire P, Canis M, Doussau M, Levardon M, Gogusev J. Source: Human Reproduction Update. 1997 March-April; 3(2): 117-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9286736&dopt=Abstract

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Human issues and medical economics of endometriosis. Three- vs. six-month GnRHagonist therapy. Author(s): Heinrichs WL, Henzl MR. Source: J Reprod Med. 1998 March; 43(3 Suppl): 299-308. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9564665&dopt=Abstract

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Human peritoneal macrophage and T lymphocyte populations in mild and severe endometriosis. Author(s): Becker JL, Widen RH, Mahan CS, Yeko TR, Parsons AK, Spellacy WN. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 1995 September; 34(3): 179-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8561876&dopt=Abstract

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Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Author(s): Anaf V, Simon P, El Nakadi I, Fayt I, Simonart T, Buxant F, Noel JC. Source: Human Reproduction (Oxford, England). 2002 July; 17(7): 1895-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093857&dopt=Abstract

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Hyperestrogenism: a relevant risk factor for the development of cancer from endometriosis. Author(s): Zanetta GM, Webb MJ, Li H, Keeney GL. Source: Gynecologic Oncology. 2000 October; 79(1): 18-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11006024&dopt=Abstract

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Hyperprolactinemia and luteal insufficiency in infertile patients with mild and minimal endometriosis. Author(s): Cunha-Filho JS, Gross JL, Lemos NA, Brandelli A, Castillos M, Passos EP. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2001 April; 33(4): 216-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383925&dopt=Abstract

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Identification of an invasive, N-cadherin-expressing epithelial cell type in endometriosis using a new cell culture model. Author(s): Zeitvogel A, Baumann R, Starzinski-Powitz A. Source: American Journal of Pathology. 2001 November; 159(5): 1839-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696444&dopt=Abstract

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Identification of the cadherin subtypes present in the human peritoneum and endometriotic lesions: potential role for P-cadherin in the development of endometriosis. Author(s): Chen GT, Tai CT, Yeh LS, Yang TC, Tsai HD. Source: Molecular Reproduction and Development. 2002 July; 62(3): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112590&dopt=Abstract

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Ileal perforation due to ileocecal endometriosis: a case with an unusual clinical and pathological presentation. Author(s): Bossotti M, Bona A, Oliveri MG, Coda R, Micca FB, Fasciano F, Bili G. Source: Chir Ital. 2000 September-October; 52(5): 597-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11190557&dopt=Abstract

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Imaging features of pelvic endometriosis. Author(s): Umaria N, Olliff JF. Source: The British Journal of Radiology. 2001 June; 74(882): 556-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11459736&dopt=Abstract

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Immunobiology of endometriosis. Author(s): Lebovic DI, Mueller MD, Taylor RN. Source: Fertility and Sterility. 2001 January; 75(1): 1-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11163805&dopt=Abstract

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Immunohistochemical analysis of the role of angiogenic status in the vasculature of peritoneal endometriosis. Author(s): Matsuzaki S, Canis M, Murakami T, Dechelotte P, Bruhat MA, Okamura K. Source: Fertility and Sterility. 2001 October; 76(4): 712-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591403&dopt=Abstract

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Immunohistochemical localization of aromatase and apoptosis-associated proteins in ovarian serous cystadenocarcinoma arising from ovarian endometriosis. Author(s): Kusuki I, Kitawaki J, Ishihara H, Koshiba H, Kado N, Ohshima K, Honjo H. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2001 September; 98(1): 114-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516810&dopt=Abstract

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Immunohistochemical staining with MIB1, bcl2 and p16 assists in the distinction of cervical glandular intraepithelial neoplasia from tubo-endometrial metaplasia, endometriosis and microglandular hyperplasia. Author(s): Cameron RI, Maxwell P, Jenkins D, McCluggage WG. Source: Histopathology. 2002 October; 41(4): 313-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383213&dopt=Abstract

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Immunomodulators and aromatase inhibitors: are they the next generation of treatment for endometriosis? Author(s): D'Hooghe TM. Source: Current Opinion in Obstetrics & Gynecology. 2003 June; 15(3): 243-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858113&dopt=Abstract

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Impact of six months of GnRH agonist therapy for endometriosis. Is there an agerelated effect on bone mineral density? Author(s): Agarwal SK. Source: J Reprod Med. 2002 July; 47(7): 530-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170527&dopt=Abstract

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Impaired natural killer cell activity in endometriosis?--A technical challenge for validation. Author(s): Somigliana E, Candiani M, Vignali M, Vigano P. Source: Fertility and Sterility. 2001 August; 76(2): 422-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11503606&dopt=Abstract

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Implantation defects in infertile women with endometriosis. Author(s): Lessey BA. Source: Annals of the New York Academy of Sciences. 2002 March; 955: 265-80; Discussion 293-5, 396-406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949954&dopt=Abstract

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Important effects of cyproterone acetate on endometriosis? Author(s): Moran C. Source: Fertility and Sterility. 2002 October; 78(4): 886; Author Reply 886-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372480&dopt=Abstract

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In search of pathogenic mechanisms in endometriosis: the challenge for molecular cell biology. Author(s): Starzinski-Powitz A, Zeitvogel A, Schreiner A, Baumann R. Source: Current Molecular Medicine. 2001 December; 1(6): 655-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11899254&dopt=Abstract

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Incisional endometriosis. Author(s): McClenathan JH. Source: Journal of the American College of Surgeons. 2001 January; 192(1): 143. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192918&dopt=Abstract

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Increase in the expression of killer cell inhibitory receptors on peritoneal natural killer cells in women with endometriosis. Author(s): Wu MY, Yang JH, Chao KH, Hwang JL, Yang YS, Ho HN. Source: Fertility and Sterility. 2000 December; 74(6): 1187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119748&dopt=Abstract

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Increased expression of cyclooxygenase-2 in local lesions of endometriosis patients. Author(s): Chishima F, Hayakawa S, Sugita K, Kinukawa N, Aleemuzzaman S, Nemoto N, Yamamoto T, Honda M. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2002 July; 48(1): 50-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12322896&dopt=Abstract

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Increased expression of endoglin in the eutopic endometrium of women with endometriosis. Author(s): Kim SH, Choi YM, Chae HD, Kim KR, Kim CH, Kang BM. Source: Fertility and Sterility. 2001 November; 76(5): 918-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704111&dopt=Abstract

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Increased killer inhibitory receptor KIR2DL1 expression among natural killer cells in women with pelvic endometriosis. Author(s): Maeda N, Izumiya C, Yamamoto Y, Oguri H, Kusume T, Fukaya T. Source: Fertility and Sterility. 2002 February; 77(2): 297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821086&dopt=Abstract

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Increased levels of interleukin-15 in the peritoneal fluid of women with endometriosis: inverse correlation with stage and depth of invasion. Author(s): Arici A, Matalliotakis I, Goumenou A, Koumantakis G, Vassiliadis S, Selam B, Mahutte NG. Source: Human Reproduction (Oxford, England). 2003 February; 18(2): 429-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571184&dopt=Abstract

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Increased nitric oxide in peritoneal fluid from women with idiopathic infertility and endometriosis. Author(s): Dong M, Shi Y, Cheng Q, Hao M. Source: J Reprod Med. 2001 October; 46(10): 887-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11725732&dopt=Abstract

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Increased pregnancy rates after ultralong postoperative therapy with gonadotropinreleasing hormone analogs in patients with endometriosis. Author(s): Rickes D, Nickel I, Kropf S, Kleinstein J. Source: Fertility and Sterility. 2002 October; 78(4): 757-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372452&dopt=Abstract

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Increased pregnancy-associated plasma protein-A (PAPP-A) concentrations in peritoneal fluid of women with endometriosis. Author(s): Arici A, Matalliotakis I, Goumenou A, Koumantakis G, Fragouli Y, Mahutte NG. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2003 February; 49(2): 70-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765344&dopt=Abstract

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Inducible nitric oxide synthase expression by peritoneal macrophages in endometriosis-associated infertility. Author(s): Osborn BH, Haney AF, Misukonis MA, Weinberg JB. Source: Fertility and Sterility. 2002 January; 77(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779590&dopt=Abstract

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Induction of monocyte chemotactic protein-1 in peritoneal mesothelial and endometrial cells by oxidized low-density lipoprotein and peritoneal fluid from women with endometriosis. Author(s): Rong R, Ramachandran S, Santanam N, Murphy AA, Parthasarathy S. Source: Fertility and Sterility. 2002 October; 78(4): 843-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372466&dopt=Abstract

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Infertility treatment by in vitro fertilization in patients with minimal or mild endometriosis. Author(s): Meden-Vrtovec H, Tomazevic T, Verdenik I. Source: Clin Exp Obstet Gynecol. 2000; 27(3-4): 191-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214948&dopt=Abstract

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Influence of pelvic endometriosis and ovarian endometrioma on fertility. Author(s): Fujishita A, Khan KN, Masuzaki H, Ishimaru T. Source: Gynecologic and Obstetric Investigation. 2002; 53 Suppl 1: 40-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834867&dopt=Abstract

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Influence of severe endometriosis on gene expression of vascular endothelial growth factor and interleukin-6 in granulosa cells from patients undergoing controlled ovarian hyperstimulation for in vitro fertilization-embryo transfer. Author(s): Yamashita Y, Ueda M, Takehara M, Yamashita H, Suzuki Y, Hung YC, Terai Y, Ueki M. Source: Fertility and Sterility. 2002 October; 78(4): 865-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372470&dopt=Abstract

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Insulin-like growth factor (IGF)-1 and IGF binding protein-1 and -3 in the follicular fluid of infertile patients with endometriosis. Author(s): Cunha-Filho JS, Lemos NA, Freitas FM, Kiefer K, Faller M, Passos EP. Source: Human Reproduction (Oxford, England). 2003 February; 18(2): 423-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571183&dopt=Abstract

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Integrin pattern in human endometrium--new diagnostic tool in pelvic endometriosis? Author(s): Szymanowski K, Skrzypczak J, Mikolajczyk M. Source: Ginekol Pol. 2003 April; 74(4): 257-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916266&dopt=Abstract

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Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms in endometriosis. Author(s): Vigano P, Infantino M, Lattuada D, Lauletta R, Ponti E, Somigliana E, Vignali M, DiBlasio AM. Source: Molecular Human Reproduction. 2003 January; 9(1): 47-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529420&dopt=Abstract

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Intraspinal endometriosis: a case report. Author(s): Sun Z, Wang Y, Zhao L, Ma L. Source: Chin Med J (Engl). 2002 April; 115(4): 622-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133314&dopt=Abstract

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Invisible microscopic endometriosis: how wrong is the sampson hypothesis of retrograde menstruation to explain the pathogenesis of endometriosis? Author(s): D'Hooghe TM. Source: Gynecologic and Obstetric Investigation. 2003; 55(2): 61-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771450&dopt=Abstract

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In-vitro adhesion of endometrium to autologous peritoneal membranes: effect of the cycle phase and the stage of endometriosis. Author(s): Debrock S, Vander Perre S, Meuleman C, Moerman P, Hill JA, D'Hooghe TM. Source: Human Reproduction (Oxford, England). 2002 October; 17(10): 2523-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351522&dopt=Abstract

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Involvement of catalase in the endometrium of patients with endometriosis and adenomyosis. Author(s): Ota H, Igarashi S, Sato N, Tanaka H, Tanaka T. Source: Fertility and Sterility. 2002 October; 78(4): 804-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372460&dopt=Abstract

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Iron overload in the peritoneal cavity of women with pelvic endometriosis. Author(s): Van Langendonckt A, Casanas-Roux F, Donnez J. Source: Fertility and Sterility. 2002 October; 78(4): 712-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372445&dopt=Abstract

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Is endometriosis really associated with pain? Author(s): Momoeda M, Taketani Y, Terakawa N, Hoshiai H, Tanaka K, Tsutsumi O, Osuga Y, Maruyama M, Harada T, Obata K, Hayashi K. Source: Gynecologic and Obstetric Investigation. 2002; 54 Suppl 1: 18-21; Discussion 213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441656&dopt=Abstract

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Isolated torsion of haematosalpinx associated with tubal endometriosis. Author(s): Ohara N, Narita F, Murao S. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 July; 23(4): 453-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881105&dopt=Abstract

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Isolated umbilical endometriosis--a rare finding. Author(s): Okunlola MA, Adekunle AO, Arowojolu AO, Oluwasola AO. Source: Afr J Med Med Sci. 2002 September; 31(3): 281-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751574&dopt=Abstract

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Isolated vesical endometriosis in the absence of previous surgery. Author(s): Thijs I, Bhal PS, Shaw R, Kynaston H. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2002 July; 22(4): 448-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521483&dopt=Abstract

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Ki-67, oestrogen receptor, and progesterone receptor proteins in the human rete ovarii and in endometriosis. Author(s): Khan MS, Dodson AR, Heatley MK. Source: Journal of Clinical Pathology. 1999 July; 52(7): 517-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10605405&dopt=Abstract

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Killer cell activity, statistics, and endometriosis. Author(s): D'Hooghe TM, Hill JA. Source: Fertility and Sterility. 1995 July; 64(1): 226-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7789576&dopt=Abstract

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Lack of association of the common immunologically anomalous LH with endometriosis. Author(s): Gazvani R, Pakarinen P, Fowler P, Logan S, Huhtaniemi I. Source: Human Reproduction (Oxford, England). 2002 June; 17(6): 1532-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042273&dopt=Abstract

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Laparascopically assisted vaginal resection of rectovaginal endometriosis. Author(s): Possover M, Diebolder H, Plaul K, Schneider A. Source: Obstetrics and Gynecology. 2000 August; 96(2): 304-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10960302&dopt=Abstract

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Laparoscopic ablation is not necessary for minimal or mild lesions in endometriosis associated subfertility. Author(s): Al-Inany H. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2001 July; 80(7): 593-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437714&dopt=Abstract

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Laparoscopic diagnosis of endometriosis. Author(s): Wood C, Kuhn R, Tsaltas J. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 August; 42(3): 277-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230063&dopt=Abstract

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Laparoscopic excision of endometriosis: the treatment of choice? Author(s): Garry R. Source: British Journal of Obstetrics and Gynaecology. 1997 May; 104(5): 513-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9166188&dopt=Abstract

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Laparoscopic management of 15 patients with infiltrating endometriosis of the bladder and a case of primary intravesical endometrioid adenosarcoma. Author(s): Nezhat CH, Malik S, Osias J, Nezhat F, Nezhat C. Source: Fertility and Sterility. 2002 October; 78(4): 872-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372471&dopt=Abstract

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Laparoscopic management of bladder endometriosis. Author(s): Chapron C, Dubuisson JB. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1999 November; 78(10): 887-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10577619&dopt=Abstract

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Laparoscopic management of colorectal endometriosis. Author(s): Jerby BL, Kessler H, Falcone T, Milsom JW. Source: Surgical Endoscopy. 1999 November; 13(11): 1125-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10556452&dopt=Abstract

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Laparoscopic management of intestinal endometriosis. Author(s): Varol N, Maher P, Woods R. Source: The Journal of the American Association of Gynecologic Laparoscopists. 2000 August; 7(3): 405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10924638&dopt=Abstract

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Laparoscopic presacral neurolysis for endometriosis-related pelvic pain. Author(s): Soysal ME, Soysal S, Gurses E, Ozer S. Source: Human Reproduction (Oxford, England). 2003 March; 18(3): 588-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615830&dopt=Abstract

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Laparoscopic resection of deep pelvic endometriosis with rectosigmoid involvement. Author(s): Duepree HJ, Senagore AJ, Delaney CP, Marcello PW, Brady KM, Falcone T. Source: Journal of the American College of Surgeons. 2002 December; 195(6): 754-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495306&dopt=Abstract

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Laparoscopic segmental resection for infiltrating endometriosis of rectosigmoid colon: a preliminary report. Author(s): Nezhat F. Source: Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. 2001 February; 11(1): 67-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11269562&dopt=Abstract

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Laparoscopic surgery for endometriosis: a long-term follow-up. Author(s): Tokushige M, Suginami H, Taniguchi F, Kitaoka Y. Source: The Journal of Obstetrics and Gynaecology Research. 2000 December; 26(6): 40916. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11152325&dopt=Abstract

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Laparoscopic surgery for pelvic pain associated with endometriosis. Author(s): Jacobson TZ, Barlow DH, Garry R, Koninckx P. Source: Cochrane Database Syst Rev. 2001; (4): Cd001300. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687104&dopt=Abstract

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Laparoscopic surgery for subfertility associated with endometriosis. Author(s): Jacobson TZ, Barlow DH, Koninckx PR, Olive D, Farquhar C. Source: Cochrane Database Syst Rev. 2002; (4): Cd001398. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519555&dopt=Abstract

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Laparoscopic treatment of complete obliteration of the cul-de-sac associated with endometriosis: long-term follow-up of en bloc resection. Author(s): Redwine DB, Wright JT. Source: Fertility and Sterility. 2001 August; 76(2): 358-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476786&dopt=Abstract

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Laparoscopic uterosacral ligament resection for dysmenorrhea associated with endometriosis: results of a randomized, controlled trial. Author(s): Vercellini P, Aimi G, Busacca M, Apolone G, Uglietti A, Crosignani PG. Source: Fertility and Sterility. 2003 August; 80(2): 310-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909493&dopt=Abstract

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Laparoscopic vesicopsoas hitch for infiltrative ureteral endometriosis. Author(s): Nezhat CH, Nezhat FR, Freiha F, Nezhat CR. Source: Fertility and Sterility. 1999 February; 71(2): 376-9. Erratum In: Fertil Steril 1998 June; 71(6): 1174. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9988415&dopt=Abstract

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Laparoscopically assisted definitive treatment of severe endometriosis. Author(s): Soysal ME, Soysal S, Vicdan K. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2001 February; 72(2): 191-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166755&dopt=Abstract

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Laparoscopically assisted vaginal management of deep endometriosis infiltrating the rectovaginal septum. Author(s): Chapron C, Jacob S, Dubuisson JB, Vieira M, Liaras E, Fauconnier A. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2001 April; 80(4): 349-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264611&dopt=Abstract

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Laser laparoscopy for endometriosis and endometriotic cysts. Author(s): Sutton CJ, Jones KD. Source: Surgical Endoscopy. 2002 November; 16(11): 1513-7. Epub 2002 July 29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140633&dopt=Abstract

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Left lateral predisposition of endometriosis and endometrioma. Author(s): Al-Fozan H, Tulandi T. Source: Obstetrics and Gynecology. 2003 January; 101(1): 164-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517662&dopt=Abstract

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Leiomyomatosis peritonealis disseminata associated with endometriosis: a case report and literature review. Author(s): Herrero J, Kamali P, Kirschbaum M. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1998 February; 76(2): 189-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9481573&dopt=Abstract

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Leukotrienes in gynaecology: the hypothetical value of anti-leukotriene therapy in dysmenorrhoea and endometriosis. Author(s): Abu JI, Konje JC. Source: Human Reproduction Update. 2000 March-April; 6(2): 200-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10782578&dopt=Abstract

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Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Lupron Add-Back Study Group. Author(s): Hornstein MD, Surrey ES, Weisberg GW, Casino LA. Source: Obstetrics and Gynecology. 1998 January; 91(1): 16-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9464714&dopt=Abstract

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Levels of antibodies to transferrin and alpha 2-HS glycoprotein in women with and without endometriosis. Author(s): Mathur SP, Holt VL, Lee JH, Jiang H, Rust PF. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 1998 August; 40(2): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9764347&dopt=Abstract

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Levels of lipid peroxides and superoxide dismutase in peritoneal fluid of patients with endometriosis. Author(s): Liu Y, Luo L, Zhao H. Source: J Tongji Med Univ. 2001; 21(2): 166-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11523228&dopt=Abstract

Studies

89

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Levels of transferrin and alpha 2-HS glycoprotein in women with and without endometriosis. Author(s): Mathur SP, Lee JH, Jiang H, Arnaud P, Rust PF. Source: Autoimmunity. 1999; 29(2): 121-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10433073&dopt=Abstract

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Liesegang rings and endometriosis. Author(s): Perrotta PL, Ginsburg FW, Siderides CI, Parkash V. Source: International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists. 1998 October; 17(4): 358-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9785137&dopt=Abstract

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Linkage and association studies of the relationship between endometriosis and genes encoding the detoxification enzymes GSTM1, GSTT1 and CYP1A1. Author(s): Hadfield RM, Manek S, Weeks DE, Mardon HJ, Barlow DH, Kennedy SH; OXEGENE Collaborative Group. Source: Molecular Human Reproduction. 2001 November; 7(11): 1073-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675474&dopt=Abstract

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Local cytokines in endometrial tissue: the role of interleukin-8 in the pathogenesis of endometriosis. Author(s): Arici A. Source: Annals of the New York Academy of Sciences. 2002 March; 955: 101-9; Discussion 118, 396-406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949939&dopt=Abstract

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Localization in tissues and secretion of eotaxin by cells from normal endometrium and endometriosis. Author(s): Hornung D, Dohrn K, Sotlar K, Greb RR, Wallwiener D, Kiesel L, Taylor RN. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 July; 85(7): 2604-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10902814&dopt=Abstract

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Location, color, size, depth, and volume may predict endometriosis in lesions resected at surgery. Author(s): Stratton P, Winkel CA, Sinaii N, Merino MJ, Zimmer C, Nieman LK. Source: Fertility and Sterility. 2002 October; 78(4): 743-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372450&dopt=Abstract

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Long-term outcome of nonconservative surgery (hysterectomy) for endometriosisassociated pain in women