The chapters in this book represent presentations at the first meeting ever held on the regulation and actions of follicle stimulating hormone. The meeting took place on the campus of Northwestern University, Evanston, Illinois, from October 25 to 28, 1990. The idea for this meeting was conceived by Neena B. Schwartz, and the valuable advice of the organizing committee contributed greatly to its scientific success. We gratefully acknowledge the funding and coordination of this meeting by Serono Symposia, USA. We also wish to acknowledge the financial contributions made by Northwestern University. We especially thank the invited speakers, poster presenters, and discussion participants who pro vided the science, interest, and enthusiasm that made this meeting on FSH a success. MARY HUNZICKER-DUNN NEENA B. SCHWARTZ vii Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv 1. An Overview of FSH Regulation and Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ULRIKE LUDERER AND NEENA B. SCHWARTZ Part I. Neuroendocrinology of FSH Secretion 2. Modulation of Gonadotropin Secretion by Proteins of the Inhibin Family: Studies in the Female Rat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 CATHERINE RIVIER AND WYLIE V ALE 3. Control of Follicle Stimulating Hormone Secretion in the Male Rhesus Monkey (Macaca mulatta) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 TONY M. PLANT 4. The Physiology of Puberty in Seasonally Breeding Birds . . . . . . . . . . . 54 BRIAN K. FOLLETT 5. Hypothalamic Regulation of FSH Secretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 JON E. LEVINE, LISA A. CONAGHAN, ULRIKE LUDERER, AND FRANK J. STROBL 6. Photoperiodic Control of Reproduction in Male Hamsters: Role of FSH in Early Stages of Photo stimulation . . . . . . . . . . . . . . . . . . . . . . . 83 FRED W. TUREK AND NEENA B."

The decision taken during the First International Congress on the Menopause in June 1976 to repeat the exercise 2 years later turned out to be a good one. In the last few years much work has been done on the subject of the menopause. I t is, of course, a subject of many facets, but of particular importance recently has been the work done as a result of the reports appearing in 1975 and 1976 alleging an increase in the incidence of endometrial carcinoma in women who had used oestrogens, and of other effects, some beneficial others deleterious, reportedly seen when oestrogens were administered. 1978 seemed the right time to re-assess the situation, and the Second Inter national Congress on the Menopause provided a good platform. The congress was held in Jerusalem in June 1978. It took the form of a series of 12 workshops, each of which, within a prescribed framework, was planned and presided over by a moderator experi enced in that particular field. The 12 moderators were free to organize their sessions in whichever way they wished, and to invite whoever they wished to present papers and to join in the discussions. In addition the workshops were open to anyone who wished to attend."

The state of health care is reflected by perinatal and neonatal morbidity and mortality as well as by the frequencies of long-term neurological and developmental disorders. Many factors, some without immediately recognizable significance to childbearing and many still unknown, undoubtedly contribute beneficially or adversely to the outcome of pregnancy. Knowledge concerning the impact of such factors on the fetus and surviving infant is critical. Confounding analyses of pregnancy outcome, especially these past 2 or 3 decades, are the effects of newly undertaken invasive or inactive therapeutic approaches coupled with the advent of high technology. Many innovations have been introduced without serious efforts to evaluate their impact prospectively and objectively. The consequences of therapeutic misadventures character ized the past; it seems they have been replaced to a degree by some of the complications of applied technology. Examples abound: after overuse of oxygen was recognized to cause retrolental fibroplasia, its restriction led to an increase in both neonatal death rates and neurologic damage in surviving infants. Administration of vitamin K to prevent neonatal hemorrhagic disease, particularly when given in what we now know as excessive dosage, occasionally resulted in kernicterus. Prophy lactic sulfonamide use had a similar end result. More recent is the observation of bronchopulmonary dysplasia as a complication of re spirator therapy for hyaline membrane disease. The decade of the eighties opened with the all-time highest rate of cesarean section in the United States."

The Helene Harris Memorial Trust has become recognized as providing one of the most important international fora for the presentation of research in ovarian cancer. Four biennial meetings have taken place, the most recent of which was held between May 11-14, 1993, in Toronto, Canada. This forum has grown in stature from its inception in 1987 and has brought together interdisciplinary clinical and scientific researchers from around the world who are endeavouring to perform 'cutting edge' studies in the field. The assembled group of presti gious investigators met on this occasion to present their data, to exchange ideas, and to arrange collaborations with the goal of developing new means of detection, treatment and cure of ovarian cancer. The incentive for the establishment of the Trust and its international forum was the prema ture loss through ovarian cancer of Helene Harris, the wife of Mr John Harris. Mr Harris and the Trustees looked for a meaningful way to honour the memory of Helene and to advance the noble cause of gaining an increase in the scientific knowledge of the subject. For those of us who spend most of our waking hours assisting patients and their families who are devastated by this disease, the Trust's generosity provides inspiration, hope and the opportunity for their practical application in a unique professional forum.

The peri-menopause is emerging more and more as a subject for study by the doctor, the psychologist, the social worker, the gerontologist, the clinical chemist, the public health specialist, the sociologist, the psychiatrist and the experimental pathologist. The results of studies are gradually becoming known to the public, particularly to the prospective clients, ageing women. Women have begun to ask for treatment and they will most likely determine whether oestrogen replacement therapy comes into vogue. Psychosomatics in peri-menopause is an important sub ject, since the life-span of the woman has extended to nearly twice that of her fertile period. The life-expectancy for women in industralized countries is now some 70-75 years. This means that most can now expect to spend one third of their lives in the post-menopause. Consequently, there is now much more time than before in which to notice, experience and be bothered by peri menopausal changes. Moreover modern medicine has much more to oner than mere moral support to sufferers from ailments connected with progressing ovarian failure during peri-menopause. Although we cannot promise eternal youth - as Wilson does -there are more possibilities for treatment than 10 years ago."

The International Women's Health Coalition was pleased to be the convenor and host of the first Christopher Tietze International Symposium, held in Berlin in September 1985. The papers in this volume represent a wide range of international views and experience with the prevention and treatment of contraceptive failure. We believe the issues discussed at the Tietze Symposium to be of interest and concern to women throughout the world and to those who would serve them. The Coalition intends to l1'ive broad distribution to this volume and encourages those interested in these issues to be in touch with the Coalition in New York City (see address below). We would like to thank The Ford Foundation, Stewart Mott, The David and Lucile Packard Foundation, the Population Crisis Committee, and The Uockefeller Foundation for their support of this Symposium. In particular we would like to express our appreciation to Sarah Lewit Tietze and Uta Landy for the devotion ann dedication which made this Symposium possible and a worthy memorial to Christopher Tietze.

The treatment of menopausal and postmenopausal symptoms is a focus of considerable debate, on account of both the medical and social factors involved. And perhaps the cause of the greatest current interest and concern is not so much the effectiveness of present-day treatment but its safety. Opinions on the subject vary; and to resolve the arguments we must turn to the results of scientific experiment, both the clinical and biological. It is only by comparing experimental results that it is possible to move forward, albeit slowly, towards a generally agreed consensus based upon objective scientific data. It is for this reason that we are particularly grateful to Ayerst Laboratories whose support and help have enabled us to turn our original proposal for an International Symposium into a reality. We are also grateful to the publishers for the efficiency with which they have organized the publication of the Proceedings. It is our hope and that of all the distinguished participants that all readers of this volume will be able to find something in it which will stimulate further thought and discussion - even though they may not necessarily agree with all the conclusions expressed - for the success of a Symposium turns not only on the subject under examination but also on the quality of debate and discussion it encourages.

This volume contains papers presented at the Conference on the Demographic and Programmatic Consequences of Contraceptive In novations, which was sponsored by the Committee on Population and held at the National Academy of Sciences, October 6-7, 1988. The papers consider how new contraceptive methods currently being developed and changes in the use of already available contraceptives could affect contraceptive practice, levels and patterns of abortion use, and the health of women. In addition, several of the papers re view the probable consequences of introducing new technology into family planning programs in developing countries. The Committee on Population sponsored this conference in order to stimulate think ing and to provide a forum for scientists, family planning program managers, and donor agency personnel to exchange information and ideas about these important issues. The committee is publishing these papers to expand the discussion of consequences of contracep tive innovations and to give scientists, policy makers, and members of the public who could not attend the conference an opportunity to learn about new developments in fertility control and their likely consequences for individuals and the societies in which they live. NEED FOR NEW METHODS While a strong case can be made that the pill and the intrauterine device (IUD) have contributed to declines in the level of unintended pregnancies around the world, it is also clear that for many couples existing methods present problems.

About 21 years ago prenatal diagnosis became part of the physician's diagnostic armamentarium against genetic defects. My first monograph in 1973 (The Prenatal Diagnosis of Hereditary Disorders) critically assessed early progress and enunciated basic principles in the systematic approach to prenatal genetic diagnosis. Six years later and under the current title, a subsequent volume provided the first major reference source on this subject. The present second (effectively third) edition, which was urged in view of the excellent reception of the two earlier volumes, reflects the remarkable growth of this new discipline and points to significant and exciting future developments. Notwithstanding these advances, the use of the new tools and techniques for the benefit of at-risk parents has taken many more years than most anticipated. Key factors have been the lack of teaching of human genetics in medical schools in the preceding decades and the difficulty of educating practicing physicians in a new scientific disci pline. Even today the teaching of genetics in medical schools leaves much to be desired and this will further delay the introduction of newer genetic advances to the bedside."

Interest in sexuality and reproductive function does not cease when people begin to age. Instead, a new set of questions arises. Women want to know if it is safe to have babies in their late thirties and early forties. They want to know more about hot flashes and other symptoms of menopause-which ones are dangerous and which are merely uncomfortable. They are eager to learn about the relative risks and benefits of estrogen replacement therapy. Men, too, are concerned about age-related changes in their sexual function. Experts in reproductive physiology, gerontology, and genetics met at the National Institutes of Health in June of 1984 to discuss these and other concerns about aging and the reproductive system. The conference on Aging, Reproduc tion, and the Climacteric was sponsored by the American Fertility Society, The National Institute on Aging, and the National Institute of Child Health and Human Development. This volume is based on the proceedings of that confer ence."

The 15th International Symposium of the Japan Human Cell Society on Cell and Molecular Biology of Endometrial Carcinoma brought together leading researchers from Japan and around the world. The papers collected here are the work of twenty-two leaders in their field and are organized in ten major categories. The first section, in vitro experimental systems, takes up the pioneering work by Kuramoto in 1968 and Nishida in 1980 in establishing, respectively, the HEC-1 and hormone-responsive endometrial carcinoma cell lines. Other topics include apoptosis, proliferation, and growth factors; cell cycle regulators; signaling pathways; angiogenesis; carcinogenesis; hormones and hormone receptors; genes and gene expression; endometrial receptivity; and chemo-resistance and -sensitivity. Presenting the latest work in the cell and molecular biology of endometrial carcinoma, this volume is a valuable resource for gynecologists, pathologists, and molecular biologists.

The no-man's-land between reproductive physiology and immunology is becoming crowded. The last 10 years have seen a revolution in our under standing of many reproductive processes, brought about by the application of ever more sophisticated immunological methods. The increasing precision of these techniques has given us specific ways of assaying, enhancing or blocking hormonal mechanisms to yield more critical and interpretable information. In this volume eleven authors have presented the current status and future prospects of some immunological aspects of reproduction and fertility con trol. These include the relationships between mother and fetus, the diagnosis of pregnancy, the immunological complications seen in clinical management of human reproduction and some novel approaches for immunological control of fertility. We hope that in these chapters we have achieved an up-to-date account of a fast-moving field that calls on several disciplines. We intend the book to provide an adequate background and a current review for research workers and clinicians who wish both to understand the complex mechanisms involved and to develop improved scientific and clinical methods. We hope too that the student and newcomer will find this a useful reference book."

Years of involvement, firsthand experience and research at the Menopause Clinic of the Groote Schuur Hospital, Cape Town, exist as the background to this book. The Clinic itself, however, as one of the first in the world to be established, if not the first, has a story and a lesson of its own to offer, and is therefore deserving of a brief description as the preface to the book. In 1967, shortly after Christiaan Barnard had completed the historical first human heart transplant at the Groote Schuur Hospital, I happened to be in West Berlin and was invited to visit a major international pharmaceutical firm. A new female hormone was mentioned, and thereby started my interest in the subject. Upon my return to Cape Town, I spent many hours in the large medical school library and completely surveyed the menopause literature to 1967. I was stunned by its general inadequacy and was bitten by a challenge to clarify what menopause really was, and to define the proper place of hormone replacement therapy.

Discrimination of self from nonself is the major function of the immune system and understanding the mechanism(s) involved a main employer of immunologists. Hence, the age-old puzzle of why a fetus that contains a panel of major histocompatibility (MHC) antigens derived from its mother and its father is not rejected (spontaneously aborted) by lymphocytes from its mother who should theoretically recognize foreign MHC molecules from the father has remained of great interest. This dilemma has enticed immunologists and developmental biologists for many years. This volume was created to present the information currently on hand in this subject to the scientific public. The guest editor, Professor Lars Olding, has a long and distinguished history of contributions in this field, having been one of the main propo nents of the argument that lymphocytes from the fetus play an active role in this process by suppressing lymphocytes from the mother from proliferating and thereby acting as killer cells. His work has defined the phenomenon and identified suppressor molecules (factors) involved in the process. In a different but related chapter, Margareta Unander extends such observations to the clinical study of women with repeated "habitual" mIS carriages."

Surgical Diseases in Pregnancy explores the special problems confronted by the gynecologic surgeon treating pregnant patients. These problems include acute appendicitis, inflammatory bowel disease, breast cancer, carcinoma of the cervix, ovarian tumors, renal stones, and incompetent cervical os. Other topics discussed are induced abortion; septic abortion and septic thrombophlebitis; ectopic pregnancy; surgical disease of the endocrine glands during pregnancy; gastroduodenal, hepato-biliary and pancreatic emergencies during pregnancy; pregnancy in the kidney transplant recipient; and pregnancy and cardiac prosthetic valves.

This book on fibroid uterus focuses on surgical challenges in minimal access surgery that a surgeon faces while treating this condition. This book explores the role of various imaging modalities in both diagnosis and planning of the treatment. Various surgical techniques, such as hysteroscopy, laparoscopy, and robotic are discussed which will help readers to understand the pros and cons of each one. Teaching practical tips from experts regarding these procedures, the book aims to help surgeons make clinical decisions while they choose surgical procedures for their patients in various clinical settings. The book highlights both the conservative (techniques of myomectomy) and hysterectomy by various methods for treating fibroids. Key Features How to use various imaging modalities for preoperative evaluation of fibroids Issues in preoperative counseling and consent before surgery for fibroids Overview of surgical treatment of fibroids Individual chapters on practical tips by experts for various surgical techniques used for both myomectomy and hysterectomy Discusses the controversy in morcellation and how to perform it safely Covers the problem of parasitic fibroids that have increased in recent times Discusses issues like breach in endometrial cavity during myomectomy, surgery for adenomyosis, uterine rupture and recurrence after myomectomy When to call it a day and convert from laparoscopy to laparotomy

It is clear today that several prostaglandins play an important role in the regulation of many of the physiological events of the reproductive organs in the human. Both naturally occurring prostaglandins and their analogues are used routinely in many countries to ripen the cervix and induce labour at term as well as to dilate the cervix and to terminate pregnancy. Prostaglandin biosynthesis inhibitors are widely used in the treatment of primary dysmenorrhoea. The editors have aimed at an accurate, thorough, yet easily under standable review of the status in 1986 of medical knowledge regarding both the physiological importance and the clinical use of prostaglan dins and their inhibitors in obstetrics and gynaecology. I believe this book will be of value for all clinicians concerned with reproductive health. The list of authors guarantees an authoritative and up-to-date review of this active field. SUNE BERGSTROM Karolinska Institutet, Stockholm, Sweden Table Examples of clinical use of natural prostaglandins and some prostaglandin analogues Indications Prostaglandin Route of administration Manufacturer Dilatation of the cervix prior 15-methyl-PGF * Intramuscular Upjohn, USA 2 to vacuum aspiration 16-phenoxy-PGE methyl sulphonylamide Intramuscular Schering AG, West Germany 2 16,16-dimethyl-PGE methyl ester 1 Vaginal ONO, Japan; May & Baker, UK Second trimester abortion Intra -amniotic Upjohn, USA; ONO, Japan PGF 20 Upjohn, USA PGE Vaginal 2 Upjohn, USA 15-methyl-PGF 2.

The commonest cause of blindness in young and middle-aged people in the Western world is diabetes mellitus. Although the mechanism underlying diabetic retinopathy is still not understood, the technology to reduce its progress exists, provided treatment is given at the appropriate time. Doctors caring for patients with diabetes should be familiar with all aspects of diabetic retinopathy as well as the other ocular complications of diabetes. They also need a basic knowledge of the special techniques used in the diagnosis and treatment of diabetic eye disease (fundus fluorescein angiography, retinal photocoagulation, vitrectomy) and to understand how these procedures affect the diabetic patient in terms of limitation of activities and time off work. To ensure the most efficient use of ophthalmic services a clear plan of referral to ophthalmologists is required. These are the concepts on which this guide is based, compiled by an ophthalmologist involved in the treatment of diabetic eye disease and a physician with a special interest in diabetes. In addition to doctors involved in the management of diabetic patients, this guide may be of value to ophthalmic opticians, medical students and nurses as a self-instruction manual. ' 7 1 Examination of the Eye Testing visual acuity Using the ophthalmoscope The normal fundus The abnormal fundus Recording the findings 9 TESTING VISUAL ACUITY Method Test one eye at a time. Test distant visual acuity. Correct the refractive error if the visual acuity is worse than 6/6.

In this book we have expert urologists and gynaecologists on the two sides of the Atlantic working together with a common interest, the inadequate female urethra. What makes this volume so valuable is that it is not restricted to one speciality or one cult, but bravely (and systematically) presents established principles and practice. Not only is the current knowledge of the anatomy and function of the continence mech anisms defined by experts carefully selected by the two authorities in the field, but this infor mation is directly applied to clinical problems for the reader to use in the care of patients. Because the basics are presented first, and followed by the methods of diagnosis, the sec tions describing each form of treatment, whether medical or surgical, are set on rational bases. These are not cookbook directions. This background is especially valuable because the incontinent female usually has a complicated disorder, each case being different, so that the responsible gynaecologists or urologists must apply as much understanding as technique if their efforts are to achieve dryness. The clear descriptions and illustrations in this book, then, act as guides as much as directives. This second edition builds on the success of the first. All of us trying to help these unfortu nate women will do more for them from having this new edition at hand."

Numerous reports demonstrate that the reproductive system could be affected by multiple potential toxicological agents. The volume includes different aspects of the development of new approaches to in vitro testing using sperm cells and systems involved on reproduction in mammals. Comparative analysis of in vivo and in vitro methods has been included to take steps towards the further development of and applications of new systems for germline toxicology.

Endometriosis is one of the most common diseases of women. This book provides a practical, clinical and thorough examination of both the medical and surgical treatment of this disease. A world renowned group of contributors address basic issues, management approaches and selected special topics, emphasizing the latest advanced operative techniques.
Topics include: - minimally invasive and advanced laparoscopic surgical technique in the treatment of endometriosis - treatment of endometriosis of the ovaries, cul-de-sac, gastrointestinal and urinary tracts, and extragenital sites - management of recurrent endometriosis - treatment of infertility and pelvic pain associated with endometriosis - guidelines for medical management and combined medical-surgical management.

Leading workers in the field of human reproduction provide both basic knowledge and useful practical information in this book about the most critical phase in the development of a new human being: the first twelve weeks of life. The period from fertilization and implantation to the end of the first trimester is still insufficiently understood and marks a new frontier. The knowledge necessary for applying our present diagnostic capabilities and for venturing into the problematic areas of fertilization technology and embryonic treatment is made easily available in this comprehensive textbook. The book is divided into two parts. The first presents basic information about physiology, anatomy, in vivo investigations, biochemistry and legal aspects. The second part focuses on pregnancy development, monitoring and the clinical diagnosis and management of disorders in the early stages of life. A full section is devoted to assisted conception and the newest possibilities in fertilizationtechnologies, whereby the ethical aspects are also discussed.

Cytologic diagnosis of cancer has its roots in clinical micro scopy as it was shaped during the first half of the 19th century. In reviewing some of the early writing on this subject, one is amazed at the accuracy of the descriptions and soundness of the observations. Cytology of the urine is no exception: in 1864 Sanders described fragments of cancerous tissue in the urine of a patient with bladder cancer (Edinburgh Med. J. 111, 273). This observation was confirmed by Dickinson in 1869 (Tr. Path. Soc. London, 20, 233). It is a source of special pride to me that in 1892 a New York pathologist, Frank Ferguson, advocated the examination of the urinary sediment as a best means of diagnosing bladder cancer, short of cystoscopy. Papanico laou freely acknowledged these contributions while estab lishing sound scientific bases for continuation and spread of this work. Papanicolaou's work in the area of the urinary tract has not fallen on dead ears. He documented to several urologists who were within his sphere of personal influence, mainly Dr. Victor Marshall, Professor of Urology at Cor nell University Medical School, that urinary tract cytology was a reliable tool in the diagnosis of urothelial carcinoma. Some of us who have attempted to spread the master's word had their share of success within institutions with which we were associated.

Several papers dealing with the clinical relevance of steroid hormone receptors in breast cancer have already been published. However, no publication has overviewed studies currently being conducted in Europe, nor is there a register of the european centers performing receptor assays. It has been our purpose to fill these gaps. A large majority of authors who we contacted kindly agreed to con tribute to our book. Papers were grouped into six main parts according to their contents. The abundance of clinical data relevant to receptor assays led us to add critical summaries to help the reader to form his own opinions on the subject. We would like to thank Drs. R. J. B. King, G. Contesso, L. Santi, and E. Engelsman, who helped us in this regard. We hope that this book will enable the reader to become acquainted with the present state of European steroid hormone receptor studies devoted to breast cancer treatment. We also hope that it will promote cooperation between European oncologists involved in this field of research."

Pathobiology of Human Germ Cell Neoplasia is a state-of-the-art compendium on a very recent branch of tumor biology. It offers an awareness and understanding of germ cell tumors: from the earliest stages to their va- rious differentiations. Original data for this volume was supplied by experts in the fields of pathology, developmental biology, genetics, molecular biology and other related fields. This compilation of knowledge provides information necessary to persons working in clinical and preclinical areas.