Polycystic Ovary Syndrome: A Guide to Clinical Management

267 Pages·2005·6.943 MB·\267

by  Adam H. Balen (Editor), Gerard Conway (Editor), Roy Homburg (Editor), Richard Legro (Editor)

Polycystic Ovary Syndrome
Polycystic Ovary Syndrome
A Guide to Clinical Management
Adam H Balen MB BS MD FRCOG
Professor of Reproductive Medicine and Surgery
Department of Reproductive Medicine
Leeds General Infirmary
Leeds
UK
Gerard S Conway MB BS MD FRCP
Consultant Endocrinologist
Department of Endocrinology
The Middlesex Hospital
London
UK
Roy Homburg MB BS
Professor of Reproductive Medicine
Department of Obstetrics and Gynecology
Reproductive Medicine, Department. Ob/Gyn
Vrije Universiteit Medisch Centrum
1007 MB Amsterdam
The Netherlands
Richard S Legro MD
Professor of Obstetrics and Gynecology
Department of Obstetrics and Gynecology
Penn State College of Medicine
Hershey, PA 17033
USA
LONDON AND NEW YORK
This work was supported by PHS K24 HD01476, the National Cooperative Program in Infertility Research (NCPIR)
U54 HD34449, U10 HD 38992 the Reproductive Medicine Network, and a GCRC grant M01 RR 10732 to
Pennsylvania State University
© 2005 Taylor & Francis, an imprint of the Taylor & Francis Group
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Contents
Foreword vii
Preface v iii
1. Introduction and overview 1
2. Defining the polycystic ovary syndrome 6
3. Epidemiology of polycystic ovary syndrome 26
4. The pathophysiology of polycystic ovary syndrome 36
5. The genetics of polycystic ovary syndrome 66
6. Body image and quality of life with polycystic ovary syndrome 84
7. The effects of obesity and diet 96
8. Long-term sequelae of polycystic ovary syndrome: diabetes and cardiovascular 1 06
disease
9. Long-term sequelae of polycystic ovary syndrome: gynecological cancer 1 49
10. Disorders of the pilosebaceous unit: hirsutism and androgenic alopecia 1 66
11. Acne 1 85
12. Menstrual disturbances 1 92
13. The management of infertility associated with polycystic ovary syndrome 1 96
14. Polycystic ovary syndrome, pregnancy and miscarriage 2 22
15. The management of women in the climacteric and menopause who have a diagnosis 2 29
of polycystic ovary syndrome
Appendix 1: Ultrasound assessment of the polycystic ovary: technical considerations 2 34
Appendix 2: Polycystic ovary syndrome history sheet 2 39
Appendix 3: Support groups and web sites 2 41
Appendix 4: Further reading 2 45
Index 2 46
vi
Foreword
Two advances have transformed our understanding of polycystic ovary syndrome. The first is the
development of pelvic ultrasound as a simple, reliable and non-invasive method of identifying the
polycystic ovary. While there may be debate over precise morphological details, there is general agreement
that ultrasound has transformed our ideas of the prevalence of polycystic ovaries, their association with
other conditions and their etiology. The authors of this book have made significant contributions to
morphological characterization and each has practical experience of the value of high-quality
ultrasonography in both research and in diagnosis and management.
The second important advance is the recognition that transformation of the symptomless woman with
ovaries that are polycystic into a case of polycystic ovary syndrome is commonly mediated through insulin
resistance with compensatory hypersecretion of insulin. The causes of insulin resistance are several; in
practical terms the most widespread is obesity. The current epidemic of obesity, particularly, but not
exclusively, in North American and the UK, means that the number of clinically apparent cases of the
syndrome will increase and begin to approach the number of cases detected only by scan. Again the authors
of this text have made significant contributions to our understanding of the causes and consequences of insulin
resistance in polycystic ovary syndrome.
This book provides its reader with an up-to-date and accessible text about a syndrome which is very
common, has very important consequences on reproductive and general health, and whose prevalence will
almost certainly increase in the coming decades. I strongly commend it to you.
Professor Howard S Jacobs
Emeritus Professor of Reproductive Endocrinology
The Middlesex Hospital and University College Hospital, London
Preface
Polycystic ovary syndrome (PCOS) excites immense interest and debate. PCOS is a condition with different
manifestations and so may present to a number of different medical specialists, from the general practitioner
to gynecologists, infertility specialists, endocrinologists, dermatologists or to those who deal with metabolic
and cardiovascular disease. Not only may the presentation vary but also the nature of the condition in an
individual may change over time. As we have begun to understand more about the origins of PCOS, its
pathophysiology and genetics, we have seen an exponential rise in the number of publications in this
exciting area of medicine.
The management of PCOS is not without controversy—from making the diagnosis to the appropriate
forms of therapy, and there are some differences around the world. We have therefore provided an overview
of PCOS with a synthesis of our current understanding of its diagnosis and management. We hope that we
have offered a pragmatic approach to treatment from the viewpoint of four busy practitioners and
researchers in the fields of endocrinology, gynecology and reproductive medicine—and also from a
transglobal perspective!
Adam Balen
Gerry Conway
Roy Homburg
Rick Legro
April 2005
Chapter 1
Introduction and overview
Many believe polycystic ovary syndrome (PCOS) to be a condition of our time. Certainly PCOS is the most
common endocrine disturbance to affect women and it appears that its prevalence is on the increase. There
is considerable heterogeneity of symptoms and signs among women with PCOS, and for an individual these
may change over time. The extreme end of the spectrum, once known as the Stein-Leventhal syndrome,
encompasses the combination of hyperandrogenism (hirsutism, acne, alopecia and elevated serum
testosterone concentrations), severe menstrual disturbance (amenorrhea or oligomenorrhea) and obesity. We
now appreciate that polycystic ovaries may exist without clinical signs of the syndrome. PCOS is familial,
and various aspects of the syndrome may be differentially inherited. There are a number of interlinking
factors that affect expression of PCOS. A gain in weight is associated with a worsening of symptoms while
weight loss will ameliorate the endocrine and metabolic profile and symptomatology. Normal ovarian
function relies upon the selection of a follicle, which responds to an appropriate signal (follicle stimulating
hormone) in order to grow, become ‘dominant’ and ovulate. This mechanism is disturbed in women with
PCOS, resulting in multiple small cysts, most of which contain potentially viable oocytes but within
dysfunctional follicles.
In recent times there has been a significant change in lifestyle in many parts of the world, with most
people experiencing a more sedentary existence combined with an abundance of food. This has resulted in
the modern epidemic of obesity and consequent hyperinsulinemia—a situation which in women may
precipitate expression of PCOS, while in men presentation is often with cardiovascular disease and type 2
diabetes in later life. Elevated serum concentrations of insulin are more common in both lean and obese
women with PCOS than in weight-matched controls. Indeed it is hyperinsulinemia that appears to be the
key to the pathogenesis of the syndrome, as insulin stimulates androgen secretion by the ovarian stroma and
appears to affect the normal development of ovarian follicles, both by the adverse effects of androgens on
follicular growth, and possibly also by suppressing apoptosis and permitting the survival of follicles
otherwise destined to disappear.
Women with polycystic ovaries may experience a range of the clinical and biochemical features that
define PCOS. These features include menstrual cycle disturbances, obesity, hirsutism, acne, and
abnormalities of biochemical profiles including elevated serum concentrations of luteinizing hormone (LH),
testosterone, androstenedione, and insulin. Presentation of the syndrome is so varied that one, all, or any
combination of the above features may be present in association with an ultrasound picture of polycystic
ovaries.
In this book we aim to provide a practical appraisal of our current understanding of PCOS. We shall
discuss in detail the diagnosis of PCOS, with reference to ultrasonography and endocrine assessment
(Chapter 2). We shall expand upon the assessment of hyperinsulinemia and its short-term and long-term health
consequences (Chapters 4, 6, 7 and 8). Women who are obese, and also many slim women with PCOS, will