Current Management of Polycystic Ovary Syndrome 1st
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Since 1973 the Royal College of Obstetricians and
Gynaecologists has regularly convened Study Groups to
address important growth areas within obstetrics and
gynaecology. An international group of eminent clinicians
and scientists from various disciplines is invited to present
the results of recent research and to take part in in-depth
discussions. The resulting volume, containing enhanced
versions of the papers presented, is published within a few
months of the meeting and provides a summary of the
subject that is both authoritative and up to date.
SOME PREVIOUS STUDY GROUP PUBLICATIONS AVAILABLE
Menopause and Hormone Multiple Pregnancy
Replacement Edited by Mark Kilby, Phil Baker,
Edited by Hilary Critchley, Ailsa Gebbie Hilary Critchley and David Field
and Valerie Beral
Heart Disease and Pregnancy
Disorders of the Menstrual Cycle Edited by Philip J Steer, Michael A
Edited by PMS O’Brien, IT Cameron Gatzoulis and Philip Baker
and AB MacLean
Teenage Pregnancy and
Infection and Pregnancy Reproductive Health
Edited by AB MacLean, L Regan and Edited by Philip Baker, Kate Guthrie,
D Carrington Cindy Hutchinson, Roslyn Kane and
Kaye Wellings
Pain in Obstetrics and Gynaecology
Edited by A MacLean, R Stones and Obesity and Reproductive Health
S Thornton Edited by Philip Baker, Adam Balen,
Lucilla Poston and Naveed Sattar
Incontinence in Women
Edited by AB MacLean and L Cardozo Renal Disease in Pregnancy
Edited by John M Davison, Catherine
Maternal Morbidity and Mortality Nelson-Piercy, Sean Kehoe and Philip
Edited by AB MacLean and J Neilson Baker
Lower Genital Tract Neoplasia Cancer and Reproductive Health
Edited by Allan B MacLean, Albert Edited by Sean Kehoe, Eric Jauniaux,
Singer and Hilary Critchley Pierre Martin-Hirsch and Philip
Pre-eclampsia Savage
Edited by Hilary Critchley, Allan Reproductive Ageing
MacLean, Lucilla Poston and James Walker Edited by Susan Bewley, William
Preterm Birth Ledger and Dimitrios Nikolaou
Edited by Hilary Critchley, Phillip Reproductive Genetics
Bennett and Steven Thornton Edited by Sean Kehoe, Lyn Chitty and
Implantation and Early Tessa Homfray
Development Maternal and Infant Deaths:
Edited by Hilary Critchley, Iain Chasing Millennium Development
Cameron and Stephen Smith Goals 4 and 5
Contraception and Contraceptive Use Edited by Sean Kehoe, James P Neilson
Edited by Anna Glasier, Kaye Wellings and Jane E Norman
and Hilary Critchley
Current management of
polycystic ovary syndrome
Edited by
Adam Balen, Stephen Franks, Roy Homburg
and Sean Kehoe
Adam Balen MD FRCOG
Professor of Reproductive Medicine and Surgery, Leeds Centre for Reproductive Medicine, Seacroft Hospital,
York Road, Leeds LS14 6UH
Stephen Franks MD FmedSci
Professor of Reproductive Endocrinology, Institute of Reproductive and Developmental Biology, Imperial
College London, Hammersmith Hospital, London W12 0NN
Roy Homburg MB BS FRCOG
Professor of Reproductive Medicine, Barzilai Medical Centre, Ashkelon, Israel, and Head of Research,
Homerton Fertility Centre, Homerton University Hospital, London
Sean Kehoe MD FRCOG
Convenor of Study Groups, Lead Consultant in Gynaecological Oncology, Oxford Gynaecological Cancer
Centre, John Radcliffe Hospital, Headington, Oxford OX3 9DU
Published by the RCOG Press at the Royal College of Obstetricians and Gynaecologists, 27 Sussex Place,
Regent’s Park, London NW1 4RG
www.rcog.org.uk
Registered charity no. 213280
First published 2010
© 2010 The Royal College of Obstetricians and Gynaecologists
No part of this publication may be reproduced, stored or transmitted in any form or by any means, without the
prior written permission of the publisher or, in the case of reprographic reproduction, in accordance with the
terms of licences issued by the Copyright Licensing Agency in the UK [www.cla.co.uk]. Enquiries concerning
reproduction outside the terms stated here should be sent to the publisher at the UK address printed on this page.
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific
statement, that such names are exempt from the relevant laws and regulations and therefore for general use.
While every effort has been made to ensure the accuracy of the information contained within this publication,
the publisher can give no guarantee for information about drug dosage and application thereof contained in this
book. In every individual case the respective user must check current indications and accuracy by consulting other
pharmaceutical literature and following the guidelines laid down by the manufacturers of specific products and the
relevant authorities in the country in which they are practising.
The rights of Adam Balen, Stephen Franks, Roy Homburg and Sean Kehoe to be identified as Editors of this work
has been asserted by them in accordance with the Copyright, Designs and Patents Act 1988.
ISBN 978-1-906985-41-7
A machine-readable catalogue record for this publication can be obtained from the British Library
[www.bl.uk/catalogue/listings.html]
Cover image: Magnetic resonance imaging of polycystic ovaries © GustoImages/Science Photo Library
RCOG Editor: Andrew Welsh
Original design by Karl Harrington, FiSH Books, London
Typesetting by Andrew Welsh
Index by Jan Ross (Merrall-Ross International Ltd)
Printed by Henry Ling Ltd, The Dorset Press, Dorchester DT1 1HD
Contents
Participants vii
Declarations of personal interest ix
Preface xi
1 Overview and definitions of polycystic ovary syndrome and the
polycystic ovary
Adam Balen 1
2 Genetics and pathogenesis of polycystic ovary syndrome
Stephen Franks 13
3 Ethnic variations in the expression of polycystic ovary syndrome
Chandrika N Wijeyaratne, Vindya Kumarapeli, Ruwanthi de A Seneviratne,
Charles N Antonypillai, S Rohini de A Seneviratne, GJ Chaminda
Garusinghe, S Chandrika Yapa and Adam Balen 25
4 Quality of life for women with polycystic ovary syndrome
Georgina Jones 47
5 Insulin resistance, the metabolic syndrome and polycystic ovary
syndrome
Gerard Conway 63
6 Management of polycystic ovary syndrome through puberty and
adolescence
Rachel Williams and David Dunger 71
7 Long-term health risks of polycystic ovary syndrome
Didier Dewailly 85
8 Approaches to lifestyle management in polycystic ovary syndrome
Renato Pasquali and Alessandra Gambineri 93
9 Management of obesity in polycystic ovary syndrome, including
anti-obesity drugs and bariatric surgery
Alexander D Miras and Carel W le Roux 105
10 Definition of hyperandrogenism
Julian H Barth, Helen P Field, Ephia Yasmin and Adam Balen 117
11 Treatment of hyperandrogenism in polycystic ovary syndrome
Alison M Layton 125
12 Choices in the treatment of anovulatory polycystic ovary syndrome
Roy Homburg 143
vi | CONTENTS
13 Predictors of ovarian response to ovarian stimulation: progress
towards individualised treatment in ovulation induction
Bart CJM Fauser 153
14 Surgical management of anovulatory infertility in polycystic ovary
syndrome
Adam Balen 165
15 The role of insulin-sensitising drugs in the treatment of polycystic
ovary syndrome
Richard S Legro 173
16 The role of in vitro maturation of oocytes for anovulatory polycystic
ovary syndrome
Tim Child 185
17 Acupuncture and/or herbal therapy as an alternative or complement
for relief of polycystic ovary syndrome-related symptoms
Elisabet Stener-Victorin 195
18 Consensus views arising from the 59th Study Group:
Current Management of Polycystic Ovary Syndrome 213
Index 217
Participants
Adam Balen
Professor of Reproductive Medicine and Surgery, Leeds Centre for Reproductive
Medicine, Seacroft Hospital, York Road, Leeds LS14 6UH, UK.
Julian H Barth
Consultant in Chemical Pathology and Metabolic Medicine, Clinical Biochemistry,
Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK.
Tim Child
Consultant Gynaecologist and Sub-specialist in Reproductive Medicine and Surgery,
Oxford Fertility Unit and the University of Oxford, Institute of Reproductive Sciences,
Oxford Business Park North, Oxford OX4 2HW, UK.
Gerard Conway
Consultant Endocrinologist, Department of Endocrinology, University College London
Hospital, London NW1 2PQ, UK.
Didier Dewailly
Head of Pole de Gynécologie, Lille University Hospital, Hôpital Jeanne de Flandre,
Avenue Eugène Avinée, Lille 59037, France.
David Dunger
Professor of Paediatrics, Department of Paediatrics, Box 116 Level 8, University of
Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK.
Bart JCM Fauser
Chair of Division of Woman & Baby, University Medical Centre Utrecht (UMC
Utrecht), Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Stephen Franks
Professor of Reproductive Endocrinology, Institute of Reproductive and Developmental
Biology, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
Roy Homburg
Professor of Reproductive Medicine, Barzilai Medical Centre, Ashkelon, Israel, and Head
of Research, Homerton Fertility Centre, Homerton University Hospital, London, UK.
Georgina Jones
Senior Lecturer (Non-clinical), Health Services Research Section, School of Health and
Related Research, University of Sheffield, Regent Court, 30 Regent Street, Sheffield
S1 4DA, UK.
Sean Kehoe
Convenor of Study Groups, Lead Consultant in Gynaecological Oncology, Oxford
Gynaecological Cancer Centre, John Radcliffe Hospital, Headington, Oxford
OX3 9DU, UK.
viii | PARTICIPANTS
Alison M Layton
Consultant Dermatologist, Department of Dermatology, Harrogate and District
Foundation Trust, Lancaster Park Road, Harrogate HG2 7SX, UK.
Carel W le Roux
Reader in Metabolic Medicine, Imperial Weight Centre, 9th Floor, Imperial College
London, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK.
Richard S Legro
Professor of Obstetrics and Gynecology, Milton S. Hershey Medical Center, Penn State
College of Medicine, 500 University Drive, H103, Hershey, PA 17033, USA.
Renato Pasquali
Head of Division of Endocrinology, Policlinico S. Orsola-Malpighi, Via Massarenti 9,
Bologna 40138, Italy.
Elisabet Stener-Victorin
Associate Professor, Institute of Neuroscience and Physiology, Department of
Physiology/Endocrinology, Box 434, Göteborg SE–405 30, Sweden.
Chandrika N Wijeyaratne
Professor in Reproductive Medicine, Department of Obstetrics and Gynaecology,
Faculty of Medicine, University of Colombo, PO Box 271, Kynsey Road, Colombo,
Sri Lanka.
Additional contributors
Charles N Antonypillai
Senior Registrar in Endocrinology, National Hospital of Sri Lanka, Colombo 10, Sri Lanka.
Helen P Field
Clinical Scientist, Clinical Biochemistry, Leeds General Infirmary, Great George Street,
Leeds LS1 3EX, UK.
Alessandra Gambineri
Clinical Lecturer, Division of Endocrinology, Policlinico S. Orsola-Malpighi, Via
Massarenti 9, Bologna 40138, Italy.
GJ Chaminda Garusinghe
Senior Registrar in Endocrinology, Diabetes and Endocrine Unit, National Hospital of
Sri Lanka, Colombo 10, Sri Lanka.
Vindya Kumarapeli
Consultant Community Physician, Non-Communicable Diseases Unit, Ministry of
Healthcare and Nutrition, No 385, Baddegama Wimalawansa Mawatha, Colombo,
Sri Lanka.
Alexander D Miras
Specialist Registrar in Endocrinology and Diabetes, St Helier Hospital, Wrythe Lane,
Carshalton SM5 1AA, UK.
Ruwanthi de A Seneviratne
House Officer, Castle Street Hospital for Women, Colombo 8, Sri Lanka.
S Rohini de A Seneviratne
Professor in Community Medicine, Department of Community Medicine, Faculty of
Medicine, University of Colombo, PO Box 271, Kynsey Road, Colombo, Sri Lanka.
PARTICIPANTS | ix
Rachel Williams
Clinical Lecturer in Paediatric Endocrinology and Diabetes, Department of Paediatrics,
Box 116, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge
CB2 0QQ, UK.
S Chandrika Yapa
Visiting Obstetrician and Gynaecologist, Base Hospital, Dehiattakandiya, Sri Lanka.
Ephia Yasmin
Specialist Registrar, Obstetrics and Gynaecology, Bradford Royal Infirmary, Bradford
LS6 3DD, UK.
DECLARATIONS OF PERSONAL INTEREST
All contributors to the Study Group were invited to make a specific Declaration of Interest in relation
to the subject of the Study Group. This was undertaken and all contributors complied with this
request. Adam Balen has received sponsorship from Ferring Pharmaceuticals and Organon/Schering
Plough. His department has received financial support from Ferring, Organon/Schering Plough and
Merck Serono. He is a consultant to or member of Infertility Network UK (INUK), PCOS UK
and Verity. He has received feed for editorial work on BJOG. Tim Child has received sponsorship
to attend meetings plus honoraria from Merck-Serono, Organon and Ferring. His department has
unrestricted educational grants from Merck-Serono and Ferring. Gerard Conway is a consultant
to the Daisy Network (ovarian failure), the Turner Syndrome Support Society and the Androgen
Insensitivity Syndrome Support Group. Didier Dewailly’s department has received research grants from
Merck Serono, Schering-Plough, Ferring and Genevrier. He is the Chief Editor of Medecine de la
Reproduction, Gynécologie, Endocrinologie at John Libbey, Paris. Bart Fauser’s department has received
research grants from commercial organisations related to obstetrics and gynaecology. He has received
fees and grant support from the following companies: Andromed, Ardana, Ferring, Genovum, Merck
Serono, Organon, Pantharel Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth.
Stephen Franks is a medical adviser to Verity (a PCOS patient support group), to its health professionals
arm PSOC UK, and to Infertility Network UK (all honorary). Georgina Jones is a member of the
Executive Board of PCOS UK. Alison Layton is a member of the executive council of PCOS UK;
this is an unpaid position. She has received some travel expenses for attendance at meetings via the
organisation. Richard Legro is an Associate Editor on the journals Fertility and Sterility and Human
Reproduction. He is on the Program Committee for the Annual Meeting of the American Society for
Reproductive Medicine. Chandrika Wijeyaratne is a member of the Women’s Health Committee, Sri
Lanka Medical Association.
Preface
Polycystic ovary syndrome (PCOS) is a heterogeneous collection of signs and symptoms
that, gathered together, form a spectrum of a disorder with a mild presentation in
some, whereas in others there may be a severe disturbance of reproductive, endocrine
and metabolic function. The definition of the syndrome has been much debated, with
key features including menstrual cycle disturbance, hyperandrogenism and obesity.
The pathophysiology of PCOS appears to be multifactorial and polygenic and is still
being actively researched. PCOS is the most common endocrine disturbance and
affects 10–15% of women in the UK. The clinical findings of hirsutism, acne, alopecia
and obesity do not always correlate with the serum biochemistry, which itself may
be difficult to assess. There is no doubt that PCOS has a significant effect on quality
of life and psychological morbidity and, as many specialists may be involved in its
management, a multidisciplinary approach is required.
The 59th RCOG Study Group brought together a wide range of experts who
treat women with PCOS and the clinical conditions related to the syndrome. The
actual definition, the accuracy of diagnostic investigations, the particular challenges in
adolescent diagnosis and management, the relationship with ethnicity and issues relating
to the clinical care of women with PCOS are all covered in this comprehensive book.
Importantly, there is a critical evaluation of current approaches to therapy, a discussion
on the potential individualisation of therapy (regarding the identification of those who
will – or will not – respond to fertility interventions) and a chapter on the role of
alternative therapies, which are employed in managing some aspects of this syndrome.
For those caring for women with PCOS, be it in primary or secondary care, this
book should prove both interesting and a valuable tool in increasing the knowledge
base and facilitating the decision-making process.
Adam Balen
Stephen Franks
Roy Homburg
Sean Kehoe (Convenor of RCOG Study Groups)
13
1
Chapter 1
Overview and definitions of polycystic
ovary syndrome and the polycystic ovary
Adam Balen
Introduction
Polycystic ovary syndrome (PCOS) is a heterogeneous collection of signs and
symptoms that, gathered together, form a spectrum of a disorder with a mild
presentation in some but a severe disturbance of reproductive, endocrine and metabolic
function in others. The pathophysiology of PCOS appears to be multifactorial and
polygenic. The definition of the syndrome has been much debated, with key features
including menstrual cycle disturbance, hyperandrogenism and obesity (see Box 1.1).
There are many extra-ovarian aspects to the pathophysiology of PCOS but ovarian
dysfunction is central.
The joint European Society of Human Reproduction and Embryology (ESHRE)/
American Society for Reproductive Medicine (ASRM) consensus meeting in 2003
agreed a refined definition of PCOS, namely the presence of two of the following
three criteria:1 (1) oligo-ovulation and/or anovulation, (2) hyperandrogenism (clinical
and/or biochemical), (3) polycystic ovaries; with the exclusion of other causes of
menstrual cycle disturbance or androgen excess (see Table 1.1).
The morphology of the polycystic ovary has been defined as an ovary with 12 or
more follicles measuring 2–9 mm in diameter and/or an increased ovarian volume
(more than 10 cm³).2
There is considerable heterogeneity of symptoms and signs among women with
PCOS and, for an individual, these may change over time.3 PCOS appears to be familial
and various aspects of the syndrome may be differentially inherited.4 Polycystic ovaries
can even exist without clinical signs of the syndrome, which may then become expressed
over time. There are a number of interlinking factors that may affect expression of
PCOS. For example, a gain in weight is associated with a worsening of symptoms, while
weight loss may ameliorate the endocrine and metabolic profile and symptomatology.5
Various factors influence ovarian function, and fertility is adversely affected by an
individual being overweight or having elevated serum concentrations of luteinising
hormone (LH). Strategies to induce ovulation include weight loss, oral anti-estrogens
(principally clomifene citrate), parenteral gonadotrophin therapy and laparoscopic
ovarian surgery.
The features of obesity, hyperinsulinaemia and hyperandrogenaemia that are
commonly seen in PCOS are also known to be factors that confer an increased risk
© Adam Balen. Volume compilation © RCOG
2 | ADAM BALEN
Box 1.1 Signs and symptoms of polycystic ovary syndrome
Symptoms:
• hyperandrogenism (acne, hirsutism, alopecia – not virilisation)
• menstrual disturbance
• infertility
• obesity
• sometimes: asymptomatic, with polycystic ovaries on ultrasound scan
Serum endocrinology:
• increasing fasting insulin (not routinely measured; insulin resistance or impaired glucose tolerance
assessed by oral glucose tolerance test)
• increasing androgens (testosterone and androstenedione)
• increasing luteinising hormone, usually normal follicle-stimulating hormone
• decreasing sex hormone-binding globulin, results in elevated ‘free androgen index’
• increasing estradiol and estrone (neither measured routinely as there is a very wide range of values)
• increasing prolactin
Possible late sequelae:
• diabetes
• dyslipidaemia
• hypertension
• cardiovascular disease
• endometrial carcinoma
• breast cancer (although data are conflicting)
of cardiovascular disease and type 2 diabetes (see Table 1.2).6 There are studies which
indicate that women with PCOS have an increased risk for these diseases that pose
long-term risks for health, and this evidence has prompted debate as to the need for
screening women for polycystic ovaries.
Elevated serum concentrations of insulin are more common in both lean and
obese women with PCOS than in weight-matched women without the syndrome.
Indeed, it is hyperinsulinaemia that seems to be key to the pathogenesis for many
women with PCOS 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. The realisation
of an association between hyperinsulinaemia and PCOS has resulted in the use of
insulin-sensitising agents such as metformin, although they have not provided the
benefit that was originally hoped.7
What is polycystic ovary syndrome?
Polycystic ovaries are commonly detected by ultrasound or other forms of pelvic
imaging, with estimates of the prevalence in the general population being of the
order of 20–33%.8,9 However, not all women with polycystic ovaries demonstrate the
clinical and biochemical features that define the syndrome. While it is now clear that
ultrasound provides an excellent technique for the detection of polycystic ovarian
morphology, identification of polycystic ovaries by ultrasound does not automatically
confer a diagnosis of PCOS.
OVERVIEW AND DEFINITIONS OF POLYCYSTIC OVARY SYNDROME AND THE POLYCYSTIC OVARY | 3
Table 1.1 Investigations for polycystic ovary syndrome
Test Normal range (may Additional points
vary with local
laboratory assays)
Pelvic ultrasound To assess ovarian morphology and endometrial
thickness; a transabdominal scan is usually
adequate in women who are not sexually active
(depends on body habitus)
Testosterone (T) 0.5–3.5 nmol/litre A total T measurement is adequate for general
screening; it is unnecessary to measure other
androgens unless the total testosterone is more
than 5 nmol/litre, in which case referral is indicated
Sex hormone-binding globulin 16–119 nmol/litre Insulin suppresses SHBG, resulting in a high
(SHBG) FAI in the presence of a normal total T; the
Free androgen index (FAI): <5 measurement of SHBG is not required in routine
T × 100 / SHBG practice and will not affect management
Estradiol Measurement is generally unhelpful to make
diagnosis; estrogenisation may be confirmed by
endometrial assessment
Luteinising hormone (LH) 2–10 IU/litre FSH and LH are best measured during days 1–3
Follicle-stimulating hormone 2–8 IU/litre of a menstrual bleed; if oligomenorrhoeic or
(FSH) amenorrhoeic, then random samples are taken
Antimüllerian hormone (AMH) Assays differ and still AMH is a good representative of the number of
being evaluated antral follicles47
Prolactin < 500 mU/litre Measures if the woman is oligomenorrhoeic or
Thyroid-stimulating hormone 0.5–5 IU/litre amenorrhoeic
(TSH) for thyroid function
Fasting insulin < 30 mU/litre Not routinely measured; insulin resistance can be
assessed by an oral glucose tolerance test
Table 1.2 Definitions of glucose tolerance
Test
Fasting glucose (mmol/litre) 2-hour glucose (mmol/litre)
Diabetes ≥ 7.0 ≥ 11.1
Impaired glucose tolerance (IGT) < 7.0 ≥ 7.8 and < 11.1
Impaired fasting glycaemia ≥ 6.1 and < 7.0 < 7.8
A 75 g oral glucose tolerance test should be performed in women with PCOS and body mass index (BMI) > 30 kg/m²; it has been
suggested that South Asian women should have an assessment of glucose tolerance if their BMI is greater than 25 kg/m² because of
the greater risk of insulin resistance at a lower BMI than seen in the white population
Despite the ESHRE/ASRM consensus meeting and definitions, controversy still
exists in some quarters over a precise definition of the syndrome and whether or not
the diagnosis should require confirmation of polycystic ovarian morphology. The
original case series of Stein and Leventhal10 in 1935 described seven women who had
enlarged polycystic ovaries and amenorrhoea. Over the years, it was appreciated that
4 | ADAM BALEN
the cardinal symptoms are chronic anovulation (oligomenorrhoea or amenorrhoea)
and hyperandrogenism (usually hirsutism and acne, and sometimes alopecia). The
1990 National Institutes of Health (NIH) conference on PCOS recommended that
the diagnostic criteria should include evidence of hyperandrogenism and ovulatory
dysfunction, in the absence of non-classic adrenal hyperplasia, and that evidence of
polycystic ovarian morphology was not essential (in a paper that is in book form only and
no longer readily available).11 In Europe and Australasia, ovarian imaging by ultrasound
became an important component in the diagnosis, largely because ovarian morphology
was part of the original disease description. Despite a degree of concordance between
the NIH definition and the addition of ovarian imaging, it became necessary to try
to gain transatlantic harmony with a new consensus held under the auspices of the
ESHRE and the ASRM, which resulted in the ‘Rotterdam criteria’.1
The generally accepted view in Europe and much of the world is that a spectrum
exists that ranges from women with polycystic ovarian morphology and no overt
abnormality at one end to those with polycystic ovaries associated with severe clinical
and biochemical disorders at the other end.
A new group, the Androgen Excess and PCOS Society (AEPS), has more recently
proposed that PCOS should be further redefined.12 The latest suggestion is that
two criteria are required: hyperandrogenism (clinical hirsutism and/or biochemical
hyperandrogenaemia) and ovarian dysfunction (oligo-ovulation or anovulation and/or
polycystic ovaries) after exclusion of other causes of androgen excess or related disorders.
The arguments for a ‘tighter definition’ include the potential for better prospects
for providing genetic and proteomic causes of PCOS and concerns about avoiding
overdiagnosis because of ‘potential lifelong and insurability implications’, yet the
latest consensus ‘recognises that there may be a number of women who have
features suggestive of PCOS but who do not fulfil the criteria’.12 Furthermore, there
appears not to have been complete consensus, as some members of the AEPS group
‘disagreed with the strong emphasis placed on hyperandrogenism’, particularly as
there is a high degree of inaccuracy in both the clinical and biochemical assessment
of androgen excess.12,13
The latest proposed definition also raises concerns about allowing the presence of
polycystic ovaries as a separate defining feature. We recognise that polycystic ovaries
are detected in 19–33% of women in the general population, of whom approximately
80% have symptoms of PCOS, albeit often mild.9 The biochemical features of the
syndrome, namely elevated serum concentrations of testosterone, androstenedione,
LH and insulin, may vary between individuals and change with time. The ovary is
the source of excess androgens, which result from dysregulation of steroidogenesis
combined with an excess of external promoters, principally LH and insulin.
Many consider that insulin resistance and hyperinsulinaemia are at the heart
of the pathophysiology of PCOS but these features are clearly not essential in the
development of the syndrome, particularly in lean women. Nevertheless, even if insulin
resistance/hyperinsulinaemia is not the initiating cause, it is certainly an amplifier of
hyperandrogenism in those who gain weight. The common association of PCOS and
obesity has a synergistic deleterious impact on glucose homeostasis and can worsen
both hyperandrogenism and anovulation. Hyperinsulinaemia also decreases the
synthesis of sex hormone-binding globulin (SHBG) by the liver, leading to an increase
in circulating free testosterone.
There are likely to be many routes to the development of PCOS, including genetic
predisposition, environmental factors and disturbances of a number of endocrine
pathways. There also appear to be significant racial differences in the expression of
