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  • Cited by 8
Publisher:
Cambridge University Press
Online publication date:
July 2014
Print publication year:
2010
Online ISBN:
9781107478343

Book description

Polycystic ovary syndrome (PCOS) is the most common endocrine disturbance, affecting 10-15% of women in the UK. The definition of PCOS has been much debated, while its pathophysiology appears to be multifactorial and is still being actively researched. There is no doubt that PCOS has a significant effect on quality of life and psychological morbidity and, as many specialists are involved in its management, a multidisciplinary approach is required. The 59th RCOG Study Group brought together a range of experts who treat women with PCOS. This book presents the findings of the Study Group, including:A definition of PCOSThe accuracy of diagnostic interventionsThe particular challenges of adolescent diagnosis and managementThe correlation to ethnicityCurrent approaches to therapyThe potential individualisation of therapy The role of the alternative therapies used to manage some aspects of PCOS.

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Contents

  • 1 - Overview and definitions of polycystic ovary syndrome and the polycystic ovary
    pp 1-12
  • View abstract

    Summary

    Polycystic ovary syndrome (PCOS) is a syndrome with varied manifestations both within different populations and between different populations. With recent increases in the understanding of the pathophysiology of PCOS and the recognition of the importance of ultrasound in defining the morphology of the polycystic ovary, the syndrome has now been defined as the presence of two of the following three criteria: oligo-ovulation and/or anovulation, hyperandrogenism (clinical and/or biochemical), polycystic ovaries; with the exclusion of other aetiologies of menstrual disturbance and androgen excess. 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. To establish the diagnosis of PCOS it is important to exclude other disorders with a similar clinical presentation, such as congenital adrenal hyperplasia, Cushing syndrome, and androgen-secreting tumours.
  • 2 - Genetics and pathogenesis of polycystic ovary syndrome
    pp 13-24
  • View abstract

    Summary

    Polycystic ovary syndrome (PCOS) usually presents during adolescence and is a heterogeneous syndrome that is classically characterised by features of anovulation together with symptoms of androgen excess. Women with PCOS become disproportionately more insulin resistant with increasing body mass index (BMI) than those without PCOS. The presentation of PCOS in adolescence suggests that there is an underlying predisposition to the typical ovarian abnormalities that has its origins well before the onset of puberty. There is now compelling evidence those genetic factors plays a major part in the aetiology of PCOS. There is also evidence for heritability of endocrine and metabolic features of PCOS. Overweight and obese girls with PCOS have at least a three-fold increase in risk of developing type 2 diabetes in later life and, alarmingly, impaired glucose tolerance and even overt diabetes have been reported in teenagers with PCOS.
  • 3 - Ethnic variations in the expression of polycystic ovary syndrome
    pp 25-46
  • View abstract

    Summary

    This chapter examines the evidence for ethnic variation in the polycystic ovary syndrome (PCOS) phenotype and explores the possible basis of this phenomenon. Evaluating ethnic variations in the expression of PCOS requires systematic review of the strength of the evidence, preferably from population-based data or from large samples in the clinic setting. The chapter evaluates reports of differing expression of hyperandrogenism, obesity, insulin resistance and metabolic manifestations. The reports discussed mainly comprise comparative and case-control studies providing level III evidence. The available data show variations in the PCOS phenotype among Caribbean Hispanic, Mexican American, Japanese, indigenous Chinese/Taiwanese, migrant versus indigenous South Asian, Thai, Malay, southern European, indigenous Canadian and migrant Arab women. Reports on the degree of hyperandrogenism in PCOS in women from different regions of the world are varied, as they are based on various diagnostic criteria, clinical settings, age and ethnic origins.
  • 4 - Quality of life for women with polycystic ovary syndrome
    pp 47-62
  • View abstract

    Summary

    This chapter provides a general overview of health-related quality of life (HRQoL) measurement and reviews the HRQoL literature in relation to polycystic ovary syndrome (PCOS) and its associated symptoms, including mental health, fertility and obesity. HRQoL measurement has an important role in measuring the impact of chronic disease and in evaluative research as a measure of outcome, particularly in clinical trials where health status tools can assist in clinical decision making regarding treatment choice and policy decisions. Studies that have compared the HRQoL of women with PCOS with that of other gynaecological populations have also reported worse HRQoL scores. The symptoms typically associated with PCOS, including hirsutism and infertility, have been shown to lead to a significant reduction in quality of life. Complementary studies and qualitative studies exploring HRQoL in adolescents with PCOS would provide beneficial contributions to the existing literature.
  • 5 - Insulin resistance, the metabolic syndrome and polycystic ovary syndrome
    pp 63-70
  • View abstract

    Summary

    Various pathogenic mechanisms have been identified in the insulin signalling pathway to explain insulin resistance in women with polycystic ovary syndrome (PCOS). Most of the evidence supports hyperinsulinaemia as the primary factor, especially the experiments in which decreasing the hyperandrogenaemia by bilateral oophorectomy or the administration of a gonadotrophin-releasing hormone (GnRH) agonist did not result in improved insulin sensitivity in women with PCOS. Recognition of the risk of type 2 diabetes in young women with PCOS provides an opportunity for early education for diabetes prevention with lifestyle measures. As part of the metabolic syndrome, women with PCOS have an array of adverse cardiovascular risk markers, including abnormal lipid profiles, increased carotid artery intima-media thickness, endothelial dysfunction and carotid artery calcification. Obesity and insulin resistance are also risk factors for non-alcoholic fatty liver disease (non-alcoholic steatohepatitis).
  • 6 - Management of polycystic ovary syndrome through puberty and adolescence
    pp 71-84
  • View abstract

    Summary

    This chapter discusses the issues around the diagnosis and management of polycystic ovary syndrome (PCOS) through puberty and adolescence. The diagnosis of PCOS may be made incidentally in girls undergoing investigation for severe obesity or prospectively in young women being investigated for irregular periods, acne or hirsutism. There may be a family history of PCOS or infertility and, although the classic biochemical features and ovarian ultrasound appearances may be not being evident immediately, diagnosis unravels over time. Symptomatic treatment focused on the restoration of regular menses is the most common starting point and the oral contraceptive pills (OCPs) are the mainstay of pharmacological therapy for PCOS for many decades. The effects of metformin administration in adolescent girls with PCOS have been assessed in both obese and non-obese populations. Irregular periods are treated with OCPs with or without the inclusion of cyproterone acetate depending on the extent of hirsutism and acne.
  • 7 - Long-term health risks of polycystic ovary syndrome
    pp 85-92
  • View abstract

    Summary

    Polycystic ovary syndrome (PCOS) is most often diagnosed in adolescents and young women who present with symptoms of hyperandrogenism and/or disorders of ovulation. The individuals and their doctors must be aware that PCOS carries various long-term health risks owing to its intrinsic hormonal derangement and also to the associated metabolic disorders such as obesity, hyperinsulinism and insulin resistance, and hyperlipidaemia. Many abnormalities found in young women with PCOS suggest that they are at risk for cardiovascular disease. The more commonly used parameters are the traditional measures of family history, body mass index (BMI), waist circumference, blood pressure and standard biochemical indices including fasting glycaemia, total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. Obesity has a great impact on the prevalence of type 2 diabetes but the risk persists in non-obese women with PCOS. The risk factors for endometrial carcinoma include obesity, hypertension, type 2 diabetes, unopposed estrogen and nulliparity.
  • 8 - Approaches to lifestyle management in polycystic ovary syndrome
    pp 93-104
  • View abstract

    Summary

    Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder that is primarily characterised by a hyperandrogenic state and ovulatory disturbances and which is associated with multiple metabolic abnormalities and a high prevalence of excess weight or obesity, particularly of the abdominal phenotype. This chapter reviews the role of obesity in the pathophysiology of PCOS and summarizes all major aspects of lifestyle intervention. The prevalence of obesity in PCOS appears to be much greater than that expected in the general population, ranging from 30% to 70% depending on ethnicity, geographical areas, environmental factors, genetic susceptibility and other still unknown factors. Infertility is associated with earlier onset obesity, and menstrual disorders are frequent with the onset of excess weight during puberty. Guidelines for the treatment of obesity can be applied, probably without any substantial specific changes, to the treatment of overweight and obese women with PCOS.
  • 9 - Management of obesity in polycystic ovary syndrome, including anti-obesity drugs and bariatric surgery
    pp 105-116
  • View abstract

    Summary

    This chapter describes the treatment of obesity in the context of polycystic ovary syndrome (PCOS) with anti-obesity medication and obesity (bariatric) surgery. Diet and increased levels of physical activity are crucial first steps in the management of obesity but are not sustainable in the long term. The use of anti-obesity medication as an adjunct to lifestyle modification has yielded reasonable results in terms of weight loss and improvement in hirsutism and infertility. The most effective treatment of obesity in women with PCOS, based on the limited data available, appears to be bariatric surgery, which results in resolution of all of the syndrome's parameters. The management of pregnancies in women following bariatric surgery should be conducted by a specialist multidisciplinary team, and recommendations ought to be robust and based on more comprehensive trials focusing on nutritional support, timing of conception and the management of complications in this high-risk group of women.
  • 10 - Definition of hyperandrogenism
    pp 117-124
  • View abstract

    Summary

    The diagnosis of hyperandrogenism is dependent on the accuracy and precision of measurement of the clinical features and the laboratory androgen assays. Hyperandrogenism in the context of polycystic ovary syndrome (PCOS) is a term used loosely to encompass both the clinical features of acne, hirsuties and androgenic alopecia and the laboratory evidence of hyperandrogenaemia. The relationship between acne and biochemical hyperandrogenaemia is well established but the number of women with acne in unselected populations is so great that it makes the link with PCOS unconvincing, particularly since the incidence of acne seems to be greater than that of PCOS. Anovulation is assessed by measuring the serum progesterone during the mid-luteal phase. Consecutive series of women with either a single symptom or various combinations of symptoms would be subjected to formal receiver operating characteristic (ROC) analysis to determine the optimal diagnostic characteristics.
  • 11 - Treatment of hyperandrogenism in polycystic ovary syndrome
    pp 125-142
  • View abstract

    Summary

    Hyperandrogenism is the most common endocrinopathy seen in women and may result from ovarian or adrenal overproduction of androgens, altered peripheral metabolism and/or end-organ hypersensitivity. The clinical manifestions of hyperandrogenism in polycystic ovary syndrome (PCOS) are frequently very visible and, as a result, produce significant psychological morbidity. The three main naturally occurring steroids responsible for androgen activity are testosterone and the weak androgens dehydroepiandrosterone (DHEA) and androstenedione. Managing the dermatological signs of hyperandrogenism, which generally present as acne, seborrhoea, hirsutism and female-pattern hair loss in PCOS, is achieved by reducing the circulating levels and effects of androgens. Potential mechanisms by which this may occur include: direct suppression of androgen production, change in androgen binding to sex hormone-binding globulin (SHBG), impairing the peripheral conversion of free testosterone to dihydrotestosterone by inhibiting 5 alpha-reductase type I and inhibiting androgens acting at the site of target tissue.
  • 12 - Choices in the treatment of anovulatory polycystic ovary syndrome
    pp 143-152
  • View abstract

    Summary

    The majority of women with anovulation or oligo-ovulation due to polycystic ovary syndrome (PCOS) have clinical and/or biochemical evidence of hyperandrogenism. This chapter describes treatment with clomifene, aromatase inhibitors, gonadotrophins, and metformin. Weight loss has the undoubted advantages of being effective and cheap with no adverse effects and should be the first line of treatment in obese women with anovulatory infertility associated with PCOS. The aromatase inhibitors letrozole (Femara, Novartis) and anastrozole (Arimidex, AstraZeneca) have mainly been employed for the treatment of postmenopausal women with advanced breast cancer. In women with PCOS, metformin is said to lower fasting insulin concentrations but also probably acts directly on theca cells and attenuates androgen production. There is now sufficient evidence that low-dose step-up gonadotrophin therapy should be preferred to the now outdated conventional therapy for anovulatory patients and particularly for those with PCOS.
  • 13 - Predictors of ovarian response to ovarian stimulation: progress towards individualised treatment in ovulation induction
    pp 153-164
  • View abstract

    Summary

    Achieving a distinct ovarian response usually represents the desired outcome of pharmacological interventions on the hypothalamic-pituitary-ovarian axis in ovulation induction and ovarian stimulation. The considerable individual variability in ovarian response to stimulation, however, necessitates close monitoring and dose adjustment for each woman. Combining prediction models for success in ovulation induction and success in conception would allow prediction of the likelihood of conception before anti-estrogen therapy is initiated, allowing women with a low percentage chance of a live birth to be directed towards another first-line treatment modality. Gonadotrophins are commonly used as a second-line treatment to restore ovarian function in women with WHO group II anovulation who have not responded to anti-estrogen therapy. Despite problems in using the current predictive tests in clinical practice, the wide variation in patients' characteristics mean that individualised patient-tailored approaches remain mandatory for safe and effective ovarian stimulation.
  • 14 - Surgical management of anovulatory infertility in polycystic ovary syndrome
    pp 165-172
  • View abstract

    Summary

    The surgical management of anovulatory infertility in polycystic ovary syndrome (PCOS) has traditionally involved the use of clomifene citrate and then gonadotrophin therapy or laparoscopic ovarian surgery in those who are clomifene-resistant. Laparoscopic ovarian surgery is a useful therapy for anovulatory women with PCOS who need a laparoscopic assessment of their pelvis or who live too far away from the hospital to be able to attend for the intensive monitoring required for gonadotrophin therapy. Commonly employed methods for laparoscopic surgery include monopolar electrocautery (diathermy) and laser. The risk of periovarian adhesion formation can be reduced by abdominal lavage and early second-look laparoscopy, with adhesiolysis if necessary. The chance of achieving a continuing pregnancy within 6 months is less than with carefully conducted ovulation induction with gonadotrophins but, if adjuvant ovulation induction agents are used in those who do not initially respond, the 12-month pregnancy rates are similar.
  • 15 - The role of insulin-sensitising drugs in the treatment of polycystic ovary syndrome
    pp 173-184
  • View abstract

    Summary

    Insulin-sensitising agents are frequently used in the treatment of women with polycystic ovary syndrome (PCOS). This chapter explores the use of insulin sensitisers, primarily metformin, for varying indications related to PCOS and discusses the evidence to develop a risk/benefit ratio for their use. These drugs were developed to treat type 2 diabetes and have been adapted as treatments for the symptoms of PCOS. Metformin has been proposed to prevent early first-trimester miscarriage. Randomised trials, primarily from one group in Spain, have shown that metformin improves many aspects of premature pubarche, including slowing the onset of puberty, reducing total and visceral fat, improving circulating lipid levels and lowering testosterone levels. There are not enough data to conclude whether insulin-sensitising agents improve hirsutism. The rationale for the use of metformin in infertility is that it lowers both circulating insulin levels and testosterone levels, and leads to increased ovulation.
  • 16 - The role of in vitro maturation of oocytes for anovulatory polycystic ovary syndrome
    pp 185-194
  • View abstract

    Summary

    A number of studies have shown that the presence of ovaries of polycystic morphology, regardless of whether there are additional features of the full polycystic ovary syndrome (PCOS), significantly increase the risk of developing moderate to severe ovarian hyperstimulation syndrome (OHSS). in vitro maturation (IVM) is an approach with the potential to increase both the simplicity and safety of assisted reproductive technology (ART) treatment through the absence of the need for ovarian stimulation. IVM is a promising technique for women with anovulatory PCOS. The success rates are currently lower than those achieved with in vitro fertilisation (IVF) but IVM is safer and easier to undertake for the woman and it avoids gonadotrophin stimulation and the attendant risk of OHSS. While IVM is apparently safer for the woman, long-term paediatric studies are required before IVM can be fully assessed, which is also the case for other ART treatments.
  • 17 - Acupuncture and/or herbal therapy as an alternative or complement for relief of polycystic ovary syndrome-related symptoms
    pp 195-212
  • View abstract

    Summary

    This chapter focuses on the possible mechanisms of action, experimental data and available clinical data of acupuncture treatment in women with polycystic ovary syndrome (PCOS). It provides examples of herbs and herbal mixtures used for symptoms associated with PCOS. Treatment of PCOS focuses on restoration of reproductive abnormalities with the aim of reducing clinical and biochemical hyperandrogenism, restoring menstrual cycles, inducing ovulation and improving reproductive outcomes. The chapter illustrates the hypothesis of how acupuncture and specifically low-frequency electro-acupuncture (EA) may improve PCOS-related symptoms via modulation of endogenous regulatory systems, including the sympathetic nervous, the metabolic, the endocrine and the neuroendocrine systems. Clinical and experimental evidence shows that acupuncture can be a suitable alternative or complement to pharmacological induction of ovulation in women with PCOS and may also relieve other symptoms. More precise standards for reporting randomised controlled trials (RCTs) of acupuncture are needed to overcome difficulties in analysis and interpretation.
  • 18 - Consensus views arising from the 59th Study Group: Current Management of Polycystic Ovary Syndrome
    pp 213-216
  • View abstract

    Summary

    This chapter describes the diagnosis, pathophysiology, treatments, and current management of polycystic ovary syndrome (PCOS). A definitive diagnosis of PCOS can be difficult to achieve in adolescence and an early diagnosis should be re-evaluated in adulthood. The management of PCOS (including its long-term health risks) is best delivered by a multidisciplinary approach, including dietary and educational counselling, exercise training, stress management and psychosocial support. All women with PCOS should be assessed for the risk of developing impaired glucose tolerance and type 2 diabetes. Metformin is overused in the treatment of PCOS and is ineffective as a solo agent or in combination to treat infertility and to achieve live births. Large cross-sectional studies are required of different ethnic communities to assess the prevalence of PCOS and longitudinal studies are required of its evolution over time, from puberty and throughout life.

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