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Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline

Helena J Teede, Marie L Misso, Amanda A Deeks, Lisa J Moran, Bronwyn G A Stuckey, Jennifer L A Wong, Robert J Norman, Michael F Costello and on behalf of the Guideline Development Groups
Med J Aust 2011; 195 (6 Suppl): S65. || doi: 10.5694/mja11.10915
Published online: 2011-09-19
Polycystic ovary syndrome: an introduction

Funding: The development of this guideline was funded by the Australian Government Department of Health and Ageing, through the Jean Hailes Foundation for Women’s Health on behalf of the PCOS Australian Alliance.

Editorial independence: This guideline is editorially independent. The funders were not involved in the development of the guideline and have not influenced the scope or recommendations of this guideline.

Polycystic ovary syndrome (PCOS) has recently been shown to affect a striking 12%–21% of Australian reproductive-age women, being more common among those who are overweight or of Indigenous background.1 PCOS can be a frustrating experience for women, a complex syndrome for clinicians and a scientific challenge for researchers, and is a major public health concern.

Although reproductive features are prominent, PCOS has potential for major metabolic consequences, including obesity and related type 2 diabetes mellitus (DM2) as well as cardiovascular disease (CVD), all of which are currently national health priority areas.2,3 It also has significant mental health and psychological impact, impairing quality of life (QoL).4,5 Because increased obesity exacerbates incidence, prevalence and severity of PCOS, and weight loss improves reproductive, metabolic and psychological features, lifestyle change should be first-line therapy for PCOS.6

It is estimated that 70% of Australian women with PCOS remain undiagnosed;1 clinical practice is inconsistent;7 psychological issues are under-recognised;5 and there is little focus on lifestyle and prevention, with most services targeting infertility and costly assisted reproductive technology. Given the prevalence, disease burden, health costs and clear gaps in care, PCOS is highlighted in national policy and has been prioritised by government, with funding for development of a national PCOS evidence-based guideline and translation of evidence into practice. Here, we present a brief general clinical introduction to PCOS, concise guideline algorithms and clinical pathways and a comprehensive summary of the Evidence based guideline for assessment and management of PCOS (available at http://www.managingpcos.org.au/pcos-evidence-based-guidelines).8

Presentation

PCOS has significant and diverse implications, including reproductive (hyperandrogenism, hirsutism, anovulation, infertility), metabolic (insulin resistance [IR], impaired glucose tolerance, DM2, adverse cardiovascular risk profiles) and psychological features (increased anxiety and depression and worsened QoL).9 Presentation varies across the life span. Hyperandrogenic features are often most prominent among adolescents,10 fertility issues most prominent among women in their 20s and 30s, and metabolic challenges most notable after this.11 The propensity to weight gain and psychological challenges affect all ages, and metabolic features can occur early, especially among those who are overweight. Variations across ethnic groups should also be noted, such as fewer hyperandrogenic dermatological features and more severe metabolic features in Asian women, even without weight gain. Indigenous women appear to have a higher prevalence and severity of PCOS.1,12 The clinical presentation of PCOS is outlined in Figure 1.

Figure 1. The aetiological, hormonal and clinical features of polycystic ovary syndrome


Adapted and reproduced from Teede at al with permission from the Royal Australian College of General Practitioners.13

Diagnosis and investigations

Diagnosis of PCOS is now largely based on the Rotterdam criteria,14 which are inclusive of the original National Institutes of Health (NIH) criteria15 and require two of three key features: oligo- or anovulation, clinical and/or biochemical hyperandrogenism and polycystic ovaries on ultrasound (Figure 2). However, as noted, PCOS phenotypes vary widely depending on life stage, genotype, ethnicity and environmental factors, including lifestyle and body weight.

Diagnostic investigations must exclude other causes and include thyroid function tests and prolactin and follicle-stimulating hormone (FSH) levels.9 For diagnosis, androgen levels should be measured; however, optimal methodology remains very controversial and is addressed in Section 1. Vaginal ultrasound is often needed for diagnosis where hyperandrogenism and anovulation are not both clearly present. Ultrasound can check for polycystic ovaries and endometrial thickness. However, vaginal ultrasound should be reserved for sexually active women. The role of ultrasound remains controversial for adolescents, among whom a polycystic appearance of the ovaries is very common, potentially leading to overdiagnosis;16 hence, this area is also covered in the guideline. Other diagnostic investigations are based on clinical discretion.

Screening is also vital to detect PCOS complications and guide prevention and treatment. Comprehensive cardiovascular risk-factor screening, including family history, ethnic group, body mass index (BMI), waist circumference, smoking status, blood pressure, glycaemic status (oral glucose tolerance test [OGTT]) and lipid profile, is important at diagnosis and should be repeated with a frequency informed by metabolic risk (eg, body weight, age, family history, ethnicity) as outlined in Section 3. Optimal methodology for the routine screening for prediabetes and DM2 has been controversial in PCOS, but because lifestyle change and metformin improve IR in PCOS, and among other at-risk groups these measures have been shown to dramatically reduce progression to diabetes, early detection, including detection of prediabetes, is vital and is addressed in the guideline.

Figure 2. The Rotterdam criteria for diagnosis of polycystic ovary syndrome (PCOS)14


The Rotterdam criteria are inclusive of National Institutes of Health (NIH) criteria in that a woman diagnosed with PCOS using the NIH criteria will also meet Rotterdam criteria; however, a woman diagnosed with PCOS using Rotterdam criteria may not meet NIH criteria.

Aetiology

PCOS is an endocrine disorder, the pathophysiology of which remains unclear. Genetic and environmental contributors combine with obesity, ovarian dysfunction and hormonal drivers to contribute to the aetiology of PCOS.17,18 The underlying hormonal imbalance may include a combination of increased androgens and/or hyperinsulinaemia secondary to IR (Figure 1). Greater understanding of cause has been hampered by a lack of ideal methods to assess either hyperandrogenism or IR. Hyperandrogenism is detected in around 60%–80% of women with PCOS, and IR is a pathophysiological contributor in around 50%–80%.19 Obesity increases reproductive features — hyperandrogenism, hirsutism, infertility and pregnancy complications — both independently and by exacerbating PCOS.20,21 Furthermore, obesity exacerbates the PCOS-related increased risk factors for impaired glucose tolerance, DM2 and CVD,22 while obesity also affects psychological features of PCOS.

Clinical features

PCOS is a chronic condition that manifests across the life course. Women with PCOS present with psychological,5,23 reproductive24 and metabolic implications. In terms of psychosocial implications, challenges to feminine identity and body image due to obesity, acne, excess hair, infertility and long-term health-related concerns compromise QoL and adversely affect mood and psychological wellbeing. With a higher prevalence and greater severity of depression and anxiety, low self-esteem, negative body image, and psychosexual dysfunction,5,25 assessment of psychological functioning in women with PCOS is vital. This is relevant to clinical care as mood disturbance, in turn, impairs QoL and adversely affects ability to self-manage and optimise lifestyle. Optimal approaches to screening and assessment of psychological functioning in PCOS are unknown and recognition is generally poor; hence, this area was prioritised in the guideline (Section 4). If mood disturbance is detected during screening, further assessment and management is required.

Reproductive and reproductive hormonal features are often the best-recognised features in PCOS as they form the basis of the diagnostic criteria.14 These include clinical and biochemical hyperandrogenism, anovulation, subfertility and polycystic ovaries on ultrasound. A key point is that fertility is not necessarily impaired in all PCOS cases — some women conceive without medical intervention, depending on the severity of the condition. Age and BMI have a critical role in infertility risk in PCOS; therefore, early family initiation (before the age of 30–35 years) combined with maintaining a BMI < 31 kg/m2 is ideal for increasing the chance of conceiving.

Metabolic features of PCOS include an apparent propensity for excess weight gain, an increased prevalence of prediabetes and DM2, a 5–10-fold risk of progression from prediabetes to DM2 and a 4–7-fold risk of DM2.11 Cardiovascular risk factors are increased and CVD appears more prevalent among women with PCOS despite inadequate long-term studies to appropriately address this question.22 In the general population, IR is a predictor of CVD.26,27 Women with PCOS also have an increased prevalence of metabolic syndrome (associated with an increased risk for DM2 and CVD),28 individual risk factors for CVD and clinical signs of atherosclerosis,29,30 which are all exacerbated by obesity. Women with PCOS are therefore a population at high risk of developing DM2 and CVD. As DM2 and subsequent CVD are the primary cause of death in Australian women, any increase in prevalence will have significant public health implications. It is also important to note that relatives of women with PCOS may have increased risk of diabetes and increased CVD risk factors. Metabolic features are often poorly appreciated in PCOS; hence, recommendations on screening and assessment of DM2 and CVD risk factors are covered in the guideline.

Obesity or excess weight is a major cause of chronic disease in Western countries. In Australia, 56% of the adult population is overweight (BMI ≥ 25 kg/m2) or obese (BMI ≥ 30 kg/m2). In 2007, 31% of women were overweight and 24% of women were obese. Recent data from the Australian Longitudinal Study on Women’s Health showed that among 26–31-year-old women, 20.4% were overweight and a further 13.9% were obese.31 Overall, the proportion of adults who are obese has doubled in the past 20 years.32 Obesity is now the primary cause of chronic disease among Australian women, with adverse outcomes including DM2 and CVD.31 Obesity has a specific impact on women’s reproductive health, increasing the prevalence and severity of PCOS, infertility, pregnancy complications, gestational diabetes and fetal pregnancy complications, with substantial and escalating economic costs.33,34 Indeed, the adverse impact of obesity on fertility, exacerbated by delay in childbearing, is resulting in a significant social, health and economic burden in Australia.35 Given the dramatic increase in obesity, the guideline addresses weight loss and prevention of weight gain through lifestyle intervention (Section 5).

Management

Therapy should focus on both the short- and long-term reproductive, metabolic and psychological features. It is important to address psychological factors initially to optimise self-efficacy, readiness to change and sustainability of lifestyle interventions as well as to improve QoL. Screening, assessment and treatment of depression and anxiety are vital, and recognition of other aspects of emotional wellbeing, including poor body image, sexual dysfunction, disordered eating and eating disorders — all more common among women with PCOS — is important for improving QoL. Optimal approaches to screening and assessment of emotional wellbeing among women with PCOS remain unclear and are also addressed in this guideline (Section 4). Once recognised, poor emotional wellbeing and mood disorders should be addressed to improve QoL among women with PCOS.

PCOS management should focus on support and education, and needs to strongly emphasise healthy lifestyle, with targeted medical therapy as required. Given the putative aetiological role of IR and obesity in PCOS, prevention of weight gain is important across the life span. Furthermore, among those who are already overweight, multidisciplinary lifestyle intervention aimed at improving IR and aiding weight management is recognised as first-line therapy for most women who are overweight.6 Modest weight loss of 5%–10% of initial body weight significantly reduces IR and has been demonstrated to ameliorate many of the features of PCOS.6 Optimal methods for achieving weight loss and prevention of weight gain remain unclear and are a focus of this guideline (Section 5).

Short-term diets rarely lead to permanent weight loss, and lifestyle change requires behavioural change. Health-coaching principles can be incorporated to optimise readiness to change, and include education and accurate risk perception, which can assist with motivation through education and tailoring the knowledge relevant to the individual. Once ready to change, support is needed to convert this to action with effective strategies including patient-driven goal setting (eg, 5% of body weight loss, small improvements in exercise), so that these incremental changes are seen as achievements. Multidisciplinary involvement in care is often useful in the early stages to support education and behaviour change and is explored further in this guideline (Section 2).

In addition to lifestyle measures, therapy in PCOS can be targeted to specific clinical presentations. Although there is a plethora of options for therapy in PCOS, in this guideline we have focused on the most controversial interventions, where little guidance is currently available. Assessment of mood disorders and emotional wellbeing is prioritised in the guideline, yet treatment is well guided by a range of existing clinical guidance tools.36-43 Hirsutism treatment is also guided by a recent and comprehensive international statement,44 so these areas are not covered in the guideline. Infertility remains a highly controversial area and is covered in detail in the guideline (Sections 6, 7 and 8). DM2 and CVD risk assessment is included (Section 3); yet treatments for these established complications are covered in other specific national evidenced-based guidelines,45,46 and have not been reproduced here. Optimal therapy for infertility is one of the most controversial areas of PCOS management and includes lifestyle interventions, medical and surgical ovulation induction, consideration of bariatric surgery for preconception weight loss, and in-vitro fertilisation (IVF). All these areas are covered in the guideline except for IVF therapy, as this was deemed to be of a lower priority than the first-line lifestyle measures and ovulation induction therapies. Potential targeted treatment options for PCOS are summarised in Box 1.

Box 1. Summary of potential targeted treatment options for polycystic ovary syndrome (PCOS)

Oligomenorrhoea/amenorrhoea

  • Lifestyle change (5%–10% weight loss + structured exercise)

  • Oral contraceptive pill (OCP) (low oestrogen doses [eg, 20 μg] may have less impact on insulin resistance)47

  • Cyclic progestins (eg, 10 mg medroxyprogesterone acetate 10–14 days every 2–3 months)

  • Metformin (improves ovulation and menstral cyclicity)

Hirsutism

Choice of options depends on patient preferences; impact on wellbeing; and access and affordability:44

  • Self-administered and professional cosmetic therapy are first line (laser recommended)

  • Eflornithine cream can be added and may induce a more rapid response

  • If cosmetic therapy is not adequate, pharmacological therapy can be considered

  • Pharmacological therapy

    • Medical therapy if patient is concerned and cosmetic therapy is ineffective/inaccessible/unaffordable

    • Primary therapy is the OCP (monitor glucose tolerance in those at risk of diabetes)

    • Anti-androgen monotherapy (eg, spironolactone or cyproterone acetate) should not be used without adequate contraception

    • Trial therapies for ≥ 6 months before changing dose or medication

    • Combination therapy — if ≥ 6 months of OCP is ineffective, add anti-androgen to OCP (twice daily spironolactone > 50 mg or cyproterone acetate 25 mg/day, days 1–10 of OCP)

Infertility

  • Lifestyle intervention (to optimise preconception health and fertility and reduce pregnancy and long-term complications)

  • Advise on folate, smoking cessation and optimal weight and exercise before conception

  • Given age-related infertility, advise women to optimise family initiation

  • Infertility therapies may include clomiphene citrate, metformin, gonadotrophins, surgery and in-vitro fertilisation.

Cardiometabolic risk

  • Lifestyle change: > 5% weight loss in those who are overweight reduces diabetes risk by approximately 50%–60% in high-risk groups48

  • Optimise cardiovascular risk factors

  • Consider metformin* (reduces the risk of diabetes by ~ 50% in adherent high-risk groups)48


Adapted and reproduced with permission from Teede et al,9 not generated directly from the evidence-based guidelines. Hirsutism therapy is summarised from existing hirsutism clinical practice guidelines.44 * Metformin and the OCP are not currently approved for use to manage PCOS by many regulatory bodies. The OCP is indicated for contraception and metformin for diabetes. However, their use is supported by evidence and is recommended by international and national specialist societies.49

Considerations for Indigenous women with PCOS

The prevalence of PCOS among Indigenous Australian women appears to be as high as 21% by the Rotterdam criteria12 and the NIH criteria,50 and increases with rising BMI.12 In a group of Indigenous women with PCOS, 30.3% were obese and 7.0% had a normal BMI.12

DM2 and obesity are associated with major morbidity among Indigenous women. The National Aboriginal and Torres Strait Islander Health Survey (NATSIHS) found that Indigenous Australians are 1.2 times more likely to be overweight or obese than non-Indigenous Australians, and this disparity is greatest for women.51 DM2 is the second-commonest cause of mortality and disability-adjusted life-years (DALY) among Indigenous women.52 The DALY rate ratios (age-standardised to total Indigenous population) for ischaemic heart disease and DM2 among Indigenous women, compared with all Australian women, are 6.6 and 6.3, respectively; and the mortality rate ratio is 5.0 for ischaemic heart disease and 18.9 for DM2.52

The risk of metabolic complications is already high among Indigenous women, independent of PCOS; therefore, PCOS can amplify metabolic risk in these women. Given that these metabolic complications are largely preventable, it is important to provide early access to care.

The leading cause of burden of disease among Indigenous women in the NATSIHS was anxiety and depression, accounting for 10% of the burden.51 Little is known about the prevalence of eating disorders and disordered eating among Indigenous women. Social and cultural factors influence emotional wellbeing, and the challenges facing many Indigenous women are likely to amplify the impact of PCOS on emotional wellbeing. Further research in this area is needed.

Access to culturally appropriate care, services and programs is currently not optimal. Access issues are a key barrier for many Indigenous women, as health services generally, and women’s health services in particular, are limited in rural and remote locations. There are many barriers to healthy lifestyles, including the high cost of maintaining a healthy diet in rural and remote locations. Socioeconomic factors, such as poverty and overcrowding, make the use of refrigerators and kitchen equipment to cook healthy food difficult. Lifestyle programs may need to be applied in different ways to engage Indigenous women and incorporate exercise into daily activities, especially in rural and remote locations, due to a lack of service provision and facilities.

Other issues for Indigenous women include that the role of ultrasound in the Indigenous setting is questionable due to limitations in care and access to ultrasound facilities and service provision in rural and remote locations; and there may be cultural factors and potential issues around acceptability of bariatric surgery.

It is important to encourage and enable Indigenous women with PCOS to access services that are available and address potential barriers presented by cultural and traditional health practices. Work is currently underway to adapt, translate and implement the recommendations outlined here to Indigenous settings.

Development of an evidence-based guideline
Rationale and methods

Given its heterogeneous clinical features across the life span, PCOS is a condition that engages many health disciplines. The associated complications are serious yet are often largely preventable; however, there is a lack of awareness of PCOS among consumers and health professionals. It is essential that consumers and health professionals recognise the life-course implications of PCOS, identify the early signs and symptoms and work together to manage PCOS and prevent its complications — especially as the burden and cost of PCOS complications, including infertility, DM2, CVD and emotional wellbeing issues are significant.

Currently, there is limited consensus among different medical specialties as to the optimal management of PCOS in Australia.7,53 Diagnosis and treatment of PCOS can therefore differ depending on the health professional consulted (eg, general practitioner, endocrinologist or gynaecologist).7 There are limited clinical guidelines and no evidence-based guidelines, either in Australia or internationally, for assessment or management of women with PCOS; rather, PCOS is briefly mentioned within guidelines for the management of obesity and DM2.45,54 Where international clinical guidelines for the assessment and management of women with PCOS exist, they are informed by expertise and, in some cases, evidence, but are not rigorously developed evidenced-based guidelines; they do not consider psychological issues; and they offer simplistic advice on lifestyle management of PCOS. There is no guidance on the assessment and management of PCOS among Indigenous women, nor any adaptation for the Australian context.

Overall, many areas of controversy remain in PCOS. Comprehensive evidence-based guidelines are warranted to optimise diagnosis, assessment and management. Accordingly, the Jean Hailes Foundation for Women’s Health has facilitated the formation of an independent PCOS Australian Alliance, bringing together health professionals, researchers, consumers and policymakers to advance knowledge and quality of care in PCOS. The federal government has funded the PCOS Australian Alliance, under the auspices of the Jean Hailes Foundation, to produce national evidence-based guidelines. The full version of the guideline has been approved by the National Health and Medical Research Council (NHMRC) (for detail about obtaining NHMRC approval, please see the full guideline), is endorsed by the Royal Australian College of General Practitioners and is freely available at http://www.managingpcos.org.au/pcos-evidence-based-guidelines.8 This is a summary version of the full guideline. The Jean Hailes Foundation was funded to translate the guideline into practice, including freely available independent evidence-based information on PCOS for health professionals and women at http://www.managingpcos.org.au.

Scope

The purpose of the guideline is to integrate the best available evidence with clinical expertise and consumer preferences; to provide health professionals, consumers and policymakers with guidance on timely diagnosis, accurate assessment and optimal management of PCOS; and to promote consistency of care and prevention of complications in primary care and specialist settings.

The guideline is relevant to the assessment and management of reproductive-age adolescents and women with PCOS, including women with PCOS who are experiencing infertility. The guideline will apply in all health care settings and to a broad audience, including: community care practitioners; Indigenous health care workers; GPs; nurses; endocrinologists; obstetricians and gynaecologists; allied health professionals — psychologists, dietitians, exercise physiologists and physiotherapists; patients; community support groups (eg, the Polycystic Ovary Syndrome Association of Australia [POSAA]); the general public; students; and policymakers.

PCOS is a syndrome, and as such, no single diagnostic criterion is sufficient for diagnosis. The 2003 Rotterdam consensus workshop concluded that PCOS diagnosis requires at least two of: oligo- or anovulation, hyperandrogenism (clinical and/or biochemical) and polycystic ovaries on ultrasound (Figure 2).14 The evidence-based guideline development groups and the Alliance agreed to endorse the Rotterdam diagnostic criteria for the guideline, while recognising there are current limitations of all definitions.

Methodology

Guidelines are intended to improve patient outcomes, promote standardised care, develop standards to assess the clinical practice of health care professionals, and promote research and translation into practice. Guidelines are developed by drawing from clinician judgement, patient preference and research evidence, and are intended to aid clinical judgement and patient preference, not to replace it (Figure 3). The ultimate decision about clinical management of an individual patient will always depend on the clinical circumstances, patient preferences, and the clinical judgement of the health care team. Although there are many types of guidelines, this NHMRC-approved evidence-based guideline followed a rigorous, systematic process of development, which is briefly outlined below and in detail in the full guideline.8

Figure 3. Evidence-based guidelines are intended as an aid to clinical judgement and patient preference, not to replace it

An independent PCOS Australian Alliance was formed in 2008 after a national workshop facilitated by the Jean Hailes Foundation for Women’s Health, which brought together key leaders from the research and multidisciplinary clinical sectors, with consumers providing a driving force through the peak national support group, POSAA. The vision of the Alliance is to improve the lives of Australian women with PCOS through education, research and evidence-based health care. One of the priorities of the Alliance was to develop an evidence-based guideline for PCOS.

This guideline was developed as outlined in the NHMRC standards and procedures for externally developed guidelines.55

The Alliance identified key clinical objectives for the guideline based on highest clinical priority, greatest knowledge gaps, factors identified by the Australian government (which funded the guideline), and the expertise of Alliance members. The identified key clinical priorities focused on care of women with PCOS to facilitate early diagnosis of PCOS; early detection and treatment of depression, anxiety and mood disorders; early detection and diagnosis of risk factors for prediabetes, DM2 and CVD; and early detection and treatment of fertility problems and prevention of pregnancy complications.

Multidisciplinary guideline development committees included a Project Board, PCOS Australia Alliance Strategic Advisory Group and four guideline development groups. Each guideline development group comprised a chair, professional group members with specific expertise in PCOS and the clinical area of interest (eg, psychologist in the emotional wellbeing guideline development group), a consumer representative from POSAA, evidence officers and, where possible, a representative to provide context for the Indigenous setting. Indigenous representation was present on the PCOS Australian Alliance Strategic Advisory Group, and the guideline development groups comprised clinicians with experience working with Indigenous communities.

These multidisciplinary groups determined and prioritised the clinical questions addressed in this guideline and developed the clinical practice and research recommendations from the evidence reviews. For more detail about the development and prioritisation of clinical questions, please see the full guideline.8

To facilitate this process using an evidence-based approach, the chairs of each guideline development group attended a 1-day workshop, facilitated by the Southern Health Centre for Clinical Effectiveness, where the methods of identifying, appraising and synthesising evidence; grading the strength of evidence and its suitability to support evidence-based recommendations; and the process of guideline development overall were described in detail.

Evidence reviews were conducted for each of the 22 identified clinical questions. Search strategies were developed according to a-priori selection criteria for each clinical question. Searches were limited to English language articles and there were no limits on year of publication. The literature was searched until November 2010. The following electronic databases were employed to identify relevant evidence: Australasian Medical Index, CINAHL, the Cochrane Library, the Cochrane Database of Systematic Reviews, DARE (Database of Abstracts of Reviews of Effects), the Cochrane Central Register of Controlled Trials, the Cochrane Database of Methodology Reviews, the Cochrane Methodology Register, Health Technology Assessment Database, the United Kingdom National Health Service Economic Evaluation Database, EMBASE, EBMR, MEDLINE and PsycINFO. Bibliographies of relevant studies identified by the search strategy and relevant reviews/meta-analyses were also searched. Included studies were classified according to the NHMRC levels of evidence56 and appraised using a-priori criteria according to study design, using a descriptive component approach to assign a risk of bias rating.57 In accordance with the selection criteria, data were extracted from included studies using a specially developed data extraction form,57 and meta-analyses were performed where appropriate. The guideline development groups were able to develop guideline recommendations from these evidence reviews. The evidence reviews for each question can be found in the supporting document to the full guideline: Evidence report: evidence based guidelines for assessment and management of PCOS, available at http://www.managingpcos.org.au/pcos-evidence-based-guidelines.

The guideline contains 38 recommendations, each of which is assigned a grade. In developing the guideline recommendations, the guideline development groups placed emphasis on accurate assessment and management of PCOS. The recommendations in this guideline are strengthened by the use of rigorous methodology for evidence review and guideline development, including use of: study designs least susceptible to bias; a-priori criteria for inclusion and appraisal of studies; extraction of study data; and meta-analysis where appropriate. The recommendations were formulated using a considered judgement process that took into account the amount and quality of available evidence as well as its generalisability and applicability to current practice in Australia.

Each evidence-based recommendation was given an overall grading from A to D, according to the NHMRC grades of recommendations for guideline developers (Table 1).56 Evidence grading is provided primarily to inform users about the strength of the evidence underpinning each recommendation. Where there was insufficient high-quality evidence in specific patient groups, lower-quality evidence or data from other patient groups, and where there was consensus among the guideline development group, combined with clinician and patient preferences, clinical consensus recommendations were developed. Clinical practice points have also been included, where important issues (such as safety, side effects or risks) arose from discussion of evidence-based or clinical consensus recommendations. Further points of relevance to the clinical implementation of recommendations were made in “implications of the recommendations” sections, including consideration of resource implications.

Table 1. National Health and Medical Research Council grades for recommendations56

A

Body of evidence can be trusted to guide practice.

B

Body of evidence can be trusted to guide practice in most situations.

C

Body of evidence provides some support for recommendation but care should be taken in its application.

D

Body of evidence is weak and recommendation must be applied with caution.

The words “should”, “could” and “should not” do not directly reflect the grade or classification allocated to a recommendation, and are independent descriptors intended to reflect the judgement of the multidisciplinary guideline development group about the practical application of the recommendation, balancing benefits and harms. Where the word “should” is used in the recommendations, the guideline development group judged that the benefits of the recommendation (whether evidence-based or clinical consensus) clearly exceed the harms, and that the recommendation can be trusted to guide practice. Where the word “could” is used, either the quality of evidence was underpowered, or the available studies demonstrated little clear advantage of one approach over another, or the balance of benefits to harm was unclear. Where the words “should not” are used, there is either a lack of appropriate evidence, or the harms outweigh the benefits.

In formulating the recommendations for this guideline, the guideline development groups recognised and took into account several factors and limitations pertaining to the available evidence. For many aspects of PCOS, there is little or no evidence or the evidence is of poor quality, with other potential biases resulting from different methods for diagnosis of PCOS and differing end points.

Public and targeted consultation on the draft guideline was conducted for 30 days commencing 5 March 2011, in accordance with the legislative requirements for approval of externally developed guidelines under Section 14A of the National Health and Medical Research Council Act 1992 (Cwlth). All aspects of the guideline were developed as outlined in the NHMRC standards and procedures for externally developed guidelines,55 and accordingly, the guideline was approved by the NHMRC in July 2011. In approving the full version of the guideline, the NHMRC is satisfied that it is based on the systematic identification and synthesis of the best available scientific evidence and makes clear recommendations for health professionals practising in an Australian health care setting.

This guideline does not seek to provide full safety and usage information on pharmacological and surgical interventions. The pharmacological and surgical interventions recommended in the guideline should not be applied without consideration of the patient’s clinical profile and personal preferences. It is recommended that the reader consults the Therapeutic Guidelines (http://www.tg.com.au) and the National Prescribing Service (http://www.nps.org.au) for detailed prescribing information, including indications, drug dosages, methods and routes of administration, contraindications, supervision and monitoring, product characteristics, and adverse effects.

It is intended that this evidence-based guideline summary be used alongside the full guideline.8 The guideline should be considered according to the limitations outlined within, and used in conjunction with clinical judgement and patient preference. For a detailed description of the methodology used to develop the guideline, please see the full guideline.8

Translation of the guideline, including the production and dissemination of guideline-associated tools and resources, is the responsibility of the Jean Hailes Foundation for Women’s Health as a national not-for-profit women’s health organisation funded by the federal government. The PCOS Alliance and POSAA provided significant contribution to these resource developments.

  • Helena J Teede1,2,3
  • Marie L Misso1,2
  • Amanda A Deeks1
  • Lisa J Moran4
  • Bronwyn G A Stuckey5,6
  • Jennifer L A Wong3
  • Robert J Norman4
  • Michael F Costello7,8
  • on behalf of the Guideline Development Groups

  • 1 Research Unit, Jean Hailes Foundation for Women’s Health, Melbourne, VIC.
  • 2 School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC.
  • 3 Department of Diabetes, Southern Health, Melbourne, VIC.
  • 4 The Robinson Institute, University of Adelaide, Adelaide, SA.
  • 5 Keogh Institute for Medical Research, Sir Charles Gairdner Hospital, Perth, WA.
  • 6 School of Medicine and Pharmacology, University of Western Australia, Perth, WA.
  • 7 School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW.
  • 8 Reproductive Medicine, Royal Hospital for Women, Sydney, NSW.

Correspondence: helena.teede@monash.edu

Competing interests:

Rob Norman has part-ownership in Fertility SA, a company providing fertility and IVF services in Adelaide; has received speaker fees from MSD Australia and Merck Serono Australia, received honoraria from MSD–Schering-Plough and Merck Serono Australia; and is a member of the MSD–Schering-Plough Advisory Board. Bronwyn Stuckey has received travel funding from Bayer Australia and Schering- Plough, both of which have interests in the oral contraceptives Diane-35 and Yasmin, which are commonly prescribed to women with PCOS. Michael Costello has shares in IVF Australia; was the recipient of a grant from Schering-Plough in 2002 for research project unrelated to PCOS (Schering-Plough manufactures FSH injections for ovulation induction and ovarian stimulation); received sponsorship to attend and present at national and international scientific meetings on a broad range of topics determined by the individual conference organising committees, from pharmaceutical companies (Merck Serono Australia and Schering-Plough) who have a commercial interest in PCOS treatment products or guidelines; and is a member of the MSD–Schering-Plough Advisory Board.

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