PrintDownload PDFGet Adobe ReaderDownload to WordDownload as HTMLDownload as XMLCitation Manager
Save to Favorites
Guideline Summary
Guideline Title
Long-term consequences of polycystic ovary syndrome.
Bibliographic Source(s)
Royal College of Obstetricians and Gynaecologists (RCOG). Long-term consequences of polycystic ovary syndrome. London (UK): Royal College of Obstetricians and Gynaecologists (RCOG); 2007 Dec. 11 p. (Green-top guideline; no. 33).  [76 references]
Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Royal College of Obstetricians and Gynaecologists (RCOG). Long-term consequences of polycystic ovary syndrome. London (UK): Royal College of Obstetricians and Gynaecologists (RCOG); 2003 May. 8 p. (Guideline; no. 33). [38 references]

The Royal College of Obstetricians and Gynaecologists (RCOG) reaffirmed the currency of this guideline in 2012.

FDA Warning/Regulatory Alert

Note from the National Guideline Clearinghouse: This guideline references a drug(s) for which important revised regulatory and/or warning information has been released.

Drug Withdrawal

  • October 8, 2010 – Meridia (sibutramine) External Web Site Policy: Abbott Laboratories and the U.S. Food and Drug Administration (FDA) notified healthcare professionals and patients about the voluntary withdrawal of Meridia (sibutramine), an obesity drug, from the U.S. market because of clinical trial data indicating an increased risk of heart attack and stroke. Physicians are advised to stop prescribing Meridia to their patients, and patients should stop taking this medication. Patients should talk to their health care provider about alternative weight loss and weight loss maintenance programs.

Scope

Disease/Condition(s)
  • Polycystic ovary syndrome (PCOS)
  • Long term consequences of PCOS: type 2 diabetes, gestational diabetes, cardiovascular disease, obstructive sleep apnea, endometrial hyperplasia and cancer

Note: This guideline does not cover infertility associated with PCOS, which has been extensively reviewed elsewhere.

Guideline Category
Counseling
Diagnosis
Evaluation
Management
Prevention
Risk Assessment
Screening
Treatment
Clinical Specialty
Endocrinology
Family Practice
Internal Medicine
Obstetrics and Gynecology
Intended Users
Advanced Practice Nurses
Nurses
Physician Assistants
Physicians
Guideline Objective(s)
  • To provide information, based on clinical evidence, to assist clinicians with a special interest in polycystic ovary syndrome (PCOS)
  • To update the generalist who manages women with PCOS, to allow them to advise women about the long-term health consequences of the syndrome
Target Population

Women in the United Kingdom with polycystic ovary syndrome

Interventions and Practices Considered

Diagnosis/Risk Assessment

  1. Body mass index
  2. Family history
  3. Exclusion of other etiologies
  4. Thyroid function tests
    • Serum prolactin
    • Free androgen index
    • 17-hydroxyprogesterone levels
    • Exclusion of androgen-secreting tumors
    • Investigations for Cushing syndrome

Management/Treatment

  1. Counseling women about long-term health risk of polycystic ovary syndrome (PCOS)
  2. Providing advice on weight control and exercise
  3. Glucose tolerance test
  4. Investigations and treatment for obstructive sleep apnea
  5. Screening and treatment for hypertension
  6. Screening for gestational diabetes before 20 weeks of gestation and referral to obstetric diabetic service if necessary
  7. Use of metformin in pregnancy (not recommended)
  8. Treatment with progestogens for oligo- or amenorrhea
  9. Use of insulin-sensitizing agents in women who are not diabetic (not licensed for such use in women with PCOS in the United Kingdom)
  10. Use of weight-reduction drugs
Major Outcomes Considered
  • Incidence of type II diabetes, cardiovascular disease, gestational diabetes, and endometrial hyperplasia and carcinoma in association with polycystic ovary syndrome (PCOS)
  • Sensitivity of risk assessment calculators

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

2007 Guideline

The Cochrane Library (including the Cochrane Database of Systematic Reviews, DARE and EMBASE), TRIP, Medline and PubMed (electronic databases) were searched for relevant randomised controlled trials, systematic reviews and meta-analyses. The search was restricted to articles published between 1966 and October 2006. The databases were searched using the relevant Medical Subject Headings (MeSH) terms including all subheadings and this was combined with a keyword search. The MeSH search included 'polycystic ovary', 'metabolic', 'diabetes', 'cardiovascular' and 'glitazone' and the search was limited to humans and the English language. The computer search was complemented by hand searching from original references and reviews.

2012 Reaffirmation

A literature search was completed and reviewed by the Guideline Development Group and was restricted to articles published between 1946 and August 2012. The following electronic databases were searched: The Cochrane Library (including the Cochrane Database of Systematic Reviews, DARE and EMBASE), TRIP, Medline and PubMed.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

Classification of Evidence Levels

Ia: Evidence obtained from meta-analysis of randomised controlled trials

Ib: Evidence obtained from at least one randomised controlled trial

IIa: Evidence obtained from at least one well-designed controlled study without randomisation

IIb: Evidence obtained from at least one other type of well-designed quasi-experimental study

III: Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies, and case studies

IV: Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities

Methods Used to Analyze the Evidence
Review of Published Meta-Analyses
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence

Once the evidence has been collated for each clinical question, it needs to be appraised and reviewed. For each question, the study type with least chance of bias should be used. If available, randomised controlled trials of suitable size and quality should be used in preference to observational data. This may vary depending on the outcome being examined.

The methods used to appraise individual study types are available from the Scottish Intercollegiate Guidelines Network (SIGN) (www.sign.ac.uk/methodology/checklists.html External Web Site Policy). An objective appraisal of study quality is essential but paired reviewing by guideline leads may be impractical because of resource constraints.

Once evidence has been collated and appraised, it can be graded. A judgement on the quality of the evidence will be necessary using the grading system (see the "Rating Scheme for the Strength of the Evidence" field). Where evidence is felt to warrant 'down-grading', for whatever reason, the rationale must be stated. Evidence judged to be of poor quality can be excluded. Any study with a high chance of bias (either 1– or 2–) will be excluded from the guideline and recommendations will not be based on this evidence. This prevents recommendations being based on poor-quality randomised controlled trials when higher-quality observational evidence is available.

Methods Used to Formulate the Recommendations
Expert Consensus
Informal Consensus
Description of Methods Used to Formulate the Recommendations

Guideline Development

The development of guidelines involves more than the collation and reviewing of evidence. Even with high-quality data from systematic reviews of randomised controlled trials, a value judgement is needed when comparing one therapy with another. This will therefore introduce the need for consensus.

Royal College of Obstetricians and Gynaecologists (RCOG) Green-top Guidelines are drafted by nominated developers, in contrast to other guideline groups such as the National Institute for Health and Clinical Excellence (NICE) and the Scottish Intercollegiate Guidelines Network (SIGN), who use larger guideline development groups. Equally, in contrast to other guideline groups, the topics chosen for development as Green-top Guidelines are concise enough to allow development by a smaller group of individuals.

In agreeing the precise wording of evidence-based guideline recommendations and in developing consensus-based 'good practice points', the Guidelines and Audit Committee (GAC) will employ an informal consensus approach through group discussion. In line with current methodologies, the entire development process will follow strict guidance and be both transparent and robust. The RCOG acknowledges that formal consensus methods have been described but these require further evaluation in the context of clinical guideline development. It is envisaged that this will not detract from the rigor of the process but prevent undue delays in development.

Rating Scheme for the Strength of the Recommendations

Grade A - Requires at least one randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation (evidence levels Ia, Ib)

Grade B - Requires the availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendations (evidence levels IIa, IIb, III)

Grade C - Requires evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates an absence of directly applicable clinical studies of good quality (evidence level IV)

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
External Peer Review
Internal Peer Review
Description of Method of Guideline Validation

Following discussion in the Guidelines and Audit Committee, each green-top guideline is formally peer reviewed. At the same time the draft guideline is published on the Royal College of Obstetricians and Gynaecologists (RCOG) website for further peer discussion before final publication.

The names of author(s) and nominated peer reviewers are included in the original guideline document.

Recommendations

Major Recommendations

In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.

Levels of evidence (Ia–IV) and grading of recommendations (A–C) are defined at the end of the "Major Recommendations" field.

Diagnosis

How Is Polycystic Ovary Syndrome (PCOS) Diagnosed?

B - Diagnosis of PCOS can only be made when other aetiologies have been excluded (thyroid dysfunction, congenital adrenal hyperplasia, hyperprolactinaemia, androgen-secreting tumours and Cushing syndrome).

The recommended baseline screening tests are thyroid function tests, a serum prolactin and a free androgen index (total testosterone divided by sex hormone binding globulin [SHBG] x 100 to give a calculated free testosterone level). In cases of clinical evidence of hyperandrogenism and total testosterone greater than 5 nmol/L, 17-hydroxyprogesterone should be sampled and androgen-secreting tumours excluded. If there is a clinical suspicion of Cushing syndrome, this should be investigated according to local practice. [Evidence level IIB]

Counselling

How Should Women Be Counselled?

B - Women diagnosed with PCOS should be informed of the possible long-term risks to health that are associated with their condition. They should be advised regarding weight control and exercise.

Long-term Consequences of PCOS

What Is the Risk of Developing Type II Diabetes in Women with PCOS?

B - Women presenting with PCOS, particularly if they are obese (body mass index greater than 30), have a strong family history of type 2 diabetes or are over the age of 40 years, are at increased risk of type 2 diabetes and should be offered a glucose tolerance test.

A sensible approach to ensuring early detection of diabetes might be to offer screening to women with PCOS with measurement of fasting blood glucose, on a regular basis, perhaps annually. However, if the fasting blood glucose is 5.6 mmol/L or greater, body mass index is greater than 30 or a strong family history of diabetes, then an oral glucose tolerance test should be arranged. Although fasting glucose was poorly discriminatory for type 2 diabetes in studies to date, it is a more appropriate test for routine screening. [Evidence level IV]

What Is the Risk of Developing Obstructive Sleep Apnoea in Women with PCOS?

B - Women diagnosed with PCOS (or their partners) should be asked about snoring and daytime fatigue/somnolence and informed of the possible risk of sleep apnoea, and offered investigation and treatment when necessary.

Sleep apnoea is an independent cardiovascular risk factor and has been found to be more common in PCOS. [Evidence level III]

What Is the Risk of Developing Cardiovascular Disease in Women with PCOS?

B - In clinical practice, hypertension should be treated but lipid-lowering treatment is not recommended routinely and should only be prescribed by a specialist.

From a clinical perspective, clinicians should continue to identify cardiovascular risk factors in women with PCOS and treat these accordingly. In clinical practice, hypertension should be treated according to the Joint British Society Guidelines, which should be referred to. These guidelines suggest that persistent blood pressures greater than or equal to 140 mmHg systolic and or 90 mmHg diastolic, not responding to lifestyle measures, need to be considered for drug therapy (women with diabetes or other high risk factors with blood pressure greater than 130 mmHg systolic and or 80 mmHg diastolic may require drug therapy). Lipid-lowering treatment is not recommended routinely and should be prescribed by a specialist. [Evidence level III]

PCOS and Pregnancy

What Are the Implications of PCOS for Pregnancy?

B - Women who have been diagnosed as having PCOS before pregnancy (such as those requiring ovulation induction for conception) should be screened for gestational diabetes before 20 weeks of gestation, with referral to a specialised obstetric diabetic service if abnormalities are detected.

D - Metformin is currently not licensed for use in pregnancy in the UK and is not recommended for use in pregnancy.

Cancer and PCOS

What Are the Risks of Cancer in Women with PCOS?

B - Oligo- or amenorrhoea in women with PCOS may predispose to endometrial hyperplasia and later carcinoma. It is good practice to recommend treatment with progestogens to induce a withdrawal bleed at least every 3 to 4 months.

C - There does not appear to be an association with breast or ovarian cancer and no additional surveillance is required.

In women with PCOS intervals between menstruation of more than 3 months may be associated with endometrial hyperplasia. Regular induction of a withdrawal bleed with cyclical gestogens, such as progestogens for at least 12 days, oral contraceptive pills or the Mirena® intrauterine system, would be advisable in oligomenorrhoeic women with PCOS. Women who are oligomenorrhoeic and do not have normal withdrawal bleeds should be investigated and managed according to local protocols. This may include ultrasound scan, endometrial sampling and/or hysteroscopy. [Evidence level IIa]

Strategies for Reduction of Risk

How Should Women with PCOS Be Advised on Lifestyle Issues?

B - Women diagnosed with PCOS should be advised regarding weight loss through diet and exercise.

In the absence of any robust long-term follow-up data for lifestyle interventions, it would seem prudent to advise regular exercise (aiming for a mean 30 minutes sweat-inducing exercise daily) as the most important lifestyle measure, and to have a healthy, balanced diet of regular, hypocalorific meals through the day. [Evidence level Ib]

Is Drug Therapy Appropriate for Women with PCOS?

B - Insulin-sensitising agents have not been licensed in the United Kingdom (UK) for use in women who are not diabetic. Although a body of evidence has accumulated demonstrating the safety of these drugs, there is currently no evidence of a long-term benefit for the use of insulin-sensitising agents.

B - Use of weight-reduction drugs may be helpful in reducing insulin resistance through weight loss.

There is evidence that metformin may modestly reduce androgen levels by around 11% in women with PCOS compared with placebo and modest reductions in body weight have been reported by some, but not all studies. Women with a body mass index of more than 37 may not respond well to metformin therapy. It must be emphasised that both metformin and the thiazolidinediones are unlicensed for use in PCOS and patients should be counselled before initiating therapy. [Evidence level Ib]

Orlistat and sibutramine* have been shown to significantly reduce body weight and hyperandrogenism in women with PCOS. However, the use of sibutramine* is not recommended in patients with systolic hypertension. There is currently no data on the use of rimonabant in women with PCOS but evidence suggests it may have benefit transferable to women with PCOS in weight reduction and improvement in the cardiometabolic profile. Bariatric surgery may be indicated in selected women with morbid obesity.

*Note from the National Guideline Clearinghouse (NGC): On October 8, 2010, Abbott Laboratories and the U.S. Food and Drug Administration (FDA) notified healthcare professionals and patients about the voluntary withdrawal of Meridia (sibutramine), an obesity drug, from the U.S. market because of clinical trial data indicating an increased risk of heart attack and stroke. Physicians are advised to stop prescribing Meridia to their patients, and patients should stop taking this medication. Patients should talk to their health care provider about alternative weight loss and weight loss maintenance programs. See the FDA Web site External Web Site Policy for more information.

Definitions:

Grades of Recommendations

Grade A - Requires at least one randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation (evidence levels Ia, Ib)

Grade B - Requires the availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendations (evidence levels IIa, IIb, III)

Grade C - Requires evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates an absence of directly applicable clinical studies of good quality (evidence level IV)

Classification of Evidence Levels

Ia: Evidence obtained from meta-analysis of randomised controlled trials

Ib: Evidence obtained from at least one randomised controlled trial

IIa: Evidence obtained from at least one well-designed controlled study without randomisation

IIb: Evidence obtained from at least one other type of well-designed quasi-experimental study

III: Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies, and case studies

IV: Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is identified and graded for selected recommendations (see the "Major Recommendations" field).

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Appropriate management of polycystic ovary syndrome and prevention of the associated long-term health consequences

Potential Harms

Not stated

Qualifying Statements

Qualifying Statements
  • These recommendations are not intended to dictate an exclusive course of management or treatment. They must be evaluated with reference to individual patient needs, resources and limitations unique to the institution and variations in local populations. It is hoped that this process of local ownership will help to incorporate these guidelines into routine practice. Attention is drawn to areas of clinical uncertainty where further research may be indicated.
  • The Royal College of Obstetricians and Gynaecologists (RCOG) produces guidelines as an educational aid to good clinical practice. They present recognised methods and techniques of clinical practice, based on published evidence, for consideration by obstetricians and gynaecologists and other relevant health professionals. The ultimate judgement regarding a particular clinical procedure or treatment plan must be made by the doctor or other attendant in the light of clinical data presented by the patient and the diagnostic and treatment options available. This means that RCOG Guidelines are unlike protocols or guidelines issued by employers, as they are not intended to be prescriptive directions defining a single course of management. Departure from the local prescriptive protocols or guidelines should be fully documented in the patient’s case notes at the time the relevant decision is taken.

Implementation of the Guideline

Description of Implementation Strategy

Auditable Standards

  1. Accurate diagnosis of polycystic ovary syndrome (PCOS) defined and based on two of the three criteria from the Rotterdam consensus.
  2. Blood pressure measurement and a fasting blood glucose should be taken.
  3. Women with a body mass index greater than 30 or a strong family history of type 2 diabetes should have a glucose tolerance test, particularly if fertility is an issue.
  4. All overweight PCOS women should be provided with dietary and lifestyle advice.
  5. Amenorrhoeic or severely oligomenorrhoeic women with PCOS should have induced withdrawal bleeds at regular intervals to reduce the risk of developing endometrial hyperplasia.
Implementation Tools
Audit Criteria/Indicators
Patient Resources
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Living with Illness
Staying Healthy
IOM Domain
Effectiveness
Patient-centeredness

Identifying Information and Availability

Bibliographic Source(s)
Royal College of Obstetricians and Gynaecologists (RCOG). Long-term consequences of polycystic ovary syndrome. London (UK): Royal College of Obstetricians and Gynaecologists (RCOG); 2007 Dec. 11 p. (Green-top guideline; no. 33).  [76 references]
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2003 May (revised 2007 Dec; reaffirmed 2012)
Guideline Developer(s)
Royal College of Obstetricians and Gynaecologists - Medical Specialty Society
Source(s) of Funding

Royal College of Obstetricians and Gynaecologists

Guideline Committee

Guidelines and Audit Committee of the Royal College of Obstetricians and Gynaecologists

Composition of Group That Authored the Guideline

Committee Members: Professor WL Ledger FRCOG, Sheffield, Professor SL Atkin, Hull and Dr Li Wei Cho, Hull

Peer Reviewers: Professor AH Balen FRCOG, Leeds; Professor S Franks FRCOG, London; Professor N Haites, Department of Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, Scotland; British Fertility Society; Diabetes UK; Mr JM Lord MRCOG, Truro; Dr J McManus FRCOG, Belfast, N Ireland; Dr. A Chavez-Badiola, Consultant Gynaecologist, West Mexico Fertility Services, Guadalajara, Mexico; Dr C Duncan, Department of Obstetrics and Gynaecology, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, Scotland; RCOG Consumers' Forum, Dr D Siassakos, SpR Obstetrics and Gynaecology, Taunton and Somerset Hospital; Mr PG Wardle FRCOG, Bristol

Guidelines and Audit Lead Reviewers: Dr MR Gazvani MRCOG, Liverpool; Mrs C Overton FRCOG, Bristol

Financial Disclosures/Conflicts of Interest

Guideline authors are required to complete a "declaration of interests" form.

Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Royal College of Obstetricians and Gynaecologists (RCOG). Long-term consequences of polycystic ovary syndrome. London (UK): Royal College of Obstetricians and Gynaecologists (RCOG); 2003 May. 8 p. (Guideline; no. 33). [38 references]

The Royal College of Obstetricians and Gynaecologists (RCOG) reaffirmed the currency of this guideline in 2012.

Guideline Availability
Availability of Companion Documents

The following are available:

  • Development of RCOG green-top guidelines: policies and processes. Clinical Governance Advice No 1a. 2006 Nov. Available from the Royal College of Obstetricians and Gynaecologists (RCOG) Web site External Web Site Policy.
  • Development of RCOG green-top guidelines: producing a scope. Clinical Governance Advice No 1b. 2006 Nov. Available from the RCOG Web site External Web Site Policy.
  • Development of RCOG green-top guidelines: producing a clinical practice guideline. Clinical Governance Advice No 1c. 2006 Nov. Available from the RCOG Web site External Web Site Policy.

In addition, auditable standards are available in section 12 of the original guideline document.

Patient Resources

The following is available:

Print copies: Available from the National Health Service (NHS) Response Line 0870 1555 455, ref: 23809. 11 Strand, London, WC2N 5HR.

Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content.

NGC Status

This NGC summary was completed by ECRI on October 17, 2005. This NGC summary was updated by ECRI Institute on June 12, 2010. This summary was updated by ECRI Institute on November 8, 2010 following the U.S. Food and Drug Administration advisory on Avandia (rosiglitazone). The currency of the guideline was reaffirmed by the developer in 2010 and this summary was updated by ECRI Institute on November 15, 2012.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.

Disclaimer

NGC Disclaimer

The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

Read full disclaimer...