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.
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]
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 for more information.
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