Polycystic ovary syndrome (PCOS) - suspected Obstetrics and Gynaecology > Gynaecology > Polycystic ovary syndrome (PCOS)
Background information
Patient information
Key messages for this pathway
When should PCOS be suspected?
History and examination
Severe, rapid onset or virilisation
Refer to Endocrinology R
Screening investigations
Diagnostic criteria for PCOS
Criteria for PCOS met and no other biochemical abnormalities
Criteria for PCOS not met or other biochemical abnormalities
Diagnosis confirmed: education, support and lifestyle modification
Consider differential diagnoses
Consider referral to Endocrinology Determine goals of treatment
R
Assessment of cardiovascular risk
Management of infertility
Management of irregular periods
Management of cardiovascular risk
Consider early referral
Consider referral
Refer to infertility
Refer to Gynaecology R
Published: 21-Apr-2011
Valid until: 30-Nov-2011
Management of hyperandrogenism
Management of obesity
Consider referral to weight management programme
R
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Polycystic ovary syndrome (PCOS) - suspected Obstetrics and Gynaecology > Gynaecology > Polycystic ovary syndrome (PCOS)
1 Background information Quick info: Scope: • evaluation and management of polycystic ovary syndrome (PCOS) Definition: • a heterogeneous syndrome involving ovarian abnormality, disturbance to the menstrual cycle, infrequent or absent ovulation, hyperandrogenism (hirsutism), acne, obesity and metabolic disturbances • diagnosed when at least two of the following are present and other causes have been excluded: • infrequent or absent ovulation • clinical or biochemical evidence of hyperandrogenism • polycystic ovaries (either 12 or more follicles measuring 2-9mm in diameter, or ovarian volume of more than 10mL) Prevalence: • up to 33% of white caucasian women have polycystic ovaries, of whom 75-80% have symptoms and so up to 15-20% have a degree of PCOS as currently defined and this is even higher in the Asian population • approximately 80% of patients with irregular periods have PCOS Risk factors: • the exact causes of PCOS are not known, but women who have a first degree relative with the condition are at increased risk • some experts suggest obesity itself is a risk factor for PCOS Management: • management has traditionally involved trying to improve the symptoms of PCOS, eg hirsutism, acne, menstrual irregularity, infertility, alopecia, sleep apnoea • there is increasing emphasis on detecting and treating the metabolic disturbances often associated with PCOS, chiefly obesity, insulin resistance, type 2 diabetes and blood lipid abnormalities References: Royal College of Obstetricians and Gynaecologists (RCOG). Long-term consequences of polycystic ovary syndrome. Guideline No.33. London: RCOG; 2007. Cahill D. Polycystic ovary syndrome. Clin Evid 2009; 1: 1408-27. Clinical Knowledge Summaries (CKS). Polycystic ovary syndrome. Newcastle upon Tyne: CKS; 2007. Balen AH, Laven JSE, Tan S-L et al. Ultrasound assessment of the polycystic ovary: International consensus definitions. Hum Reprod Update 2003; 9: 505-14. Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome (PCOS). Fertil Steril 2004; 81: 19-25. Balen AH, Homburg R, Franks S. Defining polycystic ovary syndrome. Editorial. British Medical Journal 2009; 338: 426. Polycystic Ovary Syndrome Writing Committee. American Association of Clinical Endocrinologists position statement on metabolic and cardiovascular consequences of polycystic ovary syndrome. Endocr Pract 2005; 11: 125-34. Hyperandrogenic Disorders Task Force. AACE medical guidelines for clinical practice for the diagnosis and treatment of hyperandrogenic disorders. Endocr Pract 2001; 7: 120-34. National Institute for Health and Clinical Excellence (NICE). Fertility: assessment and treatment for people with fertility problems. Clinical Guideline 11. London: NICE; 2004. American College of Obstetricians and Gynecologists (ACOG). Polycystic ovary syndrome. Washington, DC: ACOG; 2002.
2 Patient information Quick info: http://www.pcos-uk.org.uk/ http://www.verity-pcos.org.uk/
3 Key messages for this pathway Quick info:
Published: 21-Apr-2011
Valid until: 30-Nov-2011
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Polycystic ovary syndrome (PCOS) - suspected Obstetrics and Gynaecology > Gynaecology > Polycystic ovary syndrome (PCOS)
This pathway has been developed for South West Hampshire. Key messages for this pathway: • PCOS is common and presentation variable • diagnosis includes exclusion of other hyperandrogenic/ anovulatory conditions • mainstay of treatment is diet and exercise • use specific interventions to manage specific symptoms • metformin not a first line treatment (lack of good evidence) • ultrasound is not essential if menstrual disturbance and biochemical evidence of hyperandrogenism, and other conditions excluded Contributors to this pathway: • Ms Julia Bowey, NHSSC • Dr Beata Brown, SUHT • Dr Alex Freeman, NHSSC • Dr Simon Hunter, NHSH • Dr Nick Macklon, SUHT • Dr Azraai Nasruddin, SUHT • Dr Dan Tongue, NHSSC • Dr Derek Waller, SUHT
4 When should PCOS be suspected? Quick info: PCOS should be suspected if the woman has one or more clinical features of: • infrequent or no ovulation: e.g. infertility, oligomenorrhoea (>35 days) or amenorrhoea (>6 months) • hyperandrogenism: e.g. hirsutism, acne vulgaris occurring after adolescence, male pattern alopecia Patients may present from adolescence and throughout reproductive life. There may also be other features, such as: • central obesity • acanthosis nigricans, commonly affecting axillae, perineum, extensor surfaces of elbows or knuckles, neck Suspicion is increased if there is a family history of PCOS. PCOS requires exclusion of other conditions with similar presentations. NB: Polycystic ovaries do not have to be present to make the diagnosis, and finding polycystic ovaries alone does not establish the diagnosis.
5 History and examination Quick info: History: • menstrual and reproductive history • family history of: • PCOS • diabetes • acne • female hirsutism • obesity • blood lipid abnormalities • cardiovascular disease • medications
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Polycystic ovary syndrome (PCOS) - suspected Obstetrics and Gynaecology > Gynaecology > Polycystic ovary syndrome (PCOS)
• use of anabolic steroids Examination: • hair and skin: • hirsutism – if present assess pattern and severity of hair growth • acne or oily skin • male pattern alopecia • acanthosis nigricans (brown pigmentation on neck, axillae, submammary area, subpanniculus, perineum) • age and rapidity of symptom onset • signs of virilisation (eg deep voice, reduced breast size, increased muscle bulk, clitoral hypertrophy) rarely seen in PCOS • other: • body mass index (BMI) and waist to hip ratio or waist alone • blood pressure • signs and symptoms of Cushing’s disease
6 Severe, rapid onset or virilisation Quick info: The following may indicate a serious underlying cause such as an ovarian or adrenal tumour, congenital adrenal hyperplasia: • severe hirsutism • hirsutism with rapid onset • virilisation Send blood for testosterone, sex hormone binding globulin and 17-hydroxyprogesterone, and refer for specialist assessment. If there is clinical suspicion of Cushing's syndrome, send 24 hour urine for cortisol and refer for specialist assessment.
8 Screening investigations Quick info: Tests to support the diagnosis To check for biochemical hyperandrogenaemia, take blood in the morning, in follicular phase (day 1-5 if menstrual cycle present): • total testosterone: either normal (up to 2.6 nmol/L) or mildly elevated (if >5nmol/L, always seek specialist advice) • sex hormone-binding globulin (SHBG): normal or low • calculated free androgen index (FAI; total testosterone divided by SHBG) is usually high (>6.1) in PCOS • consider measuring androstenedione if testosterone normal but clinical signs of hyperandrogenism (raised in ~20% of patients with PCOS, who usually have normal testosterone and FAI) Pelvic ultrasonography is only necessary if the diagnosis of PCOS is not obvious on clinical and biochemical assessment (see diagnostic criteria). Tests for insulin resistance are not required for diagnosis. To rule out other causes of oligomenorrhoea or amenorrhoea: • luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (increased in premature ovarian failure, decreased in hypogonadotropic hypogonadism) • oestradiol, in conjunction with LH and FSH to exclude primary ovarian failure or pituitary dysfunction • prolactin: to exclude hyperprolactinaemia (may be slightly raised in PCOS) • thyroid stimulating hormone: to exclude hypothyroidism
9 Diagnostic criteria for PCOS Quick info: Diagnostic criteria for PCOS (Rotterdam Consensus workshop 2003) are the presence of 2 of the following 3 features:
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Polycystic ovary syndrome (PCOS) - suspected Obstetrics and Gynaecology > Gynaecology > Polycystic ovary syndrome (PCOS)
• oligomenorrhoea (>35 days) or amenorrhoea (>6 months) - onset at puberty • clinical or biochemical signs of hyperandrogenaemia • polycystic ovaries on ultrasound: 12 or more cysts measuring 2-9mm diameter or increased ovarian volume >10ml PLUS • exclusion of other conditions that cause similar symptoms Ultrasound is not essential if there is menstrual disturbance and biochemical evidence of hyperandrogenism, and other conditions have been excluded. 25% of healthy women have ovarian cysts. However, it may be useful to assess endometrial thickness if there have been no periods for several months.
12 Diagnosis confirmed: education, support and lifestyle modification Quick info: Education: • patients with PCOS should be educated about the possible long-term risks of the condition, namely type 2 diabetes and cardiovascular disease • they should be advised to keep weight in the normal range and to exercise regularly • oligo- or amenorrhoea in women with PCOS may lead to endometrial hyperplasia and carcinoma • treatment with progestogens to induce withdrawal bleed at least every 3-4 months may be beneficial • no association with breast or ovarian cancer has been identified Support: • offer psychological support and counselling • make patient aware of support groups including Verity
13 Consider differential diagnoses Quick info: Possible differential diagnoses include: • hyperprolactinaemia • primary hypothyroidism • idiopathic hirsutism • anabolic steroid, glucocorticoid, hormonal contraceptive use • ovarian or adrenal androgen-secreting tumours (usually very high testosterone) • congenital adrenal hyperplasia (consider measuring 17-hydroxyprogesterone if possible PCOS and BMI normal) • Cushing’s syndrome • premature ovarian failure (high FSH and LH with low oestradiol) Hyperprolactinaemia or hypothyroidism can coexist with PCOS, but should be treated before considering specific management of PCOS.
15 Determine goals of treatment Quick info: Before considering further treatment, it is important to consider the most important clinical problems: • fertility • irregular periods • hirsutism/acne • obesity
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Polycystic ovary syndrome (PCOS) - suspected Obstetrics and Gynaecology > Gynaecology > Polycystic ovary syndrome (PCOS)
16 Management of irregular periods Quick info: Management of oligomenorrhoea or amenorrhoea includes: • weight loss • combined oral contraceptive (may also improve hirsutism) • intermittent progestogen treatment: • medroxyprogesterone 5-10mg for 12-14 days every 1-3 months • levonorgestrel-releasing intrauterine system (Mirena® coil)
17 Management of infertility Quick info: Infertility in PCOS may be due to other factors, and initial investigation should involve the couple, rather than the individual. 2
Advise weight loss, especially if BMI >29 Kg/m . As little as 5% reduction in body weight may be enough to initiate ovulatory cycles. Sensible eating and exercise may improve insulin sensitivity and restore ovulation. Stimulating ovulation with clomifene citrate is less successful in those with a high BMI. Anecdotal evidence suggests some patients will ovulate if given metformin (initially 500mg daily titrating to 500mg 3x daily unlicensed use) however there is no evidence to support this from formal trials.
18 Management of hyperandrogenism Quick info: Hirsutism Weight loss may help. Mild hirsutism may respond to cosmetic measures: • shaving, waxing, plucking and bleaching • laser • electrolysis More severe hirsutism may require drug treatment, but may take 6-9 months to respond • an anti-androgen such as cyproterone acetate, may be useful in combination with oestrogen (co-cyprindiol; Dianette®). Stop if possible as soon as hirsutism resolves (to minimise risk of venous thromboembolism) • topical eflornithine cream (Vaniqa®) may be considered for restricted use in women in whom alternative drug treatment cannot be used Acne • combined oral contraceptive pill • an anti-androgen such as cyproterone acetate, may be useful in combination with oestrogen (co-cyprindiol; Dianette®). Stop if possible as soon as acne resolves (to minimise risk of venous thromboembolism) • further treatment of acne is covered in a separate pathway (see Southampton acne pathway)
19 Assessment of cardiovascular risk Quick info: Women with PCOS are considered to be at a higher risk of developing cardiovascular problems. Assess cardiovascular risk factors: • measure: • waist measurement (high risk >36 inches) • blood pressure
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Valid until: 30-Nov-2011
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Polycystic ovary syndrome (PCOS) - suspected Obstetrics and Gynaecology > Gynaecology > Polycystic ovary syndrome (PCOS)
• fasting lipids (total cholesterol, HDL cholesterol and triglycerides) 2
• fasting glucose if BMI >29Kg/m , if abnormal, consider oral glucose tolerance test Conventional cardiovascular risk calculators have not been validated for use in women with PCOS. However, guidelines from the Royal College of Obstetricians and Gynaecologists recommend their use for assessing risk. If test results are normal, retest every 3-5 years.
20 Management of obesity Quick info: Manage obesity by: • weight reduction - most important. Eat a healthy diet of regular hypocalorific meals • exercise - aim for 30 minutes sweat-inducing exercise daily • orlistat, as per NICE guidelines CG43 http://www.nice.org.uk/nicemedia/live/11000/30364/30364.pdf NB: metformin enhances insulin sensitivity but does not help with weight reduction In many obese women with PCOS, regular exercise and weight loss will: • normalise glucose metabolism • lower androgen levels and raise levels of sex hormone binding globulin hormone • restart ovulation • improve fertility • decrease risk of developing type 2 diabetes mellitus in later life by up to 58%
21 Management of cardiovascular risk Quick info: Management: • lifestyle advice, including weight loss and exercise • treat hypertension as appropriate • lipid-lowering therapy is not routinely recommended. Current guidelines suggest treatment according to standard risk calculations • metformin for glucose intolerance
22 Consider early referral Quick info: Early referral may be appropriate if the woman is older and wishes to have children. Women with PCOS who become pregnant have a greater risk of: • gestational diabetes • pre-eclampsia • premature delivery
23 Consider referral to weight management programme Quick info: People who are morbidly obese should be initially referred to a weight management service if initial measures do not achieve weight loss. South Central Specialised Commissioning Group guidance for considering surgery is applicable to people if: • they have a BMI of 45 kg/m2 or more and other significant disease (for example, type 2 diabetes mellitus, high blood pressure) that could be improved if they lost weight
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Polycystic ovary syndrome (PCOS) - suspected Obstetrics and Gynaecology > Gynaecology > Polycystic ovary syndrome (PCOS)
• they have a BMI of more than 60 kg/m2 and surgical intervention is considered appropriate; consider orlistat before surgery if the waiting time is long • an individual funding request has been made, see http://www.srbu.org/SRBU/SRBU/GP_downloads_files/SC%20HA %20Bariatric%20Form.pdf NB: NICE guidance for considering surgery is less stringent, and is applicable to people if: • they have a BMI of 40 kg/m2 or more, or between 35 kg/m2 and 40 kg/m2 and other significant disease (for example, type 2 diabetes, high blood pressure) that could be improved if they lost weight • they have a BMI of more than 50 kg/m2 and surgical intervention is considered appropriate; consider orlistat before surgery if the waiting time is long • all appropriate non-surgical measures have failed to achieve or maintain adequate clinically beneficial weight loss for at least 6 months (BMI 35-49 kg/m2) • they are generally fit for anaesthesia and surgery • they commit to the need for long-term follow-up
24 Consider referral Quick info: Women with fewer than 4 periods or withdrawal bleeds per year require referral, due to an increased risk of endometrial hyperplasia/ carcinoma. Uterine ultrasound should be requested to determine endometrial thickness.
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Valid until: 30-Nov-2011
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Polycystic ovary syndrome (PCOS) - suspected Obstetrics and Gynaecology > Gynaecology > Polycystic ovary syndrome (PCOS)
Key Dates Published: 21-Apr-2011, by Valid until: 30-Nov-2011
Evidence summary for Polycystic ovary syndrome (PCOS) - suspected The pathway is based on our interpretation of the following guidelines: 9, 16, 1, 14, 2, 12. All of these guidelines have been graded for quality and prioritised for inclusion based on their methodological quality. All intervention nodes (i.e. those concerning therapy and therapeutic advice) have been graded for the quality of the evidence underlying them (see table 1). Key non-interventional nodes have been referenced in table 2.
References This is a list of all the references that have passed critical appraisal for use in the care map Polycystic ovary syndrome (PCOS) ID Reference 1 American College of Obstetricians and Gynecologists. Polycystic ovary syndrome. Washington, DC: American College of Obstetricians and Gynecologists; 2002. 2 American College of Obstetricians and Gynecologists. Management of infertility caused by ovulatory dysfunction. Washington, DC: American College of Obstetricians and Gynecologists; 2002. 3 Balen AH. Indications for the use of metformin in polycystic ovary syndrome. Royal College of Obstetricians and Gynaecologists Scientific Advisory Committee paper 13. London: Royal College of Obstetricians and Gynaecologists; 2008. 4 Balen AH Anderson R. Impact of obesity on female reproductive health: British Fertility Society, Police and Practice Guidelines. Human Fertility 2007; 10: 195-206. 5 Balen AH Homburg R Franks S. Defining polycystic ovary syndrome. Editorial. BMJ 2009; 338: 426. 6 Balen AH, Laven JSE, Tan S-L et al. Ultrasound assessment of the polycystic ovary: International consensus definitions. Hum Reprod Update 2003; 9: 505-514. 7 Beck JI, Boothroyd C, Proctor M et al. Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation. Cochrane Database Syst Rev 2005; CD002249. http://www.ncbi.nlm.nih.gov/pubmed/15674894 8 Cahill D. Polycystic ovary syndrome. Clin Evid 2009; 1408-27. http://www.ncbi.nlm.nih.gov/pubmed/19445767 9 Clinical Knowledge Summaries (CKS). Polycystic ovary syndrome. Newcastle upon Tyne: CKS; 2007. 10 Farquhar C, Lilford RJ, Marjoribanks J et al. Laparoscopic "drilling" by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev 2007; CD001122. http://www.ncbi.nlm.nih.gov/pubmed/17636653 11 Heijnen EM Eijkemans MJ Hughes EG et al. A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update 2006; 12: 13-21. 12 Hyperandrogenic Disorders Task Force. AACE medical guidelines for clinical practice for the diagnosis and treatment of hyperandrogenic disorders. Endocr Pract 2001; 7: 120-134. http://www.aace.com/pub/pdf/guidelines/hyperandrogenism2001.pdf 13 National Institute for Health and Clinical Excellence (NICE). Fertility: assessment and treatment for people with fertility problems. Clinical Guideline No 11. London: NICE; 2004. http://www.nice.org.uk/nicemedia/pdf/CG011niceguideline.pdf 14 Polycystic Ovary Syndrome Writing Committee. American Association of Clinical Endocrinologists position statement on metabolic and cardiovascular consequences of polycystic ovary syndrome. Endocr Pract 2005; 11: 125-134. http://www.aace.com/pub/pdf/guidelines/PCOSpositionstatement.pdf 15 Rotterdam EDHRE/ASRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Fertil Steril 2004; 81: 19-25. 16 Royal College of Obstetricians and Gynaecologists (RCOG). Long-term consequences of polycystic ovary syndrome. Guideline No.33. London: RCOG; 2007. http://www.rcog.org.uk/womens-health/clinical-guidance/long-term-consequences-polycystic-ovarysyndrome-green-top-33 17 Sinawat S Buppasin P Lumbiganon P et al. Long versus short course treatment with Metformin and Clomiphene Citrate for ovulation induction in women with PCOS. Cochrane Database Syst Rev 2008; CD006226. http://www.ncbi.nlm.nih.gov/pubmed/18254096
Published: 21-Apr-2011
Valid until: 30-Nov-2011
Printed on: 12-Aug-2011
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Polycystic ovary syndrome (PCOS) - suspected Obstetrics and Gynaecology > Gynaecology > Polycystic ovary syndrome (PCOS)
ID Reference 18 Tang T Lord JM Norman RJ et al. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiroinositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 2009; CD003053: http://www.ncbi.nlm.nih.gov/pubmed/19821299
Published: 21-Apr-2011
Valid until: 30-Nov-2011
Printed on: 12-Aug-2011
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