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Women's health

Polycystic ovary syndrome

Last revised in March 2025

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with clinical features that include hirsutism and acne (due to excess androgens)

Polycystic ovary syndrome: Summary

  • Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that appears to emerge at puberty. 
  • It is characterized by hyperandrogenism (with clinical features such as acne and hirsutism), ovulation disorder (usually manifested as infrequent or no menstruation), and polycystic ovarian morphology on ultrasound. 
  • PCOS is one of the most common endocrine disorders affecting women of reproductive age.
  • The cause of PCOS is unknown. It is likely to be multifactorial, with both genetic and environmental factors playing a part.
  • Complications of PCOS include:
    • Infertility.
    • Cardiovascular disease (CVD).
    • Metabolic disorders, such as impaired glucose tolerance and type 2 diabetes.
    • Obstructive sleep apnoea.
    • Psychological disorders, such as anxiety and depression.
    • Pregnancy complications, such as pre-eclampsia and gestational diabetes.
    • Endometrial cancer.
    • Non-alcoholic fatty liver disease.
  • To help diagnose PCOS:
    • Free androgen index should be calculated to assess the amount of physiologically active testosterone present. 
    • Luteinizing hormone, follicle-stimulating hormone, prolactin, and thyroid-stimulating hormone levels should be measured to rule out other causes of oligomenorrhoea and amenorrhoea (such as premature ovarian failure, hypothyroidism, and hyperprolactinaemia).
    • Referral for an ultrasound scan is required in adult women (unless the diagnosis of PCOS is obvious on clinical and biochemical grounds). An ultrasound scan should not be used for the diagnosis of PCOS in adolescents due to the high incidence of multi-follicular ovaries in this life stage.
    • Polycystic ovaries on ultrasound is defined as the presence of 20 or more follicles in at least one ovary.
  • In adults, PCOS should be diagnosed if two of the following are present (provided other causes of menstrual disturbance and hyperandrogenism have been excluded):
    • Clinical and/or biochemical signs of hyperandrogenism.
    • Ovulatory dysfunction.
    • Polycystic ovarian morphology on ultrasound. 
  • When diagnosing PCOS in adolescents, tighter criteria requiring both hyperandrogenism and irregular menstrual cycles is recommended due to the overlap with normal pubertal reproductive physiology. 
  • Management of PCOS includes:
    • Managing the clinical features of PCOS.
    • Screening for cardiovascular risk factors and advising on healthy lifestyle measures to reduce CVD risk. Where appropriate, weight loss should be advised.
    • Assessing for (and managing) other possible complications of PCOS.
    • Providing sources of additional information and support.
  • Adolescents who have features of PCOS but do not meet the diagnostic criteria should be considered to be at 'increased risk' of PCOS and reassessed at or before full reproductive maturity (8 years post-menarche). This includes those with PCOS features before combined oral contraceptive pill commencement, those with persisting features, and those with significant weight gain in adolescence.

Have I got the right topic?

From age 12 years onwards (Female).

This CKS topic covers the diagnosis and management of polycystic ovary syndrome (PCOS) in primary care.

This CKS topic does not cover the management of PCOS in secondary care.

There are separate CKS topics on Acne vulgaris, Amenorrhoea, Contraception - combined hormonal methods, CVD risk assessment and management, Depression, Diabetes - type 2, Eating disorders, Female pattern hair loss (female androgenetic alopecia) Generalized anxiety disorder, Hirsutism, Infertility, Menopause, Obesity, and Obstructive sleep apnoea syndrome.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

Changes

March 2025 — minor update. Further information added to the basis for recommendation relating to anti-Mullerian hormone testing. 

Previous changes

July 2024 — minor update. Minor typographical error corrected. 

April 2024 — minor update. Clarification added regarding polycystic ovarian morphology and links to the International PCOS Network diagnostic criteria [International PCOS Network, 2023]. 

February 2024 — minor update. Updated the topic in line with recommendations in the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International PCOS Network. Updates include; refinements to the diagnostic criteria have been made. New advice on the assessment of PCOS in the post-menopause has been added. All women with PCOS should be offered a lipid profile and glycaemic testing with an oral glucose tolerance test regardless of BMI. 

January 2024 — minor update. Broken link fixed. 

July 2023 — reviewed. A literature search was conducted in May 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. The recommendations on the use of metformin have been updated.

May 2023 — minor update. Information that reliable assessment of biochemical hyperandrogenism is not possible in women taking hormonal contraception, and that contraception should be withdrawn for 3 months before testing has been added to this topic. 

February 2022 — minor update. The information about metformin being contraindicated in pregnancy has been removed. The manufacturer's summary of product characteristics (SPC) states that metformin can be used in pregnancy and the periconception phase if clinically needed. 

September 2018 — reviewed. A literature search was conducted in August 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. 

  • Recommendations on the diagnosis of polycystic ovary syndrome (PCOS) in adolescents have been updated in line with recommendations in the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018 issued by the International PCOS Network:
    • When diagnosing PCOS in adolescents, tighter criteria requiring both hyperandrogenism and irregular menstrual cycles is recommended due to the overlap with normal reproductive physiology.
    • Ultrasound scan is no longer recommended in the diagnosis of PCOS in those within 8 years of menarche due to the high incidence of multi-follicular ovaries in this life stage.
    • Adolescents who have features of PCOS but do not meet the diagnostic criteria should be considered to be at 'increased risk' of PCOS and reassessed at or before full reproductive maturity (8 years post-menarche). This includes those with PCOS features before combined oral contraceptive pill commencement, those with persisting features, and those with significant weight gain in adolescence.
    • Irregular menstrual cycles are defined as:
      • Normal in the first year post-menarche as part of the pubertal transition.
      • More than 1 year to less than 3 years of irregular cycles (more than 45 days or less than 21 days) after the onset of menarche.
      • More than 3 years of irregular cycles (more than 35 days or less than 21 days, or less than 8 cycles every year) post-menarche to perimenopause.
      • More than 1 year of irregular cycles (more than 90 days for any one cycle) post-menarche.
      • Primary amenorrhea by age 15 years or more than 3 years of irregular cycles post thelarche (breast development).
  • The topic has been restructured in light of these changes. 

February to June 2013 — reviewed. A literature search was conducted in February 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. New information has been added regarding when to suspect PCOS in adolescents, and about emotional wellbeing. The information on the management of infertility has been updated. There are no major changes to the recommendations.

June 2011 — minor update. A link to the CKS topic on Contraception - combined hormonal methods for a full discussion of the risks of combined oral contraceptives (COCs) has been added to the management section. Some broken links were also fixed.

March 2011 — topic structure revised to ensure consistency across CKS topics. No changes to clinical recommendations have been made.

December 2009 — minor update. The choice of COC for women with hirsutism has been updated to be in line with the CKS topic on Hirsutism. Advice on the importance of weight loss, if overweight, has been reworded. 

July to October 2009 — converted from CKS guidance to CKS topic structure. The evidence base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. There are no major changes to the recommendations.

July to September 2006 — written. Validated in December 2006 and issued in January 2007.

Update

New evidence

Evidence-based guidelines

  • International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International PCOS Network [Free-full text]

HTAs (Health Technology Assessments)

No new HTAs since 1 May 2023.

Economic appraisals

No new economic appraisals relevant to England since 1 May 2023.

Systematic reviews and meta-analyses

  • Scragg, J., Hobson, A, Willis, L., et al. (2024) Effect of Weight Loss Interventions on the Symptomatic Burden and Biomarkers of Polycystic Ovary Syndrome : A Systematic Review of Randomized Controlled Trials. Annals of Internal Medicine. https://www.acpjournals.org [Abstract]

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 May 2023.

New policies

No new national policies or guidelines since 1 May 2023.

New safety alerts

No new safety alerts since 1 May 2023.

Changes in product availability

No changes in product availability since 1 May 2023.

Goals and outcome measures

Goals

To support primary healthcare professionals to:

  • Make a diagnosis of an recognize polycystic ovary syndrome (PCOS) in its early stages.
  • Manage the clinical features of PCOS (such as acne, hirsutism, oligomenorrhoea, and alopecia).
  • Screen for and manage cardiovascular risk factors.
  • Screen for and manage other complications of PCOS, such as infertility, sleep apnoea, and psychological disorders.
  • Appropriately refer women with PCOS to secondary care or other specialist services.
  • Provide appropriate information and advice to women with PCOS.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

No NICE quality standards were found during the review of this topic.

Background information

What is it?

  • Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that appears to emerge at puberty.
  • It is characterized by hyperandrogenism (with clinical features such as acne and hirsutism), ovulation disorder (usually manifested as infrequent or no menstruation), and polycystic ovarian morphology on ultrasound. 
  • The clinical features of PCOS vary widely, with symptoms of hyperandrogenism and severe menstrual disturbances at one end of the spectrum (previously known as Stein–Leventhal syndrome) and mild symptoms at the other. Symptoms may vary over time [Balen et al, 2009].

[Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2004; RCOG, 2014; Hecht Baldauff, 2015; Witchel, 2015; Yu, 2016; Ding, 2017]

What causes it?

  • The cause of polycystic ovary syndrome (PCOS) is unknown. It is likely to be multifactorial, with both genetic and environmental factors playing a part [Conway, 2014; Witchel, 2015]. 
  • Insulin resistance and the consequent compensatory hyperinsulinaemia are key factors in the pathogenesis of PCOS in many, but not all, women.
    • Insulin resistance is present in around 65–80% of women with PCOS, independent of obesity, and is further exacerbated by excess weight [RCOG, 2014].
    • Effects of hyperinsulinaemia include [Ehrmann, 2005; Fraison, 2020a]:
      • Reduced production of sex hormone-binding globulin (SHBG) in the liver — as testosterone is bound to SHBG, more testosterone is available in the blood in the biologically active unbound form, even though the total testosterone level may be normal or only modestly elevated.
      • Increased androgen production (via several mechanisms) — an excessive increase in androgen production stops follicular development and therefore causes anovulation (failure of the ovaries to produce eggs) and menstrual disturbance.
  • Hormonal imbalance is common in women with PCOS.
    • Serum luteinizing hormone (LH) levels are elevated in approximately 40% of women with PCOS due to increased production from the anterior pituitary (increased amplitude and frequency of LH pulses) [Balen et al, 1995].
    • The theca cells of the ovary produce excess androgens due to hyperinsulinaemia or increased serum levels of LH.
      • When the concentration of LH increases relative to that of follicle-stimulating hormone, the ovaries preferentially synthesize androgens from androgen precursors rather than oestrogens [Ehrmann, 2005].
      • The theca cells in women with PCOS seem to be more efficient at converting androgen precursors to testosterone than normal theca cells [Ehrmann, 2005].
    • Women with PCOS may have increased serum oestrogen levels.
      • Follicular development is arrested at some stage short of full maturation of an ovulatory follicle. Therefore, although there is no ovulation, oestrogen production continues and there is no oestrogen deficiency. However, as a result of continued exposure to oestrogen unopposed by progestogen, the endometrium may become hyperplastic [Baird, 1997]. In addition, testosterone is converted to oestrogen in peripheral fat [Balen et al, 2005].
  • PCOS appears to have a genetic link. However, specific genes associated with the condition have not been identified [Rosenfield, 2015; Ding, 2017; BMJ, 2023].

How common is it?

  • Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age [Conway, 2014; RCOG, 2014; Fraison, 2020a; BMJ, 2023].
  • The prevalence ranges from 2.2–26% (depending on the criteria used and the population studied) [RCOG, 2014; Fraison, 2020a; Peña, 2022], with many affected women undiagnosed [International PCOS Network, 2023]. 
    • Evidence from a systematic review and meta-analysis suggests the lowest prevalence in Chinese women, and then in ascending order of increasing prevalence for Caucasian women, Middle Eastern women, and Black women [Ding, 2017].

What are the complications?

  • Complications of polycystic ovary syndrome (PCOS) include:
    • Infertility
      • PCOS is the single most common cause of infertility in young women [Rosenfield, 2015]. It is the underlying cause in 75% of women who have infertility due to anovulation [Balen, 2010].
      • Women with PCOS may have a pregnancy rate significantly less than the rate of successful ovulation induction [BMJ, 2023]. 
    • Cardiovascular disease (CVD)
      • The cardiometabolic profile is adversely altered in PCOS, and many CVD risk factors (such as body mass index [BMI], dyslipidaemia, hypertension, insulin resistance, metabolic syndrome, and deficiencies in insulin secretion) are increased [BMJ, 2023]. 
      • CVD risk factors beyond standard recognized risks (identified as 'novel risk factors') and early onset cardiovascular dysfunction (including endothelial dysfunction, arterial stiffness, plaques, and coronary artery calcification) have been noted in women with PCOS and are related to insulin resistance and obesity [RCOG, 2014].
      • High androgen levels and low sex hormone binding globulin levels have also been linked to increased CVD risk in both premenopausal and postmenopausal women with PCOS [RCOG, 2014].
      • Type 2 diabetes is a major CVD risk factor, and insulin resistance has been shown to worsen CVD risk in PCOS [RCOG, 2014]. 
    • Metabolic disorders
      • Insulin resistance is present in around 65–80% of women with PCOS. This is independent of obesity but is further exacerbated by excess weight. Insulin resistance has been shown to worsen reproductive and metabolic features and type 2 diabetes in PCOS [RCOG, 2014]. 
      • The prevalence of impaired glucose tolerance and type 2 diabetes (5-fold in Asia, 4-fold in the Americas, and 3-fold in Europe) are significantly increased in PCOS, regardless of the age of the person. This is independent of obesity but is further exacerbated by excess weight [RCOG, 2014; Teede, 2021; International PCOS Network, 2023]. 
      • About 20–40% of obese women with PCOS have glucose intolerance or type 2 diabetes by the end of their fourth decade [BMJ, 2023].
    • Obstructive sleep apnoea syndrome
      • About 20–45% of women with PCOS have OSAS or sleep-disordered breathing. Therefore, all women with PCOS should be screened for these conditions [BMJ, 2023].
      • The prevalence of obstructive sleep apnoea is increased in obese women with PCOS [RCOG, 2014].
      • Limited evidence suggests that OSAS is more common in obese PCOS women (both in adolescents and during reproductive years) compared with the general population [Conway, 2014].
      • BMI, insulin resistance, and glucose intolerance are risk factors for the development of sleep disorders in PCOS, and androgen excess may be associated with the presence of OSAS in women with PCOS [Conway, 2014].
    • Psychological disorders
      • PCOS is associated with an increased risk of many mental health conditions, including mood and anxiety disorders [RCOG, 2014; Dokras, 2018].
      • A meta-analysis found an increased risk of depressive symptoms (3.8-fold) and anxiety symptoms (5.6-fold) in women with PCOS, which remained significant in BMI-matched analyses [Cooney, 2017; BMJ, 2023].
      • One meta-analysis found that the odds of being diagnosed with an eating disorder (such as binge-eating disorder and bulimia nervosa) were 3.9-fold higher in women with PCOS compared with controls [Lee, 2019; BMJ, 2023].
    • Pregnancy complications
      • Women with PCOS have a clinically significant increased risk of pregnancy complications compared with women without PCOS [Palomba, 2015].
      • Characteristic features of PCOS, such as hyperandrogenism, obesity, insulin resistance, and metabolic abnormalities, may contribute to the increased risk of obstetric and neonatal complications [Palomba, 2015].
      • Evidence from systematic reviews and meta-analyses have shown increased rates of gestational diabetes, pregnancy-induced hypertension, pre-eclampsia, caesarean delivery, miscarriage, hypoglycaemia, preterm delivery, macrosomia, newborn admission to the neonatal intensive care unit, neonatal asphyxia, and perinatal mortality in PCOS [Kjerulff et al, 2011; Palomba, 2015; Yu, 2016; Wang, 2017; Bahri Khomami, 2019; BMJ, 2023].
      • The increased risks of miscarriage, gestational diabetes, pregnancy-induced hypertension, and caesarean section in PCOS seem to be independent of obesity [BMJ, 2023].
      • Limited data suggests that children of women with PCOS have an increased risk for future metabolic and reproductive dysfunction [Palomba, 2015].
    • Cancer
      • Women with PCOS appear to have an increased risk of endometrial cancer due to prolonged oligomenorrhoea or amenorrhoea and an increased prevalence of obesity [Conway, 2014; RCOG, 2014; BMJ, 2023; International PCOS Network, 2023]. 
      • Untreated anovulatory women with PCOS have chronic oestrogen exposure with no progesterone exposure. This could lead to abnormal uterine bleeding, endometrial hyperplasia, and cancer [BMJ, 2023].
      • Intervals between menstruation of more than 3 months (equivalent to fewer than four periods each year) may be associated with endometrial hyperplasia and later cancer [RCOG, 2014].
      • Women with PCOS have a markedly higher risk of developing endometrial hyperplasia and endometrial cancer [International PCOS Network, 2023]. 
      • There does not appear to be an association with breast or ovarian cancer and no additional surveillance is required [RCOG, 2014; Ding, 2018].
    • Non-alcoholic fatty liver disease (NAFLD) 

What is the prognosis?

  • Polycystic ovary syndrome (PCOS) is a chronic condition. There is no cure, and treatment is usually continued throughout the woman's reproductive years.
    • The aim of treatment is to [BMJ, 2023]:
      • Alleviate the signs and symptoms of PCOS.
      • Prevent the development of complications, such as type 2 diabetes and cardiovascular disease.
    • Symptoms generally recur if treatments are stopped during the woman's reproductive years.
    • As the woman gets older or reaches menopause, hyperandrogenic manifestations may improve as ovarian function declines [Winters et al, 2000; BMJ, 2023], allowing withdrawal of treatments aimed at the hyperandrogenic features of PCOS [BMJ, 2023].
  • Evidence from a retrospective cohort study suggests that the standardized mortality rate in women with PCOS is 0.9 and is no different to women without PCOS [Pierpoint et al, 1998].

Diagnosis of polycystic ovary syndrome

When should I suspect polycystic ovary syndrome?

  • In adults, suspect polycystic ovary syndrome (PCOS) if a woman has:
    • Hyperandrogenism, such as acne, female pattern hair loss and hirsutism.
    • Ovulation disorders, such as oligomenorrhoea, amenorrhoea, and infertility.
  • In adolescents, suspect PCOS if the girl has the following:
    • Clinical features of hyperandrogenism (such as severe acne and hirsutism).
    • Irregular menstrual cycles, defined as:
      • Normal in the first year post-menarche as part of the pubertal transition.
      • More than 1 year to less than 3 years of irregular cycles (more than 45 days or less than 21 days) after the onset of menarche.
      • More than 3 years of irregular cycles (more than 35 days or less than 21 days, or less than 8 cycles every year) post menarche to perimenopause.
      • More than 1 year of irregular cycles (more than 90 days for any one cycle) post menarche.
      • Primary amenorrhea by age 15 years or more than 3 years of irregular cycles post thelarche (breast development).
    • For adolescents who have features of PCOS, but do not meet diagnostic criteria, an 'increased risk' could be considered and reassessment advised at or before full reproductive maturity, 8 years post menarche. This includes those people with PCOS features before starting the combined oral contraceptive pill, those with persisting features of PCOS and those with significant weight gain in adolescence.
  • Also consider PCOS if one or more of the following are present:
    • A family history of PCOS.
    • Indirect evidence of insulin resistance, such as obesity (especially central obesity) and acanthosis nigricans.
      • Acanthosis nigricans is characterized by dry, rough skin that has grey-brown pigmentation, is palpably thickened, and is covered by a papillomatous elevation (giving it a velvety texture). The condition commonly affects the axillae, perineum, or extensor surfaces of the elbows and knuckles. When the neck is affected, there is often a thin necklace of warty fissures that can spread as a wide band.
  • If PCOS is suspected, arrange investigations to help confirm the diagnosis and exclude differential diagnoses. If a person is on a combined oral contraceptive pill and assessment of biochemical androgens is imperative, the pill should be withdrawn for a minimum of three months before testing. 

Basis for recommendation

When to suspect polycystic ovary syndrome in adults

  • This recommendation is extrapolated from the Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome published by the Rotterdam European Society of Human Reproduction and Embryology (ESHRE)/American Society for Reproductive Medicine (ASRM)-Sponsored Polycystic Ovary Syndrome (PCOS) Consensus Workshop Group [Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2004] and the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 published by the International PCOS Network [International PCOS Network, 2023]. 

When to suspect PCOS in adolescents

  • This recommendation is based on the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 published by the International PCOS Network [International PCOS Network, 2023] and The Diagnosis of Polycystic Ovary Syndrome during Adolescence, which represents the consensus of paediatric endocrine and adolescent medicine experts representing paediatric subspecialty societies [Witchel, 2015].
    • Expert opinion in the consensus guideline is that the diagnosis of PCOS should be considered in adolescents presenting with hirsutism, moderate to severe inflammatory acne, and/or menstrual irregularities [Witchel, 2015].  
  • The definition of irregular cycles is taken from the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 [International PCOS Network, 2023].

Suspecting PCOS if there is a family history of PCOS or indirect evidence of insulin resistance

  • Expert opinion in review articles is that:
    •  Family history of PCOS is a risk factor for PCOS [BMJ, 2023].
    • Acanthosis nigricans should alert the physician to the possibility of PCOS and its metabolic complications [Rosenfield, 2015]. 

Arranging investigations

  • Experts advise that a thorough medical history, physical examination, and appropriate laboratory assessment are essential to exclude other disorders associated with androgen excess [Witchel, 2015].
  • It is very difficult to reliably assess for biochemical hyperandrogenism in women on the combined oral contraceptive pill (COC) as the pill increases sex hormone binding globulin and reduces gonadotrophin-dependent androgen production. If already on the COC, yet assessment of biochemical androgens is imperative, the pill should be withdrawn for a minimum of three months and contraception should be managed otherwise during this time [International PCOS Network, 2023]. 

 

Which investigations should I arrange?

  • If polycystic ovary syndrome (PCOS) is suspected:
    • Measure total testosterone — this is normal to moderately elevated in women with PCOS.
    • Measure sex hormone-binding globulin (SHBG) — this is normal to low in women with PCOS and provides a surrogate measurement of the degree of hyperinsulinaemia.
    • Calculate free androgen index (100 multiplied by the total testosterone value divided by the SHBG value) to assess the amount of physiologically active testosterone present — this is normal or elevated in women with PCOS (the normal range is usually defined as lower than 5, but may vary within local laboratories).
      • Note that reliable assessment of biochemical hyperandrogenism is not possible in women on hormonal contraception due to effects on SHBG and altered gonadotrophin-dependent androgen production. If assessment of biochemical hyperandrogenism is indicated, hormonal contraception should be stopped for at least 3 months before the assessment. The need for a non-hormonal alternative contraceptive method should be considered. 
      • If testosterone or free testosterone is not elevated, consider measuring androstenedione and dehydroepiandrosterone sulfate (DHEAS). Note that these tests have poorer specificity and there is a greater age associated decrease in DHEAS.
    • Measure the following to rule out other causes of oligomenorrhoea and amenorrhoea (such as premature ovarian failure, hypothyroidism, and hyperprolactinaemia):
      • Luteinizing hormone and follicle-stimulating hormone — may be increased in women with premature ovarian failure, and decreased in women with hypogonadotropic hypogonadism.
      • Prolactin (normal range is less than 500 mU/L) — may be mildly elevated in women with PCOS.
      • Thyroid-stimulating hormone (normal range 0.4–4.5 mU/L).
    • Refer adults for ultrasound scan to assess for the presence of polycystic ovarian morphology [International PCOS Network, 2023] (unless the diagnosis of PCOS is obvious on clinical and biochemical grounds). 
      • Polycystic ovarian morphology on ultrasound is defined as the presence of 20 or more follicles in at least one ovary.
      • Note that polycystic ovaries do not have to be present to make the diagnosis of PCOS, and the finding of polycystic ovaries does not alone establish the diagnosis.
      • Ultrasound scan should not be used for the diagnosis of PCOS in adolescents [International PCOS Network, 2023].
    • Exclude other causes of hyperandrogenism (such as late-onset congenital adrenal hyperplasia, Cushing's syndrome, or an androgen-secreting tumour) if:
      • There are signs of virilization, for example, deep voice, reduced breast size, increased muscle bulk, and clitoral hypertrophy.
      • There is rapidly progressing hirsutism (less than 1 year between hirsutism being noticed and seeking medical advice).
      • The total testosterone level is significantly elevated (greater than 5 nmol/l or more than twice the upper limit of normal reference range).

Basis for recommendation

These recommendations are based on the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Long-term Consequences of Polycystic Ovary Syndrome [RCOG, 2014], The polycystic ovary syndrome: a position statement from the European Society of Endocrinology (ESE) [Conway, 2014], the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International Polycystic Ovary Syndrome (PCOS) Network [International PCOS Network, 2023], evidence from a small study on the biological variation of testosterone and sex hormone-binding globulin (SHBG) in PCOS [Jayagopal et al, 2003], and expert opinion in a review articles [Balen, 2010; Duncan, 2014] and textbooks [Dewailly, 2010; Homburg, 2010].

Total testosterone, SHBG, and free androgen index (FAI)

  • FAI (calculated by the ratio between total testosterone and SHBG) is the recommended baseline biochemical test for the evaluation of hyperandrogenism. It provides a simple assessment of the amount of physiologically active testosterone present [Conway, 2014; RCOG, 2014]. 
  • SHBG is a surrogate marker of insulin resistance and androgen excess that predicts the susceptibility to develop metabolic syndrome and gestational diabetes in women with PCOS [Conway, 2014].
    • Insulin suppresses SHBG [Jayagopal et al, 2003; Homburg, 2010].
    • If the SHBG level is low despite an apparently normal total testosterone level, the amount of free testosterone (which is the bioactive form) may be increased, thereby elevating the FAI [Dewailly, 2010].

Tests to rule out other causes of oligomenorrhoea and amenorrhoea 

  • Measurement of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are essential in the diagnosis of other conditions that may present with amenorrhoea [Balen, 2010].
  • Prolactin levels may be normal or mildly elevated in PCOS [Homburg, 2010]. 
  • Although thyroid-stimulating hormone is a useful screening test, the incidence of thyroid dysfunction among women with hyperandrogenism is no higher than that in women without hyperandrogenism who are of reproductive age [Homburg, 2010].

Ultrasound scan

  • The 2003 Rotterdam Consensus Workshop Group defines polycystic ovaries as the presence of 12 or more follicles (measuring 2–9 mm in diameter) in one or both ovaries and/or increased ovarian volume (more than 10 cm3) [Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2004]. However, it should be noted that polycystic ovaries do not have to be present to make the diagnosis, and the finding of polycystic ovaries does not alone establish the diagnosis. It is estimated that 20% of women will have polycystic ovaries on an ultrasound scan [Duncan, 2014].
  • According to the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 [International PCOS Network, 2023]:
    • In women with irregular menstrual cycles and hyperandrogenism, an ultrasound scan is not necessary for PCOS diagnosis, although it can be used to identify the complete PCOS phenotype.
    • Ultrasound scan should not be used for the diagnosis of PCOS in those with a gynaecological age of less than 8 years (less than 8 years after menarche) due to the high incidence of multi-follicular ovaries in this life stage.

Anti-Mullerian hormone testing

  • The International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 [International PCOS Network, 2023]  also recommends that serum anti-mullerian hormone (AMH) could be used for defining PCOM in adults. But notes that serum AMH is not necessary to make a diagnosis of PCOS in patients with irregular menstrual cycles and hyperandrogenism. Also that serum AMH should not be used as a single test for the diagnosis of PCOS.
  • The report advises that the option to use AMH is based on moderate evidence and that there is a current lack of consensus on specific cut-off levels for AMH. Further, the authors advise that serum AMH levels in those women who have follicle excess are significantly higher than those of non-follicle excess counterparts in all studies, but that there there are overlaps between these groups. 
    • Also that serum AMH should not be used in adolescents.
  • Factors which influence AMH level include:
    • Age. Serum AMH usually peaks between the ages of 20-25 years.
    • Body mass index (BMI). Serum AMH is lower in those with higher BMI.
    • Hormonal contraception and ovarian surgery.
      • Serum AMH may be suppressed by current or recent COCP use.
      • Serum AMH may vary across the menstrual cycle. 

Excluding differential diagnoses

  • The RCOG advises that the diagnosis of PCOS can only be made when other causes for irregular menstrual cycles, such as thyroid dysfunction, acromegaly, or hyperprolactinaemia, have been excluded if there is clinical suspicion [RCOG, 2014]. 
  • Expert opinion in the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 is that exclusion of ovarian and adrenal neoplastic disease, thyroid disease, hyperprolactinemia, iatrogenic causes, non-classic congenital adrenal hyperplasia and syndromes of severe insulin resistance is recommended with further evaluation recommended in those with amenorrhea and more severe clinical features, including consideration of hypogonadotropic hypogonadism, Cushing’s disease, or androgen-producing tumours [International PCOS Network, 2023].

How should I diagnose polycystic ovary syndrome?

After investigations and the exclusion of differential diagnoses:

  • Consider a diagnosis PCOS in adults if a person has two of the following:
    • Ovulatory dysfunction - manifest by infrequent or no ovulation (usually manifested as infrequent or no menstruation) and
    • Clinical and/or biochemical signs of hyperandrogenism (such as hirsutism, acne, or elevated levels of total or free testosterone). 
      • The presence of hirsutism alone should be considered predictive of biochemical hyperandrogenism and PCOS in adults.
      • Female pattern hair loss and acne in isolation (without hirsutism) are relatively weak predictors of biochemical hyperandrogenism.
    • Polycystic ovarian morphology on ultrasound scan [International PCOS Network, 2023].
      • Defined as a follicle number per ovary of 20 or more in at least one ovary. 
    • Note that:
      • Polycystic ovaries do not have to be present to make the diagnosis, and the finding of polycystic ovaries does not alone establish the diagnosis.
      • Women of non-Caucasian ethnicity may need different criteria to make a diagnosis of PCOS, due to ethnic variations in PCOS.
  • In adolescent girls, both hyperandrogenism and irregular menstrual cycles are required for a diagnosis of PCOS.
    • Great caution should be taken before diagnosing PCOS if there are clinical features of androgen excess (such as hirsutism and biochemical hyperandrogenism) without irregular menstrual cycles.  
    • Adolescents who have features of PCOS but do not meet the diagnostic criteria should be considered to be at 'increased risk' of PCOS and reassessed at or before full reproductive maturity (that is, 8 years post-menarche). This includes those with PCOS features before combined oral contraceptive pill commencement, those with persisting features, and those with significant weight gain in adolescence.
  • A diagnosis of PCOS can be considered as enduring/lifelong.
    • Both clinical and biochemical hyperandrogenism persist postmenopausally for women with PCOS.
    • A PCOS diagnosis can be considered postmenopausally, if there is a past diagnosis, or a long-term history of oligo-amenorrhoea with hyperandrogenism and/or polycystic ovary morphology on ultrasound during the earlier reproductive years (age 20-40).
    • Further investigations should be considered to rule out androgen-secreting tumours and ovarian hyperthecosis (presence of nests of luteinized theca cells in the ovarian stroma) in postmenopausal women presenting with new-onset, severe or worsening hyperandrogenism including hirsutism.

Basis for recommendation

Diagnosing polycystic ovary syndrome (PCOS) in adults

  • This recommendation is based on the Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome published by the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group [Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2004].
    • The Androgen Excess and PCOS Society Task Force challenged the Rotterdam criteria and suggested that PCOS should be defined by two criteria: the presence of hyperandrogenism (biochemical or clinical) and ovarian dysfunction (oligo- or anovulation or polycystic ovaries) [Azziz et al, 2006; Azziz et al, 2009].
    • However, the Rotterdam criteria are endorsed in several national and international guidelines, including the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Long-term Consequences of Polycystic Ovary Syndrome [RCOG, 2014], The polycystic ovary syndrome: a position statement from the European Society of Endocrinology (ESE) [Conway, 2014], and the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 published by the International PCOS Network [International PCOS Network, 2023].
  • The RCOG guideline highlights that the diagnosis of PCOS should only be made when other causes for irregular cycles, such as thyroid dysfunction, acromegaly, or hyperprolactinaemia, have been excluded if there is clinical suspicion, and that women with non-Caucasian ethnicity might need different criteria to diagnose PCOS [RCOG, 2014].

Diagnosing PCOS in adolescents

  • There is no consensus on the clinical criteria to reach the diagnosis of PCOS in adolescents.
  • The recommended criteria are based largely on the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 published by the International PCOS Network [International PCOS Network, 2023], The Diagnosis of Polycystic Ovary Syndrome during Adolescence, which represents the consensus of paediatric endocrine and adolescent medicine experts representing paediatric subspecialty societies [Witchel, 2015], and a review article on the diagnosis of PCOS during adolescence [Peña, 2022].
    • The diagnostic criteria for PCOS in adolescence are challenging, primarily because the diagnostic pathological features used in adult women, for example acne, irregular menses, and polycystic ovary morphology, may be normal pubertal physiological events [Witchel, 2015; Peña, 2022].
    • The International PCOS Network recommends tighter criteria requiring both hyperandrogenism and irregular cycles, with ultrasound not indicated, in the diagnosis of PCOS in adolescents, due to overlap with normal reproductive physiology [International PCOS Network, 2023].
    • Girls who have features of PCOS but do not meet the diagnostic criteria should be considered to be 'at risk' for PCOS. To avoid misdiagnosing physiological pubertal changes as PCOS, deferred diagnostic labelling accompanied by reassessment at or before full reproductive maturity (8 years post-menarche) are recommended [Witchel, 2015; International PCOS Network, 2023].
  • Although obesity, insulin resistance, and hyperinsulinemia are common findings in adolescents with hyperandrogenism, these features should not be used to diagnose PCOS among adolescent girls as they are not always present [Rosenfield, 2015; Witchel, 2015].

Ethnic variations in PCOS

  • The RCOG highlights that women with non-Caucasian ethnicity might need different criteria to diagnose PCOS [RCOG, 2014] due to ethnic variations.
  • Notes on ethnic variations in PCOS reported by the [International PCOS Network, 2023] include:
    • Healthcare professionals should be aware of the high prevalence of PCOS in all ethnicities and across world regions, ranging from 10-13% globally using the Rotterdam criteria.
    • Healthcare professionals should be aware that PCOS prevalence is similar across world regions and ethnicities, but may be higher in South East Asian and Eastern Mediterranean regions.
    • Healthcare professionals should be aware that the presentation of PCOS may vary across ethnic groups.

Post-menopausal assessment

  • These recommendations are based on the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 published by the International PCOS Network [International PCOS Network, 2023]. 

What else might it be?

  • The diagnosis of polycystic ovary syndrome involves the exclusion of all of the following disorders, which may have a similar clinical presentation:
    • Simple obesity
      • Raised androgen levels with or without symptoms.
      • Oligomenorrhoea or amenorrhoea is not often present.
      • See the CKS topic on Obesity for more information.
    • Primary hypothyroidism
      • Normal or mildly raised androgen levels with or without symptoms.
      • Oligomenorrhoea or amenorrhoea may be present.
      • Goitre may be present.
      • There may be elevated thyroid-stimulating hormone levels and subnormal plasma thyroxine levels.
      • Prolactin levels may be raised.
      • See the CKS topic on Hypothyroidism for more information.
    • Premature ovarian failure
      • Normal androgen levels.
      • Oligomenorrhoea or amenorrhoea is present.
      • May be associated with other autoimmune endocrinopathies.
      • Elevated plasma follicle-stimulating hormone levels and normal or subnormal estradiol levels.
    • Raised prolactin or prolactinoma
      • Normal or mildly raised androgen levels with or without symptoms.
      • Oligomenorrhoea or amenorrhoea is present.
      • Galactorrhoea.
      • Elevated plasma prolactin levels.
    • Non-classic congenital adrenal hyperplasia due to deficiency of 21-hydroxylase 
      • Raised androgen levels with or without symptoms.
      • Oligomenorrhoea or amenorrhoea is not often present.
      • There is a family history of infertility, hirsutism, or both, common in Ashkenazi Jewish people.
      • Elevated basal 17-hydroxyprogesterone levels in the morning or on stimulation.
    • Cushing's syndrome
      • Raised androgen levels with or without symptoms.
      • Oligomenorrhoea or amenorrhoea is present.
      • Symptoms include hypertension, striae, and easy bruising.
      • Elevated 24-hour urinary free cortisol levels.
    • Androgen-secreting tumour (virilizing adrenal or ovarian neoplasm) 
      • Extremely high plasma androgen levels with or without symptoms.
      • Oligomenorrhoea or amenorrhoea is present.
      • Symptoms include clitoromegaly, extreme hirsutism, and male pattern alopecia.
    • Acromegaly
      • Normal or mildly raised androgen levels with or without symptoms.
      • Oligomenorrhoea or amenorrhoea is often present.
      • Symptoms include enlargement of the extremities, coarse features, and prognathism.
      • Increased plasma insulin-like growth factor levels.
  • Also consider:
    • Hypogonadotropic hypogonadism (that is, central origin of ovarian dysfunction).
    • Hyperandrogenic-insulin resistant-acanthosis nigricans (HAIRAN) syndrome.
    • High-dose exogenous androgens.
    • Drug-related causes.
      • Androgenic drugs that may cause hirsutism include testosterone, danazol, gestrinone, adrenocorticotropic hormone, high-dose corticosteroids, androgenic progestogens in oral contraceptives, and anabolic steroids.
      • Non-androgenic drugs that may cause hirsutism include ciclosporin, diazoxide, minoxidil, phenytoin, and, rarely, carbamazepine, sodium valproate, and acetazolamide.
      • Drugs that may cause hypertrichosis include ciclosporin, diazoxide, minoxidil, and phenytoin.
    • Other causes of amenorrhoea, such as physiological causes (including pregnancy, lactation, and menopause) and hypothalamic dysfunction (by weight loss, excessive exercise, or chronic systemic illness). See the CKS topic on Amenorrhoea for more information.

Basis for recommendation

This information is taken from the Rotterdam diagnostic criteria [Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2004], review articles [Ehrmann, 2005; BMJ, 2023], and textbooks [Balen, 2012; Horne and Critchley, 2012].

Management

Scenario: Management of polycystic ovary syndrome in adults

From age 18 years onwards (Female).

How should I manage polycystic ovary syndrome in adults?

Basis for recommendation

These recommendations are based largely on the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Long-term Consequences of Polycystic Ovary Syndrome [RCOG, 2014], The polycystic ovary syndrome: a position statement from the European Society of Endocrinology (ESE) [Conway, 2014], and the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International Polycystic Ovary Syndrome (PCOS) Network [International PCOS Network, 2023].

Encouraging a healthy lifestyle
  • Lifestyle management, including healthy eating, regular physical activity, and weight loss, is recommended as the first-line treatment for overweight and obese women with PCOS [Conway, 2014; RCOG, 2014]. These changes should precede and/or accompany pharmacological treatment [RCOG, 2014].
  • Lifestyle intervention, preferably multicomponent and including diet, exercise, and behavioural strategies, should be recommended to all women with PCOS and excess weight to aid reductions in weight, central obesity, and insulin resistance [International PCOS Network, 2023].
    • Regular exercise combined with dietary advice aiming at sustained weight loss may ameliorate many aspects of PCOS in overweight or obese women [Conway, 2014].
    • Weight reduction alone may result in spontaneous ovulation in these women, and in women who do not ovulate spontaneously following weight reduction and lifestyle modifications, the response to induction of ovulation is likely to be improved by these measures [Conway, 2014]. 
    • A reduction of as little as 5% of total body weight has been shown to reduce insulin resistance and testosterone levels and improve body composition and cardiovascular risk markers [RCOG, 2014].
Providing sources of additional information and support

How should I manage the clinical features of polycystic ovary syndrome?

For women with fertility problems, see the CKS topic on Infertility for management information.

For women who are not pregnant or planning a pregnancy:

  • Encourage healthy lifestyle behaviours, including healthy eating and regular exercise.
    • Advise that healthy lifestyle behaviours will:
      • Help achieve and/or maintain a healthy weight.
      • Optimize hormonal outcomes.
      • Improve general health and quality of life. 
    • If the woman is overweight or obese, explain that weight loss may:
      • Reduce hyperinsulinism and hyperandrogenism.
      • Reduce the risk of type 2 diabetes and CVD.
      • Result in menstrual regularity.
    • See the CKS topic on Obesity for management information.
  • Offer a combined oral contraceptive (COC) pill, provided there are no contraindications (off-label use). 
    • See the CKS topic on Contraception - combined hormonal methods for prescribing information on COCs, including contraindications and cautions, choice, risks and adverse effects, and drug interactions.
    • COCs with 35 micrograms of ethinyloestradiol plus cyproterone acetate preparations should not be considered first line in polycystic ovary syndrome (PCOS) due to adverse effects, including venous thromboembolic risks.
  • For women with acne, consider adding a topical retinoid, topical antibiotics, and/or oral antibiotics as appropriate. See the CKS topic on Acne vulgaris for more information on managing acne.
  • For women with hirsutism, discuss methods of hair reduction and removal (such as shaving and waxing), as these will remain an important part of management. See the CKS topic on Hirsutism for more information. Note that oral contraceptive pills are more effective for acne than for hirsutism.
  • For women with prolonged amenorrhea (less than one period every three months) or abnormal vaginal bleeding:
    • Prescribe a cyclical progestogen (such as medroxyprogesterone 10 mg daily for 14 days) to induce a withdrawal bleed, then refer for a transvaginal ultrasound to assess endometrial thickness.
    • If endometrial thickening is present (greater than 10 mm) or the endometrium has an unusual appearance, refer for endometrial sampling to exclude endometrial hyperplasia or cancer.
    • If the endometrium is of normal thickness and appearance, advise treatment to prevent endometrial hyperplasia. The choice of treatment depends on factors such as whether the woman wishes to have regular withdrawal bleeds (at least every 3–4 months), whether she has acne or hirsutism, and whether there are any contraindications to treatment. Options include:
      • A cyclical progestogen, such as medroxyprogesterone 10 mg daily for 14 days every 1–3 months.
      • A low-dose COC. See the CKS topic on Contraception - combined hormonal methods for prescribing information on COCs, including contraindications and cautions, choice, risks and adverse effects, and drug interactions.
      • The levonorgestrel-releasing intrauterine device (LNG-IUD). See the CKS topic on Contraception - IUC for prescribing information on the LNG-IUD, including contraindications, cautions, risks, and adverse effects.
    • If the woman is unwilling to take cyclical hormone treatment or use the LNG-IUD, seek specialist advice or refer.
      • Regular ultrasonography is likely to be required (for example every 6–12 months) to assess endometrial thickness and morphology.
  • Metformin has been used off label to treat PCOS. However, there is uncertainty regarding the relative benefits compared with COC.
    • Consider seeking specialist advice before initiating metformin in primary care for women without diabetes.
    • The International PCOS Network makes the following recommendations on the use of metformin for non-fertility indications:
      • Metformin (alone or in combination with COC) may offer greater benefit in high metabolic risk groups, including those with diabetes risk factors, impaired glucose tolerance, or high-risk ethnic groups.
      • In addition to lifestyle measures, metformin should be considered in women with a body mass index (BMI) of  25kg/m2 or more for the management of weight and metabolic outcomes. 
      • In addition to lifestyle measures, metformin could be recommended for the treatment of weight, hormonal, and metabolic outcomes.
      • In combination with COC, metformin should be considered for management of metabolic features where COC and lifestyle changes do not achieve desired goals.
    • If metformin is initiated in primary care:
      • Explain that it is an off-label use. 
      • Advise that adverse effects, such as gastrointestinal symptoms and reduced vitamin B12 levels, may occur. 
      • Explain that metformin use appears safe long-term, based on use in other populations. However, ongoing requirement needs to be considered. 
      • See the section on Metformin in the CKS topic on Diabetes - type 2 for prescribing information on metformin, including initiating, monitoring, contraindications, cautions, adverse effects, and drug interactions.

Basis for recommendation

These recommendations are based largely on the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Long-term Consequences of Polycystic Ovary Syndrome [RCOG, 2014], The polycystic ovary syndrome: a position statement from the European Society of Endocrinology (ESE) [Conway, 2014], and the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International Polycystic Ovary Syndrome (PCOS) Network [International PCOS Network, 2023]. 

Encouraging a healthy lifestyle
  • Lifestyle management, including healthy eating, regular physical activity, and weight loss, is recommended as the first-line treatment for overweight and obese women with PCOS [Conway, 2014; RCOG, 2014]. These changes should precede and/or accompany pharmacological treatment [RCOG, 2014].
  • Lifestyle intervention, preferably multicomponent and including diet, exercise, and behavioural strategies, should be recommended to all women with PCOS and excess weight to aid reductions in weight, central obesity, and insulin resistance [International PCOS Network, 2023].
    • Regular exercise combined with dietary advice aiming at sustained weight loss may ameliorate many aspects of PCOS in overweight or obese women [Conway, 2014].
    • Weight reduction alone may result in spontaneous ovulation in these women, and in women who do not ovulate spontaneously following weight reduction and lifestyle modifications, the response to induction of ovulation is likely to be improved by these measures [Conway, 2014]. 
    • A reduction of as little as 5% of total body weight has been shown to reduce insulin resistance and testosterone levels and improve body composition and cardiovascular risk markers [RCOG, 2014].
Choice of treatment
  • COCs are the mainstay of the pharmacological treatment of PCOS as they can be used to manage both menstrual disorders and androgen excess symptoms (such as acne and hirsutism). Progestogens, usually given cyclically, also have a role in the management of menstrual dysfunction [Conway, 2014].
  • The International PCOS Network advises that [International PCOS Network, 2023]:
    • Provided there are no contraindications, the COC alone should be recommended in adult women with PCOS for management of hyperandrogenism and/or irregular menstrual cycles.
    • When deciding on a treatment, the woman’s personal characteristics, preferences, and values should be considered as well as the benefits, adverse effects, and contraindications of the treatment.
    • The lowest effective oestrogen doses (such as 20–30 micrograms of ethinyloestradiol or equivalent) and natural oestrogen preparations should be considered whilst balancing efficacy, metabolic risk profile, adverse effects, cost, and availability.
    • The generally limited evidence on the effects of COCs in PCOS should be considered, with practice informed by general population guidelines.
    • PCOS specific risk factors, such as high body mass index, hyperlipidaemia, and hypertension, need to be considered.
    • The 35 microgram ethinyloestradiol plus cyproterone acetate preparations should not be considered first line in PCOS as per general population guidelines, due to adverse effects including venous thromboembolic risks.
Inducing a withdrawal bleed
  • In women with PCOS, intervals between menstruation of more than 3 months (equivalent to fewer than four periods each year) may predispose to endometrial hyperplasia and later carcinoma. The RCOG states that [RCOG, 2014]:
    • It is good clinical practice to induce a withdrawal bleed at least every 3–4 months to reduce this risk. This can be done with a cyclical progestogen for at least 12 days, a combined oral contraceptive pill (COC), or a levonorgestrel-releasing intrauterine system. There is no evidence to suggest which is the most effective regimen.
      • Medroxyprogesterone is indicated for progestogenic opposition of oestrogen hormone replacement therapy (HRT) as a 14-day course within each 28-day oestrogen HRT cycle [BNF, 2023].
    • Transvaginal ultrasound should be considered in the absence of withdrawal bleeds or abnormal uterine bleeding.
    • A thickened endometrium or an endometrial polyp should prompt consideration of endometrial biopsy and/or hysteroscopy (in PCOS, an endometrial thickness of less than 7 mm is unlikely to be hyperplasia).
  • According to the International PCOS Network [International PCOS Network, 2023]:
    • Routine ultrasound screening of endometrial thickness in PCOS is not recommended. However, health professionals require a low threshold for investigation of endometrial cancer in women with PCOS or a history of PCOS.
    • Investigation by transvaginal ultrasound and/or endometrial biopsy is recommended if there is persistent thickened endometrium and/or risk factors such as prolonged amenorrhea, abnormal vaginal bleeding, or excess weight.
Managing women who are unwilling to take cyclical hormone treatment
  • These recommendations are based on expert opinion in a non-systematic review on PCOS and cancer [Balen, 2001].
Metformin
  • Metformin is licensed in the UK for the treatment of type 2 diabetes mellitus, particularly in overweight people, when dietary management and exercise alone does not result in adequate glycaemic control [ABPI, 2021].
  • Metformin is used to treat PCOS, but it is not licensed in the UK for this indication [BNF, 2024]
  • In 2013, the National Institute for Health and Care Excellence (NICE) published an Evidence Summary on the use of metformin in women not planning pregnancy [NICE, 2013].
    • The evidence for the summary was based on five small randomized controlled trials (RCTs) included in a Cochrane systematic review [Costello et al, 2007] and 4 RCTs published after the Cochrane review. Metformin was compared with co-cyprindiol (ethinylestradiol 35 micrograms plus cyproterone 2 mg) alone. No RCTs compared metformin with placebo. 
    • Metformin compared with co-cyprindiol
      • There was no good evidence that regimens containing metformin were statistically significantly different from co-cyprindiol in controlling hirsutism in women with PCOS.
      • Two small studies found no statistically significant difference between metformin and co-cyprindiol in effects on acne, but the assessment methods were unclear.
      • Metformin was less effective at improving menstrual regularity than co-cyprindiol.
      • There was no or insufficient data from which to draw conclusions on the effectiveness of metformin for long-term outcomes, such as preventing type 2 diabetes, cardiovascular events, or endometrial cancer in women with PCOS.
      • Metformin caused a significantly higher incidence of gastrointestinal (GI) adverse effects that were severe (leading to treatment discontinuation) compared with co-cyprindiol.
      • Metformin caused a significantly lower incidence of other severe adverse effects (weight gain, high blood pressure, depression, chest pain, and headache) compared with co-cyprindiol. 
  • An updated version of the Cochrane systematic review (search date: August 2019) assessed the effectiveness and safety of metformin compared with COC (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS [Fraison, 2020b].
    • The Cochrane review included 44 RCTs (n = 2253 women), which comprised 39 RCTs on adult women (n = 2047 women) and five RCTs on adolescent women (n = 206 women). The evidence quality ranged from very low to low. The main limitations were risk of bias, imprecision, and inconsistency.
    • Metformin compared with COC
      • The evidence suggested that metformin may be less effective in improving menstrual patterns compared with COC.
      • It was uncertain whether there was a difference between metformin and COC for acne.  
      • In terms of improving excessive facial and body hair, metformin may be less effective in women with a body mass index (BMI) between 25 kg/m2 to 30 kg/m2, but the effects in women with BMI less than 25 kg/m2 or greater than 30 kg/m2 were uncertain.
      • Metformin may result in a higher incidence of severe GI adverse effects and a lower incidence of severe other adverse effects. There were no trials reporting on minor adverse effects.
      • Metformin resulted in an improvement of systolic blood pressure with insufficient evidence to determine whether there was a difference in diagnosis of type 2 diabetes mellitus, diastolic blood pressure, and body weight.
      • Metformin was less effective in improving serum total testosterone and free androgen index (FAI).
      • Metformin resulted in an improvement in fasting insulin, glucose, total cholesterol, and triglycerides with insufficient evidence to determine whether there was a difference in fasting high‐density lipoprotein (HDL) or low‐density lipoprotein (LDL) cholesterol.
    • Metformin compared with metformin plus COC
      • The evidence suggested that metformin may be less effective in improving hirsutism compared with metformin plus COC.
      • There were no trials reporting on minor adverse events, menstrual patterns, or acne.
      • It was uncertain whether there was a difference between metformin and metformin plus COC for severe GI adverse events.
      • It was uncertain whether there was a difference between metformin alone and metformin plus COC for severe other adverse events (requiring stopping the medication).
      • Metformin may improve BMI compared with metformin plus COC. 
      • Metformin alone resulted in an improvement in body weight, systolic blood pressure, and diastolic blood pressure compared with metformin plus COC. There were no trials reporting on diagnosis of type 2 diabetes.
      • Metformin alone was less effective in improving serum total testosterone and FAI compared with metformin plus COC.
      • Metformin resulted in an improvement in fasting insulin, glucose, total cholesterol (in the presence of unexplained substantial heterogeneity), and triglycerides with insufficient evidence to determine whether there was a difference in fasting HDL or LDL cholesterol when compared with metformin plus COC.
    • COC compared with metformin plus COC
      • The evidence suggested that COC alone may be less effective in improving hirsutism compared with metformin plus COC. 
      • COC alone may slightly improve acne compared with metformin plus COC.
      • There were no trials reporting on menstrual patterns.
      • COC may result in a lower incidence of severe GI adverse effects, but there was uncertainty as to whether there is a difference for other severe adverse effects when compared with metformin plus COC.
      • COC may have a lower incidence of minor GI adverse effects compared with metformin plus COC.
      • It was uncertain whether there is a difference between these two interventions for BMI. 
      • There was insufficient evidence to determine whether there was a difference in body weight, systolic blood pressure, and diastolic blood pressure when comparing COC with metformin plus COC. There were no trials reporting on diagnosis of type 2 diabetes.
      • COC was less effective in improving serum total testosterone and FAI compared with metformin plus COC.
      • COC was less effective in improving fasting insulin and glucose with insufficient evidence to determine whether there was a difference in fasting lipids when compared with metformin plus COC.
  • Due to the uncertainties regarding the benefits and safety of metformin in PCOS, CKS recommends considering seeking specialist advice before initiating metformin in primary care for women without diabetes.

How should I manage cardiovascular disease risk factors in women with polycystic ovary syndrome?

  • Body mass index (BMI)
    • Offer all women with polycystic ovary syndrome (PCOS) regular monitoring for weight change and excess weight. Monitoring could be at each visit or at a minimum of 6–12 monthly, with frequency, planned and agreed with the woman.
    • At each visit, measure the woman's weight, height, and waist circumference, and calculate her BMI. 
    • For women who are overweight or obese, explain that weight loss may:
      • Reduce hyperinsulinism and hyperandrogenism.
      • Reduce the risk of type 2 diabetes and CVD.
      • Result in menstrual regularity.
      • Improve the chance of pregnancy (if it is desired). 
    • See the CKS topic on Obesity for management information.
  • Diet and physical activity
    • Encourage healthy lifestyle behaviours, including healthy eating and regular exercise.
    • Advise that healthy lifestyle behaviours will:
      • Help achieve and/or maintain a healthy weight.
      • Optimize hormonal outcomes.
      • Improve general health and quality of life. 
    • See the sections on Dietary advice and Advice on physical activity in the CKS topic on Obesity for more information.
  • Blood pressure
    • Offer routine blood pressure checks (annually, or more frequently based on global cardiovascular disease [CVD] risk).
    • If the woman has high blood pressure, see the CKS topic on Hypertension for management information.
  • Lipid levels 
    • Offer all women with PCOS, regardless of age and BMI, a fasting lipid profile (cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglyceride level) at diagnosis. Thereafter, the frequency of measurement should be based on the presence of hyperlipidaemia and global CVD risk. 
    • Refer to a specialist if dyslipidaemia requires treatment.
    • If appropriate, use the QRISK3 assessment tool to calculate the woman's estimated CVD risk within the next 10 years. For more information, see the section on CVD risk assessment in the CKS topic on CVD risk assessment and management.
      • Note that conventional cardiovascular risk calculators have not been validated in women with PCOS.
  • Glycaemic status
    • Assess glycaemic status at baseline in all women with PCOS. Thereafter, assessment should be every 1–3 years, depending on the presence of other diabetes risk factors.
    • Perform a 2-hour post 75 g oral glucose tolerance test (OGTT), fasting plasma glucose, or HbA1c to assess glycaemic status.
    • In high-risk women with PCOS, an OGTT is recommended. This includes:
      • Women with BMI of 25 kg/m2 or more (or in Asians 23 kg/m2 or more).
      • Women with additional risk factors, such as hypertension, advanced age (older than 40 years of age), history of impaired fasting glucose, impaired glucose tolerance, gestational diabetes, or family history of type 2 diabetes.
      • Women of non-Caucasian ethnicity (particularly south Asian women) regardless of their BMI, because of their propensity towards higher insulin resistance.
    • Offer an annual OGTT to women with one of the following:
      • Impaired fasting glucose (fasting plasma glucose level from 6.1 mmol/l to 6.9 mmol/l).
      • Impaired glucose tolerance (plasma glucose of 7.8 mmol/l or more but less than 11.1 mmol/l after a 2-hour OGTT).
    • See the CKS topic on Diabetes - type 2 for management information.
  • Smoking status
    • Check the woman's smoking status.
    • If appropriate, offer advice on smoking cessation. See the CKS topic on Smoking cessation for more information.

Basis for recommendation

These recommendations are based largely on the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Long-term Consequences of Polycystic Ovary Syndrome [RCOG, 2014], The polycystic ovary syndrome: a position statement from the European Society of Endocrinology (ESE) [Conway, 2014], and the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International Polycystic Ovary Syndrome (PCOS) Network [International PCOS Network, 2023].

Managing cardiovascular disease (CVD) risk
  • There is some evidence that CVD risk factors are increased in PCOS. See the section on Complications for more information.
  • CKS recommends that, in view of the possible increased risk of cardiovascular events, clinicians should give advice on measures to reduce cardiovascular risk.
  • The RCOG recommends that because the lifetime risk for CVD is higher in women with PCOS, and is mostly preventable, all women with PCOS should be assessed for CVD risk by assessing individual CVD risk factors and managing accordingly [RCOG, 2014]. 
  • The International PCOS Network advises that all women with PCOS should be assessed for cardiovascular risk factors and global CVD risk. If screening reveals CVD risk factors, including obesity, cigarette smoking, dyslipidaemia, hypertension, impaired glucose tolerance, and lack of physical activity, the woman should be considered at increased risk of CVD [International PCOS Network, 2023].
Referral if dyslipidaemia requires treatment
  • Although there is some evidence that statins improve hyperandrogenaemia and the metabolic profile in women with PCOS, they are not licensed for these indications. The RCOG advises that lipid-lowering treatment is not recommended routinely in women with PCOS and should only be prescribed by a specialist [RCOG, 2014]. 
Calculating cardiovascular risk score using the QRISK®3 tool
  • The QRISK®3 tool calculates a person's estimated risk (not lifetime risk) of CVD over a 10-year period. See the CKS topic on CVD risk assessment and management for more information.
  • The RCOG warns that while it seems prudent to assess the cardiovascular risk factors of a woman with PCOS, it should be noted that the conventional cardiovascular risk calculators have not been validated in this group of women [RCOG, 2014]. 
Offering an oral glucose tolerance test (OGTT)
  • Women with PCOS have an increased risk of impaired glucose tolerance and type 2 diabetes. See the section on Complications for more information.
  • The International PCOS Network advises that glycaemic status should be assessed at baseline in all women with PCOS. Thereafter, assessment should be every 1–3 years, depending on the presence of other diabetes risk factors [International PCOS Network, 2023].
    • The International PCOS Network recommends that an OGTT should be performed to assess glycaemic status. They note that if an OGTT cannot be performed, fasting plasma glucose and/or glycated haemoglobin (HbA1c) could be considered, noting that these tests have significantly reduced accuracy. [International PCOS Network, 2023].

How should I manage other possible complications of polycystic ovary syndrome?

  • Infertility
    • See the CKS topic on Infertility for management information.
  • Obstructive sleep apnoea syndrome (OSAS)
    • Ask about symptoms of OSAS, such as snoring and daytime fatigue/somnolence.
    • If symptoms of PCOS are present use a screening questionnaire to assess the extent and severity of symptoms. Options include:
    • If the woman has OSAS symptoms and a positive screen, refer to a specialist centre for further investigation and treatment.
    • See the CKS topic on Obstructive sleep apnoea syndrome for more information.
  • Psychological disorders
    • Screen for depression and anxiety, where appropriate. See the CKS topics on Depression and Generalized anxiety disorder for more information.
    • Consider the possibility of the following psychological disorders:
      • Psychosexual problems — hirsutism, obesity, oligomenorrhoea, and infertility may lead to feelings of being unattractive and loss of feminine identity.
      • Negative body image — women with polycystic ovary syndrome (PCOS) may feel less physically attractive, physically fit or healthy and may be less satisfied with their body size than women without PCOS.
      • Eating disorders, such as anorexia nervosa, bulimia nervosa, binge-eating disorder, and atypical eating disorders. See the CKS topic Eating disorders for more information.
      • Adverse impact of PCOS on quality of life.
  • Pregnancy complications
    • If a woman with PCOS is pregnant or considering pregnancy, offer referral for a 75-g oral glucose tolerance test (OGTT).
      • If this is not performed preconception, it should be offered before 20 weeks gestation.
      • All pregnant women with PCOS should be offered an OGTT at 24–28 weeks gestation. 
    • Consider whether any changes to drug treatment(s) should be made. For example, any hormonal treatment (such as medroxyprogesterone for inducing cyclical bleeding) should be stopped.
  • Cancer
    • Have a low threshold for investigation of endometrial cancer in women with PCOS or a history of PCOS.
    • Transvaginal ultrasound and/or endometrial biopsy is recommended for women with persistent thickened endometrium and/or risk factors, including prolonged amenorrhea, abnormal vaginal bleeding, or excess weight.
    • Optimal prevention for endometrial hyperplasia and endometrial cancer is not known.
      • A pragmatic approach could include combined oral contraceptive (COC) or progestin treatment in women with cycles longer than 90 days. See the section on Managing clinical features of PCOS for more information.
      • Routine ultrasound screening of endometrial thickness in PCOS is not recommended.
  • Non-alcoholic fatty liver disease (NAFLD)

Basis for recommendation

These recommendations are based largely on the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Long-term Consequences of Polycystic Ovary Syndrome [RCOG, 2014], The polycystic ovary syndrome: a position statement from the European Society of Endocrinology (ESE) [Conway, 2014], and the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International Polycystic Ovary Syndrome (PCOS) Network [International PCOS Network, 2023] .

Obstructive sleep apnoea syndrome (OSAS)
  • The prevalence of OSAS is increased in obese women with PCOS. See the section on Complications for more information.
  • The International PCOS Network advises that screening for obstructive sleep apnoea should only be considered to identify and alleviate related symptoms, such as snoring, waking unrefreshed from sleep, daytime sleepiness, and the potential for fatigue to contribute to mood disorders [International PCOS Network, 2023].
Psychological disorders 
  • Women with PCOS are at increased risk of psychological and behavioural disorders as well as reduced quality of life. See the section on Complications for more information.
  • The International PCOS Network advises that health professionals should be aware of the increased prevalence of psychosexual dysfunction and should consider exploring how features of PCOS, including hirsutism and body image, impact on sex life and relationships in PCOS [International PCOS Network, 2023].
  • The Androgen Excess - Polycystic Ovary Syndrome Society recommends that in women with PCOS, screening for depressive and anxiety symptoms should be offered at the time of diagnosis and screening for disordered eating should be considered [Dokras, 2018].
Pregnancy complications
  • Women with PCOS have a clinically significant increased risk of pregnancy complications compared with women without PCOS. See the section on Complications for more information.
  • The information on when and how an oral glucose tolerance test should be done is based on expert opinion in the RCOG guideline [RCOG, 2014] and the International PCOS Network guideline [International PCOS Network, 2023].
  • The recommendation to consider whether any changes to drug treatment should be made is based on what CKS considers to be good clinical practice.
Cancer
  • Women with PCOS appear to have an increased risk of endometrial cancer due to prolonged oligomenorrhoea or amenorrhoea and an increased prevalence of obesity. See the section on Complications for more information.
  • Women with PCOS share many of the risk factors associated with the development of endometrial cancer, including obesity, hyperinsulinism, diabetes, and abnormal uterine bleeding. However, routine ultrasound screening for endometrial thickness is not recommended [International PCOS Network, 2023].

Scenario: Management of polycystic ovary syndrome in adolescents

From age 12 years to 17 years (Female).

How should I manage polycystic ovary syndrome in adolescents?

In adolescents with a clear diagnosis of polycystic ovary syndrome (PCOS):

  • Offer advice on the possible long-term complications of PCOS, including type 2 diabetes and cardiovascular disease (CVD).
    • Encourage a healthy lifestyle to reduce the risk of these complications and to help improve the clinical features of PCOS.
    • For girls who are overweight or obese, offer advice on weight loss or consider referral to a dietitian. See the CKS topic on Obesity for more information.
    • Explain that weight loss may reduce hyperinsulinism and hyperandrogenism, reduce the risk of type 2 diabetes and CVD, and result in menstrual regularity.
  • Offer referral for screening for:
    • Impaired glucose tolerance and type 2 diabetes. 
    • Cardiovascular risk factors. 
  • Screen for obstructive sleep apnoea syndrome.
    • Ask about symptoms of OSAS, such as snoring and daytime fatigue/somnolence.
    • If symptoms are present, refer for investigation and treatment.
    • See the CKS topic on Obstructive sleep apnoea syndrome for more information.
  • Screen for psychological disorders.
    • Screen for depression and anxiety and manage appropriately See the CKS topics on Depression in children and Generalized anxiety disorder for more information.
    • Consider the possibility of the following psychological disorders:
      • Psychosexual problems — hirsutism, obesity, and oligomenorrhoea may lead to feelings of being unattractive and loss of feminine identity.
      • Negative body image — adolescents with PCOS may feel less physically attractive, physically fit or healthy and may be less satisfied with their body size than adolescents without PCOS.
      • Eating disorders, such as anorexia nervosa, bulimia nervosa, binge-eating disorder, and atypical eating disorders. See the CKS topic Eating disorders for more information.
      • Adverse impact of PCOS on quality of life.
  • Manage the clinical features of PCOS.
    • Consider prescribing the combined oral contraceptive (COC) pill alone for the management of clinical hyperandrogenism and/or irregular menstrual cycles, provided there are no contraindications.
      • See the CKS topic on Contraception - combined hormonal methods for prescribing information on COCs, including contraindications and cautions, choice, risks and adverse effects, and drug interactions.
      • COCs with 35 micrograms of ethinyloestradiol plus cyproterone acetate preparations should not be considered first line in PCOS due to adverse effects, including venous thromboembolic risks.
    • Metformin has been used off label to treat PCOS. However, there is uncertainty regarding the relative benefits compared with COC.
      • Seek specialist advice before initiating metformin in primary care for adolescents without diabetes.
  • Provide sources of additional information and support. For example:

Basis for recommendation

These recommendations are based on the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International Polycystic Ovary Syndrome (PCOS) Network [International PCOS Network, 2023] and The Diagnosis of Polycystic Ovary Syndrome during Adolescence, which represents the consensus of paediatric endocrine and adolescent medicine experts representing paediatric subspecialty societies [Witchel, 2015]. 

Encouraging a healthy lifestyle
  • The International PCOS Network advises that [International PCOS Network, 2023]:
    • Healthy lifestyle behaviours (including healthy eating and regular physical activity) should be recommended in all those with PCOS to achieve and/or maintain a healthy weight and to optimize hormonal outcomes, general health, and quality of life.
    • Lifestyle intervention (preferably multicomponent, including diet, exercise, and behavioural strategies) should be recommended in all those with PCOS and excess weight, for reductions in weight, central obesity, and insulin resistance.
    • Prevention of weight gain, monitoring of weight, and encouraging evidence-based and socio-culturally appropriate healthy lifestyle is important in PCOS, particularly from adolescence.
Offering screening for impaired glucose tolerance and type 2 diabetes
  • The prevalence of impaired glucose tolerance and type 2 diabetes are significantly increased in PCOS, regardless of the age of the person. See the section on Complications for more information.
  • The International PCOS Network advises that glycaemic status should be assessed at baseline in all women with PCOS [International PCOS Network, 2023]. CKS has extrapolated this recommendation to adolescents.
Offering screening for cardiovascular risk factors
  • There is some evidence that cardiovascular disease (CVD) risk factors are increased in PCOS. See the section on Complications for more information.
  • CKS recommends that, in view of the possible increased risk of cardiovascular events, clinicians should give advice on measures to reduce cardiovascular risk.
  • The International PCOS Network advises that all women with PCOS should be assessed for cardiovascular risk factors and global CVD risk [International PCOS Network, 2023]. CKS considers that this recommendation can be extrapolated to adolescents.
Obstructive sleep apnoea syndrome (OSAS)
  • The prevalence of OSAS is increased in obese people with PCOS. See the section on Complications for more information.
  • The International PCOS Network advises that screening for obstructive sleep apnoea should be considered to identify and alleviate related symptoms, such as snoring, waking unrefreshed from sleep, daytime sleepiness, and the potential for fatigue to contribute to mood disorders [International PCOS Network, 2023].
Psychological disorders 
  • There is a likely increased prevalence of moderate to severe anxiety and depressive symptoms in adolescents with PCOS. See the section on Complications for more information.
  • The International PCOS Network advises that screening for anxiety and depressive symptoms should offered to all adolescents and women with PCOS at diagnosis [International PCOS Network, 2023].
Combined oral contraceptive (COC) pill 
  • COCs are the mainstay of the pharmacological treatment of PCOS as they can be used to manage both menstrual disorders and androgen excess symptoms (such as acne and hirsutism). Progestogens, usually given cyclically, also have a role in the management of menstrual dysfunction [Conway, 2014].
  • The International PCOS Network advises that [International PCOS Network, 2023]:
    • Provided there are no contraindications the COC pill alone should be considered in adolescents with a clear diagnosis of PCOS for management of clinical hyperandrogenism and/or irregular menstrual cycles.
    • When deciding on a treatment, the person’s personal characteristics, preferences, and values should be considered, as well as the benefits, adverse effects, and contraindications of the treatment.
    • The lowest effective oestrogen doses (such as 20–30 micrograms of ethinyloestradiol or equivalent) and natural oestrogen preparations should be considered whilst balancing efficacy, metabolic risk profile, adverse effects, cost, and availability.
    • The generally limited evidence on the effects of COCs in PCOS should be considered, with practice informed by general population guidelines.
    • PCOS specific risk factors, such as high body mass index, hyperlipidemia, and hypertension, need to be considered.
Metformin
  • Metformin is licensed in the UK for the treatment of type 2 diabetes mellitus, particularly in overweight people, when dietary management and exercise alone does not result in adequate glycaemic control [BNF, 2024]. 
  • Metformin is used to treat PCOS, but it is not licensed in the UK for this indication [BNF, 2024]
  • The International PCOS Network makes the following recommendations on the use of metformin for non-fertility indications in adolescents with PCOS [International PCOS Network, 2023]:
    • In combination with the COC pill, metformin could be considered in adolescents with PCOS and body mass index (BMI) of 25kg/m2 or more where COCP and lifestyle changes do not achieve desired goals (based on low-quality evidence). 
    • In addition to lifestyle measures, metformin could be considered in adolescents with a clear diagnosis of PCOS or with symptoms of PCOS before the diagnosis is made (based on low-quality evidence). 
  • A Cochrane systematic review (search date: August 2019) assessed the effectiveness and safety of metformin compared with COC (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS [Fraison, 2020b].
    • The Cochrane review included 44 RCTs (n = 2253 women), which comprised five RCTs on adolescent women (n = 206 women) and 39 RCTs on adult women (n = 2047 women). The evidence quality ranged from very low to low. The main limitations were risk of bias, imprecision, and inconsistency.
    • Metformin compared with metformin plus COC
      • There were no trials for this comparison in adolescents.
    • COC compared with metformin plus COC
      • It was uncertain whether there is a difference between the COC alone and metformin plus COC on hirsutism, menstrual pattern (no trials reporting this outcome), acne (no trials reporting this outcome), and BMI. 
      • It was uncertain whether there is a difference between the COC alone and metformin plus COC on severe adverse effects (requiring stopping the medication) and minor adverse effects (no trials reporting this outcome).
    • Other outcomes
      • There was insufficient evidence to determine whether there was a difference in systolic and diastolic blood pressure with no RCTs reporting on diagnosis of type 2 diabetes mellitus and body weight.
      • There was insufficient evidence to determine whether there was a difference in serum total testosterone and free androgen index (FAI) when comparing the COC alone with metformin plus COC.
      • There was also insufficient evidence to determine whether there was a difference in fasting glucose and lipids when comparing COC alone with metformin plus COC, with no RCTs reporting fasting insulin.
    • Due to the uncertainties regarding the benefits and safety of metformin in adolescents with PCOS, CKS recommends seeking specialist advice before initiating metformin in primary care for adolescents without diabetes.
Providing sources of additional information and support
  • Providing sources of additional information and support is a clinical consensus recommendation in the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 [International PCOS Network, 2023].

How should I manage adolescents who are deemed 'at risk' but are not yet diagnosed with polycystic ovary syndrome?

  • In adolescents who are deemed 'at risk' but not yet diagnosed with polycystic ovary syndrome (PCOS), including those with PCOS features before combined oral contraceptive (COC) pill commencement, those with persisting features, and those with significant weight gain in adolescence:
    • Consider prescribing a COC for management of clinical hyperandrogenism and irregular menstrual cycles, provided there are no contraindications.
      • See the CKS topic on Contraception - combined hormonal methods for prescribing information.
      • COCs with 35 micrograms of ethinyloestradiol plus cyproterone acetate preparations should not be considered first line in PCOS due to adverse effects, including venous thromboembolic risks.
    • Reassess the young woman at or before full reproductive maturity (that is, 8 years post-menarche).
      • This will require withdrawing the COC for 3 months or longer to determine the persistence of hyperandrogenic anovulation, and should be accompanied by contraceptive counselling.

Basis for recommendation

These recommendations are based on the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International Polycystic Ovary Syndrome (PCOS) Network [International PCOS Network, 2023] . 

  • The International PCOS Network advises that [International PCOS Network, 2023]:
    • Provided there are no contraindications the combined oral contraceptive (COC) pill could be considered in adolescents who are deemed 'at risk' but not yet diagnosed with PCOS, for management of clinical hyperandrogenism and irregular menstrual cycles.
    • When deciding on a treatment, the person’s personal characteristics, preferences, and values should be considered, as well as the benefits, adverse effects, and contraindications of the treatment.
    • The lowest effective oestrogen doses (such as 20–30 micrograms of ethinyloestradiol or equivalent) and natural oestrogen preparations should be considered whilst balancing efficacy, metabolic risk profile, adverse effects, cost, and availability.
    • The generally limited evidence on effects of COCs in PCOS should be considered, with practice informed by general population guidelines.
    • PCOS specific risk factors, such as high body mass index, hyperlipidaemia, and hypertension, need to be considered.
Managing the clinical features of PCOS and managing adolescents who are deemed 'at risk' but not yet diagnosed with PCOS
  • Combined oral contraceptives (COCs) are the mainstay of the pharmacological treatment of PCOS as they can be used to manage both menstrual disorders and androgen excess symptoms (such as acne and hirsutism). Progestogens, usually given cyclically, also have a role in the management of menstrual dysfunction [Conway, 2014].
  • The International PCOS Network advises that [International PCOS Network, 2023]:
    • Provided there are no contraindications:
      • The COC alone should be considered in adolescents with a clear diagnosis of PCOS for management of clinical hyperandrogenism and/or irregular menstrual cycles (based on low-quality evidence).
      • The COC could be considered in adolescents who are deemed 'at risk' but not yet diagnosed with PCOS, for management of clinical hyperandrogenism and irregular menstrual cycles (based on low-quality evidence).
    • When deciding on a treatment, the woman’s personal characteristics, preferences, and values should be considered, as well as the benefits, adverse effects, and contraindications of the treatment.
    • The lowest effective oestrogen doses (such as 20–30 micrograms of ethinyloestradiol or equivalent) and natural oestrogen preparations should be considered whilst balancing efficacy, metabolic risk profile, adverse effects, cost, and availability.
    • The generally limited evidence on effects of COCs in PCOS should be considered, with practice informed by general population guidelines.
    • PCOS specific risk factors, such as high body mass index, hyperlipidaemia, and hypertension, need to be considered.
  • The information on withdrawing the COC to determine the persistence of hyperandrogenic anovulation and contraceptive counselling are based on expert opinion in a review article on the diagnosis of PCOS in adolescents [Rosenfield, 2015].

Supporting evidence

The recommendations for the management of adults are based largely on the Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome published by the Rotterdam European Society of Human Reproduction and Embryology (ESHRE)/American Society for Reproductive Medicine (ASRM)-Sponsored Polycystic Ovary Syndrome (PCOS) Consensus Workshop Group [Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2004], the Royal College of Obstetricians and Gynaecologists (RCOG) guideline Long-term Consequences of Polycystic Ovary Syndrome [RCOG, 2014], The polycystic ovary syndrome: a position statement from the European Society of Endocrinology (ESE) [Conway, 2014], and the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International PCOS Network [International PCOS Network, 2023].

The recommendations for the management of adolescents are based largely on the International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 issued by the International PCOS Network [International PCOS Network, 2023] and The Diagnosis of Polycystic Ovary Syndrome during Adolescence, which represents the consensus of paediatric endocrine and adolescent medicine experts representing paediatric subspecialty societies [Witchel, 2015]. 

How this topic was developed

This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

Search strategy

A literature search was conducted for guidelines and systematic reviews on primary care management of polycystic ovary syndrome.

Search dates

August 2018 - May 2023

Key search terms

The terms listed below are the core search terms that were used for EBSCO MEDLINE (searched 9th August 2018). These terms were combined with search filters for systematic reviews and guidelines in EBSCO MEDLINE. The strategy was adapted for The Cochrane Library databases. 

S4 S1 OR S2 OR S3

S3 AB PCOS OR TI PCOS

S2 AB (polycystic N2 ovar*) OR TI (polycystic N2 ovar*)

S1 (MH "Polycystic Ovary Syndrome")

Sources of guidelines

Sources of systematic reviews and meta-analyses

  • The Cochrane Library:
    • Systematic reviews
    • Protocols
    • Database of Abstracts of Reviews of Effects
  • Medline (with systematic review filter)
  • EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

Sources of randomized controlled trials

  • The Cochrane Library:
    • Central Register of Controlled Trials
  • Medline (with randomized controlled trial filter)
  • EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Sources of national policy

Patient experiences

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

  • Clinical accuracy.
  • Consistency with other providers of clinical knowledge for primary care.
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Principles of the consultation process

  • The process is inclusive and any individual may participate.
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  • Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
  • All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
  • All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

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  • Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
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Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

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  • First draft internal review
  • Second draft internal review
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Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

  • Animal studies
  • Original research is not written in English

Possible exclusions for reviewed literature:

  • Sample size too small or study underpowered
  • Bias evident or promotional literature
  • Population not relevant
  • Intervention/treatment not relevant
  • Outcomes not relevant
  • Outcomes have no clear evidence of clinical effectiveness
  • Setting not relevant
  • Not relevant to UK
  • Incorrect study type
  • Review article
  • Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

  • Feasibility
    • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
  • Organizational and Financial Impact Analysis
  • Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
    • Eligible population
    • Current interventions
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    • Cost of the current or new intervention mix
    • Impact on other costs
    • Condition-related costs
    • In-direct costs and service impacts
    • Time dependencies
  • Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

  • Personal financial interests
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Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.

References

  • ABPI (2021) SPC for Metformin 500 mg film coated tablets. Electronic Medicines Compendium. Datapharm Communications Ltd. https://www.medicines.org.uk/emc [Free Full-text]
  • Azziz, R., Carmina, E., Dewailly, D., et al. (2006) Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. Journal of Clinical Endocrinology & Metabolism 91(11), 4237-4245. [Abstract]
  • Azziz, R., Carmina, E., Dewailly, D., et al. (2009) The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertility and Sterility 91(2), 456-488. [Abstract]
  • Bahri Khomami, M., Joham, A. E. and Boyle, J. A. et al. (2019) Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity-A systematic review, meta-analysis, and meta-regression. Obesity reviews : an official journal of the International Association for the Study of Obesity 20(5), 659-674. [Abstract]
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