Polycystic ovary syndrome

• Polycystic ovary syndrome (PCOS) is a common, lifelong hormonal disorder in which the ovaries make excess androgens and ovulation is disrupted. It affects roughly 10 to 13 in 100 reproductive-aged women by the Rotterdam definition, and most of those women never receive a diagnosis.
• It crosses several systems at once: menstrual disturbance, excess hair and acne, difficulty conceiving, weight and insulin resistance, sleep, mood, and a higher risk of type 2 diabetes and endometrial thickening.
• The diagnosis in an adult is clinical: two of three features after other causes are excluded (the 2003 Rotterdam criteria, updated to evidence-based cut-offs in 2023). Adolescents need both hyperandrogenism and irregular cycles. ^[1]
• Treatment is tiered by the woman's goal: regulate bleeding and endometrial risk, ease hirsutism and acne, improve metabolic health, and induce ovulation only when fertility is wanted.
• Lifestyle change is first-line for every woman; the combined oral contraceptive pill is first-line for anovulatory bleeding and hirsutism, metformin for metabolic risk, and letrozole for ovulation induction. Care is shared decision-making based on age, symptoms and resources. ^[1]

By the end of this page you should be able to:

1. Define PCOS and explain why it is both a reproductive and a metabolic condition.
2. Apply the adult and adolescent diagnostic criteria, including the ultrasound and anti-Mullerian hormone (AMH) cut-offs.
3. Explain the insulin resistance and androgen excess loop from ovary to skin and endometrium.
4. Investigate a woman with suspected PCOS and exclude the conditions that mimic it.
5. Choose and titrate lifestyle measures, a combined contraceptive pill, metformin, an anti-androgen and letrozole, and know when each is first-line.
6. Protect the endometrium and screen for diabetes, blood pressure, lipids, sleep apnoea and mood.
7. Counsel about fertility, pregnancy, adolescence and menopause in PCOS.

PCOS is best understood as an endocrine disorder that begins in puberty, continues as a chronic condition, and changes its face across the lifespan. The older name "Stein-Leventhal syndrome" is now historical. ^[2]

A diagnosis is enduring in most women. Both clinical and biochemical hyperandrogenism persist after the menopause, and the diagnosis can be made after menopause when there is a past diagnosis, or a long-term history of infrequent periods with hyperandrogenism and/or polycystic morphology during the reproductive years (roughly ages 20 to 40). New, severe or worsening hyperandrogenism in a postmenopausal woman needs investigation for an androgen-secreting tumour or ovarian hyperthecosis rather than PCOS. ^[1]

The 2023 international guideline shortened the algorithm: where a woman has both irregular cycles and hyperandrogenism, neither ultrasound nor AMH is needed. ^[1] NICE's Clinical Knowledge Summary (a primary-care summary) states the same adult rule and uses tighter adolescent criteria, and both it and RCOG Green-top Guideline No. 33 (2014, now archived and replaced by the international guideline) endorse the Rotterdam criteria. ^[2]

PCOS is the most common endocrine condition of reproductive-aged women and the most common cause of anovulation worldwide. ^[4] Using the Rotterdam criteria, prevalence is 10 to 13 percent globally, broadly similar across ethnic groups but possibly higher in South East Asian and Eastern Mediterranean regions. ^[1][4] An estimated 70 percent of affected women are undiagnosed. ^[4]

PCOS is chronic and persists beyond the reproductive years. ^[4] Its prevalence in adolescents is harder to establish because irregular cycles are normal in the first years after menarche; many have PCOS features without (yet) meeting diagnostic criteria. ^[1]

The cause is not known. It is likely multifactorial, with genetic and environmental contributions; it runs in families, and a family history of PCOS or type 2 diabetes increases risk. ^[4] Insulin resistance is a key driver in many but not all women and is worsened by excess weight. ^[2][4]

Principal risk factors are:

• a first-degree relative with PCOS or type 2 diabetes;
• excess weight or central adiposity at or after puberty;
• south or south-east Asian or eastern Mediterranean ethnicity, where both prevalence and metabolic complications appear higher;
• a personal history of gestational diabetes. ^[2][4]

There is no single gene, no modifiable environmental exposure proved to cause PCOS, and no evidence that it is caused by contraception use or by ovarian cysts that existed before puberty.

PCOS physiology becomes easy when traced as one loop rather than a list. ^[1]

1. Insulin resistance and hyperinsulinaemia. Peripheral insulin resistance raises circulating insulin. Insulin acts on the ovary directly and amplifies luteinising hormone (LH) signalling.
2. Androgen excess. Theca cells produce excess androgens in response. Insulin also suppresses hepatic sex hormone-binding globulin (SHBG), so more testosterone circulates free, even when total testosterone is normal or only slightly raised.
3. Arrested folliculogenesis. The excess androgen stops follicles maturing; multiple small antral follicles stall rather than ovulate. Ovulation becomes infrequent or absent.
4. High-normal oestrogen, no progesterone. Because follicles keep producing oestrogen without ovulation, there is no corpus luteum and therefore no progesterone. The endometrium is exposed to unopposed oestrogen.
5. Endometrial risk. Long-standing unopposed oestrogen can produce endometrial thickening, hyperplasia and, in a small number of women, cancer. ^[1]
6. Metabolic amplification. Androgen excess worsens insulin resistance; central adiposity worsens both. The condition therefore feeds itself unless the loop is broken.

This mechanism explains the signs: oligo-anovulation, hirsutism, acne, female-pattern hair thinning, and increased waist circumference; and it explains why weight management and insulin-sensitising therapy help across reproductive and metabolic features. ^[1][2]

Women usually describe the problem in terms of its consequences rather than the syndrome:

• menstrual disturbance: infrequent periods (cycles longer than 35 days after the first three years from menarche), amenorrhoea, or unpredictable bleeding; ^[1]
• difficulty becoming pregnant;
• unwanted facial or body hair, acne, or oily skin;
• central weight gain;
• hair thinning in a female pattern.

On examination, look for hirsutism scored with the modified Ferriman-Gallwey (mFG) scale, acne, female-pattern hair loss, acanthosis nigricans, and central adiposity. An mFG score of 4 to 6, depending on ethnicity, is the cut-off for hirsutism. Terminal hairs only count; women often self-treat hair before the visit, so a normal examination does not exclude androgen excess. ^[1]

Psychological features are common and important: reduced quality of life, depressive and anxiety symptoms, body image distress and disordered eating. These should be screened for directly rather than assumed. ^[1]

A clinical vignette: a 22-year-old student has very infrequent periods, new hirsutism well above the ethnicity cut-off on the mFG scale, weight gain centred on her waist, and a mother with type 2 diabetes. Her total testosterone is normal but she has a low SHBG. Menstrual disturbance plus clinical hyperandrogenism is enough for the diagnosis in an adult even without an ultrasound.

Under the Rotterdam criteria as updated by the 2023 international guideline, an adult has PCOS when 2 of 3 features are present and other causes are excluded: ^[1]

• Hyperandrogenism, clinical or biochemical.
  • Total and free testosterone is preferred; free testosterone can be estimated with the free androgen index.
  • Use validated highly accurate assays (LC-MS/MS) rather than direct immunoassays; laboratory reference ranges are often poorly normalised.
  • Biochemical testing matters most when clinical signs are absent.
  • If results are markedly raised, consider androgen-secreting tumours, non-classic congenital adrenal hyperplasia, Cushing's syndrome, ovarian hyperthecosis (after menopause), severe insulin resistance.
  • Androgens are unreliable on the combined pill; if imperative, withdraw it for at least 3 months and use non-hormonal contraception during that time. ^[1]
• Ovulatory dysfunction (irregular cycles).
  • cycles under 21 or over 45 days, 1 to under 3 years after menarche; ^[1]
  • cycles under 21 or over 35 days, or under 8 cycles per year, from 3 years after menarche to perimenopause; ^[1]
  • any cycle over 90 days, 1 year after menarche; ^[1]
  • primary amenorrhoea by age 15 or more than 3 years after breast development. ^[1]
• Polycystic ovarian morphology or a raised AMH.
  • On ultrasound: at least 20 follicles per ovary in at least one ovary, or ovarian volume 10 ml or more, or 10 follicles or more per section (for older equipment). ^[1]
  • AMH may be used to define polycystic morphology instead, but not both together; AMH is not diagnostic on its own. ^[1]
  • In the transabdominal approach, report ovarian volume rather than follicle number.
  • Transvaginal ultrasound is the more accurate route when acceptable. ^[1]
  • Where there are irregular cycles and hyperandrogenism, imaging is not needed. ^[1]

Diagnose using both hyperandrogenism and ovulatory dysfunction. ^[1]

• Do not use ultrasound or AMH within 8 years of menarche, because they overlap normal puberty.
• Severe acne and hirsutism are the clinical markers; androgen levels reach adult ranges by age 12 to 15. ^[1]
• Adolescents with PCOS features who do not meet criteria should be labelled "at increased risk" and reassessed at or before full reproductive maturity. This includes those who developed features before starting the combined pill, those with persisting features, and those with significant weight gain in adolescence. ^[1]
• Take care not to overdiagnose after the pill increases SHBG; consider timing. ^[1]

NICE's Clinical Knowledge Summary states the same adult rule and explicitly endorses tighter adolescent criteria, and it retains the Rotterdam criteria as the basis for diagnosis. ^[2]

A diagnosis made earlier usually endures for life. Hyperandrogenism persists after menopause. If a postmenopausal woman presents with new severe or worsening hirsutism or hyperandrogenism, investigate for androgen-secreting tumour and ovarian hyperthecosis. ^[1]

No routine endometrial screening is recommended. Inform women of the raised risk and of the preventative strategies (weight management, cycle regulation, regular progestogen). Assess further where amenorrhoea has been long-standing and untreated, where there is higher weight or type 2 diabetes, or where a thickened endometrium is detected. ^[1][2]

PCOS is common in all ethnicities. Presentation varies, and women of non-white ethnicity may need ethnicity-specific approaches (for example mFG 4 to 6 depending on ethnicity). ^[1]

Management is lifelong and tailored. There is no cure, and symptoms generally recur if treatment is stopped during the reproductive years, while hyperandrogenic features often ease after menopause as ovarian function declines. ^[2][4]

Care is driven by the woman's priorities: menstrual regularity and endometrial safety, hirsutism and acne, metabolic health, psychological health, or fertility. Shared decision-making underpins the 2023 guideline; one practical format is the "Ask Three Questions" (what are my options; what are the pros and cons; how do I get support), reproduced in the RCOG patient guide. ^[1][2]

Lifestyle change is first-line for all women with PCOS, for metabolic health, with outcomes that appear equal to those in women without PCOS. Even women of normal weight benefit from preventing further weight gain. ^[1]

• Diet. No single diet composition has evidence of superiority for anthropometric, metabolic, hormonal, reproductive or psychological outcomes; any pattern consistent with healthy-eating guidance works and should be sustainable, individualised and flexible rather than restrictive. ^[1]
• Physical activity. A practical target is 30 minutes at least three times a week, supported by healthy eating advice. ^[2]
• Behavioural support. Goal-setting, problem-solving and self-monitoring (SMART goals), ideally in structured intensive programmes. ^[1]
• Weight. Losing even a small amount improves insulin resistance, testosterone, cycle regularity and fertility; central adiposity and the lipid profile are valid targets even when body weight does not change. Use a tailored energy deficit, clinician supported, rather than generic advice. ^[1][2]
• Weight stigma. Discuss weight sensitively; weight loss is a tool, not a verdict. ^[1]

Weight-loss medicines (orlistat, GLP-1 receptor agonists such as liraglutide or semaglutide) may be added to active lifestyle change in adults with higher weight, following general population guidance; GLP-1 agents need reliable contraception and gradual dose escalation. ^[1]

Unopposed oestrogen is the mechanism; regular withdrawal bleeding is the remedy. Women should aim for a bleed at least every 3 to 4 months, with further assessment if there has been none for 4 months. ^[2]

Options supported by the 2023 guideline and RCOG/ACOG practice:

• Combined hormonal contraception is first-line for menstrual regularity, acne and hirsutism. Prescribe the lowest effective oestrogen dose, such as 20 to 30 micrograms of ethinylestradiol or an equivalent natural oestrogen, balancing efficacy, metabolic risk, side effects, cost and availability. ^[1][3]
• Progestogen-only endometrial protection. A five-day course of progestogen tablets every 3 to 4 months induces a withdrawal bleed; a levonorgestrel-releasing intrauterine system is another option that protects the lining while usually reducing bleeding. The choice depends on whether the woman wants to conceive. ^[2]
• Metformin can be used when bleeding irregularity is the only goal and oestrogen is not desired, but it is less reliable for cycle control. ^[1]

The guideline is explicit that endometrial cancer absolute risk remains low and routine screening is not recommended, even though the relative risk is markedly raised. ^[1]

• The combined contraceptive pill is first-line medical therapy, continued for at least 6 months before judging response. ^[1]
• Cosmetic therapy (laser, electrolysis, depilatory creams, bleaching) is a real and sometimes preferred option. ^[1]
• Anti-androgens may be added after an inadequate response despite 6 or more months of a contraceptive pill with or without cosmetic therapy, or considered earlier when the pill is contraindicated; they must be used with effective contraception. ^[1]
  • spironolactone at 25 to 100 mg per day appears to have lower risk of adverse effects; ^[1]
  • cyproterone acetate at doses of 10 mg or more is not advised because of increased risk, including meningioma; ^[1]
  • finasteride carries an increased risk of liver toxicity. ^[1]
• Metformin over the pill may be chosen when the primary need is metabolic rather than hirsutism. ^[1]

Metformin alone is recommended in adults with PCOS and a BMI of 25 or above for anthropometric and metabolic outcomes, including insulin resistance, glucose and lipid profiles. It may be considered in adults with BMI under 25 and in adolescents for cycle regulation, although evidence is limited. ^{[1] [2]}

Prescribing points: ^[1]

• start low and increase by 500 mg every 1 to 2 weeks;
• extended-release preparations reduce gastrointestinal side effects;
• suggested maximum daily dose 2.5 g in adults and 2 g in adolescents;
• adverse effects are mostly mild, dose-dependent, self-limiting gastrointestinal symptoms.

Metformin and active lifestyle change have similar efficacy for weight, so discussion of priorities matters. ^[1]

Anti-obesity medicines, including orlistat and GLP-1 receptor agonists, may be added to active lifestyle change in adults with higher weight, following general population guidance. ^[1]

PCOS is the most common cause of anovulatory infertility and a leading cause of infertility overall. ^[4] A practical pathway:

• lifestyle change and weight optimisation come first; modest weight loss may restore ovulation. ^[2]
• letrozole is first-line for ovulation induction in infertile anovulatory women with PCOS and no other infertility factors. ^[1]
• letrozole and other ovulation-induction agents are off-label in many countries, so prescribing depends on local rules after an informed discussion. ^[1]
• pregnancy must be excluded before any ovulation-induction agent is started, and monitoring for adverse effects is required. ^[1]
• metformin alone should not be expected to improve live birth; it may be used within an ovulation-induction algorithm. ^[1]
• assisted reproductive technology is available and does not appear to add risk of miscarriage, preterm birth, impaired fetal growth or caesarean section over that seen in women without PCOS. ^[1]

Metformin in pregnancy has not been shown to prevent gestational diabetes, late miscarriage, hypertension, pre-eclampsia, macrosomia or high birth weight. It may be considered in selected circumstances, such as risk of preterm birth, to reduce excess gestational weight gain and preterm delivery. Side effects are mild gastrointestinal symptoms and long-term offspring effects remain uncertain, with suggestive signals of later childhood weight gain. ^[1]

• Blood pressure annually; glycaemic status every 1 to 3 years. ^[1]
• Lipid profile repeated according to hyperlipidaemia and additional risk. ^[1]
• Mood, sleep, hirsutism, acne and menstrual control reviewed after each change and at ongoing visits. ^[1]
• Endometrial status reassessed if bleeding remains scant or absent. ^[1][2]

• Infertility from anovulation, and subfertility that can persist even when ovulation is restored. ^[2][4]
• Glucose intolerance and type 2 diabetes, in all body sizes, with regional variation in relative risk. Women with PCOS should have glycaemic testing at diagnosis. ^[1]
• Dyslipidaemia, hypertension and a worse cardiovascular risk profile; women with PCOS should be considered at increased cardiovascular risk, although premenopausal absolute risk is low. ^[1]
• Obstructive sleep apnoea, more common independent of BMI. ^[1]
• Psychological morbidity: depression and anxiety symptoms, common enough to mandate routine screening. ^[1]
• Pregnancy complications: gestational diabetes, pregnancy-induced hypertension, pre-eclampsia, caesarean delivery, miscarriage and preterm birth are all increased. ^[1][2]
• Non-alcoholic fatty liver disease is common in women with PCOS. ^[3]
• Endometrial hyperplasia and cancer risk, discussed above. ^[1][2]

PCOS is a lifelong condition with no cure. ^[2][4] About 1 or 2 in 10 women with PCOS develop diabetes at some point, with higher risk after age 40 and with obesity or a family history, and about 20 to 40 percent of obese women with PCOS develop glucose intolerance or type 2 diabetes by the end of their fourth decade in older literature. ^[2] Hyperandrogenic features such as acne and hirsutism often ease after menopause, while metabolic risk can persist or worsen. ^[1][2]

There is no proved prevention of PCOS itself. What is possible is prevention of its consequences:

• healthy lifestyle for every woman with PCOS, including normal-weight women; ^[1]
• blood pressure and glucose tested from diagnosis because insulin resistance may be silent for years;
• maintaining regular bleeds to protect the endometrium;
• early detection of depression, anxiety, body image distress and sleep problems;
• identifying adolescents with PCOS features before they fulfil criteria, and reassuring and reassessing them. ^[1]

Adolescents. Diagnosis requires both hyperandrogenism and irregular cycles, without ultrasound or AMH within 8 years of menarche. Metformin may be used for cycle regulation, although evidence is limited, and the combined pill regulates bleeding and improves acne. Adolescents with risk features who do not yet qualify are followed rather than labelled. ^[1]

Pregnancy. PCOS is a high-risk condition: blood pressure and an OGTT should be checked when planning pregnancy, and an OGTT offered at the first antenatal visit and again at 24 to 28 weeks. Early lifestyle support is recommended. Metformin is not routine in pregnancy. ^[1]

Older adults and menopause. PCOS is a lifelong diagnosis; hyperandrogenism can persist, and new severe hyperandrogenism in an older woman needs tumour work-up rather than reassurance. Metabolic screening should continue. ^[1]

Families. The cardiometabolic risk of fathers and brothers of women with PCOS may be higher than in the general population. ^[1]

Low-resource settings. The diagnosis can be made from careful history, examination and basic tests (free androgen index calculated where possible; ultrasound where available). The interventions that matter most are the cheapest: lifestyle support, a monthly or quarterly progestogen course to induce withdrawal bleeds, metformin, and opportunistic blood pressure and glucose testing.

ACOG patient information describes how combined hormonal pills regulate periods and may reduce hirsutism, how weight loss helps, and how insulin-sensitising drugs are used in PCOS. ^[3] WHO describes the same criteria of 2 of 3 features after exclusions, and recommends additional blood testing for insulin resistance and overall cardiovascular risk in every newly diagnosed woman. ^[4]

• PCOS is a common lifelong syndrome defined in adults by 2 of 3 Rotterdam features after exclusions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries or a raised AMH.
• Prevalence using Rotterdam criteria is about 10 to 13 percent globally; up to 70 percent of affected women are undiagnosed.
• Insulin resistance drives the whole loop: hyperinsulinaemia raises free androgens, arrests follicles, and exposes the endometrium to unopposed oestrogen.
• A normal body weight does not rule PCOS out; both insulin resistance and hyperandrogenism can occur in lean women.
• Adolescents need both hyperandrogenism and irregular cycles, with no ultrasound or AMH within 8 years of menarche.
• Lifestyle change is first-line for every woman; no single diet has evidence of superiority.
• The combined pill is first-line for menstrual regularity, acne and hirsutism, using the lowest effective oestrogen dose such as 20 to 30 micrograms of ethinylestradiol.
• Metformin is recommended in adults with BMI 25 or above, titrated from 500 mg up to 2.5 g daily (2 g in adolescents). ^[1]
• Letrozole is first-line for ovulation induction in infertile anovulatory women with PCOS.
• Endometrial protection means a bleed at least every 3 to 4 months, using a progestogen course, combined pill, or levonorgestrel intrauterine system.
• Screen blood pressure annually, lipids at diagnosis, glycaemic status with an OGTT at diagnosis and every 1 to 3 years, plus sleep and mood.
• Endometrial hyperplasia and cancer risk are increased, but absolute risk is low and routine screening is not recommended. Breast and ovarian cancer are not associated with PCOS.
• Hyperandrogenic symptoms often ease after menopause, while metabolic risk can persist.

Menorrhagia and abnormal uterine bleeding; secondary amenorrhoea; hirsutism and androgen excess; metabolic syndrome; type 2 diabetes mellitus; infertility assessment; ovulation induction; endometrial hyperplasia; depression; sleep apnoea.