PCOS (Polycystic Ovary Syndrome) — Causes, Rotterdam Criteria & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting 6–12% of women globally (up to 20% with the broader NIH diagnostic criteria). It is a heterogeneous condition characterised by a combination of hyperandrogenism (excess male hormones), ovulatory dysfunction (irregular or absent menstruation), and polycystic ovarian morphology on ultrasound. PCOS is the leading cause of anovulatory infertility — accounting for 70–80% of cases. Beyond reproductive effects, PCOS is associated with significant metabolic consequences including insulin resistance (present in 50–70% of PCOS women, regardless of body weight), dyslipidaemia, and a threefold increased risk of type 2 diabetes. It is also associated with increased cardiovascular risk factors, endometrial hyperplasia/cancer (from prolonged anovulation), and substantial psychosocial burden including anxiety, depression, and impaired quality of life.

The aetiology of PCOS is complex and incompletely understood, involving interactions between genetic predisposition, insulin resistance, androgen excess, and gonadotrophin dysregulation. Insulin resistance and compensatory hyperinsulinaemia: insulin directly stimulates ovarian theca cell androgen production (testosterone, DHEAS) and reduces hepatic SHBG (sex hormone-binding globulin) synthesis — increasing free androgen levels. Elevated androgens disrupt follicle development, preventing dominant follicle selection and causing anovulation, leading to the accumulation of arrested antral follicles ('polycystic' appearance). Hypothalamic-pituitary dysregulation: abnormal GnRH pulse frequency increases LH secretion relative to FSH (elevated LH/FSH ratio above 2:1 in 60% of PCOS women) — preferentially stimulates theca cell androgens while inadequately stimulating granulosa cell aromatase (required to convert androgens to oestrogen). Genetic factors: PCOS is highly heritable — first-degree relatives have a 20–40% prevalence; genome-wide association studies have identified loci including DENND1A (involved in androgen biosynthesis), THADA, and LHCGR genes. Risk factors: obesity (amplifies insulin resistance and androgen excess — but PCOS affects lean women too); prenatal androgen exposure; ethnicity (higher prevalence in South Asian women — more insulin resistant; different phenotypes in East Asian women).

Menstrual irregularity: oligomenorrhoea (fewer than 9 periods per year — cycles longer than 35 days) or amenorrhoea (absence of periods) — reflects oligo/anovulation; the hallmark symptom of PCOS. Hyperandrogenism features: hirsutism (excess dark terminal hair growth in a male distribution — upper lip, chin, cheeks, chest, abdomen, inner thighs — affects 70% of women with PCOS; scored on Ferriman-Gallwey scale above 8 is clinically significant); acne (comedonal and inflammatory — jawline and lower face pattern is characteristic); alopecia (female-pattern hair loss — diffuse crown thinning); acanthosis nigricans (dark, velvety skin thickening in skin folds — marker of insulin resistance). Infertility and subfertility: irregular ovulation makes conception difficult — the most common presentation in women trying to conceive. Polycystic ovaries on ultrasound: 12 or more antral follicles (2–9 mm) per ovary, or ovarian volume above 10 mL on transvaginal ultrasound. Metabolic features: obesity (40–80% of PCOS women are overweight or obese — particularly central/abdominal adiposity); elevated fasting glucose or HbA1c; hypertriglyceridaemia; low HDL cholesterol. Psychological features: anxiety, depression, and poor body image are common — significantly impacting quality of life.

Diagnosis uses the 2003 Rotterdam Consensus Criteria (the most widely used) — requires at least 2 of 3 features: (1) oligomenorrhoea or anovulation; (2) clinical or biochemical hyperandrogenism; (3) polycystic ovaries on ultrasound. Other causes must be excluded. Blood tests: serum androgens (total testosterone — elevated in 30–60% of PCOS; free androgen index = testosterone x 100/SHBG — more sensitive; DHEAS; androstenedione; 17-hydroxyprogesterone if congenital adrenal hyperplasia suspected); SHBG (reduced — amplifies free androgen); LH/FSH ratio (elevated LH in 60%, but not required for diagnosis); serum prolactin (to exclude prolactinoma); TSH (to exclude thyroid dysfunction); fasting insulin and glucose (or HOMA-IR); HbA1c; fasting lipid profile. Pelvic ultrasound (transvaginal preferred; transabdominal if patient declines or has not been sexually active): counts antral follicles (AFC) per ovary — 20 or more per ovary using modern high-resolution ultrasound (revised 2023 PCOS guidelines); measures ovarian volume. Exclusion of other diagnoses: late-onset congenital adrenal hyperplasia (17-OHP above 10 nmol/L on early-morning blood test); Cushing's syndrome (24-hour urinary free cortisol, overnight dexamethasone suppression test); androgen-secreting tumours (rapidly progressing virilisation with very high testosterone); premature ovarian insufficiency (FSH elevated, AMH low in young woman with amenorrhoea). Endometrial assessment: endometrial biopsy for women with PCOS and amenorrhoea or prolonged oligomenorrhoea (over 12 months) — to exclude endometrial hyperplasia or cancer from unopposed oestrogen.

Treatment is individualised based on the patient's presenting concerns: menstrual regulation, hyperandrogenism, metabolic risk, or fertility. Lifestyle modification (first-line for all overweight/obese PCOS women): a 5–10% reduction in body weight through diet and exercise restores ovulation in 55–100% of anovulatory overweight PCOS women; reduces hyperandrogenism, insulin resistance, and cardiovascular risk; low glycaemic index diet is recommended; 150–300 minutes of moderate aerobic activity per week. Menstrual regulation and contraception: combined oral contraceptive pill (COCP — e.g., Yasmin, co-cyprindiol/Dianette) — first-line for menstrual regulation, hyperandrogenism (antiandrogen activity of cyproterone acetate or drospirenone), and endometrial protection; provides reliable contraception. For women not wishing contraception: medroxyprogesterone acetate or progesterone to induce withdrawal bleed every 3–4 months (to prevent endometrial hyperplasia). Hyperandrogenism treatment: COCP (reduces androgen production and increases SHBG); topical eflornithine cream (Vaniqa — reduces facial hair growth); spironolactone 50–100 mg BD (antiandrogen — not suitable in pregnancy); cyproterone acetate; cosmetic treatment (laser hair removal, electrolysis — combined with hormonal treatment). Insulin sensitisation: metformin 500–2500 mg/day — reduces insulin resistance and androgen levels; restores ovulation in some women; first-line in PCOS with impaired glucose tolerance or T2DM; may improve menstrual regularity but inferior to letrozole for ovulation induction. Ovulation induction for fertility: letrozole (aromatase inhibitor) — first-line for ovulation induction in PCOS (superior to clomifene in PCOS — 27.5% live birth rate versus 19.1% per cycle; LEGEND trial 2014, LETOP trial 2022); dose: 2.5–7.5 mg days 2–6. Clomifene citrate (selective oestrogen receptor modulator) — alternative first-line if letrozole unavailable; 50–150 mg days 2–6; 6 cycles maximum (concern about ovarian cancer risk). Gonadotrophin injections (FSH injections): second-line if oral ovulation induction fails; risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy — requires careful monitoring by specialist. In vitro fertilisation (IVF): third-line; PCOS patients are at high risk of OHSS — GnRH antagonist protocols with GnRH agonist trigger and freeze-all embryo strategy recommended. Laparoscopic ovarian drilling (LOD): surgical alternative to gonadotrophin therapy — diathermy of 3–8 points on each ovary; reduces LH and androgen levels; 50–70% ovulation rate; risk of adhesions and ovarian damage — less commonly performed since letrozole became widely available. Long-term metabolic management: annual HbA1c, fasting lipids, and blood pressure monitoring; lifestyle counselling; metformin for impaired glucose tolerance; cardiovascular risk stratification.

Long-term complications of PCOS are primarily metabolic and reproductive. Type 2 diabetes develops in approximately 40% of women with PCOS by middle age — driven by progressive insulin resistance that worsens with age, weight gain, and physical inactivity. Cardiovascular disease risk factors (dyslipidaemia, hypertension, obesity, insulin resistance, chronic low-grade inflammation) are substantially elevated; the precise magnitude of cardiovascular event risk elevation remains under study in younger populations. Endometrial hyperplasia and endometrial cancer risk is elevated 2–3-fold from prolonged unopposed oestrogen exposure in chronically anovulatory women — regular progestogen-induced withdrawal bleeds are the most important protective measure. Pregnancy complications are significantly more common — gestational diabetes (3-fold elevated), pre-eclampsia (2–4 times more common), and preterm birth occur at higher rates. Depression and anxiety disorders affect approximately 35–40% of women with PCOS. Obstructive sleep apnoea affects up to 30% of overweight PCOS women — an important but frequently underdiagnosed complication. Metabolic syndrome is present in 33–47% of women with PCOS.

PCOS cannot be prevented (it has significant genetic and prenatal programming components), but its metabolic complications can be substantially reduced through lifestyle interventions. Maintaining a healthy body weight is the most powerful modifiable factor — adiposity amplifies insulin resistance and hyperandrogenism in PCOS. Regular physical activity independently improves insulin sensitivity beyond weight loss effects. Low glycaemic index diets reduce postprandial insulin levels and may improve PCOS-related hormonal parameters. Women with PCOS should be screened for: type 2 diabetes (oral glucose tolerance test or HbA1c at diagnosis and every 1–3 years thereafter — lifetime risk approximately 40%); dyslipidaemia (fasting lipid profile at diagnosis and 3–5 yearly); obstructive sleep apnoea; depression and anxiety (using validated screening tools). Endometrial protection: women with oligomenorrhoea or amenorrhoea should induce a withdrawal bleed at least every 3–4 months (with COCP or progestogen) to prevent endometrial hyperplasia from unopposed oestrogen — significantly reduces endometrial cancer risk (which is 2–3-fold elevated in PCOS women with prolonged amenorrhoea).

See your GP if you have: fewer than 8 menstrual periods per year or cycles consistently longer than 35 days; new or worsening excess facial or body hair growth; acne that persists beyond teenage years, particularly on the jawline and chin; unexplained difficulty conceiving after 12 months of trying (6 months if aged over 35). Seek assessment if you are trying to conceive and have irregular periods — early referral to a reproductive specialist for ovulation induction is important, particularly as letrozole and clomifene are highly effective in PCOS but require specialist monitoring. Seek urgent review for: amenorrhoea lasting more than 6 months without a prior diagnosis — to exclude premature ovarian insufficiency or pituitary pathology; rapidly progressive hirsutism with signs of virilisation (deepening voice, clitoromegaly) — rare but requires urgent investigation to exclude androgen-secreting tumour. Patients diagnosed with PCOS should have regular long-term follow-up to monitor for metabolic complications — particularly risk of type 2 diabetes and cardiovascular disease.