Key Facts

PCOS is the most common endocrine disorder in women of reproductive age. It is a clinical syndrome rather than a single disease, with significant metabolic and reproductive implications.

Epidemiology

• Prevalence: 8-13% of reproductive-age women
• Up to 70% of affected women remain undiagnosed
• Higher prevalence in women with obesity, South Asian and Afro-Caribbean ethnicity
• Accounts for 80% of anovulatory infertility

Aetiology

• Multifactorial: genetic predisposition and environmental factors
• Strong genetic component with polygenic inheritance
• Insulin resistance is a central feature (present in 50-80%)
• Environmental factors: obesity, sedentary lifestyle, in-utero androgen exposure

Pathophysiology

• Hyperinsulinaemia stimulates ovarian theca cells to produce excess androgens
• Insulin also reduces hepatic sex hormone-binding globulin (SHBG) production, increasing free testosterone
• Excess androgens disrupt follicular development → multiple small follicles arrest at 2-9mm (polycystic morphology)
• Disrupted GnRH pulsatility → elevated LH relative to FSH (LH:FSH ratio >2:1, though this is no longer a diagnostic criterion)
• Chronic anovulation → progesterone deficiency → unopposed oestrogen → endometrial hyperplasia risk

Menstrual Irregularity

• Oligomenorrhoea (cycles >35 days) or amenorrhoea
• Irregular, unpredictable periods from menarche
• Some women have regular cycles despite polycystic ovaries

Hyperandrogenism

• Hirsutism (excess terminal hair in male-pattern distribution) – 60-70%
• Acne – particularly adult-onset or persistent
• Androgenic alopecia (male-pattern hair thinning)
• Acanthosis nigricans – dark, velvety skin in flexures (marker of insulin resistance)

Subfertility

• Anovulatory infertility – most common cause of anovulatory subfertility
• Increased miscarriage rate
• Higher risk of gestational diabetes and pre-eclampsia

Metabolic Features

• Obesity (40-60%), particularly central/visceral adiposity
• Insulin resistance and metabolic syndrome
• Depression and anxiety (significantly increased prevalence)

Red Flags

• Rapid virilisation (voice deepening, clitoromegaly) → exclude androgen-secreting tumour
• Galactorrhoea → exclude prolactinoma
• Cushingoid features → exclude Cushing syndrome

Bedside

• BMI and waist circumference
• Blood pressure
• Ferriman-Gallwey score for hirsutism (>8 = significant)
• Assess for acanthosis nigricans

Bloods

• Total testosterone: may be elevated (usually <5 nmol/L; if >5 nmol/L consider tumour)
• SHBG: low (calculate free androgen index = testosterone/SHBG × 100)
• TFTs: to exclude hypothyroidism
• Prolactin: to exclude hyperprolactinaemia
• FSH/LH (day 2-5): LH often elevated, FSH normal/low
• 17-OH-progesterone: if congenital adrenal hyperplasia suspected
• HbA1c or OGTT: screen for insulin resistance/diabetes (NICE NG217 recommends at diagnosis and then regularly)
• Lipid profile: increased cardiovascular risk

Imaging

• Pelvic ultrasound: ≥20 follicles (2-9mm) in either ovary and/or ovarian volume ≥10mL (not required if both hyperandrogenism and oligo-anovulation present)
• Ultrasound is not reliable in adolescents within 8 years of menarche due to physiological multi-follicular ovaries

Special Tests

• OGTT (75g): for women with BMI >25, or all women with PCOS depending on risk
• Endometrial assessment (USS/biopsy): if amenorrhoea >3 months without withdrawal bleed, to exclude endometrial hyperplasia

Non-pharmacological

• Lifestyle modification is first-line for all women with PCOS and BMI >25
• 5-10% weight loss can restore ovulation, improve insulin sensitivity, and reduce androgens
• Structured exercise programme (150 minutes/week moderate intensity)
• Psychological support for anxiety/depression (CBT, counselling)

Pharmacological

Menstrual regulation and endometrial protection:

• COCP (e.g., ethinylestradiol/levonorgestrel; or co-cyprindiol if also treating hirsutism)
• Cyclical progestogens (medroxyprogesterone 10mg for 14 days every 1-3 months)
• Mirena IUS (levonorgestrel) for endometrial protection

Hirsutism/acne:

• Co-cyprindiol (Dianette) – ethinylestradiol 35mcg/cyproterone 2mg (3-month courses)
• Topical eflornithine cream (Vaniqa) for facial hirsutism
• Spironolactone 50-200mg daily (off-label, effective anti-androgen – must use contraception)
• Physical methods: laser hair removal, electrolysis

Ovulation induction (subfertility):

• Letrozole 2.5-7.5mg days 2-6 of cycle (now first-line, per international evidence)
• Clomifene citrate 50-150mg days 2-6 (traditional first-line)
• Metformin 1500-2000mg daily – adjunct to clomifene or letrozole
• Gonadotrophins (FSH injections): second-line, with USS monitoring
• Laparoscopic ovarian drilling: if medical induction fails
• IVF: if other methods unsuccessful

Metabolic management:

• Metformin 500mg-2g daily: for insulin resistance, particularly if BMI >25
• Annual screening: HbA1c/OGTT, lipid profile, blood pressure

Referral Criteria

• Subfertility → gynaecology/reproductive medicine
• Rapid virilisation → endocrinology (exclude tumour)
• Refractory hirsutism → dermatology
• Mental health concerns → psychology/psychiatry

• PCOS is a lifelong condition requiring ongoing management
• 50% of women with PCOS develop type 2 diabetes by age 40 if untreated
• 2-4 fold increased risk of cardiovascular events
• 2-6 fold increased risk of endometrial cancer (due to unopposed oestrogen)
• 80% of women conceive with ovulation induction treatment
• Metabolic risk can be significantly reduced with lifestyle modification
• Symptoms may improve around menopause, though metabolic risks persist

Rotterdam Diagnostic Criteria (2003, reaffirmed in NICE NG217)

Requires 2 of 3:

1. Oligo-anovulation (cycles >35 days or <8 cycles/year)
2. Clinical and/or biochemical hyperandrogenism
3. Polycystic ovarian morphology on USS

After excluding: thyroid disease, CAH, Cushing syndrome, androgen-secreting tumours, hyperprolactinaemia

PCOS Phenotypes