PCOS (Polycystic Ovary Syndrome)

Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age and one of the most poorly named. The Rotterdam criteria require two of three features: oligo- or anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound — with other causes excluded. Note that ovarian appearance is optional; a woman can have PCOS with entirely normal-looking ovaries, and up to a quarter of women without PCOS have polycystic-appearing ovaries. The follicles seen on ultrasound are not cysts. They are antral follicles arrested partway through development because the hormonal environment prevents one from becoming dominant. Nothing needs draining or removing. The dominant mechanism in most cases is insulin resistance. Hyperinsulinaemia stimulates ovarian theca cells to overproduce androgens and simultaneously suppresses hepatic production of sex hormone-binding globulin, so more testosterone circulates free. Elevated androgens disrupt follicular selection, producing anovulation, and drive hirsutism and acne. This chain explains why insulin-sensitising interventions — weight loss, metformin, inositol — improve ovulation without acting on hormones directly. Phenotypes differ meaningfully. The classic insulin-resistant phenotype responds well to metabolic intervention. Lean PCOS, affecting perhaps 20-30%, involves less insulin resistance and often more prominent LH-driven androgen excess, and responds less to metabolic approaches. PCOS is also a lifelong metabolic condition, not just a fertility one. Risk of type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease, endometrial hyperplasia and depression is elevated, and management should reflect that even after childbearing is complete.

• •Irregular, infrequent or absent periods
• •Hirsutism — coarse dark hair on the face, chest or abdomen
• •Acne, often persistent along the jawline
• •Scalp hair thinning in a male pattern
• •Difficulty conceiving
• •Weight gain concentrated around the abdomen, and difficulty losing it
• •Acanthosis nigricans and skin tags
• •Mood symptoms, with elevated rates of anxiety and depression

• •Insulin resistance and compensatory hyperinsulinaemia
• •Genetic predisposition — strongly familial
• •Increased LH pulse frequency driving ovarian androgen production
• •Excess adipose tissue amplifying androgen production and insulin resistance
• •Adrenal androgen excess in a subset
• •Possible intrauterine androgen exposure influencing later development
• •Chronic low-grade inflammation

PCOS is best understood as a self-reinforcing loop between insulin and androgens. Insulin resistance leads to compensatory hyperinsulinaemia. Insulin acts on ovarian theca cells, augmenting LH-driven androgen synthesis, and suppresses hepatic SHBG synthesis, raising the free androgen fraction further. Androgens promote visceral fat deposition, which worsens insulin resistance, closing the loop. Within the ovary, high intrafollicular androgen concentrations disrupt the selection of a dominant follicle. Multiple small antral follicles accumulate in an arrested state — the ultrasound appearance — while ovulation fails to occur. Anti-Mullerian hormone, produced by those follicles, is correspondingly high and further inhibits FSH-driven follicle maturation. A parallel neuroendocrine abnormality exists: increased GnRH pulse frequency raises the LH:FSH ratio, favouring androgen production over oestrogen. Whether this is primary or secondary to androgen exposure remains debated. Genetics account for a substantial share of risk, with heritability estimates around 70% from twin studies, though no single gene dominates.