Polycystic Ovary Syndrome (PCOS): Causes, Mechanisms & Risk Factors

PCOS: A Heterogeneous Endocrine Disorder

PCOS affects 6–12% of reproductive-age women. It is defined by the Rotterdam criteria (≥2 of: oligo/anovulation, clinical/biochemical hyperandrogenism, polycystic ovarian morphology). The exact etiology is multifactorial.

Core Pathophysiologic Drivers

1. Insulin Resistance (IR) & Compensatory Hyperinsulinemia – Present in 50–70% (both lean and obese). Hyperinsulinemia stimulates ovarian theca cell androgen production and reduces SHBG → ↑ free testosterone.
2. Hyperandrogenism – Drives hirsutism, acne, alopecia, and anovulation. Sources: ovaries (theca cells), adrenals (DHEAS).
3. Gonadotropin Dysregulation – ↑ LH:FSH ratio (often >2:1) favors androgen synthesis.
4. Chronic Low-Grade Inflammation – Elevated CRP, TNF-α, IL-6; worsens IR and endothelial dysfunction.
5. Genetic Predisposition – Familial clustering; candidate genes involve insulin signaling, androgen synthesis, follicular development.
6. Environmental/Developmental Factors – Endocrine disruptors (BPA, phthalates), prenatal androgen exposure, rapid weight gain in puberty.

Metabolic & Long-Term Risks

• Type 2 diabetes, gestational diabetes
• Metabolic syndrome, NAFLD, dyslipidemia
• Endometrial hyperplasia/cancer (unopposed estrogen)
• Cardiovascular disease, sleep apnea, mood disorders

Management Pillars

• Lifestyle: Weight loss (5–10% restores ovulation), low-glycemic diet, exercise.
• Menstrual regulation: Combined OCP, cyclic progestin.
• Hyperandrogenism: OCP, spironolactone, finasteride, laser/electrolysis.
• Fertility: Letrozole (first-line), clomiphene, gonadotropins, IVF.
• Metabolic: Metformin (especially if IGT/IR).

Individualized, multidisciplinary care is essential.