What Actually Causes PCOS? A Mechanistic Reading of Polycystic Ovary Syndrome — The clinical pattern that defines treatment-resistant PCOS

A patient presents with irregular menstrual cycles, often with intervals exceeding 35 days or fewer than eight periods per year. Acne emerges in late adolescence or persists into adulthood. Hirsutism develops on the face, chest, abdomen, or back. Weight gain occurs preferentially around the abdomen and is difficult to lose. Fatigue is profound. Brain fog appears. Hair thins on the scalp while growing in unwanted areas. Mood changes accompany the cycle irregularities. Fertility becomes an issue when pregnancy is desired. The diagnostic workup confirms PCOS by the Rotterdam criteria: at least two of three features must be present: oligo-ovulation or anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound. Other causes of irregular cycles are ruled out (thyroid disease, hyperprolactinemia, congenital adrenal hyperplasia, ovarian or adrenal tumors). The diagnosis is made. The treatment cascade follows the standard guidelines. Combined oral contraceptives to regulate cycles and reduce androgen production. Metformin to address insulin resistance. Spironolactone to block peripheral androgen receptors. Letrozole or clomiphene when pregnancy is desired. Lifestyle modification with emphasis on weight loss for overweight or obese patients. Some patients respond meaningfully to this combination. Many do not, or do so incompletely. The standard