Evidence for the hypothalamic origin of the polycystic ovary syndrome

The effect of suppression of gonadotropin secretion was evaluated in 21 patients with the polycystic ovary syndrome. Medroxyprogesterone acetate (MPA) was administered intramuscularly in a dose of 400 mg every 15 days for 9 months. A significant decrease in luteinizing hormone (LH) and testosterone levels (70 and 40%, respectively) was apparent after 3 months. At the end of the treatment period, the ovaries had become impalpable and hirsutism was markedly improved in 13 of 19 women. Side effects of treatment included local pain, vaginal spotting, galactorrhea, and hyperprolactinemia. Discontinuation of therapy was followed by a rapid return of follicle-stimulating hormone levels to baseline values, whereas LH and testosterone levels recovered only partially after more than 1 year. The improvement of hirsutism and ovarian shrinkage persisted for up to 2 years, and endometrial biopsy uniformly showed a pseudodecidual reaction in the stroma. After 1 year, prolactin levels declined to 52% of the baseline value and galactorrhea disappeared. The suppression of all the peripheral abnormalities of the reproductive system in polycystic ovary syndrome with MPA treatment suggests a primary hypothalamic disorder as the cause for the syndrome.