Fourteen (64%) of 22 women receiving valproate monotherapy for epilepsy had polycystic ovaries, hyperandrogenism, or both, in a study at the Departments of Neurology, Obstetrics and Gynecology, and Pediatrics, University of Oulu, Finland. They had a progressive obesity associated with hyperinsulinemia and low serum insulin-like growth factor-binding protein 1, leading to hyperandrogenism and polycystic ovaries. The mean duration of treatment was 7 years, and the mean daily dose of valproate was 1070 mg. In contrast, polycystic ovaries/hyperandrogenism occurred in 9 (21%) of 43 women receiving carbamazepine monotherapy and 8 (19%) of 43 in a control group. 
COMMENT. Polycystic ovarian syndrome (PCOS), hyperandrogenic chronic anovulation, is characterized clinically by hirsutism and menstrual disorders. Obesity occurs in 30 to 50% of patients affected. It may have multiple etiologies, including genetic, endocrine, metabolic, and neurologic. PCOS induced by valproate medication for epilepsy has been attributed to the coincidental obesity and resultant endocrine abnormalities. An increased incidence of PCOS among untreated epileptic women is greater with left than with right-sided temporal lobe foci. Antiseizure medications other than valproate induce hepatic enzymes that reduce testosterone levels and tend to moderate hyperandogenism. Hertzog AG, at the Harvard Neuroendocrine Unit, Beth Israel Hospital, Boston, MA, suggests that valproate may not be the primary cause of PCOS, citing epileptic and neurologic factors.