Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy

N Engl J Med. 1993 Nov 4;329(19):1383-8. doi: 10.1056/NEJM199311043291904.


Background: Reproductive endocrine disorders are more common among women with epilepsy than among normal women. These disorders have been attributed to epilepsy itself, but could be related to antiepileptic-drug therapy.

Methods: We studied 238 women with epilepsy who were seen regularly at the Outpatient Department of the University Hospital, Oulu, Finland. Their mean age was 33 years (range, 18 to 45), and the mean duration of therapy was 9 years (range, 0 to 31). Twenty-nine (12 percent) were treated with valproate, 120 (50 percent) with carbamazepine, 12 (5 percent) with valproate and carbamazepine, and 62 (26 percent) with other medications; 15 (6 percent) were untreated. Vaginal ultrasonography was performed to determine ovarian size, and serum sex-hormone concentrations were measured in 41 women with epilepsy and menstrual disturbances, 57 women with epilepsy and regular menstrual cycles, and 51 normal women.

Results: Menstrual disturbances were present in 13 of the women receiving valproate alone (45 percent), 3 of the women receiving valproate in combination with carbamazepine (25 percent), 23 of the women receiving carbamazepine (19 percent), and 8 of those receiving other medications (13 percent). Forty-three percent of the women receiving valproate had polycystic ovaries, and 17 percent had elevated serum testosterone concentrations without polycystic ovaries; 50 percent of the women receiving valproate and carbamazepine had polycystic ovaries, and 38 percent had elevated serum testosterone concentrations without polycystic ovaries. Eighty percent of the women treated with valproate before the age of 20 years had polycystic ovaries of hyperandrogenism.

Conclusions: Menstrual disturbances, polycystic ovaries, and hyperandrogenism are often encountered in women taking valproate for epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Carbamazepine / therapeutic use
  • Cross-Sectional Studies
  • Epilepsies, Partial / drug therapy*
  • Epilepsy, Generalized / blood
  • Epilepsy, Generalized / drug therapy*
  • Female
  • Humans
  • Hyperandrogenism / chemically induced*
  • Menstruation Disturbances / chemically induced
  • Middle Aged
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / chemically induced*
  • Testosterone / blood
  • Valproic Acid / adverse effects*
  • Valproic Acid / therapeutic use


  • Carbamazepine
  • Testosterone
  • Valproic Acid