On the association between valproate and polycystic ovary syndrome

Epilepsia. 2001 Mar;42(3):295-304. doi: 10.1046/j.1528-1157.2001.28899.x.


Recent studies by Isojärvi et al. have raised the issue of an increased incidence of polycystic ovary syndrome (PCOS) in women with epilepsy treated with valproate (VPA) and have proposed replacement with lamotrigine (LTG). Polycystic ovaries (PCO) are a common finding, with a prevalence >20% in the general population, and are easily detected by pelvic or vaginal ultrasonography, whereas PCOS is comparatively rare: few women with PCO have fully developed PCOS, which includes hirsutism, acne, obesity, hypofertility. hyperandrogenemia, and menstrual disorders. From an extensive review of the current literature, it appears that there are no reliable data on the actual prevalence of PCOS in normal women and in women with epilepsy. The pathogenesis of PCO is multifactorial, including genetic predisposition and the intervention of environmental factors, among which weight gain and hyperinsulinism with insulin resistance may play a part. The roles of central (hypothalamic/pituitary), peripheral, and local ovarian factors are still debated. PCO and PCOS appear to be more frequent in women with epilepsy, but there are no reliable data showing a greater prevalence after VPA. The recent studies by Isojärvi et al. may have been biased by the retrospective selection of patients. To date, there is no reason to contraindicate the use of VPA in women with epilepsy. However, patients should be informed about the risk of weight gain and its consequences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Comorbidity
  • Epilepsy / drug therapy*
  • Epilepsy / epidemiology
  • Female
  • Humans
  • Hyperinsulinism / epidemiology
  • Insulin Resistance
  • Middle Aged
  • Polycystic Ovary Syndrome / chemically induced*
  • Polycystic Ovary Syndrome / epidemiology
  • Practice Guidelines as Topic
  • Practice Patterns, Physicians'
  • Prevalence
  • Valproic Acid / adverse effects*
  • Valproic Acid / therapeutic use


  • Anticonvulsants
  • Valproic Acid