Obesity and endocrine disorders in women taking valproate for epilepsy

Ann Neurol. 1996 May;39(5):579-84. doi: 10.1002/ana.410390506.


We recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy, especially when the medication was started before the age of 20 years. In the present study we evaluated the association of obesity and hyperinsulinemia with valproate-related polycystic ovaries and hyperandrogenism in women with epilepsy. Sixty-five women participated in the study. Twenty-two received valproate monotherapy and 43 received carbamazepine monotherapy. In addition to clinical examination, vaginal ultrasonography was performed to determine ovarian size, and the concentrations of serum sex hormones, insulin, insulin-like growth factor 1, and the insulin-like growth factor-binding proteins 1 and 3 (IGFBP-1 and IGFBP-3) were measured. Fifty-nine percent of the women on valproate were obese, and in a retrospective analysis an indisputable weight gain (mean, 21 kg; range, 8-49 kg) was found in 50% of the women taking valproate. Fourteen (64%) of the women on valproate had polycystic ovaries, hyperandrogenism, or both. These women were obese, and in addition to elevated serum androgen levels, they had high concentrations of fasting serum insulin and low levels of serum insulin-like growth factor-binding protein 1. Valproate therapy for epilepsy is associated with weight gain during treatment in approximately 50% of women patients. The weight gain can be progressive, and is associated with hyperinsulinemia and low serum levels of insulin-like growth factor-binding protein 1, which may lead to hyperandrogenism and polycystic ovaries.

MeSH terms

  • Adult
  • Body Weight / drug effects
  • Carbamazepine / adverse effects
  • Dehydroepiandrosterone / analogs & derivatives
  • Dehydroepiandrosterone / blood
  • Dehydroepiandrosterone Sulfate
  • Endocrine System Diseases / chemically induced
  • Endocrine System Diseases / epidemiology
  • Endocrine System Diseases / etiology*
  • Epilepsy / complications*
  • Epilepsy / drug therapy
  • Evaluation Studies as Topic
  • Female
  • Humans
  • Hyperandrogenism / chemically induced
  • Hyperandrogenism / epidemiology
  • Hyperandrogenism / etiology
  • Hyperinsulinism / chemically induced
  • Hyperinsulinism / epidemiology
  • Hyperinsulinism / etiology
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor I / drug effects
  • Insulin-Like Growth Factor I / metabolism
  • Obesity / chemically induced
  • Obesity / etiology*
  • Polycystic Ovary Syndrome / chemically induced
  • Polycystic Ovary Syndrome / epidemiology
  • Polycystic Ovary Syndrome / etiology
  • Prevalence
  • Sex Hormone-Binding Globulin / metabolism
  • Somatomedins / drug effects
  • Somatomedins / metabolism
  • Testosterone / blood
  • Time Factors
  • Valproic Acid / adverse effects*


  • Insulin-Like Growth Factor Binding Protein 1
  • Sex Hormone-Binding Globulin
  • Somatomedins
  • Carbamazepine
  • Testosterone
  • Dehydroepiandrosterone
  • Dehydroepiandrosterone Sulfate
  • Valproic Acid
  • Insulin-Like Growth Factor I