Effects of valproate, phenobarbital, and carbamazepine on sex steroid setup in women with epilepsy

Clin Neuropharmacol. 1998 Jan-Feb;21(1):52-8.


Serum levels of sex-hormones, sex-hormone binding globulin, gonadotropin, and prolactin were evaluated during the follicular and the luteal phases in 65 women with epilepsy and in 20 healthy controls. Twenty-one patients were treated with sodium valproate (VPA), 21 with phenobarbital (PB), and 23 with carbamazepine (CBZ). VPA does not stimulate liver microsome enzymes, whereas PB and CBZ do. Patients on VPA therapy showed higher body weight and body mass index, but no significant differences in hirsutism score, or in ovary volume or polycystic ovary prevalence (at ultrasound examination). Estradiol levels were lower in all patient groups than in healthy controls in the follicular but not in the luteal phases. VPA affected luteal progesterone surge in 63.6% of cases. This effect was significantly lower in the CBZ and PB groups. Furthermore, increases in testosterone and delta 4-androstenedione levels and in free androgen index, along with a higher luteinizing hormone-follicle-stimulating hormone ratio in the luteal phase, were observed in women treated with VPA. Although sex-hormone binding globulin levels were higher in CBZ and PB than in VPA-treated patients, the differences were not significant because of the wide dispersion of the carrier protein levels. Inducer antiepileptic drugs decreased dehydroepiandrosterone sulfate levels, which remained unchanged during VPA treatment. No significant differences occurred in basal gonadotropin and prolactin levels.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Body Mass Index
  • Carbamazepine / adverse effects*
  • Carbamazepine / therapeutic use
  • Epilepsy / blood*
  • Epilepsy / drug therapy
  • Female
  • Follicular Phase / blood
  • Gonadal Steroid Hormones / blood*
  • Gonadotropins / blood
  • Hirsutism / chemically induced
  • Humans
  • Luteal Phase / blood
  • Middle Aged
  • Ovary / anatomy & histology
  • Ovary / diagnostic imaging
  • Ovary / physiology
  • Phenobarbital / adverse effects*
  • Phenobarbital / therapeutic use
  • Prolactin / blood
  • Ultrasonography
  • Valproic Acid / adverse effects*
  • Valproic Acid / therapeutic use


  • Anticonvulsants
  • Gonadal Steroid Hormones
  • Gonadotropins
  • Carbamazepine
  • Valproic Acid
  • Prolactin
  • Phenobarbital