Abstracts

Rationale: There is a complex interplay between epilepsy, antiepileptic drugs, and reproductive endocrine disorders. To better understand the interaction of antiepileptic drugs and production of steroid hormones, we investigated possible effects of valproic acid, carbamazepine and levetiracetam using the H295R steroidogenesis model. Methods: H295R human adrenal carcinoma cells are capable of full steroidogenesis. Cells were exposed to three different antiepileptic drugs (valproic acid, carbamazepine and levetiracetam) for 48 hr. Medium was collected and analyzed for hormone production (estradiol, testosterone and progesterone). Results: We observed a significant, dose-dependent reduction in the production of estradiol in cells exposed to valproic acid (300 - 1500 µM). At a drug concentration of 600 µM, estradiol levels were reduced to 40% compared with controls (p<0.01, Wilcoxon signed-rank test). Testosterone levels were not significantly changed. This resulted in a dose-dependent increase of the testosterone to estradiol ratio (0.5 at 600 µM, p<0.01, Wilcoxon signed-rank test). No significant dose-response effect on hormone production was seen with carbamazepine, or levetiracetam. Conclusions: H295R cells exposed to valproic acid, carbamazepine, or levetiracetam showed different patterns of hormone production. The most prominent finding was a significant dose-dependent increase of the testosterone/estradiol ratio in cells exposed to valproic acid. This suggests valproic acid is capable of inhibiting conversion of testosterone to estradiol. No effects on sex steroid hormone production were observed with carbamazepine or levetiracetam.