The effects of enzyme-inducing AEDs on sex steroids has been known for a long time. In 1975, Christensen & Lund3 showed that urinary steroid hormone output was significantly lower in 75 men taking antiepileptic drugs than in a healthy population. They found 50% decreases in androsterone, 75% decreases in etiocholanolone and dihydroepiandrosterone, and 30% higher estrogen levels. Although these data were difficult to interpret, they indicated a profound effect of antiepileptic drugs on the metabolism of sex steroid hormones. A recent report replicated these findings.11 They compared men with partial-onset epilepsy taking carbamazepine or oxcarbazepine with men with generalized epilepsy taking valproate. The findings could be expected based on the enzyme-inducing properties of carbamazepine and oxcarbazepine at higher doses, whereas valproate is an enzyme inhibitor. They also found morphologically abnormal sperm, low sperm motility, and reduced testicular volume among all epilepsy groups compared to healthy controls.

AEDs also might affect spermatogenesis in humans as they do in vitro. Carbamazepine inhibited testosterone synthesis in Leydig cells, phenytoin inhibited testosterone conversion from progestins, and valproate had the least effect on testosterone.5 This in vitro model showed the differential effects of each AED on the metabolic pathway of sex steroid hormones.

Authored By: 
Joyce Cramer
Reviewed By: 
Steven C. Schachter MD
Orrin Devinsky MD
Wednesday, September 1, 2004