Abstracts

Rationale: Antiepileptic drugs (AEDs) may induce reproductive endocrine function in men and women. We wanted to investigate if these effects of AEDs on reproductive endocrine functions were reversible.Methods: We used a prospective, randomized and double blinded design. 160 patients which had been seizure free on AEDs for more than two years were included and randomized to withdrawal or not and 150 (80 females, 53 %) patients went through the intervention. Complete serum samples from before and 4 months after completed withdrawal/no withdrawal were obtained from 130 patients (63 females, 48 %). Of these, 84 were treated with carbamazepine, 28 with valproate, 9 with phenytoin, 4 with phenobarbital, and 5 with lamotrigine.Results: We found reversible endocrine changes in sex steroid hormone levels in both sexes after withdrawal of AEDs. For carbamazepine we found significant increases in serum testosterone concentrations and free androgen index (FAI) in both men (n=19) and women (n=19). Mean differences in change in FAI between the withdrawal group and non-withdrawal group were in men 17.49 (CI 10.16-24.81, p=<0.001), and in women 1.61 (CI 0.62-2.61, p=<0.001). For valproate, there was a reduction in testosterone concentration and FAI, an increase in FSH and a reduction in BMI after withdrawal in both males and females. However, only the reduction in BMI was statistically significant, probably due to the low number of patients in each group Conclusions: Our findings support that antiepileptic drugs may have potentially negative effects of on reproductive endocrine functions in men and women, but also that some of these changes are reversible, even after years on treatment.