Reversible effects of antiepileptic drugs on reproductive endocrine function in men and women with epilepsy - A prospective randomized double-blind withdrawal study

Purpose: Epilepsy, antiepileptic drugs (AEDs), and reproductive endocrine function have complex interactions. In this study, we wanted to investigate the effects of AEDs on reproductive endocrine function after withdrawal of AEDs and look for reversible endocrine effects. Methods: The study was prospective, randomized, and double-blinded. A total of 160 patients were included and randomized to withdrawal or not and 150 (80 females, 53%) patients went through the intervention and was included in the study for 12 months. Complete serum samples from before and 4 months after completed withdrawal/no withdrawal were obtained from 130 patients (63 females, 48%). Results: The main finding was that reversible endocrine changes in sex steroid hormone levels could be observed in both sexes after withdrawal of AEDs. For CBZ, which was the drug used by the majority of the patients, withdrawal led to 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 nonwithdrawal 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). Conclusion: Our findings provide further evidence of the potentially negative effects of CBZ treatment on reproductive endocrine functions in men and women, but also show that some of these changes may be reversible, even after years on treatment.