Male Reproductive Disorders Associated with Antiseizure Medications: Evidence from Meta-Analysis and FAERS...

Background/Objectives: Antiseizure medications (ASMs) are widely used in the management of epilepsy; however, their effects on male reproductive function in humans remain incompletely characterized. This study aimed to evaluate drug-specific associations between ASMs and male reproductive disorders through a meta-analysis of observational clinical studies and FDA Adverse Event Reporting System (FAERS)-based pharmacovigilance analyses. Methods: Clinical studies involving men with epilepsy receiving ASMs, untreated men with epilepsy, and healthy controls were systematically reviewed and quantitatively synthesized. FAERS reports from the first quarter of 2019 to the second quarter of 2026 (2019Q1-2026Q2) were analyzed using reporting odds ratios (RORs) and information components (ICs), with disproportionality signals identified by either method. Results: The meta-analysis included 20 clinical studies involving 1530 participants. Valproate was associated with adverse effects on reproductive hormones, sperm parameters, and sexual function, whereas carbamazepine and phenytoin were primarily associated with alterations in reproductive hormone levels. In the pharmacovigilance analysis, valproate showed a significant disproportionality signal for male reproductive disorders (IC₀₂₅ 1.792). Conclusions: The findings indicate that male reproductive effects are not uniform across ASMs but exhibit distinct drug-specific patterns. Valproate was associated with alterations across multiple reproductive domains, whereas carbamazepine and phenytoin were associated predominantly with reproductive hormone alterations. Reproductive health should be considered when selecting and monitoring long-term ASM therapy in men, and prospective studies are needed to further characterize the reproductive safety profiles of individual ASMs.