Effects of antiseizure medications on sexual hormones and functions in males with epilepsy: A systematic review and meta‐analysis

Abstract The fertility effects of antiseizure medications (ASMs) have been highlighted in females of reproductive age; however, the effects in males have not been extensively analyzed. This review aims to summarize the existing evidence of how ASMs affect sexual hormones and functions in males with epilepsy. We searched the Embase, PubMed, and MEDLINE databases in January 2024 to identify studies measuring sexual hormones, sexual function, or sperm parameters of males with epilepsy taking any ASM except valproic acid who were compared to a control group. A systematic review summarizing the effects of valproic acid on sexual function was published in 2018; therefore, we excluded valproic acid to avoid duplicating existing evidence. Risk of bias assessments were specific to the study type and included the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross‐Sectional Studies, NIH Quality Assessment Tool for Before‐After (Pre‐Post) Studies, and Cochrane Risk of Bias‐2 tool for randomized trials. The systematic review included 32 studies, and the meta‐analysis included 22 studies. Using random effect models, we calculated mean differences or rate ratios for studies assessing the association between ASMs and male sexual hormones or functions. Analyses were run for each combination of individual ASM or ASM characteristic, outcome, and comparison group. Males taking oxcarbazepine had significantly higher levels of testosterone, luteinizing hormone, and follicle‐stimulating hormone compared to healthy controls. Conversely, there was no evidence of differences in any outcomes between levetiracetam or lamotrigine and comparison groups. Analyses that included untreated males with epilepsy rarely differed from males taking ASMs, highlighting the potential importance of epilepsy on altered sex hormones and functions. However, results should be interpreted cautiously, as many analyses included only a few studies and had high heterogeneity.