Epilepsy, Antiseizure Medications, and Reproductive Dysfunction in Males

Abstract

Epilepsy is among the most prevalent neurological disorders, affecting not only seizure activity but also psychiatric, psychological, endocrine, and reproductive health. This review aims to evaluate optimal treatment strategies for adult male epilepsy patients with reproductive concerns by analyzing the existing literature on the impact of epilepsy and various antiseizure medications (ASMs) on sex hormones, semen quality, and sexual function. A comprehensive literature search was conducted up to May 2025 across multiple databases, including Embase, PubMed, MEDLINE, and Wanfang, using the following key terms: “epilepsy”, “antiseizure medications”, “sex hormones”, “sperm/semen”, “sexual function”, and “reproductive function”. The reference lists of the retrieved articles were further screened. The search yielded a number of articles that met the inclusion criteria, which required reporting of at least one of the following outcomes in adult male patients with epilepsy: sexual function, semen quality, or sex hormones. The selected literature encompassed various study designs, including cross-sectional studies, case reports, prospective studies, randomized controlled trials, meta-analyses, as well as animal studies and in vitro experiments. Non-human studies were incorporated to provide complementary evidence supporting the findings from clinical research. The analysis indicates a high prevalence of sexual dysfunction and significantly reduced fertility rates among male patients with epilepsy. This reproductive impairment may stem from the dual effects of seizures themselves and ASM therapy. Regarding ASMs, evidence suggests that traditional enzyme-inducing ASMs (EIASMs, e.g., carbamazepine, phenytoin) and valproic acid may have negative impacts on male sex hormones, semen parameters, and sexual function. Based on current clinical evidence, lamotrigine and oxcarbazepine appear to have relatively favorable profiles, whereas data on other agents (e.g., levetiracetam, topiramate, pregabalin, zonisamide, clobazam, felbamate) are often limited or conflicting, and may suggest potential risks.

Conclusion

For adult male epilepsy patients with reproductive concerns, treatment selection should prioritize seizure control while minimizing reproductive side effects. Where clinically appropriate, agents such as lamotrigine and oxcarbazepine may be preferable to traditional EIASMs or valproic acid. The use of other ASMs requires careful consideration due to insufficient or concerning evidence regarding reproductive safety. Individual patient factors and vigilant monitoring remain crucial.