Preserving Male Reproductive Health in Epilepsy: Clinical Implications of Antiepileptic Drug-induced Endocrine Alterations

Abstract Background: Epilepsy and prolonged antiepileptic drug (AED) therapy are known to affect endocrine function and may adversely affect reproductive hormonal balance in men. Although these effects have been extensively studied in Western populations, data on North Indian patients remain limited. Aim: The study aimed to evaluate the effects of commonly prescribed AEDs on reproductive hormone levels in male patients with epilepsy and to assess their association with therapy duration. Methods: This case–control study was conducted at a tertiary care center in North India and included 33 male patients with epilepsy aged 20–40 years receiving AED monotherapy and 23 age-matched healthy controls. Patients were categorized into three treatment groups: valproate ( n = 14), phenytoin ( n = 7), and levetiracetam ( n = 12). Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone, and estradiol were measured by standard immunoassay. Statistical analyses were performed using independent t -tests, one-way analysis of variance, and Pearson’s correlation coefficient. Results: Serum LH levels were significantly higher in the phenytoin group and significantly lower in the valproate group than in controls, whereas levetiracetam showed no significant effect. FSH levels were significantly higher in patients receiving phenytoin and levetiracetam but remained comparable to controls in the valproate group. Serum prolactin levels were significantly elevated across all AED groups, with the highest levels observed in valproate-treated patients. Testosterone levels were significantly lower in the valproate and phenytoin groups, whereas levels in the levetiracetam group remained comparable to controls. Estradiol levels were significantly elevated only in patients receiving phenytoin. Duration-of-therapy analysis showed a significant negative correlation between valproate use and estradiol levels ( r = −0.58, P = 0.030) and a significant positive correlation between levetiracetam use and testosterone levels ( r = 0.616, P = 0.033). Conclusion: Valproate and phenytoin therapy were associated with significant alterations in reproductive hormone profiles in male patients with epilepsy, particularly reduced testosterone levels. In contrast, levetiracetam demonstrated a comparatively favorable endocrine profile. These findings emphasize the importance of endocrine monitoring in men receiving long-term AED therapy and suggest that levetiracetam may be a preferable therapeutic option for sexually active male patients.