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Valproic acid contributes to reduced male fertility in epilepsy patients, warranting cautious prescribing by neurologists, early fertility monitoring and consideration of alternative remedies in reproductive-age males.
Recent results of a meta-analysis of preclinical and clinical studies put forward interesting findings that Valproic acid adversely affects male fertility and reproductive factors in male patients with epilepsy.
Valproic acid or Valproate (antiepileptic drug) often prescribed as a first-line therapy for many generalized epilepsies, has been linked to adverse effects on male fertility in several studies, though the exact cause remains unclear. This systematic review and meta-analysis by Muhammad Arif Asghar and colleagues explored the shreds of evidence regarding Valproic acid's impact on male reproductive potential and associated factors.
The Web of Science, PubMed, and PsycINFO databases were scoured for suitable studies. Factors associated with fertility in males (sperm motility, count, and abnormal sperm percentage) were examined between Valproic acid-treated groups and controls with the aid of the standardized mean difference (SMD) with 95% confidence intervals (CIs). Additionally, levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were explored.
The data regarding male fertility was mined from 7 preclinical studies (comprising 112 animals) and 5 clinical studies (comprising 274 males).
Key Findings from Animal Studies:
Sperm count: Decreased in Valproic acid-treated groups (SMD = -2.28, 95% CI: -3.39 to -1.18, P = 0.335) compared to controls.
Sperm motility: Reduced in treated groups (SMD = -2.32, 95% CI: -3.34 to -1.30, P = 0.368).
Abnormal sperm percentage: Significantly increased in treated groups (SMD = 3.27, 95% CI: 1.98 to 4.56, P = 0.019).
Testis weight: Non-significant reduction observed in treated groups.
Key Findings from Clinical Studies:
Sperm count: Non-significant decrease in Valproic acid-treated patients (SMD = -0.78, 95% CI: -1.58 to 0.03, P = 0.286) compared to controls.
Sperm motility: Significant reduction observed (SMD = -1.62, 95% CI: -2.81 to -0.43, P = 0.033).
Abnormal sperm percentage: Non-significant increase.
FSH and LH levels: Non-significant reduction.
Valproic acid leads to changes in sperm parameters and hormone levels, urging further research into oxidative stress, hormonal regulation, and therapeutic interventions, as concluded.
BMC Pharmacology and Toxicology
Understanding the impact of valproate on male fertility: insights from preclinical and clinical meta-analysis
Muhammad Arif Asghar et al.
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