SynthesisBMC pharmacology & toxicology2024
Understanding the impact of valproate on male fertility: insights from preclinical and clinical meta-analysis.
Synthesis in BMC pharmacology & toxicology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Observational
- Drug-induced male infertility: a real-world study using FAERS and EudraVigilance databases.Frontiers in pharmacology · 2026Article
- A retrospective cohort study of valproate and infertility in men with epilepsy or bipolar disorder using international health data.Nature communications · 2025Article
- Antiepileptic drugs and foetal disorders: analysis of 20-year data from the pharmacovigilance center.Frontiers in pharmacology · 2025Article
- Analysis of ASMs and male infertility using the FDA adverse event reporting system (FAERS).Frontiers in public health · 2025Article
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7 authors.
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Abstract
backgroundValproic acid (VPA) is a widely used antiepileptic drug (AED) often prescribed as a first-line treatment for many idiopathic and symptomatic generalized epilepsies. Several studies have highlighted the side effects of VPA on male fertility and reproductive factors in males, although the specific underlying etiology of these abnormalities is not clear. The present systematic review and meta-analysis aimed to assess the preclinical and clinical evidence concerning the impact of VPA on male fertility and reproductive factors.
methodsThe scientific literature was reviewed for eligibility using PubMed, Web of Science, and PsycINFO, encompassing preclinical and clinical studies. Factors related to male fertility and reproduction, such as differences in sperm count, sperm motility, and the percentage of abnormal sperm, were compared between the experimental groups treated with VPA (in both preclinical and clinical) and the control groups using the Standardized Mean Difference (SMD) with 95% confidence intervals (CIs). Additionally, differences in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were explicitly assessed in clinical studies.
resultsMale fertility data were extracted from 7 preclinical studies (112 animals) and 5 clinical studies (274 male individuals). The results of animal studies found that the sperm count (SMD = -2.28, 95% CI: -3.39 to -1.18, P = 0.335) and sperm motility (SMD = -2.32, 95% CI: -3.34 to -1.30, P = 0.368) were decreased in the treated groups compared to the control groups. The percentage of abnormal sperm (SMD = 3.27, 95% CI: 1.98 to 4.56, P = 0.019) was significantly increased, while a non-significant reduction was revealed in the weight of the testis (SMD = -2.73, 95% CI: -4.23 to -1.23, P = 0.673) in treated groups. The outcomes of clinical studies indicated a non-significant decrease in sperm count (SMD = -0.78, 95% CI: -1.58 to 0.03, P = 0.286) among patients with epilepsy treated with VPA compared to control subjects. However, a significant reduction in sperm motility (SMD = -1.62, 95% CI: -2.81 to -0.43, P = 0.033 was observed. The percentage of abnormal sperm showed a non-significant increase (SMD = 0.93, 95% CI: -0.97 to 2.84, P = 0.616) after being treated with VPA. Furthermore, there was a non-significant reduction in the levels of FSH (SMD = -1.32, 95% CI: -2.93 to 0.29, P = 0.198) and LH (SMD = -0.96, 95% CI: -1.95 to 0.04, P = 0.211) observed in clinical participants.
conclusionThis meta-analysis of both preclinical and clinical studies revealed that VPA causes a significant reduction in male fertility and reproductive factors among male patients with epilepsy. Clinical neurologists should be more cautious when prescribing VPA, especially to young male adult patients with epilepsy.
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