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There is little evidence to suggest that sodium valproate significantly impacts male fertility, according to a study published in Nature Communications.
In the retrospective cohort study, published on 15 September 2025, researchers from the University of Liverpool — with funding from the Epilepsy Research Institute — carried out an analysis of data from 91,917 men who had taken valproate and compared with data from 535,803 men who had not.
According to the study results, there was no significant difference between the two groups — who had been diagnosed with either epilepsy or bipolar disorder — in infertility diagnoses, sperm counts and testicular atrophy. The reproductive hormone levels remained within normal ranges in both cohorts.
“Prior studies linking valproate to male infertility in epilepsy mainly used healthy men without epilepsy as controls,” the authors said.
“Therefore, pragmatic evidence that is directly relevant to this decision is needed, meaning comparisons should be between drug-exposed and unexposed men with the disease, as was reported in the current study. In such circumstances, the evidence we present suggests valproate may not be linked to infertility over and above other ASMs [anti-seizure medications] or mood-stabilisers, nor over the epilepsy or bipolar disorder themselves.”
Lead author Gashirai Mbizvo, deputy director for epilepsy research at Liverpool Interdisciplinary Neuroscience Centre, said this was the largest study of its kind.
“These results are significant because fear of fertility side effects specifically attributed to valproate can lead men to discontinue the medication, risking uncontrolled seizures, mental health deterioration, hospitalisation or death in extreme cases,” he said.
“It is important to consider the wider picture of what else may be causing infertility. For example, epilepsy, in and of itself, can affect fertility rates, which are two-thirds lower in men with epilepsy than without.”
Alison Fuller, director of health improvement and influencing at the charity Epilepsy Action, said many men have expressed concern about the impact of sodium valproate on their fertility.
“This concern has become more common following the implementation of the new MHRA [Medicines and Healthcare products Regulatory Agency] guidance, which advises doctors to inform their patients of associated risks. In addition to fertility, many individuals are also concerned about the potential transgenerational effects of sodium valproate, including possible links to autism and other forms of neurodiversity in their children.
“We hope that this study provides reassurance for men prescribed this medication, but we know that current MHRA guidance still means that doctors are required to warn patients about the risks of potential infertility. Therefore, despite the new evidence, those at the frontline of epilepsy care will still be required to tell their patients that it may affect their fertility. This is concerning, as incorrectly telling male patients that they may not be able to have children could prompt them to stop taking their medication, which puts them in danger,” she said.
“Epilepsy Action has been consistently raising this issue with the MHRA and asking them to reconsider the published regulations. Given this new study, it is time for them to revisit the evidence and give it consideration.”
A spokesperson for the MHRA said that the body was aware of the study and that the findings were being considered through its established regulatory processes.
“We will carefully assess the data as part of our ongoing monitoring of the safety of valproate and will take it into account in our regulatory oversight,” they added.
The use of valproate by pregnant women has been associated with a high risk of congenital malformations and neurodevelopmental disorders in their children.
In 2024, the MHRA advised that men who take valproate — and their partners — should use effective contraception.
