To assess the effect of stimulants and epilepsy medications on semen parameters.  

Stimulants for ADHD, and antiepileptic drugs (AEDs) for epilepsy are widely used, but their effects on male fertility are less studied. While the negative impact of AEDs like valproate on female fertility (e.g., menstrual irregularities, PCOS, fetal abnormalities) is well-established, the evidence on male fertility is limited. Concerns include possible reductions in total sperm count (TSC), motility, and sperm abnormalities. This review aims to assess the impact of these medications on male fertility.

Medline, PsycInfo, and Embase databases were searched for English-language, full-text RCTs, cohort and case-control studies assessing semen parameters in men receiving stimulants or epilepsy medications. Animal and in-vitro studies were excluded. Risk of bias was assessed using the ROB-2 and ROBINS tools. Data extracted from included studies comprised of drug, dosage, length of intervention, number of participants, effect on semen parameters, and reversibility. PRISMA guidelines were followed.

1,298 papers were found and 7 (n=3 ADHD, n=4 epilepsy) were included in the review (n=6 cohort, n=1 case-control), representing a total of 19,130 patients (mean age = 33.7). Valproate was the most investigated drug (n=4), followed by methylphenidate (n=3), carbamazepine (n=2), and levetiracetam (n=1). 2 studies showed significant decreases in total sperm count (TSC), motility and semen volume, and increased sperm abnormalities in patients taking methylphenidate. 3 epilepsy studies showed significantly increased sperm abnormalities and decreased motility. Effects on sperm concentration and count were inconclusive (n=2 showing significant decreases, n=1 showing no significant difference). Reversibility was not assessed.

This study shows that both methylphenidate and AEDs are associated with adverse effects on sperm parameters. Further research needs to be done to quantify these impacts. Large-scale studies need to be done to assess the reversibility of these effects.