Attention-deficit/hyperactivity disorder stimulant use is associated with reduced semen volume in reproductive-age men: a multi-center analysis.

Abstract

Stimulant medications are increasingly prescribed for attention-deficit/hyperactivity disorder (ADHD) in men of reproductive age, yet their impact on semen quality remains poorly characterized. We aimed to evaluate whether recent stimulant exposure would negatively affect semen parameters in reproductive-age men with ADHD. We performed a multi-center retrospective analysis of 2039 men aged 18-40 years with a diagnosis of ADHD and available semen volume data between 1995-2025. We excluded men with diagnoses or treatments known to affect spermatogenesis or ejaculatory function. Exposure was defined as an active outpatient prescription for methylphenidate, amphetamine, lisdexamfetamine, dextroamphetamine, or methamphetamine within 90 days prior to semen testing. Exposed patients were matched 2:1 by age (±4 years) to stimulant-unexposed controls with ADHD. The final cohort included 388 exposed and 776 matched controls, with median ages of 33 (IQR 30-37) and 33 (IQR 29-37) years, respectively. Stimulant exposure was associated with lower semen volume (median 2.70 mL [IQR 1.9-3.7] vs. 2.95 mL [IQR 2.0-4.1], p = 0.02). No significant differences were observed between groups in other semen parameters (p > 0.25). On univariable regression, stimulant exposure was associated with a 5.7% decrease in semen volume (p = 0.02). After adjustment in multivariable regression, stimulant exposure remained associated with an 8.4% lower semen volume (p = 0.01). Among reproductive-age men with ADHD, recent stimulant use was associated with a modest decrease in semen volume, while other semen parameters remained unchanged. Importantly, preserved sperm quality suggests that stimulant use during attempts at conception is unlikely to significantly impair fertility.