Testicular Function After Long-Term Methylphenidate Treatment in Boys with Attention-Deficit/Hyperactivity Disorder

Objective: Treating attention-deficit/hyperactivity disorder (ADHD) with methylphenidate (MPH) has become increasingly common, while both animal studies and case reports have previously suggested that MPH may exert adverse effects on the reproductive system or gonadal hormones. This study aims to investigate whether long-term MPH treatment of boys with ADHD can induce testicular dysfunction (TD). Methods: A nationwide cohort that included 59,746 boys diagnosed with ADHD and 52,008 healthy subjects retrieved from the National Health Insurance database in Taiwan was also observed between 1999 and 2011. TD was defined by the International Classification of Diseases, 9th revision, Clinical Modifications codes (257.0, 257.1, 257.2, 257.8, or 257.9). Cumulative time of MPH use was categorized into nonuse, short-term use (1-365 days), and long-term use (>365 days). We compared the rate of TD diagnosis between ADHD patients and controls and analyzed the risk of developing a TD after MPH treatment. Results: Compared with the control group (0.06%), the ADHD group had a higher comorbidity rate of TD (0.14%) (adjusted odds ratio [aOR] = 1.95, 95% confidence interval [95% CI]: 1.26-3.04, p = 0.003). However, MPH did not significantly influence the risk of developing TD (adjusted hazard ratio = 1.40, 95% CI: 0.77-2.54, p = 0.272). Compared with ADHD boys without MPH treatment, patients who were prescribed short-term MPH (aOR = 0.96, 95% CI: 0.51-1.82, p = 0.900) and long-term MPH (aOR = 1.40, 95% CI: 0.69-2.83, p = 0.351) showed no significance associated with an increased risk of developing TD. Conclusions: Our nationwide cohort showed that long-term treatment with MPH has no harmful effect on the testosterone function of ADHD patients. However, due to the increased comorbidity rate of ADHD and TD, early recognition and detection of TD in ADHD children have the potential to change the trajectory of TD morbidity later in life.