Abstract
BACKGROUND/OBJECTIVES: The complex association between attention-deficit/hyperactivity disorder (ADHD) and methylphenidate (MPH) with precocious puberty (PP) is still unclear. This study aims to investigate the association between ADHD, MPH, and PP. METHODS: This is a nationwide cohort study including a total of 3,342,077 individuals, 186,681 with ADHD and 3,155,396 without. First, we compared the risk of PP between ADHD cases and non-ADHD cases. Second, we compared the risk of PP between MPH users and non-MPH users in patients with ADHD. RESULTS: Patients with ADHD were at a greater risk of PP (adjusted hazard ratio [aHR], 2.01 [95% CI, 1.91-2.11]). In our moderation analyses, the female gender was a positive additive effect modifier of the association between ADHD and PP, whereas tics and intellectual disability were negative effect modifiers. In patients with ADHD, MPH users had a significantly lower risk of PP (aHR, 0.63 [95% CI 0.57-0.70]), and females had a negative effect modification on the association between MPH and PP. CONCLUSIONS: Our study found that children with ADHD were at a greater risk of PP. Girls with ADHD were a group particularly vulnerable to PP. Comorbid tics or intellectual disability was associated with a lower risk of PP. Among patients with ADHD, MPH was protective against PP, especially in girls. However, these preliminary results need further validation due to the nature of them being from an electronic database study. Unmeasured confounding factors might affect the association between MPH and PP.