“Attention-Deficit Hyperactivity Disorder Medication Use is Associated with Testosterone Hypofunction – Results from a National Claims Database Analysis” by Ostdiek-Wille et al. [1], investigates a possible link between chronic Attention-Deficit Hyperactivity Disorder (ADHD) stimulant medication use and the associated risk of developing testosterone hypofunction in adult males. The authors used a large-scale dataset from the TriNetX LLC Research Network (TriNetX LLC, Cambridge MA, USA) that likely included a diverse and comprehensive patient population. The authors also planned to create an additional control group that takes into account the population diagnosed with ADHD alone without stimulant use. This increases the reader’s confidence in attributing the difference found in the results to stimulant medication only and eliminates the possible confounding effect of ADHD disease. An additional strength is the longitudinal design and the five-year follow-up period for assessing the occurrence of testicular hypofunction. Furthermore, the researchers employed propensity score matching to control for potential confounding variables, thereby strengthening the validity of their reports.

Despite the large dataset (17,224 men were analyzed in each group) and the appropriate statistical tests that the authors utilized, the study also has some limitations. By nature, the study has a retrospective design, therefore it is not the ideal way to establish causality in a clinical scenario. Additionally, there’s a lack of information on medication dosage which is an important factor to consider when contemplating dose-response gradient assumptions that would otherwise be sought in an adverse event-drug study. An additional limitation is that the most recent patient data goes back to 2019, which is outdated relative to the very recent publication date of December 2023.