Testosterone concentration and incident depression in older men: a longitudinal cohort study

Abstract Background Testosterone has been implicated in mood regulation, yet its role in the development and treatment of depression remains unclear. This study investigated the association between testosterone concentrations and the incidence of depression in older men. Methods We utilized data from 4,107 men aged 70 years and older who participated in the Aspirin in Reducing Events in the Elderly (ASPREE) and ASPREE-XT studies. Serum total testosterone concentrations were measured at baseline and year 3. Depressive symptoms were assessed annually using the CES-D-10 scale, with incident depression defined as a CES-D-10 score of ≥ 8. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) for incident depression, adjusted for potential confounders. Results During a median follow-up of 8.4 years, 1,449 participants experienced an episode of depression. Baseline total testosterone concentrations were not significantly associated with the risk of incident depression, whether treated as continuous variables (HR 1.00, 95% CI 0.99-1.01) or when categorized into quintiles. Similarly, changes in testosterone concentrations from baseline to year 3 did not predict incident depression (aHR 1.03, 95% CI 0.99-1.08). A subgroup analysis focusing on men with biochemical evidence of hypogonadism also found no association with incident depression. Conclusions Our findings do not support an association between testosterone concentrations and the risk of developing depression in older men. These results suggest that testosterone is not an important factor in the pathogenesis of depression in this population. There may still be individual variability in response to testosterone changes and its potential impact on mood disorders.