Depressive Syndromes in Men with Hypogonadism in the TRAVERSE Trial: Response to Testosterone Replacement Therapy.

CONTEXT:The effect of testosterone on depressive symptoms in men with hypogonadism remains incompletely understood. OBJECTIVE:We assessed the effects of testosterone replacement therapy (TRT) in improving depressive symptoms in hypogonadal men with and without depressive symptoms enrolled in the TRAVERSE cardiovascular safety trial. DESIGN:Randomized, placebo-controlled, double-blind. SETTING:316 trial sites. PARTICIPANTS:Men, 45 to 80 years, with two fasting testosterone levels <300 ng/dL, one or more hypogonadal symptoms, cardiovascular disease (CVD), or increased risk of CVD. We evaluated three subgroups of participants: 1) men with rigorously defined late-life-onset, low-grade persistent depressive disorder (LG-PDD, previously "dysthymia"); 2) all men with significant depressive symptoms (Patient Health Questionnaire-9 Score >4); and 3) all randomized men. INTERVENTION:1.62% transdermal testosterone or placebo gel. OUTCOME MEASURES:Proportions of participants 1) meeting criteria for LG-PDD or 2) with significant depressive symptoms; changes in depressive symptoms, energy, sleep quality, and cognition in testosterone- vs. placebo-treated men in the three subgroups. RESULTS:Of 5,204 randomized participants, 2,643 (50.8%) had significant depressive symptoms, but only 49 (1.5%) met rigorous criteria for LG-PDD. Among those with LG-PDD, there was no significant difference in any outcome measure between the TRT and placebo groups, possibly reflecting low statistical power. In men with significant depressive symptoms n=2643) and in all randomized participants (n=5204), TRT was associated with modest but significantly greater improvements in mood and energy but not cognition or sleep quality. CONCLUSIONS:Depressive symptoms are common in middle-aged and older men with hypogonadism, but LG-PDD is uncommon. TRT is associated with small improvements in mood and energy in hypogonadal men with and without significant depressive symptoms. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03518034.