Journal Article

Depressive Syndromes in Men With Hypogonadism in the TRAVERSE Trial: Response to Testosterone-Replacement Therapy

Pencina, Karol M, Bhasin, Shalender, Travison, Thomas G, Wannemuehler, Kathleen A, Li, Xue, Seidman, Stuart, Pope, Harrison G, Nissen, Steven E, Lincoff, A Michael, Flevaris, Panagiotis, Miller, Michael G

2024

Overview

Abstract 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. Methods A randomized, placebo-controlled, double-blind study was conducted at 316 trial sites. Participants included men, aged 45 to 80 years, with 2 fasting testosterone levels less than 300 ng/dL, 1 or more hypogonadal symptoms, cardiovascular disease (CVD), or increased risk of CVD. We evaluated 3 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 randomly assigned men. Intervention included 1.62% transdermal testosterone or placebo gel. Outcome measures included the proportions of participants (1) meeting criteria for LG-PDD or (2) with significant depressive symptoms; and changes in depressive symptoms, energy, sleep quality, and cognition in testosterone-treated vs placebo-treated men in the 3 subgroups. Results Of 5204 randomly assigned participants, 2643 (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 randomly assigned participants (n = 5204), TRT was associated with modest but significantly greater improvements in mood and energy but not cognition or sleep quality. Conclusion 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.

• Publisher: Oxford University Press
• Subject: Aged / Aged, 80 and over / Cardiovascular diseases / Clinical trials / Cognition / Depression - drug therapy / Depression, Mental / Depressive Disorder - drug therapy / Double-Blind Method / Hormone Replacement Therapy - methods / Humans / Hypogonadism / Hypogonadism - drug therapy / Hypogonadism - psychology / Male / Mental depression / Middle Aged / Mood / Patient compliance / Pharmaceutical industry / Placebos / Psychological aspects / Sleep / Statistical analysis / Testosterone / Testosterone - administration & dosage / Testosterone - therapeutic use / Treatment Outcome