Depressive symptoms common in hypogonadal men, TRT helps

Depressive symptoms are likely to occur in middle-aged and older men with hypogonadism, but low-grade persistent depressive disorder (LG-PDD) is rare, according to a study.

Testosterone-replacement therapy (TRT) may slightly improve mood and energy in hypogonadal men with and without depressive symptoms, the investigators said.

This randomized, placebo-controlled, double-blind study was conducted at 316 trial sites and included 5,204 men, aged 45‒80 years, with two fasting testosterone levels <300 ng/dL, one or more hypogonadal symptoms, cardiovascular disease (CVD), or increased CVD risk.

Participants were categorized into three subgroups: men with rigorously defined, late life-onset, LG-PDD (previously dysthymia); men with significant depressive symptoms (Patient Health Questionnaire-9 Score >4); and all randomly assigned men. For the intervention, men received either 1.62% transdermal testosterone or placebo gel.

The investigators then evaluated the following outcomes: the proportion of participants meeting the criteria for LG-PDD or with significant depressive symptoms and changes in depressive symptoms, energy, sleep quality, and cognition in testosterone- vs placebo-treated men in the three subgroups.

Of the participants, 2,643 (50.8 percent) had significant depressive symptoms, and 49 (1.5 percent) had LG-PDD. Among men with LG-PDD, no significant difference was observed in any outcomes between the TRT and placebo groups, potentially indicating low statistical power.

Moreover, TRT resulted in modest but significantly greater improvements in mood and energy, but not cognition and sleep quality, in men with significant depressive symptoms and in all randomized men.