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

Significant depressive symptoms were common among hypogonadal men enrolled in the TRAVERSE trial, but rigorously defined low-grade persistent depressive disorder (LG-PDD) was uncommon.

• Of 5204 randomly assigned participants, 2643 (50.8%) had significant depressive symptoms (PHQ-9 score >4)
• Only 49 participants (1.5%) met rigorous criteria for LG-PDD (previously termed 'dysthymia')
• Participants were men aged 45 to 80 years with 2 fasting testosterone levels less than 300 ng/dL and 1 or more hypogonadal symptoms plus cardiovascular disease or increased CVD risk
• The study was conducted at 316 trial sites

Testosterone-replacement therapy was associated with modest but statistically significant improvements in mood and energy in men with significant depressive symptoms.

• In men with significant depressive symptoms (n = 2643), TRT was associated with significantly greater improvements in mood and energy compared to placebo
• Improvements were described as 'modest but significantly greater' than placebo
• The intervention used was 1.62% transdermal testosterone gel versus placebo gel
• These improvements were observed both in the subgroup with significant depressive symptoms and in all randomly assigned participants (n = 5204)

Testosterone-replacement therapy did not produce significant improvements in cognition or sleep quality in hypogonadal men.

• In men with significant depressive symptoms (n = 2643), TRT was not associated with significantly greater improvements in cognition or sleep quality versus placebo
• This lack of effect on cognition and sleep was observed across the subgroup with significant depressive symptoms and in all randomly assigned participants
• Outcome measures assessed included changes in depressive symptoms, energy, sleep quality, and cognition

Among men with rigorously defined LG-PDD, there was no significant difference in any outcome measure between TRT and placebo groups.

• Only 49 participants (1.5% of those with significant depressive symptoms) met rigorous criteria for LG-PDD
• No significant difference was found in any outcome measure between TRT and placebo in this subgroup
• The authors noted this null finding possibly reflects low statistical power due to the small sample size
• Outcome measures in this subgroup included proportions meeting criteria for LG-PDD and changes in depressive symptoms, energy, sleep quality, and cognition

The TRAVERSE trial was a randomized, placebo-controlled, double-blind cardiovascular safety trial used as the framework for this analysis of depressive outcomes.

• The trial enrolled men aged 45 to 80 years with 2 fasting testosterone levels less than 300 ng/dL
• Eligible men had 1 or more hypogonadal symptoms and either established cardiovascular disease or increased risk of CVD
• 316 trial sites participated
• Three subgroups were evaluated: men with LG-PDD, all men with PHQ-9 score >4, and all randomly assigned men (n = 5204)