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Testosterone treatment linked with reduced depressive symptoms in men

Results from a meta-analysis published in JAMA Psychiatry showed that testosterone may have utility in the adjunct treatment of depressive symptoms in men. However, additional studies are needed to definitively establish efficacy, as well as ideal dosage, according to researchers.

“The association between testosterone and depression has been extensively debated because testosterone is a neuroactive steroid hormone influencing mood and appetitive behavior,” Andreas Walther, PhD, from the department of biological psychology, Technische Universität Dresden, Germany, and colleagues wrote. “Randomized placebo-controlled clinical trials of testosterone treatment in hypogonadal men that examine depressive symptoms have yielded inconsistent results.”

The investigators conducted a systematic review and meta-analysis to assess the link between testosterone treatment and depressive symptoms in men. They searched clinical databases for randomized, placebo-controlled clinical trials of testosterone treatment that included hypogonadal or eugonadal men reporting depressive symptoms to determine the effectiveness, efficacy and acceptability of testosterone treatment for depressive symptoms.

The random-effects meta-analysis included 27 randomized controlled trials involving 1,890 men.

The results indicated that testosterone treatment was linked with a significant decrease in depressive symptoms compared with placebo (95% CI, 0.1-0.32), which corresponded to a testosterone treatment–associated efficacy of OR = 2.3 (95% CI, 1.3-4.06). Additionally, there was no significant difference between acceptability of testosterone treatment vs. placebo (OR = 0.79; 95% CI, 0.61-1.01).

Exploratory analyses demonstrated significant interactions for testosterone treatment with dosage (beta = 0.08 SD per each additional 100 mg per week) and baseline symptom variability (beta = –0.12 SD per each additional 25% symptom variability). Walther and colleagues found that testosterone treatment remained significant when men received dosages greater than 0.5 g per week and symptom variability was low.

“This meta-analysis provides important new evidence that testosterone treatment may also be effective and efficacious for eugonadal and older men when higher testosterone dosages are administered,” the researchers wrote. “Because our results as well as previous investigations have indicated that risk of bias is considerable in most studies, we call for large, preregistered [randomized controlled trials] of good quality investigating testosterone treatment’s effect in men on depression as the primary outcome.”

In a related comment, Shalender Bhasin, MB, BS, of Harvard Medical School and Brigham and Women’s Hospital, and Stuart Seidman, MD, of Columbia University, pointed out some problems in the meta-analysis, including the heterogeneous study populations.

“Meta-analyses of such heterogeneous populations of men with diverse conditions, many of whom did not have a depressive disorder or even depressive symptoms, do not permit strong inferences about the efficacy of testosterone treatment in inducing remission of depression,” they wrote. “Clinicians should follow the Endocrine Society guideline for testosterone replacement therapy of androgen-deficient men; the available data do not support the use of testosterone treatment, especially in supraphysiologic doses, for the treatment of depressive disorders in men.” – by Savannah Demko

Disclosures: The authors report no relevant financial disclosures. Bhasin reports many research grants, consulting fees from AbbVie and OPKO and having equity interest in FPT Information System, LLC. Please see the study for a complete list of Bhasin’s relevant financial disclosures.