Testosterone Treatment Reduces Symptoms of Depression in Men

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In a select sample of men, testosterone treatment in higher doses was observed to be effective for reducing depressive symptoms.
In a select sample of men, testosterone treatment in higher doses was observed to be effective for reducing depressive symptoms.

Testosterone treatment is effective and efficacious at reducing depressive symptoms in men, according to a recent study published in JAMA Psychiatry.

In this study, the researchers conducted a meta-analysis of the literature to determine the association between testosterone treatment and depressive symptoms in adult men. Specifically, the researchers sought to estimate the adjunct effectiveness and efficacy of testosterone in reducing depressive symptoms in men (testosterone treatment vs placebo).

The meta-analysis includes studies found in peer-reviewed journals within PubMed/Medline, Embase, Scopus, PsychINFO, and the Cochrane Controlled Trials Register. The literature search was limited to those published in the English language since database inception to March 5, 2018. The authors specifically searched for study reports of randomized placebo-controlled trials (RCTs) that administered testosterone in men and reported measures of mood before and after testosterone intervention.

Candidate reports were independently searched and cross-validated by 2 authors to determine if qualified studies were identified by the systematic search. The articles were screened and selected according to the PRISMA guidelines. After retrieving 7690 records and eliminating articles that did not meet the inclusion criteria, 27 reports were selected for quantitative synthesis.

Investigators who independently searched for the articles also extracted data and performed quality control. A third investigator performed the meta-analysis. The 3 investigators resolved discrepancies about study inclusion through discussion. Risk of bias was assessed by 2 investigators using the Cochrane Collaboration Risk of Bias tool for RCTs and Jadad scoring (interrater reliability: intraclass correlation coefficient, 0.64).

Manual extraction of exclusively graphical data was performed using the WebPlotDigitizer at the highest resolution. Bibliography, baseline characteristics, treatment characteristics, and outcome characteristics were extracted. Baseline testosterone status was classified based on current guidelines (mean concentration threshold of total testosterone of 345.82 ng/dL or less or free testosterone concentration of 64.84 pg/mL or less). Three treatment criteria were primary measures: effectiveness (using Hedges g and its sampling variance), efficacy, and acceptability (odds ratio [OR]).

A meta-analysis of the 25 studies with information about treatment-related loss to follow-up (acceptability) showed no significant difference in risk of attrition in testosterone participants compared with placebo (OR 0.79; 95% CI, 0.61-1.01; log[OR] −0.24; SE, 0.13; 95% CI, −0.49 to 0.01). Regarding effectiveness and efficacy, testosterone treatment showed a significant difference of Hedges g of 0.21 SD (SE 0.05; 95% CI, 0.10-0.32; z=3.87; P <.001) in depressive symptoms compared with placebo.

Investigators note that treatment with testosterone was significant when the dose administered was > 0.5g/wk and symptom variability was kept low.  The treatment acceptability did not differ significantly between treatment with testosterone and placebo (OR 0.79, 95% CI, 0.61-1.01).

Overall, testosterone treatment was both effective and efficacious at reducing depressive symptoms in men at higher-dosage regimens. The investigators note a major limitation to their meta-analysis, which is the large number of reported RCTs with high or unclear risk of bias and the RCTs' suboptimal study methods to mainly address the effect of testosterone treatment in men with depression.

Given these limitations and the heterogeneity of the RCTs included in their analysis, the authors stated that “more preregistered trials are needed that explicitly examine depression as the primary end point and consider relevant moderators.”

Reference

Walther A, Breidenstein J, Miller R. Association of testosterone treatment with alleviation of depressive symptoms in men a systematic review and meta-analysis [published online November 14, 2018]. JAMA Psych. doi:10.1001/jamapsychiatry.2018.2734

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