Testosterone therapy (TT) moderately relieves depressive symptoms in hypogonadal and eugonadal men, according to researchers.

The Testosterone Trials and other recent studies indicated a potential mood-enhancing effect from TRT, so Andreas Walther, PhD, of the Universität Dresden in Germany conducted an updated systematic review and meta-analysis including 27 randomized controlled trials (RCTs) published 2000 to March 2018 comparing TT with placebo. Some of the 1890 men included in the studies met the definition of hypogonadism (total testosterone 345.82 ng/dL or less), whereas others had normal testosterone levels.

TT users were 2.3 times more likely to experience reduction in depressive symptoms (variably defined) compared with placebo, according to results published in JAMA Psychiatry. TT doses greater than 500 mg per week were associated with greater symptom reduction. Purported effects did not vary by age. Acceptability of TT did not differ significantly from placebo.

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“Testosterone treatment appears to be effective and efficacious in reducing depressive symptoms in men, particularly when higher-dosage regimens were applied in carefully selected samples,” Dr Walther and his collaborators concluded. They cautioned, however, that the body of research was not at the stage where TT can be recommended as adjunctive therapy for antidepressants. Included RCTs were heterogeneous in their populations, definitions of “depression,” TT doses and duration, and other particulars, and had high risks for bias. The long-term safety of TT is still unclear.

“These data should not be extrapolated to imply that testosterone treatment induces remission of major depressive disorder (MDD) or that it augments response to antidepressant therapy in such patients,” Shalender Bhasin, MB, BS, of Brigham and Women’s Hospital in Boston, and Stuart Seidman, MD, of Columbia University in New York, commented in an accompanying editorial.

Both the investigators and the editorialists urged future rigorous RCTs investigating TT.

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Walther A, Breidenstein J, and Miller R. Association of testosterone treatment with alleviation of depressive symptoms in men: A systematic review and meta-analysis. JAMA Psych. DOI:10.1001/jamapsychiatry.2018.2734 (Published online November 14, 2018)

Bhasin S, Seidman S. Testosterone treatment of depressive disorders in men: Too much smoke, not enough high-quality evidence. JAMA Psych. DOI:10.1001/jamapsychiatry.2018.2661 (Published online November 14, 2018)