The role of testosterone in the pathophysiology and treatment of depressive disorders in men has remained shrouded in controversy. We do not know whether depressive symptoms are a part of the syndrome of testosterone deficiency in men, and if so, whether testosterone replacement relieves such symptoms, whether low testosterone levels contribute to the pathophysiology of depressive disorders in men, and whether testosterone treatment is efficacious in treating men with depressive disorders. A well-performed meta-analysis by Walther et al in this issue of JAMA Psychiatry1 attempts to synthesize data from randomized, placebo-controlled clinical trials to assess the association of testosterone treatment with depressive symptoms in men. Although this meta-analysis adds to the body of data that testosterone administration may be associated with small improvements in depressive symptoms, we do not know whether these improvements are clinically meaningful. 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. Furthermore, neither the long-term safety nor the efficacy of testosterone therapy has been established in any depressive disorder. Because some of the adverse effects of testosterone are associated with its dose and on-treatment concentrations, the use of supraphysiologic doses of testosterone could be associated with increased risk of adverse effects and is currently not recommended.2
Bhasin S, Seidman S. Testosterone Treatment of Depressive Disorders in Men: Too Much Smoke, Not Enough High-Quality Evidence. JAMA Psychiatry. 2019;76(1):9–10. doi:10.1001/jamapsychiatry.2018.2661
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