Testosterone treatment has potential as an adjunct therapy for men with depressive disorders, a meta-analysis has suggested. However, more research is needed.
“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,” Andreas Walther, PhD, and his coauthors wrote Nov. 14 in JAMA Psychiatry. However, they noted that safety monitoring in testosterone treatment trials remained important because of an absence of sufficiently powered, long-term studies to assess the increased risk of adverse events with treatment.
The link between testosterone and depression has been debated extensively because testosterone is a neuroactive steroid hormone known to influence mood and appetitive behavior, Dr. Walther and his coauthors wrote. Although testosterone treatment for various disorders in hypogonadal men has been backed by evidence, the results of randomized, placebo-controlled clinical trials for its use in depression have been inconsistent. Indeed, testosterone treatment was currently not recommended in national or international guidelines because of an “prevailing uncertainty about its efficacy, age criteria, dosage, ideal duration and method of application,” wrote Dr. Walther, of the department of biological psychology at Technische Universität Dresden (Germany).
For the current review, the researchers identified 27 randomized, controlled trials altogether including 1,890 men who were receiving testosterone treatment and had reported depressive symptoms on validated depression scales.
Results showed evidence for a moderate antidepressant association of testosterone treatment, compared with placebo (Hedges g, 0.21; 95% confidence interval, 0.10-0.32), and an efficacy odds ratio of 2.30 (95% CI, 1.30-4.06). According to the researchers, based on reference ranges for depressive symptoms, “The National Institute for Health and Care Excellence guidelines on depression suggest a reduction of 3.0 and 2.0 points on BDI scores to be clinically significant for normal depression and treatment-resistant depression, respectively,” they wrote.
Testosterone treatment also showed an efficacy OR of 2.30, a finding that the authors said suggested the “potential of testosterone treatment as adjunct therapy for men with depressive disorders.”
They said the results suggested that better treatment response might require higher doses but acknowledged that the finding required replication.
In addition, Dr. Walther and his coauthors found acceptability of testosterone treatment was high, with an OR of 0.79 for testosterone treatment–related loss to follow-up, compared with placebo. Remarkably, they added, initial testosterone status did not moderate the effects of testosterone treatment on depressive symptoms.
“Large, preregistered RCTs of good quality investigating testosterone treatment’s effect in men on depression as the primary outcome” are needed, they concluded.
Dr. Walther and his coauthors cited a few limitations, including the low number of randomized, controlled trials addressing the effects of testosterone treatment in men who were depressed but otherwise healthy.
No conflicts of interest were reported.
SOURCE: Walther A et al. JAMA Psychiatry. 2018 14 Nov. doi: 10.1001/jamapsychiatry.2018.2734.