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Testosterone supplementation may improve depressive symptoms for a subset of male patients with low or borderline testosterone levels suffering from refractory depression. A randomized, double-blind, placebo-controlled trial in 23 patients with a low or borderline serum testosterone level (range 100-350 ng/dl; normal range is 270-1,070 ng/dl) who met the DSM-IV criteria for current MDD and were being treated with antidepressant medications prior to and during the trial received either testosterone gel (1% gel, 10 g/day) or placebo for 8 weeks (335). There was significantly greater improvement in HAM-D scores in the testosterone-treated group compared to placebo in both the vegetative and affective symptom subscales of the HAM-D Scale. Overall, the testosterone gel was well tolerated. One patient in the study experienced exacerbation of benign prostatic hyperplasia, which may be attributed to testosterone supplementation and was withdrawn from the study, although the relationship of testosterone supplementation to prostate cancer has been challenged. The mechanism of testosterone's antidepressant action is not known.

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