Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial.

Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI.
Biological Psychiatry Laboratory, McLean Hospital, 115 Mill St., Belmont, MA
02478-9106, USA. pope@mclean.harvard.edu
Am J Psychiatry. 2003 Jan;160(1):105-11.

OBJECTIVE: Testosterone supplementation may produce antidepressant effects in
men, but until recently it has required cumbersome parenteral administration.
In an 8-week randomized, placebo-controlled trial, the authors administered a
testosterone transdermal gel to men aged 30-65 who had refractory depression
and low or borderline testosterone levels.

METHOD: Of 56 men screened, 24 (42.9%) displayed morning serum
total testosterone levels of 350 ng/dl or less (normal range=270-1070). Of these men,
23 entered the study. One responded to an initial 1-week single-blind placebo period,
and 22 were subsequently randomly assigned: 12 to 1% testosterone gel, 10 g/day,
and 10 to identical-appearing placebo. Each subject continued his existing
antidepressant regimen. Ten subjects receiving testosterone and nine receiving
placebo completed the 8-week trial.

RESULTS: The groups were closely matched on baseline demographic and
psychiatric measures. Subjects receiving testosterone gel had significantly greater
improvement in scores on the Hamilton Depression Rating Scale than subjects
receiving placebo. These changes were noted on both the vegetative and affective
subscales of the Hamilton Depression Rating Scale. A significant difference
was also found on the Clinical Global Impression severity scale but not the
Beck Depression Inventory. One subject assigned to testosterone reported
increased difficulty with urination, suggesting an exacerbation of benign prostatic
hyperplasia; no other subject reported adverse events apparently attributable to
testosterone.

CONCLUSIONS: These preliminary findings suggest that testosterone gel may
produce antidepressant effects in the large and probably underrecognized
population of depressed men with low testosterone levels.