A Randomized, Double-Blind, Placebo-Controlled Study of Testosterone Treatment in Hypogonadal Older Men With Subthreshold Depression

Abstract

Hypogonadism and subthreshold depression are common conditions in elderly men. The objective of this study was to examine the effect of testosterone treatment in older, hypogonadal men with subthreshold depression. A randomized, double-blind, placebo-controlled study was conducted at a university-affiliated Veterans Affairs Medical Center among men aged 50 years or older (N = 33) with screening total testosterone levels of <or= 280 ng/dL and subthreshold depression (dysthymia or minor depression, according to DSM-IV). Recruitment for the study was conducted from November 2002 through May 2005. Participants received either 7.5 g of testosterone gel or placebo gel daily for 12 weeks, followed by a 12-week open-label extension phase during which all subjects received 7.5 g of testosterone gel. The primary outcome measure was the change in the Hamilton Rating Scale for Depression (HAM-D) score from baseline to the end of the double-blind phase. Secondary outcome measures were remission of subthreshold depression (defined a priori as a HAM-D score <or= 7) and changes in the Hopkins Symptom Checklist depression scale, the Medical Outcomes Study 36-Item Short-Form Health Survey, and the short-form 16-item Quality of Life Enjoyment and Satisfaction Questionnaire. At the end of the double-blind phase, testosterone-treated men had a greater reduction in HAM-D scores (p = .024) and a higher remission rate of subthreshold depression (52.9% vs. 18.8%, p = .041) than did placebo-treated men, but there were no differences in other secondary outcome measures between groups. At the end of the open-label phase, the testosterone group had sustained improvement, the control group improved, and there were no differences between groups in any outcome measures. These results suggest that testosterone replacement may be efficacious treatment for subthreshold depression in older men with hypogonadism. Larger studies are needed to corroborate these findings. clinicaltrials.gov Identifier: NCT00202462.