Background: Testosterone replacement therapy is an effective treatment of some depressive symptoms in hypogonadal men, and may be an effective augmentation treatment for SSRI-refractory major depression in such men. Methods: We treated five depressed men who had low testosterone levels and had not responded to an adequate SSRI trial with 400 mg testosterone replacement biweekly for 8 weeks. Four patients underwent single-blind placebo discontinuation. Patients were assessed at baseline and biweekly thereafter using the Hamilton Depression Rating Scale (HAM-D) and the Endicott Quality of Life Enjoyment and Satisfaction Scale (Q-LES-Q). Results: Patients' mean age was 40 years, and mean testosterone level 277 ng/dl. All had a rapid and dramatic recovery from major depression following testosterone augmentation: mean 21-item HAM-D decreased from 19.2 to 7.2 by week 2, and to 4.0 by week 8; mean Q-LES-Q increased from 45% to 68%. Three of four subjects who underwent discontinuation of testosterone under single-blind placebo treatment began to relapse. Conclusion: Testosterone replacement therapy may be an effective treatment of depressive symptoms in some men, and warrants further research.
