Testosterone replacement therapy for hypogonadal men with major depressivedisorder: A randomized, placebo-controlled clinical trial

Background: Symptoms of male hypogonadism include low libido, fatigue, and dysphoria and are alleviated with testosterone replacement, The prevalence of major depressive disorder (MDD) in hypogonadal men is not known, nor is the antidepressant efficacy of testosterone replacement in depressed, hypog onadal men. Method: A B-week double-blind, placebo-controlled clinical trial was conduc ted in 32 men with DSM-IV MDD and a low testosterone level, defined as tota l serum testosterone less than or equal to 350 ng/dL. Patients were randoml y assigned to receive weekly 1-mL intramuscular injections of either testos terone enanthate, 200 mg, or sesame seed oil (placebo). The primary outcome measure was the 24-item Hamilton Raring Scale for Depression (HAM-D). Results: Thirty patients were randomly assigned to an intervention; 13 rece ived testosterone, and 17 received placebo. Mean +/- SD age was 52 +/- 10 y ears, mean testosterone level was 266.1 +/- 50.6 ng/dL, and mean baseline H AM-D score was 21 +/- 8, All patients who received testosterone achieved no rmalization of their testosterone levels. The HAM-D scores decreased in bot h testosterone and placebo groups, and there were no significant between-gr oup differences: reduction in group mean HAM-D score from baseline to endpo int was 10.1 in patients who received testosterone and 10.5 in those who re ceived placebo, Response rate, defined as a 50% or greater reduction in HAM -D score, was 38.5% (5/13) for patients who received testosterone and 41.2% (7/17) for patients who received placebo. Patients receiving testosterone had a marginal but statistically significant improvement in sexual function (p =.02). Conclusion: In this clinical trial with depressed, hypogonadal men, antidep ressant effects of testosterone replacement could not be differentiated fro m those of placebo.