Testosterone Replacement Therapy for Hypogonadal Men With Major Depressive Disorder: A Randomized, Placebo-Controlled Clinical Trial

Background: Symptoms of male hypogonadisminclude low libido, fatigue, and dysphoria and are alleviatedwith testosterone replacement. The prevalence of major depressivedisorder (MDD) in hypogonadal men is not known, nor is theantidepressant efficacy of testosterone replacement in depressed,hypogonadal men.

Method: A 6-week double-blind,placebo-controlled clinical trial was conducted in 32 men withDSM-IV MDD and a low testosterone level, defined as total serumtestosterone <= 350 ng/dL. Patients were randomly assigned toreceive weekly 1-mL intramuscular injections of eithertestosterone enanthate, 200 mg, or sesame seed oil (placebo). Theprimary outcome measure was the 24-item Hamilton Rating Scale forDepression (HAM-D).

Results: Thirty patients were randomly assignedto an intervention; 13 received testosterone, and 17 receivedplacebo. Mean ± SD age was 52 ± 10 years, mean testosteronelevel was 266.1 ± 50.6 ng/dL, and mean baseline HAM-D score was21 ± 8. All patients who received testosterone achievednormalization of their testosterone levels. The HAM-D scoresdecreased in both testosterone and placebo groups, and there wereno significant between-group differences: reduction in group meanHAM-D score from baseline to endpoint was 10.1 in patients whoreceived testosterone and 10.5 in those who received placebo.Response rate, defined as a 50% or greater reduction in HAM-Dscore, was 38.5% (5/13) for patients who received testosteroneand 41.2% (7/17) for patients who received placebo. Patientsreceiving testosterone had a marginal but statisticallysignificant improvement in sexual function (p = .02).

Conclusion: In this clinical trial withdepressed, hypogonadal men, antidepressant effects oftestosterone replacement could not be differentiated from thoseof placebo.