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Peter J. Schmidt, MD; Kate L. Berlin, BA; Merry A. Danaceau, RN, MSNCS; Amy Neeren, BA; Nazli A. Haq, MA; Catherine A. Roca, MD; David R. Rubinow, MD

Arch Gen Psychiatry. 2004;61:997-1004.

Background  The effects of declining androgen secretion on mood regulation and the potential psychotropic efficacy of androgen replacement in men are largely undetermined.

Objective  To examine the effects on mood of the acute suppression of testosterone secretion.

Design  A double-blind, placebo-controlled, crossover (self-as-own-control) study.

Setting  An ambulatory care clinic in a research hospital.

Participants  Thirty-one healthy adult men with no history of psychiatric illness or substance or anabolic steroid abuse.

Interventions  Men received depot leuprolide acetate (Lupron, 7.5 mg intramuscularly) every 4 weeks for 3 months. After the first month of Lupron alone, all men received (in addition to Lupron) testosterone enanthate (200 mg intramuscular) or placebo (sesame oil as color-matched vehicle) every 2 weeks for 1 month each in a crossover design. The order of administration of testosterone and placebo was randomly assigned and counterbalanced.

Main Outcome Measures  Mood and behavior rating scores (self-report and rater administered).

Results  With the exceptions of hot flushes, libido, and the feeling of being emotionally charged, none of the symptoms measured showed a significant difference across eugonadal, Lupron plus placebo, and Lupron plus testosterone conditions. Despite the absence of a uniform effect of Lupron plus placebo on mood, 3 men experienced clinically relevant mood symptoms during this induced hypogonadal condition. High baseline levels of sexual functioning predicted the greatest decline in sexual function during Lupron plus placebo.

Conclusions  These data, the first to describe the effects on mood of induced hypogonadism in healthy young men, suggest that short-term hypogonadism is sufficient to precipitate depressive symptoms in only a small minority of younger men. The predictors of this susceptibility remain to be determined.

Author Affiliations: Behavioral Endocrinology Branch, National Institute of Mental Health, National Institutes of Health (Drs Schmidt, Roca, and Rubinow and Mss Berlin, Neeren, and Haq), and the Department of Nursing, National Institutes of Health Clinical Center (Ms Danaceau), Bethesda, Md.

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