The effects of pharmacologically induced hypogonadism on mood in healthy men

Arch Gen Psychiatry. 2004 Oct;61(10):997-1004. doi: 10.1001/archpsyc.61.10.997.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Affect / drug effects*
  • Case-Control Studies
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Double-Blind Method
  • Health Status*
  • Hormone Replacement Therapy / methods
  • Humans
  • Hypogonadism / blood
  • Hypogonadism / chemically induced*
  • Hypogonadism / psychology*
  • Leuprolide / pharmacology*
  • Libido / drug effects
  • Male
  • Middle Aged
  • Placebos
  • Sexual Behavior / drug effects
  • Sexual Dysfunctions, Psychological / chemically induced
  • Sexual Dysfunctions, Psychological / drug therapy
  • Sexual Dysfunctions, Psychological / psychology
  • Testosterone / analogs & derivatives
  • Testosterone / blood
  • Testosterone / pharmacology
  • Testosterone / therapeutic use


  • Delayed-Action Preparations
  • Placebos
  • Testosterone
  • testosterone enanthate
  • Leuprolide