Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with human immunodeficiency virus-associated weight loss: a randomized, double-blind, placebo-controlled, multicenter trial

J Clin Endocrinol Metab. 2007 Feb;92(2):563-70. doi: 10.1210/jc.2006-0954. Epub 2006 Nov 7.


Context: Reduced energy intake is a primary factor in HIV-associated wasting. Megestrol acetate (MA) stimulates appetite and weight gain. However, much of the weight gained is fat, possibly as a result of MA-induced hypogonadism.

Objective: The objective of the study was to determine whether coadministration of testosterone with MA could enhance lean body mass (LBM) accrual and evaluate the effects of MA, alone or combined with testosterone, on sexual functioning and the hypothalamic-pituitary-adrenal axis.

Design: This was a randomized, double-blind, placebo-controlled, multicenter trial.

Setting: Fourteen AIDS Clinical Trials Units in the United States participated in the study.

Subjects: Seventy-nine HIV-positive men with 5% or more weight loss or body mass index less than 20 kg/m2 took part in the study.

Intervention: Subjects were randomized to receive MA (800 mg daily) plus testosterone enanthate (200 mg; MA/TE; n = 41) or placebo (MA/PL; n = 38) biweekly for 12 wk.

Main outcome measures: Weight, body composition (bioelectric impedance analysis), adrenal and gonadal hormones, and sexual functioning (questionnaire) were measured.

Results: Both groups experienced robust increases in weight (median 5.3 and 7.3 kg in MA/TE and MA/PL, respectively), LBM (3.3 and 3.3 kg), and fat (3.0 and 3.8 kg). There were no significant differences between groups in the magnitude or composition of weight gain (P = 0.44, 0.90, and 0.11 for weight, LBM, and fat, respectively). Trough testosterone concentrations decreased to a greater extent in MA/PL (-12.3 vs. -6.1 nmol/liter in MA/TE; P = 0.04). Cortisol levels became nearly undetectable in subjects with plasma MA levels greater than 150 ng/ml. Sexual functioning was preserved with MA/TE but worsened in MA/PL.

Conclusions: MA produced robust weight gain. Coadministration of testosterone preserved sexual functioning but did not enhance LBM accrual.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androgens / administration & dosage*
  • Androgens / adverse effects
  • Androgens / blood
  • Appetite Stimulants / administration & dosage*
  • Appetite Stimulants / adverse effects
  • Body Composition / drug effects
  • Double-Blind Method
  • Drug Therapy, Combination
  • HIV Wasting Syndrome / drug therapy*
  • Humans
  • Hydrocortisone / blood
  • Male
  • Megestrol Acetate / administration & dosage*
  • Megestrol Acetate / adverse effects
  • Middle Aged
  • Placebos
  • Protein-Energy Malnutrition / drug therapy
  • Protein-Energy Malnutrition / virology
  • Quality of Life
  • Sexuality
  • Testosterone / administration & dosage*
  • Testosterone / adverse effects
  • Testosterone / blood
  • Treatment Outcome
  • Weight Loss / drug effects


  • Androgens
  • Appetite Stimulants
  • Placebos
  • Testosterone
  • Megestrol Acetate
  • Hydrocortisone