title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, multicenter trial.
  
  
  METHODS
  Fourteen AIDS Clinical Trials Units in the United States participated in the study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine, University of California, San Francisco, California 94110, USA. kmulligan@sfghgcrc.ucsf.edu
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
authors.forename: Robert
authors.initials: R
authors.lastname: Zackin
authors.forename: Jamie H
authors.initials: JH
authors.lastname: Von Roenn
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Chesney
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
authors.forename: Fred R
authors.initials: FR
authors.lastname: Sattler
authors.forename: Constance A
authors.initials: CA
authors.lastname: Benson
authors.forename: Tun
authors.initials: T
authors.lastname: Liu
authors.forename: Triin
authors.initials: T
authors.lastname: Umbleja
authors.forename: Sharon
authors.initials: S
authors.lastname: Shriver
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Auchus
authors.forename: Morris
authors.initials: M
authors.lastname: Schambelan
mesh_terms: D000328:Adult; D000728:Androgens / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D019167:Appetite Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D001823:Body Composition / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D019247:HIV Wasting Syndrome / Q000188:drug therapy*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D019290:Megestrol Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010919:Placebos; D011502:Protein-Energy Malnutrition / Q000188:drug therapy / Q000821:virology; D011788:Quality of Life; D019529:Sexuality; D013739:Testosterone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000728:Androgens; D019167:Appetite Stimulants; D010919:Placebos; D013739:Testosterone; D019290:Megestrol Acetate; D006854:Hydrocortisone