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.
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.
Mulligan
Kathleen
K
Department of Medicine, University of California, San Francisco, California 94110, USA. kmulligan@sfghgcrc.ucsf.edu
Zackin
Robert
R
Von Roenn
Jamie H
JH
Chesney
Margaret A
MA
Egorin
Merrill J
MJ
Sattler
Fred R
FR
Benson
Constance A
CA
Liu
Tun
T
Umbleja
Triin
T
Shriver
Sharon
S
Auchus
Richard J
RJ
Schambelan
Morris
M
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
D000728:Androgens; D019167:Appetite Stimulants; D010919:Placebos; D013739:Testosterone; D019290:Megestrol Acetate; D006854:Hydrocortisone