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.

TitleTestosterone 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.
Publication TypeJournal Article
Year of Publication2007
AuthorsMulligan K, Zackin R, Von Roenn JH, Chesney MA, Egorin MJ, Sattler FR, Benson CA, Liu T, Umbleja T, Shriver S, Auchus RJ, Schambelan M
Corporate AuthorsACTG 313 Study Team
JournalJ Clin Endocrinol Metab
Volume92
Issue2
Pagination563-70
Date Published2007 Feb
ISSN0021-972X
KeywordsAdult, Androgens, Appetite Stimulants, Body Composition, Double-Blind Method, Drug Therapy, Combination, HIV Wasting Syndrome, Humans, Hydrocortisone, Male, Megestrol Acetate, Middle Aged, Placebos, Protein-Energy Malnutrition, Quality of Life, Sexuality, Testosterone, Treatment Outcome, Weight Loss
Abstract

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.

DOI10.1210/jc.2006-0954
Alternate JournalJ. Clin. Endocrinol. Metab.
PubMed ID17090640
Grant ListAI25859 / AI / NIAID NIH HHS / United States
AI25915 / AI / NIAID NIH HHS / United States
AI27663 / AI / NIAID NIH HHS / United States
AI27668 / AI / NIAID NIH HHS / United States
AI27670 / AI / NIAID NIH HHS / United States
AI27673 / AI / NIAID NIH HHS / United States
AI32770 / AI / NIAID NIH HHS / United States
AI34853 / AI / NIAID NIH HHS / United States
AI38844 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
DK45833 / DK / NIDDK NIH HHS / United States
RR-00043 / RR / NCRR NIH HHS / United States
RR-00051 / RR / NCRR NIH HHS / United States
RR-00052 / RR / NCRR NIH HHS / United States
RR-00083 / RR / NCRR NIH HHS / United States
RR-05096 / RR / NCRR NIH HHS / United States