Despite the advent of HAART, HIV-associated wasting remains a concern, along with peripheral fat loss (lipoatrophy) associated with certain antiretroviral drugs.

Reduced energy (calorie) intake is a primary factor in HIV-associated wasting. Megestrol acetate (Megace) stimulates appetite and weight gain. However, much of the weight gained is in the form of fat, possibly as a result of hypogonadism (low testosterone production) induced by megestrol acetate.

As reported in the November 7, 2006 electronic edition of the Journal of Clinical Endocrinology and Metabolism, researchers sought to determine whether co-administration of testosterone with megestrol acetate could enhance accrual of lean body mass. They also evaluated the effects of megestrol acetate, alone or with testosterone, on sexual functioning and the hypothalamic-pituitary-adrenal axis.

This randomized, double-blind, placebo-controlled trial was conducted at 14 AIDS Clinical Trials Group (ACTG) units in the U.S. and included 79 HIV positive men with at least 5% weight loss or a body mass index (BMI) less than 20 kg/m2. Subjects were randomly assigned to receive megestrol acetate (800 mg daily) plus either testosterone enanthate (200 mg)(n = 41) or placebo (n = 38) biweekly for 12 weeks.

Results

Both the megestrol acetate/testosterone and megestrol acetate/placebo groups experienced robust increases in:

- weight (median 5.3 and 7.3 kg in, respectively);
- lean body mass (3.3 and 3.3 kg, respectively);
- fat (3.0 and 3.8 kg, respectively).

There were no significant differences between the groups in the magnitude or composition of weight gain (P = 0.44, 0.90, and 0.11 for weight, lean body mass, and fat, respectively).

Trough testosterone concentrations decreased to a greater extent in the megestrol acetate/placebo arm compared with the megestrol acetate/testosterone arm (12.3 vs 6.1 nmol/L in, respectively; P = 0.04).

Cortisol levels became nearly undetectable in subjects with plasma megestrol acetate levels > 150 ng/mL.

Sexual functioning was preserved with megestrol acetate/testosterone, but worsened in the megestrol acetate/placebo arm.

Conclusion

In conclusion, the researchers wrote, "Megestrol acetate produced robust weight gain. Co-administration of testosterone preserved sexual functioning but did not enhance lean body mass accrual."

University of California San Francisco/San Francisco General Hospital, San Francisco, CA; Harvard University, Boston, MA; Northwestern University Medical Center, Chicago, IL; National Institutes of Health, Bethesda, MD; University of Pittsburgh, Pittsburgh, PA; University of Southern California, Los Angeles, CA; University of California San Diego, San Diego, CA; Social and Scientific Systems, Silver Spring, MD; University of Texas Southwestern Medical Center, Dallas, TX.

12/08/06

Reference
K Mulligan, R Zackin, J H von Roenn, and others. Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with HIV-associated weight loss: a randomized, double-blind, placebo-controlled multicenter trial. Journal of Clinical Endocrinology and Metabolism. November 7, 2006 [Epub ahead of print].