Background: Whole body and abdominal obesity are associated with increased risk of diabetes mellitus and heart disease. The effects of testosterone therapy on whole body and visceral fat mass in HIV-infected men with abdominal obesity are unknown.

Objective: To determine the effects of testosterone therapy on intra-abdominal fat mass and whole body fat distribution in HIV-infected men with abdominal obesity.

Methods: In this multicenter, randomized, placebo-controlled, double-blind trial, 88 HIV+ men with abdominal obesity (waist-to-hip ratio>0.95 or mid-waist circumference>100 cm) and total testosterone 125-400ng/dL, or bioavailable testosterone<115ng/dL or free testosterone<50 pg/mL on stable antiretroviral regimen and HIV RNA<10,000 copies/mL were randomized to receive 10g testosterone gel or placebo daily for 24-weeks. Fat mass and distribution were determined by abdominal CT and DEXA during weeks 0, 12, and 24. We used an intention-to-treat approach and non-parametric statistical methods.

Results: Baseline characteristics were balanced between groups. In 75 evaluable subjects, median percent change from baseline to week 24 in visceral fat did not differ significantly between groups [testosterone +0.3%, placebo +3.1%, p=0.75]. Total [testosterone -1.5%, placebo +4.3%, p=0.04] and subcutaneous [testosterone -7.2%, placebo +8.1%, p<0.001] abdominal fat mass decreased in testosterone-treated men, but increased in placebo group. Testosterone therapy was associated with significant decrease in whole body, trunk and appendicular fat mass by DEXA (all p<0.001), while whole body and trunk fat increased significantly in the placebo group. The percent of individuals reporting a decrease in abdomen (p=0.01), neck (p=0.08), and breast size (p=0.01) at week 24 was significantly greater in testosterone-treated than placebo-treated men. Testosterone-treated men had greater increase in lean body mass than placebo [testosterone +1.3%, placebo -0.3, p=0.02]. Plasma insulin, fasting glucose, and total, HDL and LDL cholesterol levels did not change significantly. Testosterone therapy was well tolerated.

Conclusions: Testosterone therapy in HIV+ men with abdominal obesity and low testosterone was associated with greater decrease in whole body, total and subcutaneous abdominal fat mass and a greater increase in lean mass compared to placebo. However, changes in visceral fat mass were not significantly different between groups. Further studies are needed to determine testosterone effects on insulin sensitivity and cardiovascular risk.