Background:  Abdominal obesity is commonly seen in HIV⁺ men following use of potent ART. In the general population, increases in visceral adipose tissue have been linked to increased risk of cardiovascular disease. Testosterone replacement decreases visceral adipose tissue, as well as insulin levels, and improves lipids in hypogonadal HIV^­ middle-aged men. Therefore, we conducted a prospective, multicenter, randomized, placebo-controlled, double-blind study to determine the effects of testostserone replacement on abdominal fat mass (CT) and whole body and regional fat composition and lean body mass (DEXA).

Methods:  We randomized to receive 10 g of testosterone gel (AndroGel® 1% CIII) or placebo once daily for an initial 24-week double-blind phase, followed by an additional 24-week open-label phase, 88 HIV⁺ men characterized by:  abdominal obesity (waist-to-hip ratio >0.95 or mid-waist circumference >100 cm); mildly to moderately reduced testosterone levels (serum total testosterone 125 to 400 ng/dL mg, or if serum total testosterone >400 ng/dL, then bioavailable testosterone <115 ng/dL by ammonium sulfate bioavailability test or free testosterone <50 pg/mL by equilibrium dialysis); on stable potent ART for at least 3 months; and plasma HIV RNA <10,000 copies/mL. Single-slice abdominal CT and whole body DEXA were performed at week 0, 12, 24, and 48. Analysis used an intent-to-treat approach with LVCF and non-parametric statistical tests. 

Results:  Baseline characteristics in CD4, HIV RNA, and CT visceral adipose tissue were balanced between groups. At 24 weeks in 75 evaluable subjects, median percentage change in CT visceral adipose tissue did not differ significantly between groups (testosterone 0.3%, placebo 3.1%, p = 0.76). There was a significant difference in median subcutaneous and total abdominal fat changes compared to placebo (subcutaneous testosterone –7.2%, placebo 8.1%, p <0.001; total testosterone –1.5%, placebo 4.3%, p = 0.04). Testosterone replacement was associated with decreases in whole body, trunk and appendicular fat mass compared to placebo (all p <0.001). Lean body mass by DEXA increased in testosterone-treated men compared to placebo (testosterone 1.3%, placebo –0.3, p = 0.02).

Conclusions:  Testosterone replacement in HIV⁺ men with abdominal obesity and low testosterone levels was associated with a decrease in whole body and abdominal subcutaneous fat content and with an increase in lean mass compared to placebo; changes in visceral fat mass were not significantly different between the 2 groups. Further studies are needed to examine testosterone’s effects on insulin sensitivity, lipids, and atherosclerosis progression.