Effects of androgen administration on the growth hormone-insulin-like growth factor I axis in men with acquired immunodeficiency syndrome wasting

It is unknown whether hypogonadism contributes to decreased insulin-like growth factor I (IGF-I) production and/or how testosterone administration may effect the GH-IGF-I axis in human immunodeficiency virus (HIV)-infected men with the acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS). In this study, we investigate the GH-IGF-I axis in men with the AWS and determine the effects of testosterone on GH secretory dynamics, pulse characteristics determined from overnight frequent sampling, arginine stimulation, and total and free IGF-I levels. Baseline GH-IGF-I parameters in hypogonadal men with AWS (n = 51) were compared before testosterone administration (300 mg, im, every 3 weeks vs. placebo for 6 months) with cross-sectional data obtained in two age-matched control groups: eugonadal men with AIDS wasting (n = 10) and healthy age-matched normal men (n = 15). The changes in GH-IGF-I parameters were then compared prospectively in testosterone- and placebo-treated patients. Mean overnight GH levels [1.8 +/- 0.3 and 2.4 +/- 0.3 vs. 0.90 +/- 0.1 mu g/L (P = 0.04 and P = 0.003 vs, healthy controls)] and pulse frequency [0.35 +/- 0.06 and 0.37 +/- 0.02 vs. 0.22 +/- 0.03 pulses/h (P = 0.06 and P = 0.002 vs, healthy controls)] were comparably elevated in the eugonadal and hypogonadal HIV-positive groups, respectively, compared to those in the healthy control group. No significant differences in pulse amplitude, interpulse interval, or maximal GH stimulation to arginine administration (0.5 g/kg, iv) were seen between either the eugonadal and hypogonadal HIV-positive or healthy control patients. In contrast, IGF-I levels were comparably decreased in both HIV-positive groups compared to the healthy control group [143 +/- 16 and 165 +/- 14 vs. 216 +/- 14 mu g/L (P = 0.004 and P = 0.02 vs. healthy controls)]. At baseline, before treatment with testosterone, overnight GH levels were inversely correlated with IGF-I (r = -0.42; P = 0.003), percent ideal body weight (r = -0.36; P = 0.012), albumin (r = -0.37; P = 0.012), and fat mass (r = -0.52; P = 0.0002), whereas IGF-I levels correlated with free testosterone (r = 0.35; P = 0.011) and caloric intake (r = 0.32; P = 0.023) in the hypogonadal HIV-positive men. In a stepwise regression model, albumin (P = 0.003) and testosterone (P = 0.011) were the only significant predictors of GH [mean GH (mu g/L) = -1.82 x albumin (g/dL) + 0.003 x total testosterone (mu g/L) + 6.5], accounting for 49% of the Variation in GH. Mean overnight GH levels decreased significantly in the testosterone-treated patients compared to those in the placebo-treated hypogonadal patients (-0.9 +/- 0.3 vs. 0.2 +/- 0.4 mu g/L; P = 0.020). In contrast, no differences in IGF-I or free IGF-I were observed in response to testosterone administration. The decrement in mean overnight GH in response to testosterone treatment was inversely associated with increased fat-free mass (r = -0.49; P = 0.024), which was the only significant variable in a stepwise regression model for change in GH [change in mean GH (mu g/L) = -0.197 x kg fat-free mass - 0.53] and accounted for 27% of the variation in the change in GH. In this study, we demonstrate increased basal GH secretion and pulse frequency in association with reduced IGF-I concentrations, consistent with GH resistance, among both hypogonadal and eugonadal men with AIDS wasting. Testosterone administration decreases GH in hypogonadal men with AIDS wasting. The change in GH is best predicted by and is inversely related to the magnitude of the change in lean body mass in response to testosterone administration. These data demonstrate that among hypogonadal men with the AWS, testosterone administration has a significant effect on the GH axis.