Loss of lean body and muscle mass correlates with androgen levels in hypogonadal men with acquired immunodeficiency syndrome and wasting

The acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS) is a devastating complication of human immunodeficiency virus infection characterized by a disproportionate decrease in lean body mass. The pathogenesis of the AWS is unknown, but recent data suggest that endogenous secretion of the potent anabolic hormone, testosterone; is decreased in 30-50% of men with AIDS. However, it is unknown whether decreased androgen levels are associated with decreased lean body mass and/or functional decreases in muscle strength and aerobic capacity in hypogonadal men with the AWS. In addition, testosterone is known to have stimulatory effects on GH secretion, and the loss of these effects on the GH-insulin-like growth factor I (IGF-I) axis may be an additional mechanism of decreased lean body mass in this population. Twenty hypogonadal subjects (free-testosterone < 12 pg/mL) with weight loss > 10% of preillness weight or absolute weight < 90% ideal body weight (IBW) were enrolled in the study. None of the subjects were receiving Megace. Lean body mass and fat-free mass were determined by potassium-40 isotope analysis (40K) and dual-energy x-ray absorptiometry, respectively, and analyzed with respect to gonadal function by linear regression analysis. Muscle mass was determined by urinary creatinine excretion, and exercise functional capacity was assessed by a 6-min walk test, a sit-to-stand test, and a timed get-up-and-go test. Results also were compared with gonadal function by regression analysis. IGF-I and mean overnight GH levels, determined from frequent sampling (q20 min from 2000-0800 h), were compared with results obtained from age- and sex-matched normal controls. Subjects were 26-58 yr of age (39 +/- 7 yr, mean +/- SD) with a CD4 cell count of 150 +/- 186 cells/mm3. Serum levels of FSH were elevated in 30% of the subjects. Muscle mass was significantly reduced, compared with expected mass for height (23.3 +/- 5.5 vs. 29.3 +/- 1.7 kg, P = 0.0001) and was decreased disproportionately to weight (77% of expected value for muscle mass vs. 93% of expected value for weight). Free-testosterone levels were correlated with total body potassium (R = 0.45, P < 0.05) and muscle mass (R = 0.45, P < 0.05). Total-testosterone levels were correlated with exercise functional capacity (R = 0.64, P = 0.01 for the sit-to-stand test and R = 0.53, P < 0.05 for the 6-min walk test). Mean GH levels were significantly increased (3.03 +/- 1.76 vs. 0.90 +/- 0.37 ng/mL, P < 0.00