The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men

Testosterone has immune-modulating properties, and current in vitro evidence suggest that testosterone may suppress the expression of the proinflammatory cytokines TNFalpha, IL-1beta, and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10. We report a randomized, single-blind, placebo-controlled, crossover study of testosterone replacement (Sustanon 100) vs. placebo in 27 men (age, 62+/-9 yr) with symptomatic androgen deficiency (total testosterone, 4.4+/-1.2 nmol/liter; bioavailable testosterone, 2.4+/-1.1 nmol/liter). Compared with placebo, testosterone induced reductions in TNFalpha (-3.1+/-8.3 vs. 1.3+/-5.2 pg/ml; P=0.01) and IL-1beta(-0.14+/-0.32 vs. 0.18+/-0.55 pg/ml; P=0.08) and an increase in IL-10 (0.33+/-1.8 vs. -1.1+/-3.0 pg/ml; P=0.01); the reductions of TNFalpha and IL-1beta were positively correlated (r(S)=0.588; P=0.003). In addition, a significant reduction in total cholesterol was recorded with testosterone therapy (-0.25+/-0.4 vs. -0.004+/-0.4 mmol/liter; P=0.04). In conclusion, testosterone replacement shifts the cytokine balance to a state of reduce inflammation and lowers total cholesterol. Twenty of these men had established coronary disease, and because total cholesterol is a cardiovascular risk factor, and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque, these properties may have particular relevance in men with overt vascular disease.