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 suggests that testosterone may suppress the expression of the proinflammatory cytokines TNFα, IL-1β, 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 TNFα (−3.1 ± 8.3 vs. 1.3 ± 5.2 pg/ml; P = 0.01) and IL-1β (−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 TNFα and IL-1β were positively correlated (rS = 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 reduced 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.