The Effect of Testosterone Replacement on Endogenous Inflammatory Cytokines and Lipid Profiles in Hypogonadal Men

TLDR

Testosterone modulates immunity by suppressing pro‑inflammatory cytokines TNFα, IL‑1β, IL‑6 and enhancing anti‑inflammatory IL‑10 in vitro. The study randomized 27 symptomatic hypogonadal men to receive Sustanon 100 or placebo in a single‑blind crossover design. Testosterone replacement lowered TNFα and IL‑1β, raised IL‑10, and reduced total cholesterol, indicating a shift toward reduced inflammation that may benefit men with cardiovascular disease.

Abstract

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.