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

Abstract

Testosterone has immune-modulating properties, and current in vitro evidence suggests 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 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.

Relationship between insulin and hypogonadism in men with metabolic syndrome

“…We have not found a significant difference in HDLcholesterol levels nor in total cholesterol levels in either group of patients. These results might be interpreted based on the previous observations that testosterone supplementation can decrease total cholesterol levels without affecting HDL-cholesterol levels (53,55).…”

“…Testosterone supplementation was able to reduce abdominal circumference and waist-hip ratio, and to improve insulin sensitivity and glycemic control in men with hypogonadism and type 2 diabetes mellitus (6,8,53,54). Testosterone replacement was also able to decrease the levels of pro-inflammatory cytokines (TNF-alpha, IL-1 and IL-6) produced by visceral adipocytes and associated with insulin resistance (27,55). Although the impact of these findings on an individual's cardiovascular risk have not been systematically investigated, concomitant improvements in glycemic control, insulin resistance, lipid profile and visceral adiposity probably represent an overall reduction in cardiovascular risk.…”

Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

“…T is essential for the development of the male reproductive system and the maintenance of male reproductive functions (1,2). In addition to defects in reproductive system, its deficiency in the adult contributes to other symptoms that include increased body fat, decreased muscle mass, increased fatigue, depressed mood, decreased cognitive function (3,4), and reduced immune response (5,6). In aged men, low T has been reported to contribute to mortality (7).…”

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

“…Aging is itself associated with declining testosterone levels and a high incidence of primary/compensated hypogonadism (7)(8)(9). Because low testosterone levels are also associated with generalized proinflammatory changes (10,11), frailty, and risk of dying in aging men (12), what determines an adult man's testosterone level is of fundamental importance.…”