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 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.
Malkin
Chris J
CJ
Cardiology Department, Royal Hallamshire Hospital, Sheffield, United Kingdom S10 2JF. chris.malkin@sth.nhs.uk
Pugh
Peter J
PJ
Jones
Richard D
RD
Kapoor
Dheeraj
D
Channer
Kevin S
KS
Jones
T Hugh
TH
D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood*; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000097:blood*; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D013739:Testosterone / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008078:Cholesterol, LDL; D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013739:Testosterone; D002784:Cholesterol