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Department of Cardiology, Royal Hallamshire Hospital (C.J.M., P.J.P., K.S.C.), Sheffield, United Kingdom S10 2JF; Academic Unit of Endocrinology, Division of Genomic Medicine, University of Sheffield (R.D.J., D.K., T.H.J.), Sheffield, United Kingdom S10 2RX; and Center for Diabetes and Endocrinology, Barnsley District General Hospital (D.K., T.H.J.), Barnsley, United Kingdom S75 2EP
Address all correspondence and requests for reprints to: Dr. Chris J. Malkin, Cardiology Department, Royal Hallamshire Hospital, Sheffield, United Kingdom S10 2JF. E-mail: chris.malkin{at}sth.nhs.uk.
Testosterone has immune-modulating properties, and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNF
, IL-1ß, 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 TNF (–3.1 ± 8.3 vs. 1.3 ± 5.2 pg/ml; P = 0.01) and IL-1ß (–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 TNF and IL-1ß 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.
This work was supported by the Central Sheffield University Hospitals Pilot Research Fund.
Abbreviations: HDL, High-density lipoprotein; LDL, low-density lipoprotein; PSA, prostate-specific antigen.
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