Objectives: Pro-inflammatory cytokine levels are elevated in heart failure and have been implicated in disease progression. Testosterone has been shown to have anti-inflammatory properties and plasma levels may be reduced in men with heart failure. We studied the relation of endogenous testosterone with plasma cytokines in men with chronic heart failure and the effects of testosterone administration.
Methods: Baseline plasma levels of total and bio-available testosterone, tumour necrosis factor-alpha (TNF), interleukin- (Il-) 1beta and Il-6 were measured between 0800 and 0900 in 30 men with stable chronic heart failure. In addition, the ex-vivo production of cytokines by whole blood in response to lipopolysaccharide (LPS) (1mcg/ml) was measured following 3 hours co-incubation. Twenty subjects were subsequently randomised to receive testosterone (Sustanon100) or normal saline (1ml) by fortnightly intramuscular injection in a 3 month double-blind study.
Results: Mean total testosterone level was 12.7 ± 7.1nmol/L, bio-available testosterone was 4.9 ± 2.6nmol/L; left ventricular ejection fraction was 32.5 ± 9.1%. There was an inverse correlation between plasma levels of bio-available testosterone and cytokines, although this only reached statistical significance with Il-1beta (r=-0.43, p=0.027 for Il-1beta; r=-0.33, p=0.12 for TNF; r=-0.23, p=0.13 for Il-6). An inverse relationship between total testosterone and plasma TNF approached significance (r=-0.36, p=0.09). Lower testosterone levels were also associated with higher ex-vivo production of Il-1beta in response to LPS (r=-0.38, p=0.05). Subjects with total testosterone <10nmol/L or bio-available testosterone <2.5nmol\/L had higher plasma levels of TNF (2.22 ± 0.89pg/ml v 1.44 ± 0.59pg/ml, p=0.03). Plasma levels of cytokines were not significantly altered by testosterone or placebo administration.
Conclusion: We found an inverse relationship between endogenous testosterone and pro-inflammatory cytokines in men with chronic heart failure. Exogenous testosterone administration does not appear to influence cytokine levels.
08 - 11 Apr 2002
British Endocrine Societies