Endocrine Abstracts

Chronic heart failure (CHF) is associated with maladaptive and prolonged neurohormonal and pro-inflammatory cytokine activation causing a metabolic shift favouring catabolism, vasodilator incapacity, and loss of skeletal muscle bulk and function. In men, androgens are important determinants of anabolic function and physical strength and also possess anti-inflammatory and vasodilatory properties. We conducted a randomised, double blind, placebo controlled trial of testosterone therapy (5mg Androderm) at physiological doses in 76 men (mean age 64years) with CHF (mean plus/minus SEM ejection fraction, 32.5plus/minus1.3%) over a maximum follow-up of 12 months. The primary endpoint was functional capacity as assessed by the incremental shuttle walk test (ISWT). At baseline, 18(24%) had serum testosterone below the normal range (total <7.5nmol/L and/or bioavailable <2.5nmol/L) and bioavailable testosterone level correlated with distance walked in metres (m) in the initial ISWT (r=0.3, p=0.01). Exercise capacity significantly improved with testosterone therapy compared with placebo (mean treatment effect and [95% confidence] at 6 months was 38m [11.6m to 64m, p=0.006]) corresponding to an 18% [4 to 31%, p=0.01] improvement from baseline. The increase in exercise capacity in the treatment group (19.2plus/minus8.3 metres) was positively correlated with the rise in serum bioavailable testosterone level (2.02plus/minus0.9nmol/L), (rS = 0.36, p=0.02). Symptoms improved by at least one New York Heart Association functional class on testosterone in 13(35%) vs 3(8%) on placebo, p=0.01). No changes were found in handgrip strength, skeletal muscle bulk by cross-sectional computed tomography or in cytokine activation. Testosterone therapy was safe with no excess of serious adverse events. The correction of the metabolic maladaptations of CHF by drug therapies has proven efficacy. Many patients with heart failure very low levels of serum testosterone and most have borderline androgen deficiency. Testosterone replacement therapy improves functional capacity and symptoms in men with moderate to severe CHF.