Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial.
OBJECTIVE
Chronic heart failure 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.


RESULTS
We conducted a randomized, double-blind, placebo-controlled parallel trial of testosterone replacement therapy (5 mg Androderm) at physiological doses in 76 men (mean+/-SD, age 64+/-9.9) with heart failure (ejection fraction 32.5+/-11%) over a maximum follow-up period 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 and bioavailable testosterone correlated with distance walked on the initial ISWT (r=0.3, P=0.01). Exercise capacity significantly improved with testosterone therapy compared with placebo over the full study period (mean change +25+/-15 m) corresponding to a 15+/-11% improvement from baseline (P=0.006 ANOVA). Symptoms improved by at least one functional class on testosterone in 13 (35%) vs. 3 (8%) on placebo (P=0.01). No significant changes were found in handgrip strength, skeletal muscle bulk by cross-sectional computed tomography, or in tumour necrosis factor levels. Testosterone therapy was safe with no excess of adverse events although the patch preparation was not well tolerated by the study patients.


CONCLUSIONS
Testosterone replacement therapy improves functional capacity and symptoms in men with moderately severe heart failure.
Malkin
Chris J
CJ
Department of Cardiology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
Pugh
Peter J
PJ
West
John N
JN
van Beek
Edwin J R
EJ
Jones
T Hugh
TH
Channer
Kevin S
KS
D000328:Adult; D000368:Aged; D000728:Androgens / Q000627:therapeutic use*; D002908:Chronic Disease; D015331:Cohort Studies; D004311:Double-Blind Method; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000627:therapeutic use*; D016896:Treatment Outcome
D000728:Androgens; D013739:Testosterone