Clinical Research
Heart Failure
Effect of Long-Acting Testosterone Treatment on Functional Exercise Capacity, Skeletal Muscle Performance, Insulin Resistance, and Baroreflex Sensitivity in Elderly Patients With Chronic Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Study

https://doi.org/10.1016/j.jacc.2009.04.078Get rights and content
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Objectives

This study investigated the effect of a 12-week long-acting testosterone administration on maximal exercise capacity, ventilatory efficiency, muscle strength, insulin resistance, and baroreflex sensitivity (BRS) in elderly patients with chronic heart failure (CHF).

Background

CHF is characterized by a metabolic shift favoring catabolism and impairment in skeletal muscle bulk and function that could be involved in the pathophysiology of heart failure.

Methods

Seventy elderly patients with stable CHF—median age 70 years, ejection fraction 31.8 ± 7%—were randomly assigned to receive testosterone (n = 35, intramuscular injection every 6 weeks) or placebo (n = 35), both on top of optimal medical therapy. At baseline and at the end of the study, all patients underwent echocardiogram, cardiopulmonary exercise test, 6-min walk test (6MWT), quadriceps maximal voluntary contraction (MVC), and isokinetic strength (peak torque) and BRS assessment (sequences technique).

Results

Baseline peak oxygen consumption (VO2) and quadriceps isometric strength showed a direct relation with serum testosterone concentration. Peak VO2significantly improved in testosterone but was unchanged in placebo. Insulin sensitivity was significantly improved in testosterone. The MVC and peak torque significantly increased in testosterone but not in placebo. The BRS significantly improved in testosterone but not in placebo. Increase in testosterone levels was significantly related to improvement in peak VO2and MVC. There were no significant changes in left ventricular function either in testosterone or placebo.

Conclusions

These results suggest that long-acting testosterone therapy improves exercise capacity, muscle strength, glucose metabolism, and BRS in men with moderately severe CHF. Testosterone benefits seem to be mediated by metabolic and peripheral effects.

Key Words

baroreflex sensitivity
congestive heart failure
exercise capacity
glucose metabolism
testosterone

Abbreviations and Acronyms

6MWT
6-min walk test
BP
blood pressure
BRS
baroreflex sensitivity
CHF
chronic heart failure
HF
heart failure
HOMA-IR
homeostasis model assessment
IM
intramuscular
LVEF
left ventricular ejection fraction
MVC
maximal voluntary contraction
NYHA
New York Heart Association
PSA
prostate-specific antigen
PT
peak torque
VE/VCO2
ventilation/carbon dioxide output
VO2
oxygen consumption

Cited by (0)

This study was supported by the Italian Ministry of Health, as a part of Finalized Research 2005 Grant. This study was also supported, in part, by Agenzia Spaziale Italiana, Grant ASI I/006/06/0 to Dr. Iellamo.