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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

Giuseppe Caminiti, MD^_*, Maurizio Volterrani, MD^_*, Ferdinando Iellamo, MD^_*,,_*, Giuseppe Marazzi, MD^_*, Rosalba Massaro, MD^_*, Marco Miceli, MD^_*, Caterina Mammi, MD^_*, Massimo Piepoli, MD, Massimo Fini, MD^_* and Giuseppe M.C. Rosano, MD^_*

^_* Centre for Clinical and Basic Research, Cardiovascular Research Unit, Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy
Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy
Department of Cardiology, "Guglielmo da Saliceto" Hospital, Piacenza, Italy

Manuscript received February 10, 2009; revised manuscript received April 8, 2009, accepted April 29, 2009.

^_* Reprint requests and correspondence: Dr. Ferdinando Iellamo, Dipartimento di Medicina Interna, IRCCS San Raffaele Pisana, Università di Roma "Tor Vergata," Via O. Raimondo, 8 00173 Rome, Italy (Email: iellamo{at}med.uniroma2.it).

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 VO₂ significantly 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 VO₂ and 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

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