Effect of Exercise Training and Testosterone Replacement on Skeletal Muscle Wasting in Patients With Heart Failure With Testosterone Deficiency

Abstract

Objective: To examine whether combined testosterone replacement and exercise training (ET) therapies would potentiate the beneficial effects of isolated therapies on neurovascular control and muscle wasting in patients with heart failure (HF) with testosterone deficiency.

Patients and methods: From January 10, 2010, through July 25, 2013, 39 male patients with HF, New York Heart Association functional class III, total testosterone level less than 249 ng/dL (to convert to nmol/L, multiply by .03467), and free testosterone level less than 131 pmol/L were randomized to training (4-month cycloergometer training), testosterone (intramuscular injection of testosterone undecylate for 4 months), and training + testosterone groups. Muscle sympathetic nerve activity was measured using microneurography, forearm blood flow using plethysmography, body composition using dual X-ray absorptiometry, and functional capacity using cardiopulmonary test. Skeletal muscle biopsy was performed in the vastus lateralis.

Results: Muscle sympathetic nerve activity decreased in ET groups (training, P<.01; training + testosterone, P<.01), whereas no changes were observed in the testosterone group (P=.89). Forearm blood flow was similar in all groups. Lean mass increased in ET groups (training, P<.01; training + testosterone, P<.01), whereas lean mass decreased in the testosterone group (P<.01). The response of cross-sectional area of type I (P<.01) and type II (P<.05) fibers increased in the training + testosterone group as compared with the isolated testosterone group.

Conclusion: Our findings provide evidence for a superior effect of combined ET and testosterone replacement therapies on muscle sympathetic nerve activity, muscle wasting, and functional capacity in patients with HF with testosterone deficiency.