Testosterone improves functional performance in elderly men with chronic heart failure

August 2010

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. Caminiti G, Volterrani M, Iellamo F, et al. J Am Coll Cardiol 2009; 54(10): 919-927.


  • Long-acting testosterone treatment (Nebido) for 3 months in frail elderly patients was well tolerated
  • Nebido significantly improved skeletal muscle function, cardiorespiratory parameters and metabolic parameters, including insulin resistance
  • Patients with lower testosterone at baseline achieved the greatest improvements, but eugonadal patients also benefited

This 12-week, double-blind, placebo-controlled, randomised study evaluated the effect of long-acting testosterone treatment in elderly men with stable chronic heart failure (CHF). Seventy patients (median age 70 years) were recruited and randomised 1:1 to receive intramuscular Nebido or intramuscular saline at 6 week intervals. The baseline characteristics of testosterone and placebo groups were well balanced, and approximately one-third of patients in each group had hypogonadism. The study found that 12 weeks of testosterone treatment provided significant improvements from baseline in skeletal muscle function, cardiorespiratory indices and insulin resistance (HOMA-IR) that were not seen in the placebo group (Table). Furthermore, the improvements in VO2 (a measure of physical fitness) and MVC (a measure of skeletal muscle strength) were dose-dependent, i.e. the higher the change in testosterone levels, the greater the improvement. Patients were already on comprehensive therapy for heart failure, and testosterone treatment was well tolerated in these frail patients, many of whom were on multiple concomitant medications.

What is known

Heart failure in the elderly is associated with a high mortality. Studies have shown high rates of hypogonadism in this group, and low testosterone is considered a negative prognostic marker in patients with CHF. Nevertheless, testosterone therapy in these patients is far from routine because of the high burden of disease and concerns about possible adverse events and drug interactions. Small studies have suggested improved functional and cardiac performance in CHF patients but larger studies are needed.

Parameter Change from baseline*
  Testosterone (n=35) Placebo (n=35)
Peak VO2, ml/kg/min 18.9 ± 3.3 3.0 ± 1.1
6 minute walk test, m 86.2 ± 14.5 37.3 ± 8.7
Quadriceps muscle strength
MVC, Nm 18.9 ± 3.3 3.0 ± 1.1
PTmax, Nm 9.6 ± 1.2 2.1 ± 0.5
HOMA-IR -0.8 ± 0.02 0.1 ± 0.006
*Between group differences were significant at p < 0.05
Peak VO2 = maximum capacity of an individual's body to transport and utilize oxygen during incremental exercise, which reflects the physical fitness of the individual
MVC = maximum voluntary contraction
PTmax = isokinetic power torque

What this study adds

This study adds to the weight of evidence that testosterone treatment in patients with CHF is safe and effective. The range of assessments used, including direct measures of functional capacity, indicate that the clinical improvements delivered by testosterone treatment are due to peripheral effects on skeletal muscle and metabolic parameters, rather than on cardiac function. It is noteworthy that these improvements, including HOMA-IR scores, were observed following only 3 months of treatment. Cardiac effects would be expected to take longer and a weakness of the study was its limited duration, meaning that despite improvements in parameters prognostic for CHF, the study was not able to comment on clinical outcome. Nevertheless, the benefits delivered by testosterone treatment were meaningful and occurred early in treatment. Furthermore, the benefit was seen in patients who were on optimal medical therapy for CHF. Patients with lower testosterone at baseline achieved greatest benefits but eugonadal patients also demonstrated significant improvements.

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