Testosterone Supplementation Benefits Men with Heart Failure

Dr. Giuseppe Caminiti of the Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana in Rome, reported that long-acting testosterone injections improved exercise capacity and insulin sensitivity in elderly men with heart failure.

“The increase in functional capacity and muscle strength is related to the increase in plasma levels of testosterone and not related to changes in left ventricular function,” noted the authors.  

Dr. Pål Aukrust of Oslo University Hospital, wrote in an accompanying editorial that, “Testosterone deficiency, decreased insulin sensitivity, and impaired muscle performance might represent a pathogenic loop” in the progression of heart failure as a syndrome which involves not only the heart and circulation but also encompasses “other organs and organ systems such as the skeletal muscle, the lungs, and the brain.”

The study randomized 70 elderly patients, median age 70 years, with stable chronic heart failure (CHF) to either long-acting testosterone undecanoate (1000 mg), or placebo intramuscular injections given at baseline, 6, and 12 weeks, in addition to optimal medical therapy.

Echocardiographic examination, muscle strength assessment, and cardiopulmonary exercise testing, as well as a 6-minute walk test (6MWT) were performed at the same three time points. Blood samples were taken at these time points to measure testosterone and insulin, among other parameters. Baroreceptor cardiac reflex sensitivity (BRS) was assessed at the start and end of the study.

At baseline, 21 patients in the testosterone group and 9 in the placebo group had total and free testosterone levels below the normal range — a phenomenon that has been well documented in CHF patients. Baseline testosterone levels correlated with peak oxygen consumption (VO₂), distance reached in the 6MWT, and isometric strength.

As expected, testosterone levels normalized in the treatment group but not the placebo group, and improved testosterone levels correlated with improved VO₂ and quadriceps maximal voluntary contraction. Insulin resistance, as estimated by the homeostasis model assessment, was significantly reduced in the treated group, from 2.6 to 1.8, but not in the placebo group (from 2.5 to 2.6). BRS improved with treatment but not with placebo. There were no significant changes in left ventricular function in either group.

The authors suggested that testosterone’s ability to improve such extra-cardiac problems of muscle performance and glucose metabolism might not only improve the symptoms but possibly the pathophysiology and worsening of heart failure syndrome.

Am. Coll. Cardiol. 2009 August 24 [doi:10.1016/j.jacc.2009.04.078]