Testosterone Improves Function with Heart Failure
Chronic heart failure (CHF) is a disease increasingly recognized as a health burden worldwide. An improvement in survival rate has been reported in CHF in the last decade (1), which should be ascribed mainly to therapeutic strategies targeted to the pathophysiological mechanisms sustaining the progression and worsening of the disease, mainly the prolonged neurohumoral activation. CHF is also characterized by, in addition to neurohumoral activation, a metabolic shift favoring catabolism and impairment in skeletal muscle bulk and function; the latter is involved not only in symptoms development but even in the pathophysiology of the heart failure (HF) syndrome (2).
In men, androgens are important determinants of anabolic function and muscle strength. Low plasma levels of testosterone have been reported in patients with CHF (3–5), and it has been hypothesized that a relative hypotestosteronemia could be involved in the impairment of skeletal muscle function and exercise tolerance that occur in the HF syndrome (6). Indeed, anabolic hormone depletion has been reported to be relatively common in CHF and to carry a negative prognosis (7). Hence, improving the anabolic status of patients with CHF could represent an additional therapeutic target acting on a pathophysiological mechanism that sustains the progression of the disease, possibly affecting survival (7).
In the last few years, some reports have suggested the effectiveness of testosterone supplementation in improving the hemodynamic status and New York Heart Association (NYHA) functional class of patients with CHF (6,8–10). These studies would seem promising as to the benefits of testosterone supplementation in patients with CHF; however, they were limited by the indirect assessment of individual functional capacity and by the evaluation of muscle performance of small muscle masses (e.g., forearm muscles). Until now, there were no data on the effect of testosterone replacement on standard measures of functional capacity in patients with CHF that carry important prognostic implication, such as oxygen consumption (VO2) and ventilatory efficiency (11,12). In addition, the performance (e.g., the strength) of larger weight-bearing muscle masses might be more relevant to the effort intolerance of CHF syndrome and to the effect of anabolic drug supplementation.
Accordingly, the aim of this study was to assess the effects of a long-acting testosterone treatment, given on top of optimal medical therapy, on functional capacity and ventilatory efficiency in elderly male patients with moderate-to-severe HF. We also addressed the effect of testosterone on quadriceps muscle performance to test the hypothesis that testosterone supplementation could improve functional capacity and ventilatory efficiency through an improvement of muscle performance. Finally, the effect of testosterone supplementation on vagally mediated arterial baroreceptor cardiac reflex sensitivity (BRS) was also addressed, because animal studies have consistently shown that testosterone administration improves BRS (13–15), a major negative prognostic indicator in CHF (16).