Background: We investigated whether anabolic deficiency was linked to exercise intolerance in men with chronic heart failure (CHF). Anabolic hormones (testosterone, dehydroepiandrosterone sulfate, insulin-like growth factor 1 [IGF1]) contribute to exercise capacity in healthy men. This issue remains unclear in CHF.
Methods and results: We studied 205 men with CHF (age 60 +/- 11 years, New York Heart Association [NYHA] Class I/II/III/IV: 37/95/65/8; LVEF [left ventricular ejection fraction]: 31 +/- 8%). Exercise capacity was expressed as peak oxygen consumption (peak VO(2)), peak O(2) pulse, and ventilatory response to exercise (VE-VCO(2) slope). In multivariable models, reduced peak VO(2) (and reduced peak O(2) pulse) was associated with diminished serum total testosterone (TT) (P < .01) and free testosterone (eFT; estimated from TT and sex hormone globulin levels) (P < .01), which was independent of NYHA Class, plasma N-terminal pro-brain natriuretic peptide, and age. These associations remained significant even after adjustment for an amount of leg lean tissue. In multivariable models, high VE-VCO(2) slope was related to reduced serum IGF1 (P < .05), advanced NYHA Class (P < .05), increased plasma NT-proBNP (P < .0001), and borderline low LVEF (P = .07). In 44 men, reassessed after 2.3 +/- 0.4 years, a reduction in peak VO(2) (and peak O(2) pulse) was accompanied by a decrease in TT (P < .01) and eFT (P <or= .01). Increase in VE-VCO(2) slope was related only to an increase in plasma NT-proBNP (P < .05).
Conclusions: In men with CHF, low circulating testosterone independently relates to exercise intolerance. The greater the reduction of serum TT in the course of disease, the more severe the progression of exercise intolerance. Whether testosterone supplementation would improve exercise capacity in hypogonadal men with CHF requires further studies.