We thank Pascual-Figal et al for their insightful comments on our article, 1 in which we have demonstrated that multiple anabolic deficiency is common in men with stable systolic chronic heart failure (CHF) and adversely relates to long-term survival.Spironolactone interacts with androgen steroid synthesis and metabolism; it is not clear whether a reduction in serum levels of sex steroids in men is a consequence of spironolactone therapy. 2 Of 208 CHF men in our study, 53 (25.5%) were treated with spironolactone at baseline (25 mg per 24 h). According to European Society of Cardiology guidelines, low-dose spironolactone therapy should be restricted to patients with severe CHF. The men treated with spironolactone had more advanced CHF, as evidenced by higher New York Heart Association class (PϽ0.0001), lower left ventricular ejection fraction (PϽ0.0001), and higher plasma N-terminal-pro-brain natriuretic peptide levels (PϽ0.01). They also demonstrated reduced serum levels of total testosterone (PϽ0.01) and dehydroepiandrosterone sulfate (PϽ0.0001), and similar levels of insulin-like growth factor type 1 (PϾ0.2).To assess the impact of spironolactone therapy on relationships between anabolic deficiency and survival, we undertook multivariate analyses (see Table 4 of our original article), 1 further adjusting for spironolactone therapy at the beginning of follow-up. Serum levels of all anabolic hormones (all PϽ0.05) and, similarly, a number of anabolic deficiencies (PϽ0.001) were independently related to prognosis in men with CHF, irrespective of spironolactone treatment.In our study, the use of spironolactone was associated with worse symptoms and cardiac function, both important prognosticators; it also was associated with lower serum total testosterone and dehydroepiandrosterone sulfate. In clinical trials, spironolactone improves survival in patients with advanced heart failure; this is the opposite of what would be expected if one considered only the results of association studies. We cannot know from our study whether there is a cause-and-effect relationship between spironolactone treatment and anabolic deficiency. Prospective studies comparing effects of spironolactone or eplerenone versus placebo are needed to establish these relationships. But, we can conclude that spironolactone does not impact the strong relationship between multiple anabolic deficiency and survival in men with CHF.Patients with CHF often suffer from muscle wasting and cachexia. 3 Improving anabolic status in these patients may translate into improvements of exercise capacity, quality of life, and, possibly, survival. This approach may need to be accompanied by nutritional and/or antiinflammatory interventions. 4 We need to start prospective intervention trials, and the best option would be to focus on patients with anabolic deficiency. DisclosuresNone. Ewa

Background-The age-related decline of circulating anabolic hormones in men is associated with increased morbidity and mortality. We studied the prevalence and prognostic consequences of deficiencies in circulating total testosterone (TT) and free testosterone, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor-1 (IGF-1) in men with chronic heart failure (CHF). Methods and Results-Serum levels of TT, DHEAS, and IGF-1 were measured with immunoassays in 208 men with CHF (median age 63 years; median left ventricular ejection fraction 33%; New York Heart Association class I/II/III/IV, 19/102/70/17) and in 366 healthy men. Serum levels of free testosterone were estimated (eFT) from levels of TT and sex hormone binding globulin. Deficiencies in DHEAS, TT, eFT, and IGF-1, defined as serum levels at or below the 10th percentile of healthy peers, were seen across all age categories in men with CHF. DHEAS, TT, and eFT were inversely related to New York Heart Association class irrespective of cause (all PϽ0.01). DHEAS correlated positively with left ventricular ejection fraction and inversely with N-terminal pro-brain natriuretic peptide (both PϽ0.01). Circulating TT, eFT, DHEAS, and IGF-1 levels were prognostic markers in multivariable models when adjusted for established prognostic factors (all PϽ0.05). Men with CHF and normal levels of all anabolic hormones had the best 3-year survival rate (83%, 95% CI 67% to 98%) compared with those with deficiencies in 1 (74% survival rate, 95% CI 65% to 84%), 2 (55% survival rate, 95% CI 45% to 66%), or all 3 (27% survival rate, 95% CI 5% to 49%) anabolic endocrine axes (PϽ0.0001). Conclusions-In male CHF patients, anabolic hormone depletion is common, and a deficiency of each anabolic hormone is an independent marker of poor prognosis. Deficiency of Ͼ1 anabolic hormone identifies groups with a higher mortality.

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