Circulating testosterone and estradiol, autonomic balance and baroreflex sensitivity in middle-aged and elderly men with heart failure

Background: Heart failure (HF) is considered as a cardiogeriatric syndrome. Its fundamental pathophysiological feature is autonomic imbalance (and associated abnormalities within cardiovascular reflex control), but recent evidence suggests the involvement of deranged hormone metabolism. Both these neural and endocrine pathologies have serious clinical and prognostic consequences in patients with HF. We investigated the relations between autonomic status, baroreflex sensitivity (BRS) and hormone status in men with mild systolic HF. Methods: We examined 46 men with stable systolic HF (age: 62 +/- 10 years, NYHA class I/II: 10/36 [22%/78%], ischemic aetiology: 72%, left ventricular ejection fraction: 32 +/- 8%). Serum hormone levels (i.e. total testosterone [TT], dehydroepiandrosterone sulphate [DHEAS], oestradiol [E2], insulin-like growth factor type 1 [IGF-1] and cortisol) were assessed using immunoassays. Estimated free testosterone (eFT) was estimated using the Vermeulen's equation. Heart rate variability (HRV) was assessed in time and frequency domains, based on 10-min resting recordings. BRS was estimated using the sequence method (BRS-Seq) and the phenylephrine test (BRS-Phe). Results: Deficiencies in circulating TT, eFT, DHEAS and IGF-1 (defined as a serum hormone <= the 10th percentile calculated for the adequate age category in the cohort of healthy men) were found in respectively 13%, 30%, 55% and 93% of men with systolic HF. Serum SHBG >= 50 nmol/L and cortisol >= 700 nmol/L characterised, respectively 44% and 29% of men with HF. In multivariable models after the adjustment for clinical variables, the following relationships were found in examined men: DHEAS and SDNN (time domain of HRV defined as a standard deviation of average R-R intervals) (beta = 0.29, p = 0.03); E2 and: HRV-LF (ms(2)) (beta = 0.37, p = 0.01), HRV-HF (ms(2)) (beta = 0.44, p = 0.02) and BRS-Phe (beta = 0.51, p = 0.008); TT and: HRV-HF (%) (beta = 0.35, p = 0.02), HRV-LF/HF ratio (beta = -0.35, p = 0.02) and BRS-Seq (beta = 0.33, p = 0.04). Conclusions: The observed associations between reduced circulating androgens, oestrogens and lower HRV and depleted BRS, irrespectively of HF severity suggest the pathophysiological links between these two mechanisms. These results constitute the premises to investigate whether the pharmacological supplementation of depleted hormones would enable to restore the autonomic balance and improve the efficacy of reflex control within the cardiovascular system in men with systolic HF.