Influence of estradiol deficiency on the mineralocorticoid receptor response in postmenopausal women: a cross-sectional study

Premenopausal women (PreM) have a cardioprotective advantage over postmenopausal women (PostM) due to estrogen. The interaction of estrogen with the mineralocorticoid receptor (MR) pathway remains unexplored. This study aimed to identify changes in aldosterone, renin and sexual steroid levels and MR surrogate biomarkers in PostM that may explain changes in blood pressure and renal damage. A cross-sectional study was carried out with 47 normotensive and hypertensive Chilean women distributed between PreM and PostM. Clinical, anthropometric and biochemical parameters, including aldosterone, plasma renin activity (PRA) and surrogate markers of MR activity, were assessed. PostM had greater systolic blood pressure (SBP) (<i>p</i> &lt; 0.001) than PreM. A negative correlation was observed between estradiol and fractional excretion of potassium (FEK) (<i>ρ</i> = –0.29; <i>p</i> = 0.023), adjusted for age and SBP. Compared with hypertensive PreM, hypertensive PostM (PostM-HT) showed reduced PRA (<i>p</i> = 0.045) and greater FEK (<i>p</i> = 0.04). Normotensive PostM (Post-NT) exhibited greater SBP (<i>p</i> = 0.03), neutrophil gelatinase-associated lipocalin (NGAL) levels (<i>p</i> = 0.04) and FEK (<i>p</i> = 0.03) than normotensive PreM. Our results suggest enhanced MR sensitivity not only in PostM-HT, as evidenced by lower PRA and elevated FEK, but also in PostM-NT, who exhibited greater FEK and NGAL levels, surrogate markers of MR activation. These results support a novel role of MR activation and cardiovascular risk in PostM women.