Faulkner JL, et al. - Compelling clinical evidence suggests that protective influences of female sex-hormones are superseded by obesity and its related metabolic abnormalities, which also predispose premenopausal women to cardiovascular disease, and the overactivation of the aldosterone-MR (mineralocorticoid receptor) axis has been suggested as a reason for sex-specific cardiovascular risk in obese females. With these things in mind, researchers investigated whether females vs males have a higher endogenous expression of endothelial MR, predisposing them to obesity-related, leptin-mediated endothelial dysfunction. Novel findings indicate that progesterone was identified as a driver of sex-differences in endothelial MR expression and was recognized as the reason for predisposition to leptin-induced endothelial dysfunction in female mice. This implies that the risk of cardiovascular diseases in obese premenopausal women could be attenuated with the use of MR antagonists as a sex-specific therapy.