Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications

Abstract Men and women exhibit well-established differences in electrolyte regulation, susceptibility to hypertension, kidney disease prevalence, and response to therapies for cardiovascular and renal disorders. Among these, plasma potassium regulation emerges as a key area of sex-specific divergence. Clinical and experimental studies consistently show that women are more susceptible to hypokalemia, while men are more prone to hyperkalemia, a pattern most evident during physiological or pathological stressors such as specific dietary patterns, exercise, medication use, and diseases like chronic kidney disease or cardiorenal syndrome. In this review, we synthesize current evidence from both human and animal studies on sex differences in potassium homeostasis and discuss their clinical implications. We also explore the physiological and molecular mechanisms underlying these differences, and highlight critical knowledge gaps. Advancing our understanding of these biological differences and their underlying mechanisms is essential to move beyond one-size-fits-all nutritional recommendations and disease management strategies. Graphical Abstract