The double-edged sword effect of estrogen in kidney disease and its precision modulation.

Estrogen, a critical sex hormone, exerts a complex dual role in renal physiology and pathology. While it confers protective effects through anti-inflammatory, anti-fibrotic, and hemodynamic-related signaling pathways-slowing chronic kidney disease (CKD) progression and improving renal function-it may also promote disease under specific pathological contexts. Sexual dimorphism, mediated primarily by estrogen receptor (ER) signaling networks, plays a pivotal role in this duality. This review focuses on the molecular mechanisms of estrogen in kidney disease, the influence of sexual dimorphism, and the double-edged nature of its effects, with an emphasis on precision modulation strategies. By integrating recent basic and clinical findings, we analyze the diverse roles of estrogen across kidney disease models and evaluate its therapeutic potential. Furthermore, we discuss the prospects of applying sex-based precision medicine to kidney disease management, aiming to provide theoretical foundations and guidance for future research and clinical practice.