Estrogen Deficiency-Induced Lipid Dysregulation in Menopause: Mechanisms, Metabolic Consequences, and Therapeutic Strategies.

Abstract

Menopause is a universal physiological transition marked by the permanent cessation of ovarian estrogen secretion, with far-reaching consequences for cardiometabolic health. Among these consequences, lipid dysregulation stands as one of the most clinically significant, substantially elevating the risk of cardiovascular disease and metabolic syndrome in postmenopausal women. Estrogen deficiency disrupts hepatic lipid metabolism, alters lipoprotein particle composition, promotes visceral adiposity, and triggers a chronic low-grade inflammatory state, collectively establishing an atherogenic lipid profile. Although the broad association between menopause and dyslipidemia has long been recognized, the precise cellular and molecular mechanisms underlying this relationship remain incompletely characterized. This review synthesizes current evidence on the pathophysiological mechanisms linking estrogen deficiency to lipid dysregulation in menopause, encompassing alterations in LDL and HDL metabolism, triglyceride accumulation, changes in lipoprotein lipase (LPL) activity, hepatic lipid accumulation, and the roles of estrogen receptor signaling in adipose tissue and liver. Current and emerging therapeutic strategies are also discussed, including hormone replacement therapy (HRT), lifestyle modifications, lipid-lowering pharmacotherapy, and novel molecular targets. Advancing the mechanistic understanding of these processes is essential to developing precision therapeutic approaches that effectively address the heightened cardiometabolic risk in postmenopausal women.