The Mechanism: Estrogen-Dependent Regulation of LDL Clearance The elevation of serum Low-Density Lipoprotein (LDL) cholesterol during the menopausal transition is primarily driven by the withdrawal of estradiol, which plays a critical role in hepatic lipid metabolism through two primary molecular pathways: 1. Transcriptional Upregulation of LDLR In a premenopausal state, estrogen binds to hepatic estrogen receptors (primarily ER-alpha). This complex acts as a transcription fa