Physiological Mechanisms and Intervention Strategies for the Increased Cardiovascular Risk in Perimenopausal Women
DOI:
https://doi.org/10.62051/ijsspa.v10n1.09Keywords:
Perimenopause, Estrogen, Cardiovascular Disease, Endothelial Dysfunction, Arterial Stiffness, Hormone Replacement Therapy, Timing HypothesisAbstract
Cardiovascular disease (CVD) is the leading cause of female mortality worldwide, and risk rises sharply during the perimenopausal transition as circulating estrogen declines. This review synthesizes macro-to-micro physiological mechanisms linking estrogen loss to vascular and cardiac dysfunction, including adverse shifts in blood pressure and lipid profiles, increased arterial stiffness, endothelial nitric oxide (NO) impairment, heightened oxidative stress with mitochondrial dysfunction, pro-fibrotic remodeling, and reduced angiogenic repair capacity. We further discuss how differential signaling through ERα, ERβ, and G protein–coupled estrogen receptor (GPER) contributes to heterogeneous cardioprotective effects across individuals and clinical phenotypes. Current intervention strategies are evaluated, emphasizing additive benefits of lifestyle modification and guideline-directed pharmacotherapies (e.g., statins and antihypertensives) for risk reduction. Hormone replacement therapy (HRT) remains controversial; evidence supports a timing-dependent “critical window” in which early initiation near menopause may confer vascular benefit, whereas late initiation offers limited protection and may increase thrombotic or cerebrovascular risk depending on formulation and route. Finally, we highlight emerging biomedical engineering approaches-particularly AI-enabled risk stratification using electronic health records, wearable data, and imaging biomarkers-as promising tools to enable earlier detection and personalized prevention for perimenopausal women.
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