Endothelial Dysfunction in Sex-Specific Disparities in Cardiovascular Diseases: Biological Mechanisms, Diagnostic-Therapeutic Differences, and Translational Medicine Strategies

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Sex-specific disparities in the pathogenesis and outcomes of cardiovascular diseases (CVDs) highlight critical gaps in current clinical paradigms, particularly regarding endothelial dysfunction as a pivotal mediator of such differences. Males have a higher incidence of atherosclerosis-related CVD, while postmenopausal females experience microvascular dysfunction due to estrogen loss and androgen dominance. Estrogen confers cardioprotective effects via nitric oxide (NO)-mediated vasodilation and antioxidant pathways. In contrast, androgens exert dual pathological effects by promoting inflammation and oxidative stress in a concentration-dependent manner. Clinically, men develop obstructive coronary disease, whereas women present with underdiagnosed microvascular ischemia due to sex-neutral thresholds. Sex-specific risks (e.g., smoking/diabetes in women) and treatment disparities persist in CVDs, meaning sex-stratified diagnostics/therapeutics and trial reforms are needed to advance precision cardiology. Unlike traditional reviews that focus on mechanisms, this study aims to link molecular insights with translational strategies by proposing endothelial-targeted therapies, sex-adjusted diagnostic algorithms, and policy-driven trial reforms. By prioritizing the endothelial-sex hormone crosstalk as the nexus of pathophysiology and clinical translation, this synthesis advances precisi

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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