Endometriosis-Associated Cardiovascular Remodeling: Mechanistic Insights and the Modulatory Role of Flavonoids

Background Endometriosis is a systemic gynecological disorder that affects approximately 10% of women of reproductive age and shares certain pathophysiological features with cardiovascular disease (CVD). Despite this, the connections between endometriosis and alterations in cardiac structure, as well as its relationship with cardiovascular disease, remain inadequately characterized, with underlying mechanisms and potential interventions yet to be clearly defined. Methods We analyzed data from the UK Biobank, including 6,158 women with and 229,453 women without endometriosis, and validated our findings in a hospital-based cohort comprising 612 women with laparoscopically confirmed endometriosis and 612 matched controls. Multivariable-adjusted Cox proportional hazards models were employed to estimate the associations between endometriosis and the incidence of cardiovascular disease. Generalized linear models assessed links with cardiac magnetic resonance (CMR) metrics. Mediation analyses evaluated metabolic, inflammatory, hormonal, and oxidative stress pathways. Finally, we assessed whether flavonoid intake modified these associations. Results Over a median 13-year follow-up, 23,239 CVD events occurred. Endometriosis was found to be associated with an 18% increased risk of composite CVD and a 25% increased risk of coronary heart disease. These findings were validated in an external hospital-based cohort, where similar associations with composite CVD and coronary heart disease were observed. Cardiac magnetic resonance imaging revealed subtle yet significant structural and functional cardiac alterations, including increased interventricular septal thickness and regional wall motion abnormalities, with trends indicating greater left ventricular wall thickness and systolic longitudinal wall thickening. Biomarkers indicative of metabolic, inflammatory, and oxidative stress pathways collectively mediated the association between endometriosis and CVD. Notably, high dietary intakes of specific flavonoid subclasses, particularly flavones and flavanones, were observed to attenuate this association. Conclusions Endometriosis is linked to increased CVD risk and early cardiac remodeling, partly via metabolic, inflammatory, and oxidative stress pathways. Increased flavone and flavanone intake may help reduce cardiovascular risk, highlighting potential dietary interventions.