Association Between Endometriosis and Cardiovascular Disease: Insights From the UK Biobank

BACKGROUND: Endometriosis has been associated with a higher risk of cardiovascular disease (CVD), but the underlying mechanisms remain incompletely understood. METHODS: Using UK Biobank data, we assessed the relationship between endometriosis and CVD (defined as a composite of fatal and non-fatal coronary heart disease, peripheral artery disease, and stroke), cardiovascular mortality, and all-cause mortality, applying Cox regression analysis while adjusting for conventional and emerging, lifestyle and demographic, and female-specific CVD risk factors. Furthermore, we performed subgroup analysis across age and female-specific factors, and mediation analysis to study the role of hysterectomy and oophorectomy. RESULTS: We included 264 740 women without CVD at baseline (median age 57 [25th-75th percentile 50-63] years; 8194 with endometriosis) from the UK Biobank. During 3 484 788 person-years of follow-up, 22 283 women developed CVD. Endometriosis was associated with an 18% higher risk of CVD (hazard ratio 1.18 [95% CI 1.10-1.28]), mainly driven by coronary heart disease (1.24 [1.12-1.37]). Conversely, endometriosis was related to a 12% lower risk of all-cause mortality (0.88 [0.80-0.98]). The association with cardiovascular mortality was not significant (0.85 [0.63-1.13]). Mediation analysis suggested that hysterectomy may partially mediate the association between endometriosis and CVD. Subgroup analyses did not yield significant differences. CONCLUSIONS: Endometriosis is associated with a higher risk of CVD, especially coronary heart disease. Mediation analysis suggests that hysterectomy partly explains this association. Whether hysterectomy may proxy endometriosis severity instead of being a true mediator remains to be elucidated. These findings highlight the need for studies that unravel the causal mechanisms linking endometriosis, its treatments, and cardiovascular outcomes.