Abstract Body: Background: Endometriosis has been linked to a higher risk of cardiovascular disease, although the mechanisms are not fully understood. It has been suggested that undergoing a hysterectomy, with or without removal of the ovaries (oophorectomy), may partly explain the relationship between endometriosis and cardiovascular disease.

Methods: We used data from the UK Biobank to examine the association between endometriosis and composite cardiovascular disease, defined as a combination of fatal and non-fatal coronary heart disease and stroke, as well as cardiovascular mortality and overall mortality. Cox regression models were applied, adjusting for conventional and emerging cardiovascular risk factors, lifestyle and demographic risk factors, and female-specific risk factors. In addition, we conducted counterfactual mediation analyses to explore whether hysterectomy with or without oophorectomy contributes to the link between endometriosis and cardiovascular disease.

Results: Our study included 261,581 females with a median age of 57 years, of whom 8,101 had endometriosis. Over a total of 3,440,869 person-years of follow-up, 22,066 females developed cardiovascular disease. Endometriosis was associated with an 18% higher risk of cardiovascular disease (HR 1.18 [95% CI 1.09-1.28, P<0.001]), primarily driven by angina (HR 1.43 [1.23-1.66, P<0.001]). In contrast, endometriosis was linked to a 12% lower risk of all-cause mortality (HR 0.88 [0.79-0.98, P=0.019]). No significant association was found with cardiovascular mortality. Mediation analysis indicated that hysterectomy accounted for 61% (95% CI 27-94%) of the excess cardiovascular risk (indirect HR 1.11 [1.09-1.12, P<0.001]).

Conclusion: Women with endometriosis have an increased risk of cardiovascular disease, particularly angina. The results suggest that hysterectomy, with or without oophorectomy, may partially explain this association. These findings underscore the importance of monitoring cardiovascular risk in women with endometriosis and evaluating the long-term effects of treatment options.