Uncovering cardiovascular risk in women with endometriosis

Abstract Background Endometriosis has been associated with increased cardiovascular risk, but the characteristics of women who develop myocardial infarction (MI) or ischemic stroke and the impact of treatment strategies remain poorly described. Purpose To describe baseline characteristics in a contemporary cohort of women with endometriosis and to examine associations between endometriosis treatments and subsequent MI or ischemic stroke. Methods In this Danish nationwide register-based cohort study, we identified all women diagnosed with endometriosis between 1 Jan 2000 and 31 Jan 2024. Women were followed from diagnosis until MI or ischemic stroke, emigration, or end of study. Surgical treatments included hysterectomy and oophorectomy, whereas medical treatments included NSAIDs, combined oral contraceptives (COCs), estrogen therapy, progestins, intrauterine devices (IUDs), and GnRH analogues. Multivariable logistic regression was used to estimate odds ratios (ORs) for MI or ischemic stroke according to treatment initiation and post-diagnosis hysterectomy or oophorectomy, with adjustment for age, educational level, prior MI or ischemic stroke, prior hysterectomy/oophorectomy, and cardiovascular comorbidities. Results Among 38,418 women with incident endometriosis, 735 developed MI or ischemic stroke during follow-up, at a median age of 55.3 years (IQR 47.7–66.5). Women developing MI or ischemic stroke were older at the time of endometriosis diagnosis compared with those without events (45.9 years, IQR 38.9–54.0 vs 35.9 years, IQR 28.9–43.6; p<0.0001) and had lower educational attainment. Moreover, cardiometabolic comorbidity was strikingly more prevalent: prior MI (3.5% vs 0.2%), prior ischemic stroke (5.3% vs 0.5%), diabetes (8.6% vs 1.7%), peripheral vascular disease (1.5% vs 0.2%), heart failure (3.0% vs 0.4%), and hypertension (25.0% vs 5.4%). Initiation of medical treatments, particularly contraceptives, was less frequent (e.g., COCs 22.2% vs 41.9%), whereas post-diagnosis hysterectomy and oophorectomy were more frequent (18.0% vs 5.0%, and 15.2% vs 5.8%, respectively). In adjusted analyses, hysterectomy (OR 2.35, 95% CI 1.90–2.90), oophorectomy (OR 1.69, 95% CI 1.35–2.12), initiation of COCs (OR 1.25, 95% CI 1.01–1.54), and NSAID use (OR 1.22, 95% CI 1.00–1.50) were associated with higher odds of MI or ischemic stroke (Figure 1). Conversely, treatments with IUDs (OR 0.59, 95% CI 0.45-0.78) or progestins (OR 0.46, 95% CI 0.34–0.62) were associated with lower odds. Conclusion In this nationwide cohort, women with endometriosis who developed MI or ischemic stroke had a greater cardiometabolic burden, used contraceptives less frequently, and more often underwent surgical treatment. Treatment-specific differences in cardiovascular risk were observed. These findings support cardiovascular risk assessment in women with endometriosis, particularly those presenting with cardiometabolic comorbidity or requiring surgical treatment.