Stroke risk in women with or without hysterectomy and/or bilateral oophorectomy: evidence from the NHANES 1999-2018 and meta-analysis

Objective: We aimed to assess the relationship between hysterectomy and/or bilateral oophorectomy and the risk of stroke—a topic of ongoing debate in current research. Methods: We utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 to estimate both crude and multivariable-adjusted hazard ratios (HRs) and 95% CIs, applying survey-weighted Cox proportional hazards regression model. The modeling incorporated sampling weights and design variables to address NHANES’s multistage probability sampling framework. In addition, a meta-analysis was conducted, incorporating findings from NHANES with those from other cohort studies identified through database search. Results: This unweighted NHANES cohort included 21,240 women with 8.3 median follow-up years, documenting 193 stroke-related deaths. Compared with no hysterectomy, hysterectomy was not significantly associated with stroke mortality (HR: 1.28, 95% CI: 0.89-1.85). However, a meta-analysis of 2,065,490 participants from NHANES and 15 other studies demonstrated hysterectomy was linked to a 9% higher stroke risk (HR: 1.09, 95% CI: 1.04-1.15) compared with no hysterectomy. Similar finding was identified for bilateral oophorectomy (HR: 1.13, 95% CI: 1.09-1.17) compared with no bilateral oophorectomy. Subgroup analyses stratified by surgical indication, ovarian conservation status, and reference population consistently demonstrated elevated risks. Conclusions: In summary, the data from NHANES and other studies indicate women with hysterectomy and/or bilateral oophorectomy may be associated with an increased stroke risk. Additional prospective studies are needed to confirm the association between hysterectomy and/or bilateral oophorectomy and stroke risk.