Cardiovascular outcomes after hysterectomy: a systematic review and meta-analysis

Background Hysterectomy is a common nonobstetric surgical procedure performed in women. However, the cardiovascular effects of hysterectomy remain unclear. This meta-analysis compared cardiovascular outcomes in women with and without a history of hysterectomy.

A comprehensive search of four databases was conducted from inception to March 25, 2025. Studies were included if they reported cardiovascular outcomes in women with versus without hysterectomy.

A total of 28 studies involving 2,942,404 participants were included in this meta-analysis. Cardiovascular disease occurred more frequently among women undergoing hysterectomy than among those without hysterectomy (pooled hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.09–1.29; P < 0.01). A higher incidence of stroke was observed in women with hysterectomy (pooled HR 1.11, 95% CI 1.01–1.22, P = 0.03). The association between hysterectomy and cardiovascular outcomes differed by timing of surgery. An increased risk of stroke, coronary artery disease, and cardiovascular disease was identified following premenopausal hysterectomy. In contrast, no significant association with cardiovascular events was found for postmenopausal procedures. Additionally, a higher occurrence of stroke, myocardial infarction, and cardiovascular disease was observed in women undergoing hysterectomy with bilateral oophorectomy.

Cardiovascular events occurred more frequently following hysterectomy, particularly among women before menopause. Cardiovascular risk assessment may be warranted in this population.

Cardiovascular, coronary artery disease, heart failure, hysterectomy, stroke Hysterectomy is one of the most common nonobstetric surgical procedures performed in women worldwide.1 Hysterectomy is a treatment option for several gynecologic conditions, including uterine fibroids, endometriosis, and uterine prolapse.2 Due to its relatively low perioperative risk, cost-effectiveness, and definitive therapeutic effect, the indications for hysterectomy have broadened, and it is increasingly performed in younger women of reproductive age as well as those in perimenopause.3 Despite advancements in less invasive treatment options, the incidence rate of hysterectomy has remained relatively stable worldwide.1,3–5 In the US alone, approximately 400,000 hysterectomies are performed annually.6 Globally, cardiovascular disease represents the predominant cause of mortality in women, contributing to nearly one-third of all deaths.7,8 Although advancements in cardiovascular treatments have contributed to a decline in mortality, recent data indicate a plateau in the reduction of cardiovascular disease incidence and mortality, particularly among younger women.7–9 Women have several unique sex-specific cardiovascular risk factors that contribute to differences in cardiovascular outcomes compared to men. Since hysterectomy is a common procedure, understanding the cardiovascular outcomes postprocedure is crucial. Although multiple studies have evaluated cardiovascular outcomes following hysterectomy, findings across studies remain inconsistent.10–12 The impact of hysterectomy on overall cardiovascular outcomes, as well as on specific cardiovascular events, remains unclear. Accordingly, we conducted a systematic review and meta-analysis to assess cardiovascular outcomes following hysterectomy.

Search strategy, study selection, and data extraction This study was designed as a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.13 Prior to study initiation, the protocol was registered in PROSPERO, the International Prospective Register of Systematic Reviews. A comprehensive literature search was conducted in four databases—PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL)—from inception to March 25, 2025, without restrictions on language. The literature search incorporated terms for hysterectomy, bilateral oophorectomy, and cardiovascular outcomes, with detailed strategies reported in the Supplemental Data. Eligible studies met the following criteria: inclusion of patients who underwent hysterectomy; comparison with a nonsurgical control group; reporting of cardiovascular outcomes; and use of randomized or observational study designs. Case reports, case series, conference abstracts, and studies enrolling <5 participants per group were excluded. Abstracts and full-text articles were independently screened by two reviewers (T.A. and K.K.), with disagreements resolved by discussion and further review involving a third reviewer (S.A.). A final consensus was made with agreement among all three reviewers. The primary outcome was cardiovascular death. Secondary outcomes were cardiovascular disease, coronary artery disease (CAD), myocardial infarction (MI), and stroke. Data from eligible studies were independently extracted by two investigators (T.A. and K.K.) using a standardized extraction form, capturing study design, country, population characteristics, and funding sources. When overlapping study populations were identified, only the publication with the highest number of participants was retained for analysis. Quality assessment Two reviewers (T.A. and K.K.) independently assessed the risk of bias of nonrandomized studies using the ROBINS-I tool; disagreements were resolved through consensus with a third reviewer (S.A.).14 Data synthesis methods Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were derived using a random-effects model for all outcomes. Hysterectomy timing was categorized as premenopausal or postmenopausal for subgroup analyses, based on definitions applied within individual studies. Heterogeneity across studies was evaluated with Cochran’s Q and the I2 statistic, and publication bias was assessed using funnel plots and Egger’s test. Statistical significance was defined as a two-sided P value < 0.05. Statistical analyses were conducted using STATA version 16.1 software (StataCorp LLC, College Station, TX).

Study characteristics After removal of duplicates, 14,178 records were identified through database searching. Of these, 14,075 were excluded during title and abstract review, and 103 articles proceeded to full-text assessment. Finally, 28 studies were included in this meta-analysis, comprising 2,942,404 participants.10–12,15–39 The study selection process is summarized in Figure 1.40 The included studies were published between 1981 and 2023, with the number of participants ranging from 1543 to 824,484. Each study included in the analysis was nonrandomized in design. Among the included studies, 23 reported outcome data specifically for patients with hysterectomy without bilateral oophorectomy,10–12,16–22,25–32,34,36,37,39 while 11 reported outcome data specifically for patients with hysterectomy with bilateral oophorectomy.16–20,22,25,27,30,31,34 Several studies reported outcomes for both groups separately and therefore contributed data to both categories. The follow-up duration ranged from 5.1 to 29.5 years. Across the included studies, participant stratification was most commonly based on age at hysterectomy, with cutoff values typically ranging from 40 to 50 years. The study characteristics are presented in Table 1 and Supplemental Table 1. Table 1. | First author, year | Study design, country | Data source | Definition of operation | Definition of control population | Exposure measurement | Outcome measurement | CVD definition | Follow-up time | Adjustment | Funding | |---|---|---|---|---|---|---|---|---|---|---| | Cheng, 2022 | Cross-sectional survey, USA | NHANES 2007-2018 | Self-report hysterectomy | Self-report no hysterectomy | Self-report | Self-report | – | – | Age, race, education level, marital status, annual family income, BMI, alcohol consumption in the past 12 months, having smoked at least 100 cigarettes in a lifetime, HT, hypercholesterolemia, DM | None | | Choi, 2018 | Prospective cohort, Korean | Korean National Health Insurance Service-National Cohort | 1. Hysterectomy alone group 2. Hysterectomy with BO group = either an oophorectomy performed concurrent with the hysterectomy or hysterectomy and BO once or unilateral oophorectomy twice | Matched control participants who never underwent a hysterectomy between 2002 and 2013 | Korean Classification of Operations and Major Procedures Code | ICD-10 | – | Hysterectomy group: Mean 74.3 ± 41 mo Control group: Mean 72.3 ± 41 months | Age, income, region of residence, HT, DM, and dyslipidemia | Yes1 | | Choi, 2022 | Prospective cohort, Korean | Korean National Health Insurance Service-National Cohort | 1. Hysterectomy alone group 2. Hysterectomy with BO group = either an oophorectomy performed concurrent with the hysterectomy or hysterectomy and BO once or unilateral oophorectomy twice | Matched control participants who never underwent a hysterectomy between 2002 and 2013 | Korean Classification of Operations and Major Procedures Code | ICD-10 | – | NA | Obesity, smoking, alcohol consumption, and CCI scores | Yes2 | | Colditz, 1987 | Prospective cohort, USA | Nurse’s Health Study cohort | Hysterectomy (with or without unilateral oophorectomy) group Hysterectomy with BO group | Premenopause | Self-report | Self-report, data from National Death Index | – | NA | Age, smoking, follow-up interval, high blood pressure, high cholesterol, DM, parenteral history of MI, Quetelet’s index | Yes3 | | Falkeborn, 2000 | Case-control, Sweden | Uppsala Health Care Region of Sweden | Hysterectomy alone group Hysterectomy with BO | Premenopause | Medical records | ICD codes | – | Mean 8.9 y | – | NA | | Farland, 2023 | Prospective cohort, USA | Nurses’ Health Study II cohort | Hysterectomy alone Hysterectomy with BO group | No hysterectomy or oophorectomy | Self-report | Self-report and medical records | MI or stroke | – | Age, family history of MI, family history of stroke, history of DM at baseline, history of HT at baseline, history of high cholesterol at baseline, age at menarche, BMI, smoking history, alcohol intake, oral contraceptive use history, parity, AHEI diet, physical activity, tubal ligation, hysterectomy and oophorectomy (tubal ligation analysis), menopausal hormone therapy use, age at menopause | Yes4 | | Gierach, 2014 | Prospective cohort, USA | Breast Cancer Detection Demonstration Project | Hysterectomy (with or without unilateral oophorectomy) | Patients with intact uterus with retention of at least one ovary | Self-report | ICD-9 or ICD-10 | – | Mean 22 y | BMI, alcohol use, smoking, menopausal hormone therapy use, and birth cohort | None | | Howard, 2005 | Prospective cohort, USA | Women’s Health Initiative observational study | Hysterectomy alone group Hysterectomy plus BO | No hysterectomy and no bilateral oophorectomy | Self-report | Medical records | Coronary death, MI, stroke, or coronary revascularization | Mean 5.1 y | Age, ethnicity, family history of early MI, education, income | Yes5 | | Ingelsson, 2011 | Prospective cohort, Sweden | Swedish Inpatient Register | Hysterectomy alone group | No hysterectomy and no bilateral oophorectomy | Swedish Classification of Operations and Major Procedures Codes | ICD-8 or ICD-9 | – | Median 10.4 y | Age, calendar time and county | Yes6 | | Iversen, 2005 | Prospective cohort, England | Royal College of General Practitioners’ oral contraception study | Hysterectomy | No hysterectomy | Surgical and operation codes | ICD-8 | – | Mean 250.3 ± 87.1 mo | Social class, smoking, age, parity, use of oral contraceptives and hormone replacement therapy, history of malignancy, uterine fibroma, HT, or cardiovascular disease | Yes7 | | Kharazmi, 2007 | Cross-sectional, Finland | Finnish National Public Health Institute Database | Hysterectomy (with or without unilateral oophorectomy) group Hysterectomy with BO group | No hysterectomy | Self-report | Self-report | – | None | Age, fasting blood glucose and cholesterol, education, smoking, BMI and hormone replacement therapy | NA | | Kim, 2015 (Black) | Prospective cohort, USA | The Reasons for Geographic and Racial Differences in Stroke cohort | Hysterectomy alone group | Men | Self-report | Medical records | – | Mean 5.7 ± 2 y | Age, age at menopause <45 years, less than high school education, annual income ≤$35 000, BMI, waist circumference, level of total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, albumin-creatinine ratio, and C-reactive protein; current smoking, DM, never exercise, use of antihypertensive, statins, estrogen therapy | Yes8 | | Kim, 2015 (White) | Prospective cohort, USA | The Reasons for Geographic and Racial Differences in Stroke cohort | Hysterectomy alone group | Men | Self-report | Medical records | – | Mean 5.7 ± 2 y | Age, age at menopause <45 years, less than high school education, annual income ≤$35 000, BMI, waist circumference, level of total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, albumin-creatinine ratio, and C-reactive protein; current smoking, DM, never exercise, use of antihypertensives, statins, estrogen therapy | Yes8 | | Laughlin-Tommaso, 2015 | Case-control, USA | Rochester Epidemiology Project records-linkage system | Hysterectomy alone | Women who had never received a hysterectomy and were matched with age | Procedural code | Diagnostic code | MI, CAD, congestive heart failure, or stroke | Hysterectomy group: Median 19.3 y (IQR 11.4–28.1) Control group: Median 16.8 y (IQR 9.2–23.5) | DM, hyperlipidemia, HT, obesity, and polycystic ovary syndrome | None | | Laughlin-Tommaso, 2017 | Prospective cohort, USA | Rochester Epidemiology Project records-linkage system | Hysterectomy alone | Women who had never received a hysterectomy and were matched with age | Procedural code | Diagnostic code | – | Hysterectomy group: Median 22.5 y (IQR 15.2–28.8) Control group: Median 21.9 y (IQR 14.2–28.7) | 20 chronic conditions present at baseline, years of education, race, age and calendar year at baseline | Yes9 | | Luoto, 1995 | Cross-sectional, Finland | Mini-Finland Health Survey | Hysterectomy alone group Hysterectomy plus BO | No hysterectomy | Self-report | ICD-8 | – | – | Age, BMI, use of hormone replacement, total cholesterol, HDL, triglyceride, glucose, smoking, alcohol, level of education | Yes10 | | Michelsen, 2013 | Cross-sectional, Norway | Nord-Trøndelag Health Study | Hysterectomy alone group | Age-matched control with no hysterectomy | Self-report | Self-report | MI, angina, or stroke | – | DM, age, use of hormonal replacement therapy, and positive family history of MI | NA | | Michelsen, 2023 | Prospective cohort, Norway | Nord-Trøndelag Health Study | Hysterectomy alone group | No hysterectomy and no oophorectomy | Self-report | Norwegian Cause of Death Registry | – | Hysterectomy alone group: Median 17.1 y Control group: Median 17.3 y | Age, cancer, BMI, DM, smoking, total and HDL cholesterol, physical inactivity, blood pressure, no paid work, and current use of hormone therapy | Yes11 | | Palmer, 1992 | Case-control, USA | Central and eastern Massachusetts | Hysterectomy (with or without unilateral oophorectomy) group | Natural menopause | Self-report | Medical record in hospital admission | – | – | Cigarette smoking, HT, DM, family history of MI, physical activity, BMI, coffee drinking, alcohol consumption, years of education, estrogen used, occupation | Yes12 | | Peters, 2018 | Prospective cohort, England | UK Biobank | Hysterectomy alone group Hysterectomy with the BO group | No hysterectomy and no oophorectomy | Self-report | ICD-10 | Coronary heart disease or stroke | Median 7.1 y (IQR 6.4.-7.8) | Age, Townsend deprivation index, smoking status, systolic blood pressure, history of DM, and BMI | NA | | Poorthuis, 2022 | Prospective cohort, China | China Kadoorie Biobank | Hysterectomy alone group Hysterectomy with BO (concurrent) | No hysterectomy and no oophorectomy | Self-report | ICD-10 | – | Mean 9.8 ± 2 y | Age at risk, study area, level of education, household income, smoking, alcohol use, physical activity, BMI, SBP, DM, self-reported poor health | Yes13 | | Rivera, 2009 | Prospective cohort, USA | Mayo Clinic Cohort Study of Oophorectomy and Aging | Hysterectomy with unilateral oophorectomy group | Age-matched control with no oophorectomy | Medical records | International Classification of Diseases, Adapted Codes for Hospitals (a modification of the ICD-8) | – | Hysterectomy group: Median 29.5 y Control group: Median 26.4 y | None | Yes14 | | Rosenberg, 1981 | Case-control, USA | American Nurse Association | Hysterectomy without the BO group | Premenopause | Self-report | Self-report and medical records | – | – | – | Yes15 | | Shen, 2023 | Prospective cohort, USA | NHANES 2005–2018 | Hysterectomy | No hysterectomy | Self-report | Self-report | – | Median 85 mo | Age, ethnicity, marital status, poverty income ratio, educational level, depression severity | NA | | Tuesley, 2020 | Retrospective cohort, Australia | Western Australian Data Linkage Branch | Hysterectomy alone group Hysterectomy plus BO | No hysterectomy and no oophorectomy | Procedural codes | ICD-9 or ICD-10 | – | Median 24.2 y | Tubal ligation and parity as time-varying variables, age at entry, area of residency, and area-level socioeconomic status and stratified by birth cohort | NA | | Wang, 2021 | Cross-sectional survey, US | NHANES 2007–2018 | Hysterectomy | No hysterectomy | Self-report | Self-report | – | – | Age, race, education level, annual family income, BMI, waist circumference, smoking status, alcohol consumption, physical activity, HT, DM, hypercholesterolemia, family history of heart attack, BO and female hormone use | NA | | Xu, 2022 | Prospective cohort, Australia | UK Biobank | Hysterectomy (with or without unilateral oophorectomy) group | Natural menopause | Self-report | ICD-10 | – | Mean 10 y | Race/ethnicity, year of birth, BMI, smoking, years of education, age at menarche, parity and family history of cardiovascular disease | Yes16 | | Yeh, 2013 | Prospective, Taiwan | Taiwan National Health Insurance database | Hysterectomy alone | Women without hysterectomy, selected by matching the age, hypertension, diabetes, dyslipidemia, and commencement date of follow-up | NA | ICD-9 CM | Stroke or coronary heart disease | – | Hormone replacement therapy | Yes17 | | Yuk, 2023 | Retrospective cohort, Korea | Korean National Health Insurance Service | Hysterectomy with or without oophorectomy | Matching age at 5-year intervals, year at inclusion, socioeconomic status, region, CCI score, HT, DM, dyslipidemia, menopause before inclusion, menopausal hormone therapy before inclusion, and adnexal surgery | Procedures Code | ICD-10 | First hospitalization or death for MI, coronary artery revascularization, or stroke | Hysterectomy group: Median 7.9 y (IQR 6.8–8.9) Control group: Median 7.9 y (IQR 6.8–8.8) | Age, socioeconomic status, region, CCI, HT, DM, dyslipidemia, menopause before inclusion, menopausal hormone therapy before inclusion, adnexal surgery before inclusion, and menopausal hormone therapy | Yes18 | 1Hallym University Medical Center Research Fund. 2Hallym University Medical Center Research Fund. 3National Institutes of Health. 4The Eunice Kennedy Shriver National Institute of Child Health and Human Development. 5The WHI program is funded by the National Heart, Lung, and Blood Institute, US Department of Health and Human Services. 6Swedish Research Council. 7The oral contraception study has received support from the British Heart Foundation, Cancer Research UK, Medical Research Council, Royal College of General Practitioners, Organon Laboratories, Ortho Pharmaceutical, Schering AG, Schering Health Care, Syntex Pharmaceuticals, GD Searle, Syntex Pharmaceuticals, John Wyeth, and Brother. 8National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services. 9Office of Research on Women’s Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Building Interdisciplinary Research Careers in Women’s Health. 10Academy of Finland and the Unsimaa Regional Fund of the Finnish Cultural Foundation. 11South and Eastern Norway Regional Health Authority. 12The National Heart, Lung, and Blood Institute. 13The China Kadoorie Biobank study is jointly coordinated by the University of Oxford and the Chinese Academy of Medical Sciences. 14National Institute of Neurological Disorders and Stroke. 15National Institutes of Health. 16Australian National Health and Medical Research Council. 17Taipei Veterans General Hospital, National Health Research Institutes, Taipei Medical University, WanFang Hospital. 18InterLACE project is funded by the Australian National Health and Medical Research Council project grant. Risk of bas Twenty-three nonrandomized studies were assessed as having a moderate overall risk of bias, according to the ROBINS-I. These studies were primarily downgraded due to a moderate risk of bias from confounding. Five nonrandomized studies were considered to have a serious overall risk of bias, all of which were downgraded due to a serious risk of bias from confounding. A summary of the risks of bias assessments is presented in Supplemental Figure 1. Cardiovascular mortality Cardiovascular mortality did not differ significantly between women with and without hysterectomy in a meta-analysis of five studies involving 67,735 participants (pooled HR, 0.77; 95% CI, 0.59–1.02; P = 0.07).10–12,33,34 The forest plot is shown in Figure 2. Cochran’s Q test was statistically significant, and the I2 value was 86.03%, indicating substantial heterogeneity, suggesting considerable variability across studies. The funnel plot (Supplemental Figure 2) was asymmetrical, and Egger’s test was statistically significant, suggesting the presence of publication bias. Patients were categorized into two subgroups according to age at hysterectomy. A meta-analysis of six studies, comprising 689,602 participants, demonstrated no significant difference in cardiovascular mortality following premenopausal hysterectomy compared with no hysterectomy (HR, 1.20; 95% CI, 0.98–1.47; P = 0.08) (Supplemental Figure 3).10,12,21,24,34,36 Considerable heterogeneity was detected, as indicated by a significant Cochran’s Q test and an I2 of 70.38%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 4). Similarly, a meta-analysis of three studies, comprising 73,585 participants, showed no association between hysterectomy performed at a postmenopausal age and risk of cardiovascular mortality, with a pooled HR of 1.00 (95% CI 0.48–2.08), P = 1.00 (Supplemental Figure 5).10,24,36 Considerable heterogeneity was detected, as indicated by a significant Cochran’s Q test and an I2 of 68.30%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 6). Cardiovascular disease The definitions of cardiovascular disease used in each included study are detailed in Table 1. Across studies, cardiovascular disease was primarily defined as a composite outcome including CAD and stroke. A meta-analysis of eight studies, comprising 859,708 participants, showed that hysterectomy was associated with a higher rate of cardiovascular disease compared to no hysterectomy, with a pooled HR of 1.19 (95% CI 1.09–1.29), P < 0.01.20,22,26,28,30,31,37,38 The forest plot is presented in Figure 3. Considerable heterogeneity was detected, as indicated by a significant Cochran’s Q test and an I2 of 74.52%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 7). Similarly, a meta-analysis of five studies comprising 1,169,247 participants found a higher risk of cardiovascular disease in women undergoing hysterectomy before menopause (pooled HR of 1.16; 95% CI 1.09–1.23, P < 0.01) (Supplemental Figure 8).20,23,30,31,37 Considerable heterogeneity was detected, as indicated by a significant Cochran’s Q test and an I2 of 66.74%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 9). In contrast, in pooled analyses of six studies including 1,053,931 participants, cardiovascular disease risk did not differ significantly between women undergoing hysterectomy after menopause and those without hysterectomy, with a pooled HR of 1.04 (95% CI 0.97–1.12), P = 0.27 (Supplemental Figure 10).20,23,26,30,31,37 Considerable heterogeneity was detected, as indicated by a significant Cochran’s Q test and an I2 of 71.29%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 11). For hysterectomy with bilateral oophorectomy, four studies comprising 692,302 participants were included in the meta-analysis of cardiovascular disease risk.20,22,30,31 Hysterectomy with bilateral oophorectomy was linked to an increased risk of cardiovascular disease, with a pooled HR of 1.15 (95% CI 1.06–1.25), P < 0.01 (Supplemental Figure 12). Moderate heterogeneity was detected, as indicated by a nonsignificant Cochran’s Q test and an I2 of 57.17%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 13). Cardiovascular disease risk following hysterectomy with bilateral oophorectomy at a premenopausal age was examined using data from two studies totaling 384,845 participants.20,31 Hysterectomy with bilateral oophorectomy at a premenopausal age was associated with a higher rate of cardiovascular disease compared to controls (pooled HR 1.37; 95% CI 1.03–1.83, P = 0.03) (Supplemental Figure 14). Considerable heterogeneity was detected, as indicated by a significant Cochran’s Q test and an I2 of 80.72%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 15). Cardiovascular disease risk following hysterectomy with bilateral oophorectomy at a postmenopausal age was examined using data from two studies totaling 384,845 participants.20,31 Similarly, hysterectomy with bilateral oophorectomy at a postmenopausal age had a higher risk of cardiovascular disease compared to controls, with a pooled HR of 1.17 (95% CI 1.06–1.28), P < 0.01 (Supplemental Figure 16). No substantial heterogeneity was detected, as indicated by a nonsignificant Cochran’s Q test and an I2 of 0%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 17). Stroke Stroke occurred more frequently among women who underwent hysterectomy than among those without hysterectomy across nine studies comprising 851,332 participants (HR, 1.11; 95% CI, 1.01–1.22; P = 0.03).15,17,20,25,26,30,31,37,38 The forest plot is presented in Figure 4. Cochran’s Q test was statistically significant, and the I2 value was 56.68%, indicating moderate heterogeneity. No evidence of publication bias was detected, as indicated by funnel plot symmetry and a nonsignificant Egger’s test (Supplemental Figure 18). Based on age at hysterectomy, eight studies comprising 1,134,764 participants were included in the meta-analysis of premenopausal hysterectomy and stroke risk.15,17,21,23,26,30,31,37 Hysterectomy at a premenopausal age was associated with a significantly increased risk of stroke compared to no hysterectomy, with a pooled HR of 1.18 (95% CI 1.06–1.31), P < 0.01 (Supplemental Figure 19). Considerable heterogeneity was detected, as indicated by a significant Cochran’s Q test and an I2 of 76.83%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 20). In contrast, a meta-analysis of seven studies, comprising 995,259 participants, indicated no significant difference in stroke risk between postmenopausal hysterectomy and no hysterectomy, with a pooled HR of 1.02 (95% CI 0.93–1.12), P = 0.73 (Supplemental Figure 21).15,17,23,26,30,31,37 Considerable heterogeneity was detected, as indicated by a significant Cochran’s Q test and an I2 of 69.15%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 22). For hysterectomy with bilateral oophorectomy, five studies comprising 630,577 participants were included in the meta-analysis of stroke risk.17,20,25,30,31 Hysterectomy with bilateral oophorectomy was associated with an increased risk of stroke compared to controls, with a pooled HR of 1.14 (95% CI 1.02–1.28), P = 0.02 (Supplemental Figure 23). Low heterogeneity was detected, as reflected by a nonsignificant Cochran’s Q test and an I2 of 26.04%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 24). Coronary artery disease A meta-analysis of 12 studies, comprising 950,865 participants, showed no significant association between hysterectomy and the risk of CAD, with a pooled HR of 1.08 (95% CI 0.97–1.20), P = 0.17 (Supplemental Figure 25).11,16,18,20,25–27,30,31,35,37,38 Cochran’s Q test was statistically significant, and the I2 value was 68.73%, indicating substantial heterogeneity, suggesting considerable variability across studies. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 26). Based on age at hysterectomy, seven studies involving a total of 1,121,328 participants were included in the meta-analysis evaluating CAD risk following premenopausal hysterectomy.16,21,23,26,30,31,37 Hysterectomy at a premenopausal age was associated with a higher risk of CAD compared to no hysterectomy (pooled HR 1.14; 95% CI 1.10–1.17, P < 0.01) (Supplemental Figure 27). Low heterogeneity was detected, as reflected by a nonsignificant Cochran’s Q test and an I2 of 0%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 28). In contrast, in pooled analyses of six studies including 950,693 participants, CAD risk did not differ significantly between women undergoing hysterectomy after menopause and those without hysterectomy, with a pooled HR of 1.03 (95% CI 0.92–1.14), P = 0.64 (Supplemental Figure 29).16,23,26,30,31,37 Low heterogeneity was detected, as reflected by a nonsignificant Cochran’s Q test and an I2 of 0%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 30). Seven studies, comprising 722,026 participants, were included in the meta-analysis of hysterectomy with bilateral oophorectomy and CAD risk.16,18,20,25,27,30,31 Hysterectomy with bilateral oophorectomy was not significantly associated with CAD risk, with a pooled HR of 1.09 (95% CI 0.94–1.27), P = 0.26 (Supplemental Figure 31). Moderate heterogeneity was detected, as indicated by a nonsignificant Cochran’s Q test and an I2 of 43.63%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 32). Myocardial infarction In pooled analyses of six studies including 253,908 participants, MI risk did not differ significantly between women with and without hysterectomy, with a pooled HR of 0.90 (95% CI 0.63–1.29), P = 0.57 (Supplemental Figure 33).11,19,20,26,32,38 Considerable heterogeneity was detected, as indicated by a significant Cochran’s Q test and an I2 of 79.73%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 34). Based on age at hysterectomy, two studies comprising 17,472 participants were included in the meta-analysis of hysterectomy at a premenopausal age and MI.19,29 Hysterectomy at a premenopausal age was not associated with a risk of MI, with a pooled HR of 1.30 (95% CI 0.77–2.18), P = 0.33 (Supplemental Figure 35). Moderate heterogeneity was detected, as indicated by a nonsignificant Cochran’s Q test and an I2 of 53.26%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 36). Three studies, comprising 18,955 participants, were included in the meta-analysis of hysterectomy at a postmenopausal age and MI.19,26,29 Hysterectomy at a postmenopausal age was not associated with a risk of MI, with a pooled HR of 0.85 (95% CI 0.52–1.38), P = 0.51 (Supplemental Figure 37). Low heterogeneity was detected, as reflected by a nonsignificant Cochran’s Q test and an I2 of 0%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 38). For hysterectomy with bilateral oophorectomy, two studies involving a total of 127,727 participants were included in the meta-analysis assessing MI risk.19,20 MI occurred more frequently in women undergoing hysterectomy with bilateral oophorectomy compared with controls, with a pooled HR of 1.28 (95% CI 1.05–1.56), P = 0.02 (Supplemental Figure 39). Low heterogeneity was detected, as reflected by a nonsignificant Cochran’s Q test and an I2 of 0%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 40). Heart failure The meta-analysis of heart failure risk after hysterectomy included two studies comprising 11,357 participants.26,27 Hysterectomy was not associated with a risk of heart failure compared to no hysterectomy, with a pooled HR of 0.87 (95% CI 0.25–3.04), P = 0.83 (Supplemental Figure 41). Considerable heterogeneity was detected, as indicated by a significant Cochran’s Q test and an I2 of 82.05%. The funnel plot appeared symmetric, and Egger’s test did not show statistical significance, indicating no evidence of publication bias (Supplemental Figure 42).

Cardiovascular disease and stroke occurred more frequently among women with hysterectomy in a meta-analysis of 28 studies involving 2,942,404 participants. Higher incidences of CAD, cardiovascular disease, and stroke were observed among women undergoing hysterectomy at a premenopausal age. In contrast, no significant increase in cardiovascular event rates was observed following hysterectomy performed after menopause. Furthermore, hysterectomy was not significantly associated with increased risk of cardiovascular mortality, heart failure, or MI. The addition of bilateral oophorectomy to hysterectomy was associated with higher rates of cardiovascular disease, stroke, and MI. Our findings suggest that hysterectomy, particularly when performed at a younger age, is linked to higher cardiovascular risk. Age at the time of surgery appears to be a key modifier for the cardiovascular outcome of hysterectomy. MI risk did not differ significantly with hysterectomy alone, whereas higher risk was observed when bilateral oophorectomy accompanied hysterectomy. These associations may be partly explained by hormonal disruption following surgery. Previous studies have demonstrated that women experience an increased risk of cardiovascular events following the onset of menopause.41 Moreover, the onset of CAD in women generally occurs later than in men, likely due to the protective effects of estrogen.41 Estrogen has favorable effects on lipid profiles, including lowering low-density lipoprotein (LDL) cholesterol, a key contributor to atherosclerosis.42 Cohort studies have shown that serum LDL levels are higher in men than in age-matched premenopausal women. In addition, menopause is associated with increased LDL and decreased high-density lipoprotein (HDL) cholesterol levels.42,43 Beyond lipid metabolism, estrogen also plays a favorable role in cardiovascular health by maintaining vascular function, exerting anti-inflammatory effects, reducing fibrosis, and slowing atherosclerotic plaque progression.44 Although the uterus is not an endocrine organ, hysterectomy has been proposed to disrupt sex hormone balance through impaired ovarian blood flow.45 However, data on estrogen levels following hysterectomy are limited. One cross-sectional study in postmenopausal women found no difference in estradiol levels between participants who underwent hysterectomy with ovarian conservation and participants with an intact uterus.46 Another cross-sectional study involving premenopausal and perimenopausal women reported no significant impact of hysterectomy on estradiol levels, while another cross-sectional study reported decreased estradiol levels in perimenopausal women after hysterectomy.47 Interestingly, cohort studies in premenopausal women have shown that hysterectomy nearly doubles the risk of ovarian failure.48 The timing after hysterectomy may influence estradiol levels, highlighting the need for longitudinal studies to clarify this association. Differences in patient characteristics may also influence cardiovascular outcomes. Baseline data from several large cohort studies have shown that patients who underwent hysterectomy often had higher baseline cardiovascular risk, along with higher socioeconomic status.49 Additionally, a large cross-sectional database study found a correlation between socioeconomic status and hysterectomy status.50 Several gynecological conditions that commonly lead to hysterectomy, such as uterine fibroids, are also associated with increased cardiovascular risk. Patients with uterine fibroids often have more cardiovascular risk factors, likely due to shared risk factors.51 Furthermore, some evidence suggests a bidirectional relationship between uterine fibroids and cardiovascular risk factors, including hypertension.49,52 Based on these findings, women undergoing hysterectomy may already have a higher baseline risk of cardiovascular events. To reduce potential confounding related to baseline cardiovascular risk, adjusted HRs were preferentially used when available. Adjusted HRs accounting for potential confounders were reported in the majority of included studies; only three studies provided only unadjusted HRs. However, the included studies used different multivariable models, and unmeasured confounding cannot be excluded. Further studies with matching or stratification of baseline cardiovascular risk are needed to clarify the independent effect of hysterectomy on cardiovascular outcomes. This meta-analysis has several limitations. First, all included studies were observational in design, which introduces the possibility of residual confounding despite adjustment for known variables. Second, heterogeneity was observed in our meta-analysis. This heterogeneity may be due to the differences in indications of hysterectomy; however, current evidence stratified by hysterectomy indication remains limited. Additionally, the duration since hysterectomy may influence cardiovascular outcomes, but most included studies did not adjust for the duration posthysterectomy. Third, important population-level factors were not consistently reported across studies, including the geographic distribution of participants (e.g., developed versus developing countries), baseline cardiovascular risk, access to preventive care, and variability in cardiovascular risk factor management, all of which may influence cardiovascular risk and study outcomes. Fourth, funnel plot evaluation indicated the possibility of publication bias, potentially influencing the interpretation of the results. Lastly, while this meta-analysis identified associations between hysterectomy and cardiovascular outcomes, the underlying pathophysiological mechanisms remain unknown. In conclusion, our meta-analysis indicates a higher incidence of cardiovascular events, including stroke and overall cardiovascular disease, among women undergoing hysterectomy. An increased risk of stroke, CAD, and cardiovascular disease was identified following premenopausal hysterectomy. In contrast, no significant association with cardiovascular events was found for postmenopausal procedures. These findings highlight the importance of cardiovascular risk assessment in women undergoing hysterectomy, particularly those at a premenopausal age. Nevertheless, these results should be interpreted with caution due to methodological limitations and the inherent variability among the included studies. Further studies are warranted to develop appropriate primary and secondary prevention strategies and to refine cardiovascular risk stratification tools for this population. Supplementary Material AUTHOR CONTRIBUTIONS Tanawat Attachaipanich: Conceptualization; Formal analysis; Methodology; Writing – original draft; Writing – review and editing. Kotchakorn Kaewboot: Conceptualization; Formal analysis; Methodology; Writing – original draft; Writing – review and editing. Suthinee Attachaipanich: Conceptualization; Formal analysis; Methodology; Writing – original draft; Writing – review and editing. Disclosure statement/Funding The authors report no funding or conflicts of interest.

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