Uterine Fibroids and All-Cause and Cause-Specific Mortality: Analysis From the National Health and Nutrition Examination Survey

Abstract

Background:

The association between uterine fibroids and mortality remains inconclusive. This study evaluated the relationship between uterine fibroids and all-cause, cancer-specific, and cardiovascular disease (CVD)-specific mortality using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006.

Methods:

A cohort analysis was conducted using NHANES data from 1999 to 2006. Weighted Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) to assess associations between uterine fibroids, age at diagnosis, and mortality outcomes. Subgroup analyses and interaction tests were performed to evaluate potential effect modification.

Results:

The study cohort comprised 5547 women aged 20–54 years across four survey cycles. During a median follow-up of 16.75 years, 290 deaths were recorded. After adjustment for confounders, no statistically significant associations were observed for all-cause mortality (HR: 0.96; 95% CI: 0.65–1.42), cancer-specific mortality (HR: 1.12; 95% CI: 0.64–1.96), or CVD-related mortality (HR: 0.90; 95% CI: 0.38–2.14). Age-stratified analyses similarly revealed no significant associations across diagnostic age groups.

Conclusions:

These results indicate no elevated risk of all-cause, cancer-specific, or CVD-specific mortality associated with uterine fibroids.

Graphical abstract

Keywords

uterine fibroids / mortality / cohort / NHANES / risk

1. Introduction

Uterine fibroids represent the most common benign tumors arising from the smooth muscle of the uterus in the female reproductive tract [1, 2, 3]. In 2019, an estimated 9.6 million new cases were reported globally, contributing to a worldwide prevalence of approximately 226 million cases [1]. These fibroids may manifest as solitary or multiple lesions of variable size and often remain asymptomatic. Symptomatic cases, however, may involve menorrhagia, pelvic pain, urinary disturbances, and reproductive dysfunction [3], all of which can profoundly compromise quality of life by impairing work performance and mental health. The economic impact is substantial, with the United States healthcare costs increasing by 20.3%—from \$34.4 billion in 2010 to \$41.4 billion in 2020 [4].

A hallmark of uterine fibroid pathophysiology is the presence of endocrine dysregulation [5]. Notably, uterine fibroids exhibit genetic overlap with endometriosis [6], a chronic, multisystem inflammatory disorder characterized by systemic inflammation, elevated oxidative stress, and proatherogenic lipid profiles [7]. Moreover, uterine fibroids, neoplastic conditions, and cardiovascular diseases (CVD) share modifiable risk factors such as obesity, physical inactivity, poor dietary patterns, and psychosocial stress [8, 9, 10, 11, 12, 13, 14, 15]. These shared etiological pathways suggest that fibroid development may function as an early clinical indicator of broader health risks in women. Integrating fibroid status into risk stratification frameworks may facilitate the implementation of individualized lifestyle interventions and tailored screening strategies, potentially mitigating long-term morbidity. Emerging evidence points to associations between uterine fibroids and increased risks of malignancies including breast [16, 17], ovarian [18], and endometrial cancers [19, 20], as well as cardiometabolic disorders such as hypertension [21, 22], dyslipidemia, and metabolic syndrome [23]. However, these associations remain controversial due to inconsistent findings across studies [24, 25]. The relationship between uterine fibroids and both all-cause and cause-specific mortality remains inadequately characterized. For example, Shen et al. (2017) [17] reported lower mortality from breast cancer among individuals diagnosed with fibroids compared to those without. In contrast, data from the 2024 Nurses’ Health Study II showed no association between uterine fibroids and all-cause premature mortality, although did identify an elevated risk of cancer-specific mortality [26]. When accounting for cancer types, the observed association was more pronounced in cases involving malignant gynecologic neoplasms [26]. To address this gap, the association between uterine fibroids and both all-cause and cause-specific mortality was investigated using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2006.

2. Materials and Methods

2.1 Study Design

This study was conducted under the NHANES framework, a nationally representative surveillance program that systematically collects data on health conditions, dietary patterns, and behavioral risk factors across the U.S. population through interviews, physical examinations, and laboratory assessments. All participants provided written informed consent, and study protocols were approved by the Ethics Review Board of the National Center for Health Statistics (NCHS) under Protocols #98-12 and #2005-06. A retrospective cohort design was employed to evaluate the association between uterine fibroids and both all-cause and cause-specific mortality, with results reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [27].

2.2 Determining Study Population

Uterine fibroid data were collected exclusively during four NHANES survey cycles spanning 1999 to 2006. Due to confidentiality regulations, outcome variables were not available for individuals younger than 18 years. Thus, public access to their mortality data was restricted. The participant selection process is depicted in Fig. 1. Of the initial 21,210 female respondents, exclusions were made for the following reasons: (1) 9352 individuals were under 18 years of age, (2) 6306 lacked information on fibroid status, and (3) 5 had insufficient identifiers for linkage with the National Death Index. After these exclusions, the final analytic cohort comprised 5547 eligible participants.

2.3 Determining Uterine Fibroids

Uterine fibroid status was determined using specific items from the reproductive health questionnaire, including “RHQ380: Told by doctor had uterine fibroids?” and “RHQ390: Age when first told had uterine fibroids”. Respondents selecting “Refused” or “Don’t know” for RHQ380 were categorized as missing and excluded from the analysis.

2.4 Determining Mortality and Follow-up Time

Mortality outcomes were ascertained through linkage with the National Death Index. Classification of mortality followed the 10th revision of the International Classification of Diseases (ICD-10). This study investigated the association between uterine fibroids and all-cause mortality, cancer-specific mortality defined by ICD-10 codes C00–C97, and cardiovascular mortality defined by codes I00–I09, I11, I13, I20–I51, and I60–I69. Follow-up began at the time of the NHANES interview and continued through December 31, 2019, or until death, whichever occurred first.

2.5 Statistical Analyses

Statistical analyses adhered to NHANES complex survey design protocols and incorporated appropriate sampling weights using R software (version 3.4.3, Vienna, Austria; https://www.r-project.org/). p-value of less than 0.05 is considered a significant difference. Four survey cycles from 1999 to 2006 were included. Weighting adjustments were made by applying 2/4 \times “wtmec4yr” for the 1999–2000 and 2001–2002 cycles and 1/4 \times “wtmec2yr” for the 2003–2006 cycles.

Categorical variables were described using frequencies and proportions and compared using chi-square test, while non-normally distributed continuous variables were summarized as medians with interquartile ranges (Q1–Q3) and compared using Wilcoxon rank sum test. The analysis compared participants with a history of uterine fibroids—further stratified by age at diagnosis (\le30 and \ge31 years)—to those without fibroids. Associations between fibroid status and mortality outcomes were assessed using Cox proportional hazards models with follow-up time as the underlying time metric. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to quantify the strength of these associations.

Two Cox regression models were developed NHANES design and a thorough review of prior literature: an unadjusted model and a multivariable-adjusted model controlling for potential confounders. To maximize analytical completeness, missing values with low frequency were imputed—categorical variables using mode substitution and continuous variables using the median. For variables with more than 20% missing data (e.g., age at menopause, number of live births, hysterectomy status, and high cholesterol), a separate “missing” category was created to preserve participant inclusion. The adjusted model incorporated a comprehensive set of covariates, including: age (continuous); race/ethnicity (non-Hispanic White, non-Hispanic Black, Other), marital status (married/living with a partner, never married, widowed/divorced/separated); education level (high school or less, more than high school), family poverty income ratio (PIR: \le1.30, 1.31–3.5, >3.5); and personal history of hypertension (yes/no), hypercholesterolemia (yes/no/unknown), diabetes (yes/no/borderline), CVD (yes/no), cancer (yes/no), smoking status (never/former/current), alcohol consumption (never/former/current), body mass index (BMI, 25, 25–29.9, \ge30 kg/m²), oral contraceptive use (never/ever), hormone replacement therapy (never/ever), age at menarche (\le11, 12–13, \ge14 years), age at menopause (\le35, 36–40, 41–45, 46–50, \ge51 years, unknown), endometriosis (yes/no), hysterectomy (yes/no/unknown), oophorectomy (yes/no), number of pregnancies (1, 2, 3, \ge4), and number of live births (0, 1, 2, 3, 4, \ge5, unknown).

An exploratory analysis was conducted to evaluate all-cause mortality, incorporating subgroup analyses and interaction tests across race, education, marital status, PIR, and clinical variables including hypertension, hypercholesterolemia, diabetes, cancer, CVD, and reproductive health conditions such as oral contraceptive use, hormone replacement therapy, endometriosis, hysterectomy, and oophorectomy. Due to limited statistical power, cause-specific mortality related to cancer or CVD was not assessed in these stratified models.

3. Results

A total of 5547 women aged 20 to 54 years, drawn from four NHANES survey cycles conducted between 1999 and 2006, were included in the analytic cohort. This sample corresponds to a weighted estimate of approximately 66,011,902 women in the U.S. population. The median duration of follow-up was 16.75 years, during which 290 deaths occurred, representing an estimated 3,411,632 deaths. Baseline characteristics are summarized in Table 1. Compared to women without uterine fibroids, those with a diagnosis were more likely to be older, non-Hispanic Black, and either married/living with a partner or widowed/divorced/separated. They also demonstrated higher economic status and exhibited increased prevalence of hypertension, hypercholesterolemia, and diabetes. Additionally, women with fibroids were more likely to report a history of cancer or CVD and were more frequently classified as current or former smokers and alcohol users. Elevated rates of oral contraceptive use, hormone replacement therapy, hysterectomy, oophorectomy, and endometriosis were also observed in this group.

Initial unadjusted analyses indicated significantly elevated risks of all-cause mortality (HR = 1.59; 95% CI: 1.11–2.29; p-value = 0.012) and cancer-specific mortality (HR = 2.25; 95% CI: 1.32–3.84; p-value = 0.003) among women with uterine fibroids relative to those without. No statistically significant association was observed for CVD-specific mortality (HR = 1.48; 95% CI: 0.67–3.26; p-value = 0.331). However, these associations were no longer statistically significant after adjustment for potential confounders. The adjusted HRs and 95% CIs were 0.96 (0.65–1.42) for all-cause mortality (p-value = 0.828), 1.12 (0.64–1.96) for cancer-specific mortality (p-value = 0.685), and 0.90 (0.38–2.14) for CVD-related mortality (p-value = 0.818). Age-stratified analyses by age at fibroid diagnosis yielded no significant associations across all diagnostic age categories (Table 2).

An exploratory analysis of all-cause mortality was performed, incorporating subgroup evaluations and interaction testing across race, educational attainment, marital status, PIR, and medical histories including hypertension, hypercholesterolemia, diabetes, cancer, CVD, and reproductive health factors such as oral contraceptive use, hormone replacement therapy, endometriosis, hysterectomy, and oophorectomy. A significant association between uterine fibroids and all-cause mortality emerged among non-Hispanic Black women (HR = 1.67; 95% CI: 1.07–2.61; p-value = 0.023), with no comparable associations observed in other subgroups (Table 3). Interaction analyses revealed significant heterogeneity by race (p-value for interaction = 0.036), high cholesterol (p-value for interaction = 0.009), ovariectomy (p-value for interaction = 0.048), and marital status, (p-value for interaction = 0.017).

4. Discussion

In the NHANES 1999–2006 cohort comprising 5547 women (weighted to represent 66,011,902 individuals), no statistically significant associations were identified between uterine fibroids and either all-cause or cause-specific mortality.

To date, only two studies have evaluated the long-term impact of uterine fibroids on mortality outcomes [17, 26]. The 2024 Nurses’ Health Study II, involving 110,091 women aged 25–42 years with a median follow-up of 27.2 years, reported findings that align with those of the present study—no significant association was observed between uterine fibroids and all-cause premature mortality (death before age 70) [26]. Similarly, no significant associations emerged for cause-specific mortality attributed to cardiovascular, respiratory, or other non-cancer causes. However, a notable exception was an observed association between uterine fibroids and increased cancer-specific mortality [26]. Stratified analyses further indicated elevated mortality risk from gynecologic cancers in women with fibroids, whereas no associations were detected for other cancer types, including breast, gastrointestinal, respiratory, lymphatic, hematopoietic, bone, connective tissue, or skin cancers [26]. Conversely, an investigation involving an Asian cohort of 107,357 women reported lower breast cancer–related mortality among individuals with uterine leiomyoma [17]. Several factors may explain these divergent findings: (1) the possibility of chance findings; (2) the Asian population-specific genetic profiles, lifestyle patterns, and environmental exposures; and (3) limitations of the National Health Insurance Research Database, including the absence of detailed data on reproductive history, familial predisposition, environmental risk factors, and health behaviors such as smoking and alcohol use—all of which may act as unmeasured confounders and introduce bias [17]. These discrepancies highlight the need for additional large-scale, ethnically diverse, and well-controlled studies.

The joint effect of endometriosis and uterine fibroids on health outcomes was also examined in the Nurses’ Health Study II, where co-occurrence was associated with elevated all-cause mortality (HR = 1.31; 95% CI: 1.12–1.53) [26]. In the present NHANES-based analysis, 21.67% of participants had both conditions. Subgroup and interaction analyses demonstrated comparable mortality risk patterns regardless of endometriosis status. However, race-stratified analysis revealed significantly increased mortality risk among Black women with uterine fibroids, a pattern absent in White women. This racial disparity was statistically confirmed through interaction testing (p-value for interaction = 0.036). Notably, uterine fibroid prevalence is approximately two to three times higher in Black women than in their White counterparts [8], suggesting a potentially disproportionate burden of adverse outcomes in this subgroup. An additional and unexpected observation emerged: women with both uterine fibroids and hyperlipidemia appeared to exhibit a lower mortality risk. One possible explanation is that individuals diagnosed with hyperlipidemia may engage more consistently in health-promoting behaviors and have greater access to or utilization of healthcare services, contributing to better overall outcomes. However, given the wide CIs surrounding this estimate, these findings should be interpreted with caution and warrant further validation in future research.

Hysterectomy remains a common surgical intervention for managing uterine fibroids and is frequently performed in conjunction with oophorectomy. Existing evidence suggests that hysterectomy may precipitate ovarian failure by disrupting ovarian tissue integrity or impairing vascular supply, thereby reducing ovarian sex steroid production and advancing the onset of menopause—ultimately diminishing the cardioprotective and antineoplastic benefits of endogenous estrogens [28, 29, 30, 31, 32, 33, 34]. Epidemiological studies have further linked hysterectomy to elevated risks of several types of malignancies, CVD, coronary heart disease, and stroke [35, 36, 37]. To assess these potential modifiers, stratified analyses were conducted by hysterectomy and oophorectomy status. While hysterectomy alone did not significantly alter the relationship between uterine fibroids and mortality, stratification by oophorectomy revealed a significant interaction (p for interaction = 0.048). Given the small number of participants with unilateral oophorectomy, these findings should be interpreted with caution.

This investigation has some merits, including a nationally representative cohort design, control for a broad range of potential confounders, and detailed subgroup and interaction analyses. Nonetheless, several limitations should be considered. First, as an observational study, residual confounding—particularly related to factors such as myomectomy or pharmacological treatment for fibroid symptoms—cannot be excluded. Second, reliance on self-reported data introduces potential misclassification bias, especially for exposure variables. Third, the use of NHANES data from 1999 to 2006 may limit applicability to more contemporary populations, potentially affecting generalizability. Fourth, while the median follow-up duration of 16.75 years is substantial, it may still be inadequate to capture the full spectrum of long-term mortality risks associated with a typically benign condition like uterine fibroids. Finally, the inclusion of only diagnosed cases may have led to underascertainment of asymptomatic fibroids, potentially biasing effect estimates toward the null.

5. Conclusions

In conclusion, this study observed no significant association between uterine fibroids and increased risk of all-cause or cause-specific mortality, reinforcing the need for further research to clarify long-term health outcomes and identify subpopulations at elevated risk.

Availability of Data and Materials

The raw data from NHANES is publicly available on the NHANES website (https://wwwn.cdc.gov/nchs/nhanes/Default.aspx).

References

[1] Dai Y, Chen H, Yu J, Cai J, Lu B, Dai M, et al. Global and regional trends in the incidence and prevalence of uterine fibroids and attributable risk factors at the national level from 2010 to 2019: A worldwide database study. Chinese Medical Journal. 2024; 137: 2583–2589. https://doi.org/10.1097/CM9.0000000000002971.

[2] Langton CR, Harmon QE, Baird DD. Family History and Uterine Fibroid Development in Black and African American Women. JAMA Network Open. 2024; 7: e244185. https://doi.org/10.1001/jamanetworkopen.2024.4185.

[3] Wise LA, Laughlin-Tommaso SK. Epidemiology of Uterine Fibroids: From Menarche to Menopause. Clinical Obstetrics and Gynecology. 2016; 59: 2–24. https://doi.org/10.1097/GRF.0000000000000164.

[4] Hazimeh D, Coco A, Casubhoy I, Segars J, Singh B. The Annual Economic Burden of Uterine Fibroids in the United States (2010 Versus 2022): A Comparative Cost-Analysis. Reproductive Sciences (Thousand Oaks, Calif.). 2024; 31: 3743–3756. https://doi.org/10.1007/s43032-024-01727-0.

[5] Bulun SE. Uterine fibroids. The New England Journal of Medicine. 2013; 369: 1344–1355. https://doi.org/10.1056/NEJMra1209993.

[6] Gallagher CS, Mäkinen N, Harris HR, Rahmioglu N, Uimari O, Cook JP, et al. Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. Nature Communications. 2019; 10: 4857. https://doi.org/10.1038/s41467-019-12536-4.

[7] Mu F, Rich-Edwards J, Rimm EB, Spiegelman D, Missmer SA. Endometriosis and Risk of Coronary Heart Disease. Circulation. Cardiovascular Quality and Outcomes. 2016; 9: 257–264. https://doi.org/10.1161/CIRCOUTCOMES.115.002224.

[8] Pavone D, Clemenza S, Sorbi F, Fambrini M, Petraglia F. Epidemiology and Risk Factors of Uterine Fibroids. Best Practice & Research. Clinical Obstetrics & Gynaecology. 2018; 46: 3–11. https://doi.org/10.1016/j.bpobgyn.2017.09.004.

[9] Avgerinos KI, Spyrou N, Mantzoros CS, Dalamaga M. Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism: Clinical and Experimental. 2019; 92: 121–135. https://doi.org/10.1016/j.metabol.2018.11.001.

[10] GBD 2021 Stroke Risk Factor Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet. Neurology. 2024; 23: 973–1003. https://doi.org/10.1016/S1474-4422(24)00369-7.

[11] Lin W, Jiang X, Chen J, Yuan Y, Li Q, Wu H, et al. Global, regional and national burden of ischaemic heart disease attributable to high body mass index and low physical activity from 1990 to 2021. Diabetes, Obesity & Metabolism. 2025; 27: 2561–2572. https://doi.org/10.1111/dom.16256.

[12] Everson-Rose SA, Roetker NS, Lutsey PL, Kershaw KN, Longstreth WT, Jr, Sacco RL, et al. Chronic stress, depressive symptoms, anger, hostility, and risk of stroke and transient ischemic attack in the multi-ethnic study of atherosclerosis. Stroke. 2014; 45: 2318–2323. https://doi.org/10.1161/STROKEAHA.114.004815.

[13] Song H, Saito E, Sawada N, Abe SK, Hidaka A, Shimazu T, et al. Perceived stress level and risk of cancer incidence in a Japanese population: the Japan Public Health Center (JPHC)-based Prospective Study. Scientific Reports. 2017; 7: 12964. https://doi.org/10.1038/s41598-017-13362-8.

[14] Bahri N, Fathi Najafi T, Homaei Shandiz F, Tohidinik HR, Khajavi A. The relation between stressful life events and breast cancer: a systematic review and meta-analysis of cohort studies. Breast Cancer Research and Treatment. 2019; 176: 53–61. https://doi.org/10.1007/s10549-019-05231-x.

[15] Funada S, Shimazu T, Kakizaki M, Kuriyama S, Sato Y, Matsuda-Ohmori K, et al. Body mass index and cardiovascular disease mortality in Japan: the Ohsaki Study. Preventive Medicine. 2008; 47: 66–70. https://doi.org/10.1016/j.ypmed.2008.03.010.

[16] Tseng JJ, Chen YH, Chiang HY, Lin CH. Increased risk of breast cancer in women with uterine myoma: a nationwide, population-based, case-control study. Journal of Gynecologic Oncology. 2017; 28: e35. https://doi.org/10.3802/jgo.2017.28.e35.

[17] Shen TC, Hsia TC, Hsiao CL, Lin CL, Yang CY, Soh KS, et al. Patients with uterine leiomyoma exhibit a high incidence but low mortality rate for breast cancer. Oncotarget. 2017; 8: 33014–33023. https://doi.org/10.18632/oncotarget.16520.

[18] Tseng JJ, Huang CC, Chiang HY, Chen YH, Lin CH. Prior uterine myoma and risk of ovarian cancer: a population-based case-control study. Journal of Gynecologic Oncology. 2019; 30: e72. https://doi.org/10.3802/jgo.2019.30.e72.

[19] Rowlands IJ, Nagle CM, Spurdle AB, Webb PM, Australian National Endometrial Cancer Study Group, Australian Ovarian Cancer Study Group. Gynecological conditions and the risk of endometrial cancer. Gynecologic Oncology. 2011; 123: 537–541. https://doi.org/10.1016/j.ygyno.2011.08.022.

[20] Wise LA, Sponholtz TR, Rosenberg L, Adams-Campbell LL, Kuohung W, LaValley MP, et al. History of uterine leiomyoma and risk of endometrial cancer in black women. Cancer Causes & Control: CCC. 2016; 27: 545–552. https://doi.org/10.1007/s10552-016-0728-3.

[21] Haan YC, Diemer FS, Van Der Woude L, Van Montfrans GA, Oehlers GP, Brewster LM. The risk of hypertension and cardiovascular disease in women with uterine fibroids. Journal of Clinical Hypertension (Greenwich, Conn.). 2018; 20: 718–726. https://doi.org/10.1111/jch.13253.

[22] Madika AL, MacDonald CJ, Gelot A, Hitier S, Mounier-Vehier C, Béraud G, et al. Hysterectomy, non-malignant gynecological diseases, and the risk of incident hypertension: The E3N prospective cohort. Maturitas. 2021; 150: 22–29. https://doi.org/10.1016/j.maturitas.2021.06.001.

[23] Uimari O, Auvinen J, Jokelainen J, Puukka K, Ruokonen A, Järvelin MR, et al. Uterine fibroids and cardiovascular risk. Human Reproduction (Oxford, England). 2016; 31: 2689–2703. https://doi.org/10.1093/humrep/dew249.

[24] Shen F, Liu Y, Lin L, Zhao M, Chen Q. Association of benign gynaecological diseases and risk of endometrial and ovarian cancers. Journal of Cancer. 2020; 11: 3186–3191. https://doi.org/10.7150/jca.39626.

[25] Laughlin-Tommaso SK, Fuchs EL, Wellons MF, Lewis CE, Calderon-Margalit R, Stewart EA, et al. Uterine Fibroids and the Risk of Cardiovascular Disease in the Coronary Artery Risk Development in Young Adult Women’s Study. Journal of Women’s Health (2002). 2019; 28: 46–52. https://doi.org/10.1089/jwh.2018.7122.

[26] Wang YX, Farland LV, Gaskins AJ, Wang S, Terry KL, Rexrode KM, et al. Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study. BMJ (Clinical Research Ed.). 2024; 387: e078797. https://doi.org/10.1136/bmj-2023-078797.

[27] von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Medicine. 2007; 4: e296. https://doi.org/10.1371/journal.pmed.0040296.

[28] Laughlin GA, Barrett-Connor E, Kritz-Silverstein D, von Mühlen D. Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: the Rancho Bernardo Study. The Journal of Clinical Endocrinology and Metabolism. 2000; 85: 645–651. https://doi.org/10.1210/jcem.85.2.6405.

[29] Xiangying H, Lili H, Yifu S. The effect of hysterectomy on ovarian blood supply and endocrine function. Climacteric: the Journal of the International Menopause Society. 2006; 9: 283–289. https://doi.org/10.1080/13697130600865774.

[30] Huang Y, Wu M, Wu C, Zhu Q, Wu T, Zhu X, et al. Effect of hysterectomy on ovarian function: a systematic review and meta-analysis. Journal of Ovarian Research. 2023; 16: 35. https://doi.org/10.1186/s13048-023-01117-1.

[31] Luo G, Zhang Y, Wang L, Huang Y, Yu Q, Guo P, et al. Risk of colorectal cancer with hysterectomy and oophorectomy: A systematic review and meta-analysis. International Journal of Surgery (London, England). 2016; 34: 88–95. https://doi.org/10.1016/j.ijsu.2016.08.518.

[32] Iorga A, Cunningham CM, Moazeni S, Ruffenach G, Umar S, Eghbali M. The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biology of Sex Differences. 2017; 8: 33. https://doi.org/10.1186/s13293-017-0152-8.

[33] Yu L, Yu P, Lu Y. Is hysterectomy associated with kidney cancer risk? A meta-analysis of cohort studies. Frontiers in Oncology. 2023; 13: 1181112. https://doi.org/10.3389/fonc.2023.1181112.

[34] Fu S, Lu Y, Liu Y. The risk of thyroid cancer after hysterectomy and oophorectomy: a meta-analysis. Frontiers in Oncology. 2024; 14: 1446303. https://doi.org/10.3389/fonc.2024.1446303.

[35] Poorthuis MHF, Yao P, Chen Y, Guo Y, Shi L, Li L, et al. Risks of Stroke and Heart Disease Following Hysterectomy and Oophorectomy in Chinese Premenopausal Women. Stroke. 2022; 53: 3064–3071. https://doi.org/10.1161/STROKEAHA.121.037305.

[36] Yuk JS, Kim BG, Lee BK, Seo J, Kim GS, Min K, et al. Association of Early Hysterectomy With Risk of Cardiovascular Disease in Korean Women. JAMA Network Open. 2023; 6: e2317145. https://doi.org/10.1001/jamanetworkopen.2023.17145.

[37] Hassan H, Allen I, Sofianopoulou E, Walburga Y, Turnbull C, Eccles DM, et al. Long-term outcomes of hysterectomy with bilateral salpingo-oophorectomy: a systematic review and meta-analysis. American Journal of Obstetrics and Gynecology. 2024; 230: 44–57. https://doi.org/10.1016/j.ajog.2023.06.043.