Hysterectomy in young women associates with higher risk of stroke: A nationwide cohort study

doi:10.1016/j.ijcard.2013.03.042

International Journal of Cardiology

Volume 168, Issue 3, 3 October 2013, Pages 2616-2621

https://doi.org/10.1016/j.ijcard.2013.03.042 Get rights and content

Abstract

Background and purpose

Hysterectomy is a common procedure for treatment of numerous gynecologic diseases. However, reduction of endogenous sex hormone levels has been reported in hysterectomized women, and the association of hysterectomy with the cardiovascular risk remains controversial. We aimed to investigate the influence of hysterectomy on the risk of stroke and coronary heart disease, with adjustment for traditional risk factors.

Methods

A nationwide population-based study was conducted using the Taiwan National Health Insurance database from 1 million sampling cohort data set. A total of 7605 women who underwent hysterectomy without simultaneous oophorectomy from 1997 to 2009 were identified. The control group consisted of 30,420 women without hysterectomy, selected by matching the age, hypertension, diabetes, dyslipidemia, and the commencement date of follow-up.

Results

A total of 558 strokes and 599 coronary heart diseases (CHD) developed during a median 7.24 years follow-up. The difference was not significant between women with and without hysterectomy for stroke (2.34 vs. 2.08 per 1000 person-year, p = 0.26) and CHD (2.39 vs. 2.26, p = 0.53). However, of the women who underwent hysterectomy before 45 years, the hazard ratio of hysterectomy was 2.29 (95% CI, 1.52–3.44) for stroke and 1.14 (95% CI, 0.71–1.83) for CHD.

Conclusions

Categorized by the patients' age at operation, the associations between hysterectomy and the risk of stroke were different. The excess risk of stroke was observed in women who had hysterectomy before 45 years and remained significant even after accounting for baseline cardiovascular risk factors.

Introduction

Hysterectomy is the second most common major gynecologic surgery performed in women in western countries after cesarean delivery. Due to low perioperative morbidity and cost effectiveness, hysterectomy is an attractive and definite treatment option for numerous gynecological disorders. In the United States, approximately 600,000 women undergo this procedure each year [1]. Around 20% of women in the UK received a hysterectomy by age 55 [2]. In Taiwan, the incidence of hysterectomy was approximately 268 to 303 per 100,000 women from 1996 to 2001 [3]. Because elective bilateral salpingo-oophorectomy (BSO) decreases the risk of ovarian cancer [4], it is performed in conjunction with more than half of hysterectomies [5]. However, cardiovascular disease (CVD) risks may be increased after BSO as a result of the reduction of endogenous sex hormone levels following the procedure [4], [6], [7], [8]. As a consequence, the American Congress of Obstetricians and Gynecologists specifically advocates for ovarian conservation in premenopausal women with no known genetic risk for ovarian cancer [9]. Nonetheless, it has been demonstrated that the endogenous sex hormone levels were also reduced considerably in hysterectomized women even with intact ovaries as compared to women who did not have hysterectomy [10], [11], [12]. These findings inevitably raise concern about the long-term health consequences that follow hysterectomy. Until now, due to previous conflicting relations in studies including hysterectomized women [5], [7], [13], [14], it is important to reconfirm the correlation of hysterectomy and the risk of stroke and coronary heart diseases (CHD) with a more definitive study population and a more rigorous study design, which may provide better evidence for surgeons to form clinical decisions and choose appropriate surgical interventions. Therefore, it was the aim of this nationwide, population-based cohort study to clarify the exact influence of hysterectomy for benign indication on the risk of stroke and CHD after accounting for traditional risk factors.

Section snippets

Study population

National Health Insurance is a single-payer insurance program in Taiwan, and has operated since 1995 covering 98% of the Taiwanese population. The database includes patients' demographics, diagnosis and prescriptions in hospital and in outpatient claims. Currently, the National Health Research Institutes (NHRI) is in charge of the National Health Insurance Research database (NHIRD) in Miaoli (Taiwan) (available at: www.nhri.org.tw/nhird/) and provides researchers with the complete National

Results

The women without hysterectomy were randomly selected to match subjects with hysterectomy by the age and the status of hypertension, diabetes, and dyslipidemia in one-to-four pairs. Therefore, the means and distributions of age, the prevalence of hypertension and diabetes, and dyslipidemia between women with and without hysterectomy were the same (all p-value = 1.000) (Table 1).

A total of 870 strokes, 936 CHD, and 1627 CVD developed during the whole follow-up period. After excluding the

Discussion

The present nationwide population cohort study, consisting of 7605 women who underwent hysterectomy without simultaneous oophorectomy and 30,420 matched controls with a median follow-up of 7.24 years, demonstrated that the women with age at operation less than 45 years had different risk profiles of cardiovascular events from those above 45 years. The significantly increased risk for stroke was observed in women who had hysterectomy at age less than 45 years, and the excess risk remained

Conclusion

Hysterectomy for benign disease may carry increased cardiovascular risks in young women. A randomized controlled trial on this issue for premenopausal women with benign uterine disease may be needed.

Sources of funding

This work was supported in part by an intramural grant from the Taipei Veterans General Hospital (grant no. V100B-031), grants from National Health Research Institutes (grant no. PH-100-PP-55 and PH-101-PP-24) and grant from Taipei Medical University WanFang Hospital (grant nos. 102-wf-eva-30 and 102swf05).

Acknowledgments

This study is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health and managed by National Health Research Institutes. The interpretation and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health or National Health Research Institutes.

References (25)

M.P. Wu et al.
Trends in various types of surgery for hysterectomy and distribution by patient age, surgeon age, and hospital accreditation: 10-year population-based study in Taiwan
J Minim Invasive Gynecol
(2010)
W.H. Parker
Bilateral oophorectomy versus ovarian conservation: effects on long-term women's health
J Minim Invasive Gynecol
(2010)
A. Oldenhave et al.
Hysterectomized women with ovarian conservation report more severe climacteric complaints than do normal climacteric women of similar age
Am J Obstet Gynecol
(1993)
M. Falkeborn et al.
Risk of myocardial infarction after oophorectomy and hysterectomy
J Clin Epidemiol
(2000)
N. Siddle et al.
The effect of hysterectomy on the age at ovarian failure: identification of a subgroup of women with premature loss of ovarian function and literature review
Fertil Steril
(1987)
Y.T. van der Schouw et al.
Age at menopause as a risk factor for cardiovascular mortality
Lancet
(1996)
E. Lokkegaard et al.
The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy
Maturitas
(2006)
R. Luoto et al.
Cardiovascular morbidity in relation to ovarian function after hysterectomy
Obstet Gynecol
(1995)
R.M. Merrill
Hysterectomy surveillance in the United States, 1997 through 2005
Med Sci Monit
(2008)
M.P. Vessey et al.
The epidemiology of hysterectomy: findings in a large cohort study
Br J Obstet Gynaecol
(1992)

B.V. Howard et al.

Risk of cardiovascular disease by hysterectomy status, with and without oophorectomy: the Women's Health Initiative Observational Study

Circulation

(2005)

W.H. Parker et al.

Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses' health study

Obstet Gynecol

(2009)

Cited by (26)

Hysterectomy and ischemic heart disease: An observational study using propensity score methods in NHANES 2007–2018
2021, Atherosclerosis
Citation Excerpt :
Moreover, there are only few studies focusing on different types of CVD. A cohort study of Taiwan National Health Insurance (NHI) database found hysterectomy was not significantly associated with risk of CAD but could increase the risk of stroke if the hysterectomy was performed before 45 years [25]; another NHI cohort study showed that hysterectomy could increase the risk of CAD [26]; and Palmer et al. discovered that hysterectomy with ovaries preservation before 45 years was related to the risk of myocardial infarction in a case-control study [27]. In all types of CVD, ischemic heart disease plays the most vital role in CVD health loss globally [28].
The association between hysterectomy and cardiovascular disease (CVD) remains controversial and research focusing on different types of CVD, especially ischemic heart disease, is scant.
This observational study was conducted with the National Health and Nutrition Examination Survey (NHANES) 2007–2018 using propensity score matching, propensity score overlap weighting, and logistic regression.
Among 15,257 women, 3476 (22.78%) had hysterectomy. Compared with non-hysterectomized women, hysterectomized women are more likely to be older, obese, with lower education level, and lower annual family income. Less favorable outcomes often occurred in unadjusted analysis. In adjusted, matched, and weighted analyses, the associations between hysterectomy and all outcomes were consistent, including ischemic heart disease (OR_unadjusted = 3.18[95%CI, 2.76–3.66]; OR_adjusted = 1.38[95%CI, 1.09–1.73]; OR_matched = 1.37[95%CI, 1.07–1.75]; OR_weighted = 1.38[95%CI, 1.12–1.71]), coronary heart disease (OR_unadjusted = 3.31[95%CI, 2.71–4.05]; OR_adjusted = 1.43[95%CI, 1.04–1.98]; OR_matched = 1.46[95%CI, 1.04–2.05]; OR_weighted = 1.45[95%CI, 1.06–1.99]), heart attack (OR_unadjusted = 3.04[95%CI, 2.51–3.68]; OR_adjusted = 1.47[95%CI, 1.09–1.99]; OR_matched = 1.42[95%CI, 1.03–1.95]; OR_weighted = 1.45[95%CI, 1.10–1.91]) and angina pectoris (OR_unadjusted = 3.29[95%CI, 2.66–4.08]; OR_adjusted = 1.34[95%CI, 0.95–1.89]; OR_matched = 1.30[95%CI, 0.91–1.87]; OR_weighted = 1.33[95%CI, 0.98–1.81]). In hysterectomized women, there were no significant associations between bilateral ovariectomy and ischemic heart disease (OR_unadjusted = 1.24[95%CI, 0.99–1.54]; OR_adjusted = 1.05[95%CI, 0.80–1.38]; OR_matched = 1.16[95%CI, 0.86–1.55]; OR_weighted = 0.93[95%CI, 0.68–1.27]), female hormones use and ischemic heart disease (OR_unadjusted = 0.94[95%CI, 0.76–1.16]; OR_adjusted = 0.81[95%CI, 0.62–1.07]; OR_matched = 0.89[95%CI, 0.66–1.20]; OR_weighted = 1.14[95%CI, 0.88–1.49]).
Hysterectomy may increase the risk of ischemic heart disease, especially for coronary heart disease and heart attack, but not for angina pectoris. As for the hysterectomized women, bilateral ovariectomy and female hormones use do not affect ischemic heart disease.
Hysterectomy status and all-cause mortality in a 21-year Australian population-based cohort study
2019, American Journal of Obstetrics and Gynecology
Citation Excerpt :
Our previous research has shown associations between hysterectomy (with and without bilateral oophorectomy) and poorer physical8 and mental9 health. Hysterectomy has also been associated with chronic diseases such as diabetes,10 stroke,11 and certain cancers.12,13 For diabetes, stroke, and poorer physical health, young age at surgery increases this risk.8,10,11
Hysterectomy is a common surgical procedure, predominantly performed when women are between 30 and 50 years old. One in 3 women in Australia has had a hysterectomy by the time they are 60 years old, and 30% have both ovaries removed at the time of surgery. Given this high prevalence, it is important to understand the long-term effects of hysterectomy. In particular, women who have a hysterectomy/oophorectomy at younger ages are likely to be premenopausal or perimenopausal and may experience greater changes in hormone levels and a shortened reproductive lifespan than women who have a hysterectomy when they are older and postmenopausal. Use of menopausal hormone therapy after surgery may compensate for these hormonal changes. To inform clinical decisions about postsurgery management of women who have a hysterectomy prior to menopause (ie, average age at menopause 50 years), it is useful to compare women with a hysterectomy to women with no hysterectomy and to stratify the hysterectomy status by whether or not women have had a bilateral oophorectomy, or used menopausal hormone therapy.
We sought to investigate whether women who had a hysterectomy with ovarian conservation or a hysterectomy and bilateral oophorectomy before the age of 50 years were at a higher risk of premature all-cause mortality compared to women who did not have this surgery before the age of 50 years. We also sought to explore whether use of menopausal hormone therapy modified these associations.
Women from the midcohort (born 1946 through 1951) of the Australian Longitudinal Study on Women’s Health were included in our study sample (n = 13,541). Women who reported a hysterectomy (with and without both ovaries removed) before the age of 50 years were considered exposure at risk and compared with women who did not report these surgeries before age 50 years. To explore effect modification by use of menopausal hormone therapy we further stratified hysterectomy status by menopausal hormone therapy use. Risk of all-cause mortality was assessed using inverse-probability weighted Cox regression models.
During a median follow-up of 21.5 years, there were 901 (6.7%) deaths in our study sample. Overall, there was no difference in all-cause mortality between women who reported a hysterectomy with ovarian conservation (hazard ratio, 0.86; 95% confidence interval, 0.72–1.02) or women who reported a hysterectomy and bilateral oophorectomy (hazard ratio, 1.02; 95% confidence interval, 0.78–1.34) and women with no hysterectomy. When stratified by menopausal hormone therapy use, women with hysterectomy and ovarian conservation before the age of 50 years were not at higher risk of all-cause mortality compared to no hysterectomy, regardless of menopausal hormone therapy use status. In contrast, among nonusers of menopausal hormone therapy only, women who reported a hysterectomy-bilateral oophorectomy before the age of 50 years were at a higher risk of death compared to women with no hysterectomy (hazard ratio, 1.81; 95% confidence interval, 1.01–3.25).
Hysterectomy with ovarian conservation before the age of 50 years did not increase risk of all-cause mortality. Among nonmenopausal hormone therapy users only, hysterectomy and bilateral oophorectomy before the age of 50 years was associated with a higher risk of death.
Hysterectomy does not increase the risk of hemorrhagic or ischemic stroke over a mean follow-up of 6 years: A longitudinal national cohort study
2018, Maturitas
Citation Excerpt :
Because previous studies have reported that endogenous sex steroid hormone levels were reduced after hysterectomy with ovarian conservation compared to intact uterus, concerns have been raised about the long-term health consequences after hysterectomy [11,12]. Several previous studies have analyzed the association between hysterectomy and stroke, but these studies showed conflicting results [13–17]. It is important to reassess the correlation between hysterectomy and the risk of stroke with a large-scale population-based study.
This study sought to evaluate the association between hysterectomy and the occurrence of stroke in a Korean national cohort.
Data from 2002 to 2013 were collected for individuals in the Korean National Health Insurance Service-National Cohort. We extracted data for patients who had undergone a hysterectomy (N = 11,280) and a 1:4 matched control group (N = 45,120) and then analyzed the occurrence of stroke. The patients were matched according to age, sex, income, region of residence, and medical history.
Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox proportional hazards model. Subgroup analyses were based on age (those under and those over 45 years of age) and type of hysterectomy (with or without bilateral oophorectomy).
No significant difference in risk of hemorrhagic stroke (adjusted HR = 0.91, p = 0.592) or ischemic stroke (adjusted HR = 0.85, p = 0.188) was found between women with and without hysterectomy. No significant differences were found in the subgroup analyses according to age or type of hysterectomy for hemorrhagic and ischemic stroke.
Over a mean follow-up of 6 years, hysterectomy is not associated with an increased risk of either ischemic or hemorrhagic stroke at any age after adjusting for CVD risk factors including, hypertension, diabetes mellitus, and dyslipidemia, regardless of bilateral oophorectomy.
Hysterectomy risk in premenopausal-aged military veterans: Associations with sexual assault and gynecologic symptoms
2016, American Journal of Obstetrics and Gynecology
Several gynecological conditions associated with hysterectomy, including abnormal bleeding and pelvic pain, have been observed at increased rates in women who have experienced sexual assault. Previous findings have suggested that one of the unique health care needs for female military veterans may be an increased prevalence of hysterectomy and that this increase may partially be due to their higher risk of sexual assault history and posttraumatic stress disorder (PTSD). Although associations between trauma, PTSD, and gynecological symptoms have been identified, little work has been done to date to directly examine the relationship between sexual assault, PTSD, and hysterectomy within the rapidly growing female veteran population.
The objective of the study was to assess the prevalence of hysterectomy in premenopausal-aged female veterans, compare with general population prevalence, and examine associations between hysterectomy and sexual assault, PTSD, and gynecological symptoms in this veteran population.
We performed a computer-assisted telephone interview between July 2005 and August 2008 of 1004 female Veterans Affairs (VA)–enrolled veterans ≤ 52 years old from 2 Midwestern US Veterans Affairs medical centers and associated community-based outreach clinics. Within the veteran study population, associations between hysterectomy and sexual assault, PTSD, and gynecological symptoms were assessed with bivariate analyses using χ², Wilcoxon-Mann-Whitney, and Student t tests; multivariate logistic regression analyses were used to look for independent associations. Hysterectomy prevalence and ages were compared with large civilian populations represented in the Behavioral Risk Factor Surveillance System and American College of Surgeons National Surgical Quality Improvement Program databases from similar timeframes using χ² and Student t tests.
Prevalence of hysterectomy was significantly higher (16.8% vs 13.3%, P = .0002), and mean age at hysterectomy was significantly lower (35 vs 43 years old, P < .0001) in this VA-enrolled sample of female veterans compared with civilian population-based data sets. Sixty-two percent of subjects had experienced attempted or completed sexual assault in their lifetimes. A history of completed lifetime sexual assault with vaginal penetration (LSA-V) was a significant risk factor for hysterectomy (age-adjusted odds ratio, 1.85), with those experiencing their first LSA-V in childhood or in military at particular risk. A history of PTSD was also associated with hysterectomy (age-adjusted odds ratio, 1.83), even when controlling for LSA-V. These associations were no longer significant when controlling for the increased rates of gynecological pain, abnormal gynecological bleeding, and pelvic inflammatory disease seen in those veterans with a history of LSA-V.
Premenopausal-aged veterans may be at higher overall risk for hysterectomy, and for hysterectomy at younger ages, than their civilian counterparts. Veterans who have experienced completed sexual assault with vaginal penetration in childhood or in military and those with a history of PTSD may be at particularly high risk for hysterectomy, potentially related to their higher risk of gynecological symptoms. If confirmed in future studies, these findings have important implications for women’s health care providers and policy makers within both the VA and civilian health care systems related to primary and secondary prevention, costs, and the potential for increased chronic disease and mortality.
Key drivers of hysterectomy among women of reproductive age in three states in India: comparative evidence from NFHS-4 and NFHS-5
2024, BMC Women's Health
Hysterectomy With and Without Oophorectomy, Tubal Ligation, and Risk of Cardiovascular Disease in the Nurses' Health Study II
2023, Journal of Women's Health

View all citing articles on Scopus

¹: A co-first author.

View full text

Hysterectomy in young women associates with higher risk of stroke: A nationwide cohort study

Abstract

Background and purpose

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Results

Discussion

Conclusion

Sources of funding

Acknowledgments

J Minim Invasive Gynecol

J Minim Invasive Gynecol

Am J Obstet Gynecol

J Clin Epidemiol

Fertil Steril

Lancet

Maturitas

Obstet Gynecol

Hysterectomy surveillance in the United States, 1997 through 2005

Med Sci Monit

The epidemiology of hysterectomy: findings in a large cohort study

Br J Obstet Gynaecol

Risk of cardiovascular disease by hysterectomy status, with and without oophorectomy: the Women's Health Initiative Observational Study

Circulation

Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses' health study

Obstet Gynecol