Hysterectomy, non-malignant gynecological diseases, and the risk of incident hypertension: The E3N prospective cohort

Highlights

• In this study, hysterectomy, with or without oophorectomy, was associated with an increased risk of hypertension.

• Endometriosis was associated with an increased risk of hypertension.

• A history of uterine fibroids was associated with an increased risk of hypertension.

• Associations between hypertension and non-malignant gynecological diseases were independent of a history of hysterectomy.

Abstract

Objectives

While it has been reported that women with uterine fibroids or endometriosis are commonly overweight and hypertensive, the association between non-malignant gynecological diseases and the risk of hypertension has been little studied prospectively. The aim of this study was to investigate in a large French cohort of women whether a history of hysterectomy, uterine fibroids, or endometriosis was prospectively related to an increased risk of incident hypertension.

Study design

We analyzed 50,286 women from the E3N cohort who were free of hypertension at baseline, with a median follow-up of 16.4 years.

Main outcome measures

Gynecological diseases were based on self-report. Cox proportional hazards models with age as the timescale were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Covariates included smoking status, body mass index (BMI), physical activity, and hormonal factors.

Results

A total of 12,073 women (24%) developed hypertension during follow-up. Women with a history of hysterectomy had an increased risk of incident hypertension, which persisted after adjustment for potential confounding factors (adjusted HR=1.18, 95% CI 1.12–1.24). Risk was similar in women with hysterectomy with or without oophorectomy. Risk of hypertension was higher in women with a history of endometriosis (HR_{endometriosis} 1.19, 95%CI 1.11–1.22) or uterine fibroids (HR_fibroids 1.18, 95%CI 1.13–1.22), irrespective of hysterectomy. Associations were similar after further adjustment for BMI.

Conclusions

Hysterectomy and non-malignant gynecological diseases were associated with an increased risk of hypertension in this large prospective study. Women with these conditions may benefit from blood pressure monitoring.

ClinicalTrials.gov identifier: NCT03285230

Introduction

Hypertension is the main risk factor for cardiovascular diseases (CVD), which are the primary cause of death in women [1]. Recent epidemiological studies have shown that the proportion of deaths attributable to CVD is higher in women (49%) than in men (40%) [1]. An increase in the incidence of CVD has been observed in younger women (under 60 years old) due to the modernization of lifestyle over the past decades [1, 2]. Better knowledge is therefore needed to fill the gender gap and improve cardiovascular health in women [3].

Hypertension affects 26% of the world population with a steady increase in prevalence [4,5]. It is often silent, underdiagnosed, and undertreated, especially in women [5, 6]. Hypertension is more frequent in women after menopause than in men [4] and has a more deleterious impact on the risk of cardiovascular events in women as compared to men [7, 8]. Identification of risk factors for hypertension is therefore crucial to early diagnose and manage hypertension in order to prevent its cardiovascular complications [3]. Several female-specific risk factors for hypertension have been identified, including preeclampsia and use of oral contraceptives [3]. Other factors such as hysterectomy or non-malignant gynecological disease could also be associated with the risk of hypertension but results from previous studies are unclear [9], [10], [11], [12], [13], [14], [15].

Hysterectomy is one of the most common gynecological procedures and is most often performed in case of non-malignant diseases such as fibroma or endometriosis [16, 17]. Women undergoing this surgery may experience metabolic changes by losing the protective effect of estrogens on cardiovascular health [18, 19]. An association between hysterectomy, with or without oophorectomy, and hypertension and cardiovascular risk has been reported in previous studies [9], [10], [11], [12], but results are inconsistent. Risk of hypertension was increased after hysterectomy in some studies [9, 11, 12] but not in all studies [10]. Most of these studies were based on small population without prospective follow-up and did not analyze major potential confounding such as body mass index (BMI), often increased in women with hysterectomy [11], and use of hormone replacement therapy (HRT).

Similarly, associations between non-malignant gynecological conditions, such as endometriosis and fibroids, and the risk of hypertension are unclear, and the confounding or mediating effects by other risk factors or by hysterectomy, frequent treatment of these diseases, are still unknown [11, [13], [14], [15], [20], [21], [22], [23]]. Additional large cohort studies are warranted to confirm the association between these conditions and the risk of incident hypertension.

This study aimed to prospectively assess the association between hysterectomy, non-malignant gynecological diseases (uterine fibroids and endometriosis), and the risk of incident hypertension in a large prospective cohort of French women.