Mortality of Midlife Women With Surgically Verified Endometriosis

A Cohort Study Including 2.5 Million Person-years of Observation

L. Saavalainen; A. But; A. Tiitinen; P.Härkki; M. Gissler; J. Haukka; O. Heikinheimo

Disclosures

Hum Reprod. 2019;34(8):1576-1586. 

In This Article

Abstract and Introduction

Abstract

Study Question: Is all-cause and cause-specific mortality increased among women with surgically verified endometriosis?

Summary Answer: The all-cause and cause-specific mortality in midlife was lower throughout the follow-up among women with surgically verified endometriosis compared to the reference cohort.

What is Known Already: Endometriosis has been associated with an increased risk of comorbidities such as certain cancers and cardiovascular diseases. These diseases are also common causes of death; however, little is known about the mortality of women with endometriosis.

Study Design, Size, Duration: A nationwide retrospective cohort study of women with surgically verified diagnosis of endometriosis was compared to the reference cohort in Finland (1987–2012). Follow-up ended at death or 31 December 2014. During the median follow-up of 17 years, 2.5 million person-years accumulated.

Participants/Materials, Setting, Methods: Forty-nine thousand nine hundred and fifty-six women with at least one record of surgically verified diagnosis of endometriosis in the Finnish Hospital Discharge Register between 1987 and 2012 were compared to a reference cohort of 98 824 age- and municipality-matched women. The age (mean ± standard deviation) of the endometriosis cohort was 36.4 ± 9.0 and 53.6 ± 12.1 years at the beginning and at the end of the follow-up, respectively. By using the Poisson regression models the crude and adjusted all-cause and cause-specific mortality rate ratios (MRR) and 95% confidence intervals (CI) were assessed. Calendar time, age, time since the start of follow-up, educational level, and parity adjusted were considered in the multivariate analyses.

Main Results and the Role of Chance: A total of 1656 and 4291 deaths occurred in the endometriosis and reference cohorts, respectively. A lower all-cause mortality was observed for the endometriosis cohort (adjusted MRR, 0.73 [95% CI 0.69 to 0.77])—there were four deaths less per 1000 women over 10 years. A lower cause-specific mortality contributed to this: the adjusted MRR was 0.88 (95% CI 0.81 to 0.96) for any cancer and 0.55 (95% CI 0.47 to 0.65) for cardiovascular diseases, including 0.52 (95% CI 0.42 to 0.64) for ischemic heart disease and 0.60 (95% CI 0.47 to 0.76) for cerebrovascular disease. Mortality due to alcohol, accidents and violence, respiratory, and digestive disease-related causes was also decreased.

Limitations, Reasons for Causation: These results are limited to women with endometriosis diagnosed by surgery. In addition, the study does not extend into the oldest age groups. The results might be explained by the characteristics and factors related to women's lifestyle, and/or increased medical attention and care received, rather than the disease itself.

Wider Implications of the Findings: These reassuring data are valuable to women with endometriosis and to their health care providers. Nonetheless, more studies are needed to address the causality.

Study Funding/Competing Interest: This research was funded by the Hospital District of Helsinki and Uusimaa and The Finnish Medical Foundation. None of the authors report any competing interest in relation to the present work; all the authors have completed the disclosure form.

Introduction

Endometriosis is a chronic inflammatory disease affecting ~5 to 10% of fertile-aged women. It causes substantial individual and societal burden, comparable to other chronic diseases (Simoens et al., 2012; Vercellini et al., 2014). Chronic inflammation is linked to various adverse health outcomes, such as increased risk of cardiovascular disease, cancer, and neurodegenerative diseases such as Alzheimer's disease (Nogueira et al., 2015).

Indeed, endometriosis has been linked to increased risk of several associated conditions, including malignant, autoimmune, rheumatoid, and cardiovascular diseases. There is also an increased risk of several cancers, especially endometrioid and clear cell types of ovarian cancers and less clearly that of melanoma, non-Hodgkin lymphoma, and thyroid carcinoma (Kvaskoff et al., 2015). The Nurses' Health study recently found that the risk of coronary heart disease is significantly increased (1.5 to 2-fold) among women with laparoscopically diagnosed endometriosis. In addition to chronic inflammation, surgical and/or medical treatments of endometriosis may contribute to this increased risk (Mu et al., 2016).

Ischemic heart disease has long been the leading cause of death worldwide, and cancer is the leading cause of death in younger women in the western world (Lozano et al., 2012; Naghavi et al., 2017). In the present study, we examined the risk of death in a large cohort of women with surgically verified endometriosis in comparison to age and municipality matched reference women using high-quality Finnish administrative and health registers (Gissler and Haukka, 2004; Sund, 2012; Pukkala et al., 2018). There is only one previous Swedish study assessing cancer survival in women with endometriosis (Melin et al., 2011).

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