Surgically verified endometriosis is associated with lower short. A long-term risk of death

Abstract

Introduction Endometriosis is a chronic disease where endometrial-like tissue is situated outside the uterine cavity affecting 5–10% of fertile-aged women. Chronic inflammation is linked to increased risk of various adverse health outcomes such as increased risk of cardiovascular disease, cancer, and neurodegenerative diseases such as Alzheimer's disease. Endometriosis has also been linked to increased risk of several associated conditions, such as malignant disease, autoimmune/rheumatoid diseases, cardiovascular and atopic diseases. This register-based cohort study aims to assess the mortality risks between women with surgically verified endometriosis as compared to a reference cohort. A cohort of 49,956 women with surgically verified endometriosis and a reference cohort of 98,824 women matched with age and residence was retrieved from the Finnish Hospital Discharge Registry between 1987–2012 and followed for deaths (Statistics Finland) until 2014. Methods We calculated the crude overall and cause-specific (classification of death causes by Statistics Finland) mortality rate ratios (MRR) as the number of deaths divided by person-years. The adjusted MRRs were calculated by applying multivariable Poisson models controlling for the calendar time at baseline, time-varying attended age and duration of follow-up (cubic splines), the highest educational level, parity as time-dependent covariate, and gynecological organ (uterus, ovary/ovaries, both) removals during the follow-up. Results In total, 2.5 million person-years (34% in endometriosis cohort) accumulated during the median follow-up time of 17.3 years. The mean age of the study population at the end of the follow-up was 53.7 (± 12.1) years. There were 1656 and 4291 deaths in the endometriosis and reference cohorts, respectively. In endometriosis cohort, we observed a lower risk of death from any cause (crude MRR = 0.76, 95% confidence interval [0.72–0.80], adjusted MRR = 0.72 [0.67–0.77]). The difference between the cohorts of age-adjusted MRR remained significant over the follow-up time of 28 years. The major contributors to the overall mortality in the endometriosis cohort were deaths due malignant neoplasms (49%), diseases of the circulatory system (16%), accidents and violence (7%), and alcohol-related diseases and accidental poisoning by alcohol (5%). The overall mortality of malignant neoplasms was decreased in endometriosis cohort as compared to reference cohort (crude MRR 0.91 [0.83–0.98], adjusted MRR 0.71 [0.64–0.78]), whereas no statistically significant difference was seen for any specific cancer. The mortality due diseases of the circulatory system was significantly lower in endometriosis patients (crude MRR 0.60 [0.52–0.68], adjusted MRR 0.71 [0.60–0.85]) when compared to the reference cohort, and difference persisted across specific diseases: cardiovascular diseases (crude MRR 0.58 [0.50–0.68], adjusted MRR 0.72 [0.59–0.78]), ischemic heart disease (crude MRR 0.55 [0.45–0.68], adjusted MRR 0.75 [0.57–0.98]) and cerebrovascular diseases (crude MRR 0.63 [0.50–0.80], adjusted MRR 0.69 [0.51–0.93]). Mortality due to alcohol-related causes and accidental poisoning by alcohol was lower in endometriosis cohort (crude MRR = 0.43 [0.34–0.54], adjusted MRR 0.60 [0.46–0.79]). Decreased mortality was also seen for other death causes, such as respiratory system diseases, total accidents, diabetes. No difference in mortality was seen with dementia, Alzheimer's disease nor these together, other diseases of the nervous system and sense organs, suicides. Conclusion The overall mortality was not increased among endometriosis cohort. The statistically significant difference persisted across the major causes of death, such as circulatory diseases, cancer, accidents, alcohol-related causes and accidental poisoning by alcohol. The decreased mortality could result partly from the attention and care received by endometriosis patients, but also hormonal and life style factors may play an important role.