Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study

Objective To prospectively assess the effect of endometriosis and uterine fibroids on the long term risk of premature mortality (younger than 70 years). Design Prospective cohort study Setting The Nurses’ Health Study II, United States (1989-2019). Participants 110 091 women aged 25-42 years in 1989 without a history of hysterectomy before endometriosis or fibroids diagnosis, cardiovascular diseases, or cancer. Main outcome measures Hazard ratios (estimated by Cox proportional hazards models) for total and cause specific premature mortality according to laparoscopically confirmed endometriosis or ultrasound or hysterectomy confirmed uterine fibroids reported in biennial questionnaires. Results 4356 premature deaths were recorded during 2 994 354 person years of follow-up (27.2 years per person), including 1459 from cancer, 304 from cardiovascular diseases, and 90 from respiratory diseases. The crude incidence of all cause premature mortality for women with and without laparoscopically confirmed endometriosis was 2.01 and 1.40 per 1000 person years, respectively. In age adjusted models, laparoscopically confirmed endometriosis was associated with a hazard ratio of 1.19 (95% confidence interval 1.09 to 1.30) for premature death; these models were strengthened after also adjusting for potential confounders including behavioral factors (1.31, 1.20 to 1.44). Cause specific mortality analyses showed that the association was largely driven by mortality from senility and ill-defined diseases (1.80, 1.19 to 2.73), non-malignant respiratory diseases (1.95, 1.11 to 3.41), diseases of the nervous system and sense organs (2.50, 1.40 to 4.44), and malignant neoplasm of gynecological organs (2.76, 1.79 to 4.26). Ultrasound or hysterectomy confirmed uterine fibroids were not associated with all cause premature mortality (1.03, 0.95 to 1.11), but were associated with a greater risk of mortality from malignant neoplasm of gynecological organs (2.32, 1.59 to 3.40) in cause specific mortality analyses. The risk of mortality caused by cardiovascular and respiratory diseases varied according to joint categories of endometriosis and uterine fibroids, with an increased risk of all cause premature mortality among women reporting both endometriosis and uterine fibroids. Conclusion Women with a history of endometriosis and uterine fibroids might have an increased long term risk of premature mortality extending beyond their reproductive lifespan. These conditions were also associated with an increased risk of death due to gynecological cancers. Endometriosis was associated with a greater risk of non-cancer mortality. These findings highlight the importance for primary care providers to consider these gynecological disorders in their assessment of women's health. The data used in the present study will not be made publicly available, but they are accessible by contacting the research staff from NHSII at . The analytic SAS codes are available from the corresponding author and can also be found in supporting materials.