Yi-Xin Wang

Menstrual cycle characteristics and incident cancer: a prospective cohort study

AbstractSTUDY QUESTIONAre menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk?SUMMARY ANSWERIrregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers.WHAT IS KNOWN ALREADYLong and irregular menstrual cycles have been associated with lower risk of pre-menopausal breast cancer and higher risk of endometrial cancer, but associations with other malignancies are less clear.STUDY DESIGN, SIZE, DURATIONProspective cohort study. Prospective follow-up of 78 943 women participating in the Nurses’ Health Study II between 1989 and 2015.PARTICIPANTS/MATERIALS, SETTING, METHODSWe followed 78 943 pre-menopausal women without cancer history who reported the usual length and regularity of their menstrual cycles at different ages (14–17, 18–22 and 29–46 years). Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian and post-menopausal breast) or non-obesity-related. We fitted Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association between menstrual cycle characteristics and cancer incidence.MAIN RESULTS AND THE ROLE OF CHANCEWe documented 5794 incident cancer cases during 1 646 789 person-years of follow-up. After adjusting for BMI and other potential confounders, women reporting irregular cycles at age 29–46 years had an 11% (95% CI: 2–21%) higher risk of total invasive cancer than women reporting very regular cycles at the same age. This association was limited to obesity-related cancers, with a 23% (95% CI: 9–39%) higher risk and was strongest for endometrial cancer (HR = 1.39; 95% CI: 1.09–1.77). Findings were comparable for cycle characteristics earlier in life and for menstrual cycle length. Very irregular cycles at age 14–17 years were associated with significant increase in risk of colorectal cancer (HR = 1.36; 95% CI: 1.02–1.81).LIMITATIONS, REASONS FOR CAUTIONOur study might be subject to recall bias for findings pertaining to cycle characteristics in adolescence and early adulthood, as these were retrospectively reported. Generalizability to non-White women may be limited, as 96% of participants were White.WIDER IMPLICATIONS OF THE FINDINGSWomen with irregular or long menstrual cycles in mid-adulthood had a statistically significantly higher risk of developing cancer, especially obesity-related cancers. This association was not limited to gynecological cancers. Obesity-related cancers may need to be added to the spectrum of long-term health consequences of long or irregular cycles, possibly warranting targeted screening among women who experience long or irregular cycles in mid-adulthood.STUDY FUNDING/COMPETING INTERESTThis work was supported by grants U01 CA176726, U01 HL145386 and R01 HD096033 from the National Institutes of Health. The authors have no conflicts of interest to declare.TRIAL REGISTRATION NUMBERN/A.

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

Abstract 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.