Prospective cohort study. MATERIALS AND METHODS: We followed 93,775 women participating in the Nurses' Health Study II between 1991 and 2013 who had no prior history of cardiovascular disease, cancer, or diabetes and who reported the usual length and regularity of their menstrual cycles at ages of 14-17, 18-22, and 28-48 years. We obtained hazard ratios (HR) and 95% confidence intervals (CI) for the relationships between menstrual cycle characteristics and mortality from Cox proportional hazards models adjusted for relevant confounders including body mass index, race/ethnicity, and physical activity, and lifestyle factors.RESULTS: We documented 1679 deaths, including 828 from cancer, and 166 from cardiovascular disease, during 1,729,410 person-years of followup. After adjustment for various covariates, women reported that their menstrual cycles were always irregular between the ages of 14-17 and 18-22 were 21% [HR¼1.21 (95% CI: 1.04, 1.40)] and 34% [HR¼1.34 (95% CI: 1.08, 1.66)], respectively, more likely to die from any causes during follow-up than women reporting very regular menstrual cycles in the same age range. A similar relation was observed with irregular menstrual cycles between the ages of 28-48 years. Likewise, women reporting a current usual cycle length of 32-39 days or of R40 days were more likely to die from any causes during follow-up than women whose current usual cycle length was 26-31 days [HRs ¼1.23 (95% CI: 1.04, 1.45), and 1.28 (95% CI: 1.05, 1.55), respectively]. Elevated HR for cardiovascular and cancer mortality was also associated with longer menstrual cycle lengths (>32 days) between the ages of 28-48 years.CONCLUSIONS: Irregular and long menstrual cycles are associated with an increased risk of mortality.

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