Menstrual Cycle Characteristics Across the Reproductive Lifespan, Lifestyle Factors and Risk of Type 2 Diabetes

Abstract

Background: Menstrual cycle dysfunction is associated with insulin resistance; however, the evidence linking irregular/long menstrual cycles with type 2 diabetes (T2D) is scarce and inconsistent. It is also unclear whether this relation can be modified by lifestyle factors. Methods: Between 1993 and 2017, we followed 75,546 premenopausal women without T2D at baseline who reported the usual length and regularity of their menstrual cycles at ages of 14-17, 18-22, and 29-46 years, as well as data on body weight, smoking status, physical activity, and diet every 2-4 years during follow-up. Time-dependent Cox proportional hazards regression models were constructed to estimate the hazard ratios (HRs) and 95% confidential intervals (CI) for the associations between menstrual cycle characteristics and T2D risk. Findings: We documented 5,608 new cases of T2D. After adjusting for potential confounders including BMI and lifestyle factors, women reporting always having irregular menstrual cycles between the ages of 14-17, 18-22, and 29-46 years were, respectively, 33% (95% CI: 23, 45%), 42% (95% CI: 23, 63%), and 66% (95% CI: 49, 84%) more likely to develop T2D than women reporting very regular cycles in the same age range. Similarly, women reporting usual cycle length ≥40 days between the ages of 18-22 and 29-46 years also had a higher risk of T2D than women reporting a usual cycle length of 26-31 days in the same age range (HRs=1.37; 95% CI: 1.20, 1.58 and 1.49; 95% CI: 1.36, 1.64, respectively). These relations were stronger for women with overweight/obesity and a lower level of physical activity when additive interaction was evaluated. Interpretation : Irregular and long menstrual cycles throughout life are associated with a higher risk of T2D, with a particularly elevated risk among women who were overweight/obesity and physical inactivity. Funding Statement: The National Institutes of Health grants U01-HL145386, U01-CA176726, R01-HL034594, R01-HL088521, DK120870, and DK112940. Declaration of Interests: The authors declare no competing interest. Ethics Approval Statement: Study procedures have been approved by the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health.