Menstrual Cycle Characteristics in Adolescence and Early Adulthood Are Associated With Risk of Early Natural Menopause

Context: Early natural menopause (i.e., before age 45 years) is associated with increased risk of adverse outcomes. Associations of earlier menopause with younger age at menarche and short and/or regular cycle length are suggested, but study findings are inconsistent and few address early menopause risk. Objective: To evaluate the relationship between menstrual cycle characteristics in early life with incident early natural menopause. Design: The prospective Nurses' Health Study 2 (1989 to 2011). Setting and Participants: Women ages 25 to 42 years and premenopausal in 1989 (N = 108,811). Main Outcome Measure(s): Risk of early natural menopause not due to surgery, radiation, or chemotherapy (n = 2794) was evaluated with Cox proportional hazards models. Anti-Mullerian hormone (AMH) levels were considered in a nested case-control sample (n = 820). Results: In adjusted models, risk was associated with earlier age at menarche (P for trend = 0.05), shorter (P for trend < 0.0001), and more-regular cycles (P for < 0.0001). The hazard ratio (HR) for women with age at menarche <= 9 (vs. 12) years was 1.28 (95% CI, 0.99 to 1.67). Women reporting usual menstrual cycle lengths,25 days at ages 18 to 22 years had substantially higher risk of early menopause (HR, 1.70; 95% CI, 1.47 to 1.96) than women with 26- to 31-day cycles, whereas women with >= 40 day cycles had lower risk (HR, 0.44; 95% CI, 0.34 to 0.58). Women with irregular cycle length had lower risk compared with women with regular cycles (HR, 0.51; 95% CI, 0.43 to 0.60). Associations with AMH concentrations among the nested case-control subset were consistent with these findings. Conclusion: Results from this large prospective study of early menopause suggest an influence of accelerated oocyte depletion on risk and may help clarify the etiology of early menopause.