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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-Müllerian 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.