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Caren G. Solomon, MD; Frank B. Hu, MD; Andrea Dunaif, MD; Janet Rich-Edwards, DSci; Walter C. Willett, MD; David J. Hunter, MD; Graham A. Colditz, MD; Frank E. Speizer, MD; JoAnn E. Manson, MD

JAMA. 2001;286:2421-2426.

Context  Although oligomenorrhea has been associated cross-sectionally with insulin resistance and glucose intolerance, it is not known whether oligomenorrhea is a marker for increased future risk of type 2 diabetes mellitus (DM).

Objective  To prospectively assess risk of type 2 DM in women with a history of long or highly irregular menstrual cycles.

Design and Setting  The Nurses' Health Study II, a prospective observational cohort study.

Participants  A total of 101 073 women who had no prior history of DM and who reported their usual menstrual cycle pattern at age 18 to 22 years on the baseline (1989) questionnaire.

Main Outcome Measure  Incident reports of DM, with follow-up through 1997, compared among women categorized by menstrual cycle length (5 categories).

Results  During 564 333 person-years of follow-up, there were 507 cases of type 2 DM. Compared with women with a usual cycle length of 26 to 31 days (referent category) at age 18 to 22 years, the relative risk (RR) of type 2 DM among women with a menstrual cycle length that was 40 days or more or was too irregular to estimate was 2.08 (95% confidence interval [CI], 1.62-2.66), adjusting for body mass index at age 18 years and several other potential confounding variables. The RR of type 2 DM associated with long or highly irregular menstrual cycles was greater in obese women, but was also increased in nonobese women (at body mass indexes at age 18 years of <25, 25-29, and 30 kg/m², RRs were 1.67 [95% CI, 1.14-2.45], 1.74 [95% CI, 1.07-2.82], and 3.86 [95% CI, 2.33-6.38], respectively).

Conclusion  Women with long or highly irregular menstrual cycles have a significantly increased risk for developing type 2 DM that is not completely explained by obesity.

Author Affiliations: Division of Women's Health (Drs Solomon and Dunaif), Division of General Medicine (Dr Solomon), Channing Laboratory (Drs Willett, Hunter, Colditz, Speizer, and Manson), and Division of Preventive Medicine (Dr Manson), Department of Medicine, Brigham and Women's Hospital; the Departments of Maternal and Child Health (Dr Rich-Edwards), Nutrition (Drs Hu and Willett), and Epidemiology (Drs Willett, Hunter, Colditz, and Manson), Harvard School of Public Health; and Department of Ambulatory Care and Prevention, Harvard Medical School, and Harvard Pilgrim Health Plan (Dr Rich-Edwards), Boston, Mass. Dr Dunaif is now with the Department of Medicine, Northwestern University Medical School, Chicago, Ill.

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