Menstrual cycle characteristics and history of ovulatory infertility in relation to breast cancer risk in a large cohort of US women

Menstrual cycle characteristics and ovulatory infertility were evaluated in relation to breast cancer risk among 116,678 women in the Nurses' Health Study II, a prospective cohort study of female registered nurses who were aged 25-42 years and living in 14 US states at enrollment in 1989. During 396,299 person-years of follow-up between return of the baseline questionnaire and June 1993, 251 cases of breast cancer were identified in this cohort. The multivariate relative risk (RR) associated with age at menarche >13 years compared with age less than or equal to 12 years was 0.66 (95% confidence interval (CI) 0.44-0.99). Short and long menstrual cycle lengths at ages 18-22 years were associated with reduced risk. Compared with menstrual cycle length 26-31 days, the multivariate relative risks (95% Cls) for more extreme cycle lengths were: <26 days, 0.50 (0.25-0.98); 32-39 days, 0.81 (0.51-1.28); and >39 days or too irregular for estimation of a usual cycle length, 0.41 (0.18-0.94). The multivariate relative risk associated with a history of ovulatory infertility, compared with no such history, was 0.41 (95% CI 0.18-0.93). These results are consistent with the hypothesis that reduced exposure to ovulatory menstrual cycles provides a protective effect against breast cancer.