Objective: To verify whether a population-based hypothesis (age at menarche and age at natural menopause have an inverse relationship) also applies at the level of the individual and to investigate what other factors predict age at natural menopause.
Design: Prospective cohort study (the Doorlopend Onderzoek Morbiditeit/Mortaliteit [DOM] project).
Setting: Prevention Breast Cancer Screening Centre, Utrecht, The Netherlands.
Patient(s): A cohort of 3,756 Dutch women, born between 1911 and 1925, participating in a population-based breast cancer screening program, who experienced a natural menopause. Three samples of women were studied: a sample who did not use oral contraceptives (OCs) (n = 3,347), a sample of OC users (n = 409), and a combined sample of OC users and nonusers (n = 3,756).
Main outcome measure(s): Age at menopause and menarche, fertility patterns, OC use, height, weight, smoking, and demographic variables.
Result(s): No relation was found between age at menarche and age at natural menopause. The total percentage of variance in age at natural menopause explained by multiple regression including all factors was minimal, ranging from 1.3% to 9.7% in OC users. Linear regression analysis indicated a slight secular trend in age at menopause.
Conclusion(s): Frisch's hypothesis could not be corroborated at the individual level. These results suggest that age at menarche and menopause should be treated as independent risk factors for breast cancer. Modification of age at menopause by lifestyle factors (except possibly for OC use) appears minimal.