In 511 nulliparous women aged 15-19 years and 347 aged 30-39, an analysis has been undertaken of the relationship of urine concentrations of the three principal estrogens to age, age at menarche and Quetelet's index of adiposity. The analysis was undertaken by means of multiple regression, controlling for each of the 12 centers from which the data originated, as well as for the other study variables. In the younger women, age was strongly and positively related to concentrations of E1 and E2 and less so to E3. In the age group 30-39, follicular phase specimens showed positive relationships with age for all three fractions but luteal specimens did not. Age at menarche showed inverse relationships to levels of E1 and E2 which were significant in the younger but not in the older age group. The associations of estrogens with Quetelet's index were weak and not statistically significant. The data suggest that women whose menarche occurs early not only have a longer duration of exposure to estrogens during years which are probably important in the initiation of breast cancer but, in addition, their exposures are at a higher level during those years and probably at later ages also. These observations support the hypothesis that the mechanism of the association of early menarche with breast cancer risk is via the association of both with estrogen stimulus.
An analysis is undertaken of the frequency of ovulation in 17 groups of women aged 15 to 19 who had been the subjects of other studies. A urine specimen of at least 8 h accumulation had been provided on the 20th or 21st day of a menstrual cycle by 681 women. Analysis is restricted to 431 specimens which had been collected between 11 and 3 days prior to the onset of the subsequent menstrual period. A pregnanediol concentration of less than 1 mg per litre in such a specimen was taken as evidence that the cycle was anovular. The probability of a cycle being anovular was inversely and significantly related to the number of years since menarche, and, with years since menarche held constant, was positively but not significantly associated with age at menarche. This observation indicates that women with early menarche do not have a longer duration of exposure to anovular cycles than do those whose menarche is delayed, and that variation in the duration of exposure to post-menarcheal anovular cycles does not explain the association of breast cancer risk with early age at menarche. The 17 groups of women were classified into four categories according to ethnic origin and breast cancer incidence in the populations from which they derived. Anovular cycles were not more common in the high-risk groups; indeed, the two centers in the lowest risk category had the highest proportion of anovular cycles.
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