Equipe E3N, Institut Gustave-Roussy, 94805 Villejuif, France
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Abstract |
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Key words: cohort study/evolution/menarche/menstrual cycle
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Introduction |
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As the evolution of these factors may influence the breast cancer burden, we examined both age at first menstruation and age at onset of regular cycling in a large sample of women participating in the E3N-EPIC cohort study, which is part of the European Prospective Investigation into Cancer (Riboli et al., 1992).
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Materials and methods |
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For this analysis, we examined answers to the following questions: `How old were you when you had your first menstrual period?' and `How old were you when your periods became regular?'. Answers ranged from 7 to 20 years of age for the first question and 7 to 25 for the second question, with additional possibilities for women who had never menstruated or who had never had regular periods.
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Results |
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Discussion |
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As with most cohort studies, our study used self-administered questionnaires as the source of information. Information on menstruation is thus potentially prone to recall bias. In one study (Bean et al., 1979), 10% of women (n = 160) misclassified age at menarche by over 1 year. Two other studies found that age at menarche was recalled by 62% in the correct annual age group 19 years after the original study (Damon et al., 1974) and by 50% 39 years after the study (Damon and Bajema, 1974
). Recall of the regularity of menstrual cycles was also analysed by Bean et al. (Bean et al., 1979
). Agreement was better for younger than for older women and was very dependent on the definition of regularity. In a subgroup of 549 women who answered the question on menarche twice, with an 18 month interval between replies, we found that 70.7% reported an identical age at first menstruation and 98.5% an age within a year of that initially reported. An increase in the rate of uncertainty about age at menarche with increasing interval since menarche is likely. In our population, the rate of missing answers to age at menarche remained stable across the birth cohorts, whereas the percentage of women who gave no answer to age at onset of regular cycling (which was the question following age at menarche) was, surprisingly, higher in the youngest cohorts. However, errors due to retrospective assessment and to self-reporting would have to be systematically biased to account for the results we observed in the evolution of age at menarche and age at onset of regular cycling.
Ethnic differences may potentially play a role in the characteristics of menstrual bleeding (Harlow and Campbell, 1996; Koprowski et al., 1999
). However, they cannot account for the changes we observed, as our population was ethnically homogeneous.
A secular trend towards earlier menarche has been clearly identified, with a decrease of 34 months per decade over the past century: 2.1 months for women born between 1840 and 1980 in France (Ducros and Pasquet, 1978
), 3.0 for women born between 1840 and 1990 in England (Rees, 1993
), 3.4 between women born in 1900 and 1950 in Iceland (Tryggvadottir et al., 1994
), 2.9 between women born around 1830 and 1960 in Norway (Rosenberg, 1991
), 2.8 between women born between 1949 and 1976 in two rural counties in China (Graham et al., 1999
), 2.0 for Japanese atomic bomb survivors born between 1902 and 1942 (Hoel et al., 1983
) and 3.2 between women born around 1920 and 1940 in the United States (Wyshak, 1983
). Age at menarche was
15.3 years around 1840 in occidental countries, whereas in the early 1980s it averaged 12.8 (Ducros and Pasquet, 1978
). The downward trend seems now to have stopped (Rees, 1993
; Wellens et al., 1990
) or to have reversed (Dann and Roberts, 1993
). Genetic factors as well as external ones such as climate, sunshine and chronic diseases have been put forward as being possibly linked to the evolution of age at menarche. Factors such as unhealthy diet, stress or psychological factors experienced during World War II might be responsible for the increase in age observed in our population for the 19251930 birth cohorts.
Few data are available on the evolution of age at onset of regular cycling. A similar trend towards increasing age at onset of regular cycling can be computed from the data of Rockhill (Rockhill et al., 1998): the percentages of women with an interval of 5 years or more before regular cycling were 8.9, 11.7, 12.2 and 13.6 respectively among controls who had experienced menarche before 11, and at 12, 13 and 14 years or over. Absolute values cannot be compared, however, as the study of Rockhill et al. concerned women born between 1920 and 1975 (Rockhill et al., 1998
). In an other study, time from menarche to the establishment of regular cycles was weakly positively correlated with age at menarche (Garland et al., 1998
).
The increase in the length of time before the onset of regular cycles was more apparent among women in the younger birth cohorts, in whom menarche occurred late. Use of hormonal treatments cannot account for our findings, as exclusion of ever users of these treatments (treatments to regularize cycles, or oral contraceptives, or both) did not modify our results. It is well documented that excessive leanness before menarche may delay menarche until as late as 1920 years of age (Frisch, 1990) and that weight loss results in amenorrhoea due to hypothalamic dysfunction. A high percentage of body fat (
2628% of body composition) in mature women is necessary for regular ovulatory cycles (Frisch, 1990
). A change in dietary intake and/or in physical activity to achieve the slim figure possibly desired by girls of the youngest cohorts might be responsible for this increase (Stoll, 1998
).
The role of early menarche in breast cancer risk is attributed to earlier exposure to circulating ovarian hormones. Few investigations have evaluated the effects of age at onset of regular cycling on breast cancer risk, and their findings are heterogeneous. In an early study (Brinton et al., 1988), there was some evidence of a trend of increasing risk with increasing interval between menarche and onset of regular periods, though no consistent pattern of risk was maintained within age-at-menarche categories. In other studies (Garland et al., 1998
; Rockhill et al., 1998
; Titus-Ernstoff et al., 1998
; Butler et al., 2000
), there were very modest variations in risks by length of time before onset of regular cycling overall or across different age-at-menarche strata. After menarche, there is probably a transient period with anovular cycles before cycles are ovulatory. One study (MacMahon et al., 1982
) showed an increase in the percentage of anovular cycles with increasing age at menarche. Other cited studies (Harlow and Ephross, 1995
) have reported that the probability of anovulation relative to age was
5060% for cycles in 1014 year old girls. Several studies have shown that the prevalence of ovulatory cycles increased with increasing interval since menarche, from 1544% in the first 2 years to 7581% after 6 years or more (MacMahon et al., 1982
; Apter, 1996
). These percentages also depended on age at onset of menarche, earlier menarche being characterized by an earlier onset of ovulatory cycles (Apter and Vihko, 1983
; Apter, 1996
).
The causes and consequences of the increase in length of time before onset of regular cycling observed in our data have to be considered as well. We suggest that a change in food intake and/or in physical activity to achieve a fashionably slim figure, even more pronounced among members of the youngest cohorts, might be responsible for this increase.
There are various possible reasons for oligomenorrhoea in adolescence. An immature hypothalamicpituitaryovarian axis may result in oligomenorrhoea and anovular cycles. An earlier age at menarche and a later age at onset of regular cycling increase exposure to anovulatory cycles and therefore to hormonal imbalance during adolescence, a period where breast cells have not undergone the maturation process and may thus be initiated under the influence of a carcinogen. Oligomenorrhoea may also reflect relative hyperinsulinaemia and hyperandrogenism related to obesity or to a polycystic ovarian syndrome leading to high LH or androgen concentrations (Stoll, 1998). One study (Van Hooff et al., 2000
) found that, compared to girls with regular cycles, oligomenorrhoeic girls had significantly higher concentrations of LH, androstenedione and testosterone.
Further studies are needed to identify the endocrine characteristics associated with early menarche and with late age at onset of regular cycling, to elucidate whether these characteristics are transitory or are maintained until adulthood and, ultimately, to explore the consequences of our observations on breast cancer incidence.
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Acknowledgements |
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Notes |
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References |
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Submitted on May 18, 2001; accepted on September 26, 2001.