Menstrual cycle length preceding menopause in relation to age at menopause
Introduction
In 1980 Korenman proposed the “oestrogen window hypothesis of the etiology of breast cancer” [1]. It had been postulated in previous work that normal oestrogenic stimulation in the absence of sufficient cyclic progesterone secretion could explain the protective effect of an early first pregnancy and an early ovariectomy and the enhancing effect of an early menarche, late menopause and nulliparity on breast cancer risk 1, 2.
Korenman assumed the existence of two `oestrogen windows', periods during which a woman is susceptible to the induction of breast cancer. The first window is the period prior to ovulatory menstrual cycles (around menarche) and the second window is during the perimenopausal period, when irregular and anovulatory menstrual cycles again become common. One of the predictions from the oestrogen window hypothesis was that susceptibility to tumour induction declines with the establishment of normal–luteal-phase progesterone secretion [1]. Korenman assumed that women with an early menarche had a larger window than women with a late menarche and that women with a late menopause had a larger window than women with an early menopause. In this way his hypothesis would explain why early age at menarche and late age at menopause are risk factors for breast cancer.
In 1985, Henderson et al. published an alternative hypothesis, just opposite to Korenman's hypothesis, entitled: “Do regular ovulatory cycles increase breast cancer risk?” [3]. This hypothesis was based on evidence that frequent regular ovulatory cycles are a risk factor for breast cancer. For instance, it had become apparent from epidemiological studies that women with an early age at menarche have ovulatory cycles sooner than women with a late age at menarche 4, 5, 6. With respect to the second window, in a study from the Menstrual and Reproductive History Research Program (MRHRP) women with late onset of menopause were shown to have longer and more variable cycles in the years prior to menopause than those with early onset [7]. This relationship was, however, only present in the 4 years preceding menopause [7]. The variation in menstrual cycle length in the study from the MRHRP by Wallace et al. [7]relates both to variation within one woman and to variation between women. The greater variability in cycle length in women with later age at menopause might well be explained by greater variability between women instead of greater variability within one woman. In another study from the MRHRP the median duration of the menopausal transition (the period between the onset of progressively expanding variability preceding menopause and age at menopause) was estimated to be 4.8 years (mean 5.0 years) [8]. But no data were presented according to categories of age at menopause.
In this study we investigated, in a period from 1 to 9 years prior to menopause, whether women with a late age at menopause have a higher mean menstrual cycle length and a higher variation in cycle length within one woman than women with an early age at menopause.
Section snippets
Subjects and methods
In 1986 we started the so-called `Second Window-project'. Subjects were recruited from 12 184 women born between 1932 and 1941 who participated in 1982–1985 in a breast cancer screening project (the DOM-project) in Utrecht, The Netherlands. A number of the women (8682) who were still menstruating in the year preceding their visit to the breast cancer screening and free from breast cancer were eligible for the Second Window-project. To all women a calendar to note all days of vaginal bleeding
Results
Fig. 1 shows that the median of the mean menstrual cycle length per woman (MP) increases when age at menopause is approached. During the 9 years prior to menopause women with a late age at menopause (55–59 years) have a somewhat higher mean menstrual cycle length (MP) than women with an age at menopause between 44–49 and 50–54 years (P=0.0008). The slight tendency observed from Fig. 1 that the increase in cycle length starts about 1 year earlier in women with a late age at menopause (55–59
Discussion
The main findings of this study are that women with a late age at menopause have a higher mean menstrual cycle length, but not more variable cycles than women with an earlier age at menopause during the 9 years prior to menopause. The possibility that women with long menstrual cycles in the period before menopause did already have long cycles from the beginning of their reproductive life, and that a late age at menopause is a consequence of having long cycles cannot be excluded. Women with
Acknowledgements
We would like to express our thanks to De Vereniging van Vriendinnen van het DOM-Projekt for financial and practical support. This project was further funded by the L.K.-Research Fonds, International Health Foundation, Schering, Organon and Stichting `De Drie Lichten'. We would like to thank Prof. Dr. D.E. Grobbee (Julius Center for Patient Oriented Research, University of Utrecht) for valuable comments and Mr P.A.J. Timmermans for data management and statistical analyses.
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