The role of genetic factors in age at natural menopause

J.P. de Bruin, H. Bovenhuis, P.A.H. van Noord, P. Pearson, J.A.M. van Arendonk, E.R. ter Velde, W.W. Kuurman

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226 Citations (Scopus)


Background: Environmental factors explain only a small part of the age variance at which menopause commences. The variation in natural menopause is a trait predominantly determined by interaction of multiple genes, whose identity and causative genetic variation remains to be determined. Menopause is a retrospective marker for the reproductive capacity of preceding years, since subfertility and infertility precede menopause at distinct time-intervals. In the present study we have investigated the contribution of genetic factors to menopausal age. Methods: Data were collected from a random population sample of singleton and twin sisters participating in a prospective breast cancer screening project, who had subsequently experienced natural menopause. Heritability of menopausal age was estimated with analysis of variance, Mx modelling and Gibbs sampling. Results: All produced almost identical heritability estimates of 0.85-0.87 for singleton sisters, suggesting a strong genetic contribution to menopausal age. Twin data were used to distinguish additive genetic from common environmental effects; a heritability of 0.71-0.72 was determined, which does not deviate significantly from the estimate for singleton sisters. Conclusions: According to our findings, a woman with a family history of early menopause risks early menopause and consequently early reproductive failure herself.
Original languageEnglish
Pages (from-to)2014-2018
JournalHuman Reproduction
Issue number9
Publication statusPublished - 2001

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