Human Reproduction, Vol. 16, No. 9, 2014-2018,
September 2001
© 2001 European Society of Human Reproduction and Embryology
The role of genetic factors in age at natural menopause
1 1Department Of Obstetrics and Gynaecology, Diakonessen Hospital Utrecht, 2 Institute of Animal Sciences, Wageningen University, Wageningen, 3 Julius Center for Patient Oriented Research, Utrecht University, 4 Department of Human Genetics, 5 Department of Obstetrics and Gynaecology, University Medical Centre Utrecht, The Netherlands and 6 Department of Animal Science, University of Illinois, Urbana, USA
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.
Key words: fertility/genetics/heritability/menopause/reproductive failure
7 To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, Diakonessen Hospital Utrecht, Bosboomstraat 1, 3582 KE Utrecht, The Netherlands. E-mail: jp{at}debruin-kers.demon.nl
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