Puberty, ageing and hormone replacement. The role of genetic factors in age at natural menopause

• Published in: Human reproduction (Oxford) 2001-09, Vol.16 (9), p.2014
• Main Authors: J.P. de Bruin, Bovenhuis, H, P.A.H. van Noord, Pearson, P L, J.A.M. van Arendonk, E.R. te Velde, Kuurman, W W, Dorland, M
• Format: Article
• Language: English
• ISSN: 0268-1161; 1460-2350

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.