The role of genetic factors in age at natural menopause

BACKGROUND: Environmental factors explain only a small part of the age vari ance at which menopause commences. The variation in natural menopause is a trait predominantly determined by interaction of multiple genes, whose iden tity and causative genetic variation remains to be determined. Menopause is a retrospective marker for the reproductive capacity of preceding years, s ince subfertility and infertility precede menopause at distinct time-interv als. In the present study we have investigated the contribution of genetic factors to menopausal age. METHODS: Data were collected from a random popul ation sample of singleton and twin sisters participating in a prospective b reast cancer screening project, who had subsequently experienced natural me nopause. Heritability of menopausal age was estimated with analysis of vari ance, Mx modelling and Gibbs sampling. RESULTS: All produced almost identic al heritability estimates of 0.85-0.87 for singleton sisters, suggesting a strong genetic contribution to menopausal age. Twin data were used to disti nguish additive genetic from common environmental effects; a heritability o f 0.71-0.72 was determined, which does not deviate significantly from the e stimate for singleton sisters. CONCLUSIONS: According to our findings, a wo man with a family history of early menopause risks early menopause and cons equently early reproductive failure herself.