The role of genetic factors in age at natural menopause.
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.
de Bruin
J P
JP
Department Of Obstetrics and Gynaecology, Diakonessen Hospital Utrecht, The Netherlands. jp@debruin-kers.demon.nl
Bovenhuis
H
H
van Noord
P A
PA
Pearson
P L
PL
van Arendonk
J A
JA
te Velde
E R
ER
Kuurman
W W
WW
Dorland
M
M
D000375:Aging / Q000502:physiology*; D004777:Environment; D005260:Female; D006801:Humans; D008499:Medical Records; D008593:Menopause / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D008954:Models, Biological