Trisomy and age at menopause: predicted associations given a link with rate of oocyte atresia

The association of trisomy with advancing maternal chronological age suggests that some aspect of physiological aging is accelerated in women with trisomic pregnancies. This paper develops a quantitative theoretical model based on the hypothesis that trisomy risk is primarily a function of the size of the oocyte pool and, in particular, that risk is increased in women with accelerated rates of oocyte atresia and hence smaller pools at given chronological ages. Since the rate of oocyte atresia is a determinant of age at menopause, this hypothesis leads to the prediction that women who have had trisomic pregnancies reach menopause earlier than women who have not. We used data relating chronological age to oocyte number, trisomy and menopause to deduce the distribution of oocyte atresia rates in all women and in women with trisomic pregnancies. Given certain simplifying assumptions, we predict that associations between trisomy and age at menopause will vary with a woman's age at the time of trisomy such that trisomies at 34-43 years will be associated with a 1-3.4 year earlier onset of menopause, while trisomies at younger or older ages will have no or little association with age at menopause. This model, while vulnerable to the uncertainties that attend its assumptions, provides a testable prediction that permits separation of one aspect of physiological age from chronological age.