PURPOSE
Women who carry a FMR1 premutation are at risk for fragile X-associated primary ovarian insufficiency (FXPOI) and should be counseled for a potentially reduced fertility. Multiple factors can affect the age of onset and severity of FXPOI. Here, we assessed the predictive power of several factors with menopausal age, a surrogate measure of onset of FXPOI.
METHODS
Genetic, environmental and reproductive factors were analysed by Cox proportional hazard models in 1,068 women, 385 of fragile X families ascertained through the Nijmegen study and 683 of fragile X families or general population families ascertained through the Atlanta study.
RESULTS
The highest association with menopausal age among FMR1 premutation carriers was found for risk index by CGG repeat size (HR 1.43) and smoking (HR 1.34). Women from the Nijmegen cohort showed an overall lower age at menopause onset, for which a correction was made. A prediction model based on these two parameters, mean menopausal age of first degree relatives with the same mutation status and the correction for ascertainment site, estimated the probability of becoming postmenopausal for premutation carriers, with a margin of 7-10%.
CONCLUSION
We conclude that this model serves as a first step towards clinical application of FXPOI prediction.