Curvilinear association of CGG repeats and age at menopause in women with FMR1 premutation expansions

In a sample of post-menopausal premutation carrier mothers of children with the full mutation of fragile X syndrome (n = 88), this study examined the co-occurrence of the reproductive and psychiatric phenotypes associated with FMR1 premutations. Mean age at menopause was 43.1 years, and 35.2% of premutation carriers reported cessation of menses prior to age 40 (premature ovarian failure), but only 18% of carriers had been medically diagnosed by a physician as having Fragile X-associated Primary Ovarian Insufficiency. There was a significant curvilinear association between CGG repeat length and age at menopause, with women who had mid-range repeats having the earliest menopause, similar to the pattern that has been found for the psychiatric phenotype of the FMR1 premutation.