Increased serum FSH in female fragile X premutation carriers with either regular menstrual cycles or on oral contraceptives

Fragile X premutations are known to be a risk factor for diminished ovarian function at a relatively young age, We studied endocrine profiles of femal e fragile X family members (n = 79) at risk of premature ovarian failure (P OF), Of these 79 women aged <40 years, 45 had menstrual cycles, and 34 were using oral contraceptives, Of the women with menstrual cycles, the premuta tion carriers had higher serum FSH concentrations than women who were not c arrying the premutation, Even premutation carriers with regular cycles show ed increased serum FSH concentrations. Moreover, premutation carriers using oral contraceptives also demonstrated increased serum FSH concentrations. Irrespective of whether oral contraceptives were used, a serum FSH concentr ation of <greater than or equal to>15 IU/l was more common in the premutati on carriers than in the other women. One premutation carrier using oral con traceptives had a serum FSH concentration of >40 IU/l, the threshold that d efines POF. We confirmed that premutation carriers with menstrual cycles de monstrate premature ovarian dysfunction, However, we also found endocrine s igns of unrecognized ovarian dysfunction in premutation carriers using oral contraceptives, despite endocrine alterations by oral contraceptives. Prem utation carriers may have a poorer prognosis for future pregnancy, either a chieved spontaneously or by assisted reproductive technology. We recommend that premutation carriers should be counselled not to wait too long if they wish to start a family.