Rdl. Hundscheid et al., Increased serum FSH in female fragile X premutation carriers with either regular menstrual cycles or on oral contraceptives, HUM REPR, 16(3), 2001, pp. 457-462
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.