OBJECTIVE: Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are 
significantly associated with risk of developing breast and ovarian cancers, in 
turn, associated with female infertility. BRCA-1 mutations have also been 
associated with occult primary ovarian insufficiency (OPOI), as have different 
mutations of the FMR1 gene. We, therefore, hypothesized that FMR1 genotypes may 
be associated with menarcheal and menopausal ages of BRCA mutation carriers.
PATIENTS: We compared the FMR1 genotype and sub-genotype distribution in 99 
BRCA1/2 positive women and in 182 healthy women without a known history of 
familial breast and ovarian cancer and searched for associations with age at 
menarche and menopause. T-test was used to assess differences in menarcheal and 
menopause ages, with times of menarche and menopause as continuous variables.
RESULTS: Women with BRCA1/2 mutations showed significantly different FMR1 
genotype and sub-genotype distributions when compared with the control group 
(p<0.001). This result remained stable in a sub-group analysis of Caucasian 
BRCA1/2 carriers and healthy controls (p<0.001). In addition, BRCA1/2 carriers 
indicated a trend toward shorter reproductive lifespan (p=0.18).
CONCLUSIONS: Our data confirm the previously reported highly skewed distribution 
of FMR1 genotypes and sub-genotypes toward a high preponderance of low FMR1 
alleles in BRCA1/2 carriers. We could demonstrate that BRCA-1 mutations are 
associated with an earlier onset of menopause compared to BRCA-2 carriers, 
although the distribution of the het-norm/low genotype is similar in both 
groups. Our findings suggest that there may be other factors beside the genotype 
that has an influence on menarche and especially menopause age in BRCA mutation 
carriers.