title: The association of CGG repeats in the FMR1 gene and timing of natural menopause.
abstract: OBJECTIVE
  Is there an association between the number of CGG repeats in the FMR1 gene in the normal and intermediate range and age at natural menopause?
  
  
  CONCLUSIONS
  The number of CGG repeats in the normal and intermediate range in the FMR1 gene was not associated with age at natural menopause.
  
  
  BACKGROUND
  Excessive triple CGG repeats in the FMR1 gene have been widely associated with primary ovarian insufficiency. Recently, the number of CGG repeats in the normal and intermediate range (up to 55 repeats) was found to be associated with serum levels of anti-Müllerian hormone and follicle-stimulating hormone, as markers for ovarian ageing. This suggests that repeats in the normal and intermediate range could be involved in the rate of exhaustion of the ovarian primordial follicle pool and ultimately the timing of menopause.
  Cross-sectional study in a population-based sample of 3611 Caucasian women with natural menopause.
  
  
  METHODS
  The FMR1 CGG repeat number was determined by PCR amplification in 3611 women with a known age at natural menopause. A possible relation between CGG repeats in the normal and intermediate range (up to 55 repeats) and menopausal age were analysed in various ways, including linear regression analysis and analysis of variance.
  
  
  RESULTS
  The number of CGG repeats in the normal and intermediate range in the FMR1 gene was not associated with age at natural menopause. The mean age at menopause was 50.30 (± 4.2) years for women with <45 repeats and 50.64 (± 3.4) years for women with intermediate-sized repeats (P = 0.37). Linear regression analysis of the number of CGG repeats showed no association with menopausal age (β = 0.019, P = 0.16).
  
  
  CONCLUSIONS
  In our cohort, age at menopause was self-reported and determined retrospectively.
  
  
  CONCLUSIONS
  Earlier observations suggesting that the number of CGG repeats in the normal and intermediate range is associated with the individual variation of the ovarian ageing process could not be confirmed in the current, large sample size study. A relation between the number of CGG repeats in the normal and intermediate range and age at natural menopause appeared to be absent. This finding questions the role of CGG repeat sizes in the ovarian ageing process.
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. m.voorhuis@umcutrecht.nl
authors.forename: M
authors.initials: M
authors.lastname: Voorhuis
authors.forename: N C
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: B C J M
authors.initials: BC
authors.lastname: Fauser
authors.forename: H K
authors.initials: HK
authors.lastname: Ploos van Amstel
authors.forename: Y T
authors.initials: YT
authors.lastname: van der Schouw
authors.forename: F J
authors.initials: FJ
authors.lastname: Broekmans
mesh_terms: D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D003430:Cross-Sectional Studies; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D016014:Linear Models; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018911:Trinucleotide Repeats
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human