title: Predictors and risk model development for menopausal age in fragile X premutation carriers.
abstract: OBJECTIVE
  Women who carry a fragile X mental retardation 1 premutation are at risk for fragile X-associated primary ovarian insufficiency and should be counseled for a potentially reduced fertility. Multiple factors can affect the age of onset and severity of fragile X-associated primary ovarian insufficiency. In this study, we assessed the predictive power of several factors with menopausal age, a surrogate measure of onset of fragile X-associated primary ovarian insufficiency.
  
  
  METHODS
  Genetic, environmental, and reproductive factors were analyzed by Cox proportional hazard models in 1068 women, 385 of fragile X families ascertained through the Nijmegen study and 683 of fragile X families or general population families ascertained through the Atlanta study.
  
  
  RESULTS
  The highest association with menopausal age among fragile X mental retardation 1 premutation carriers was found for risk index by CGG repeat size (hazard ratio, 1.43) and smoking (hazard ratio, 1.34). Women from the Nijmegen cohort showed an overall lower age at menopause onset, for which a correction was made. A prediction model based on these two parameters, mean menopausal age of first-degree relatives with the same mutation status and the correction for ascertainment site, estimated the probability of becoming postmenopausal for premutation carriers, with a margin of 7-10%.
  
  
  CONCLUSIONS
  We conclude that this model serves as a first step toward clinical application of fragile X-associated primary ovarian insufficiency prediction.
authors: Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. M.Spath@obgyn.umcn.nl
authors: Marian A
authors: MA
authors: Spath
authors: Ton B
authors: TB
authors: Feuth
authors: Arie P T
authors: AP
authors: Smits
authors: Helger G
authors: HG
authors: Yntema
authors: Didi D M
authors: DD
authors: Braat
authors: Chris M G
authors: CM
authors: Thomas
authors: Ad Geurts
authors: AG
authors: van Kessel
authors: Stephanie L
authors: SL
authors: Sherman
authors: Emily G
authors: EG
authors: Allen
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