title: Anti-Mullerian hormone is a more accurate predictor of individual time to menopause than mother's age at menopause.
abstract: OBJECTIVE
  In the prediction of time to menopause (TTM), what is the added value of anti-Müllerian hormone (AMH) when mother's age at natural menopause (ANM) is also known?
  
  
  CONCLUSIONS
  AMH is a more accurate predictor of individual TTM than mother's age at menopause.
  
  
  BACKGROUND
  Mother's ANM is considered a proxy for daughter's ANM although studies on its predictive accuracy are non-existent. AMH is a biomarker with a known capacity to predict ANM. However, its added value on top of known predictors, like mother's ANM, is unknown.
  
  
  METHODS
  Population-based cohort studies were used. To assess any additive predictive value of mother's ANM, 164 mother-daughter pairs were used (Group 1). To assess the added value of AMH, a second group of 150 women in whom AMH and mother's ANM were recorded prior to a 12-year follow-up period during which daughter's ANM was assessed was used (Group 2).
  
  
  METHODS
  Group 1 consisted of participants of the DOM cohort (an ongoing breast cancer study). Group 2 was a pooled cohort of women with regular menstrual cycles from two independent published studies. Cox proportional hazards analysis estimated uni- and multivariate regression coefficients for female age at study entry, mother's ANM and AMH in the prediction of TTM. Discrimination of models was assessed with C-statistics. Clinical added value of AMH was quantified with a net reclassification index (NRI).
  
  
  RESULTS
  A model with female age and mother's ANM had a c-statistic of 79 and 85% in groups 1 and 2, respectively. Both age and mother's ANM were significantly associated with TTM (HR 1.54 and HR 0.93 for age and mother's ANM in Cohort 1 and HR 1.59 and HR 0.89 in Group 2, respectively. P-value for all <0.001). In Group 2, the multivariate model with age, mother's ANM and AMH had a c-statistic of 92%, and only female age and AMH remained significantly associated with TTM (HR 1.41 P < 0.0001; HR 0.93 P = 0.08 and HR 0.06 P < 0.0001 for age, mother's ANM and AMH, respectively). The mean weighted NRI suggests that a 47% improvement in predictive accuracy is offered by adding AMH to the model of age and mother's ANM. In conclusion, AMH and mother's ANM both have added value in forecasting TTM for the daughter based on her age. In comparison, AMH is a more accurate added predictor of TTM than mother's ANM.
  
  
  CONCLUSIONS
  The cohort of women is relatively small and different cohorts of women were pooled.
  
  
  CONCLUSIONS
  This study shows that AMH is a more accurate predictor of ANM than mother's ANM. However, before achieving clinical applicability, the certainty with which a woman's prediction is made must improve. The association between mother's ANM and TTM in daughters did not appear to be influenced by whether ANM was recorded by mothers or daughters--an important finding because in the clinical setting daughters usually provide this information.
  
  
  BACKGROUND
  No funding was received and there were no competing interests in direct relation to this study.
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Dólleman
authors.forename: M
authors.initials: M
authors.lastname: Depmann
authors.forename: M J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: J
authors.initials: J
authors.lastname: Heimensem
authors.forename: S L
authors.initials: SL
authors.lastname: Broer
authors.forename: E M
authors.initials: EM
authors.lastname: van der Stroom
authors.forename: J S E
authors.initials: JS
authors.lastname: Laven
authors.forename: I A J
authors.initials: IA
authors.lastname: Van Rooij
authors.forename: G J
authors.initials: GJ
authors.lastname: Scheffer
authors.forename: P H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Y T
authors.initials: YT
authors.lastname: van der Schouw
authors.forename: C B
authors.initials: CB
authors.lastname: Lambalk
authors.forename: F J M
authors.initials: FJ
authors.lastname: Broekmans
mesh_terms: D000328:Adult; D000367:Age Factors; D054304:Anti-Mullerian Hormone / Q000097:blood* / Q000235:genetics; D005260:Female; D005544:Forecasting; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009035:Mothers; D019655:Quantitative Trait, Heritable
chemical_list: D054304:Anti-Mullerian Hormone
keywords: anti-Müllerian hormone; menopause; ovarian reserve