title: The relationship between anti-Müllerian hormone in women receiving fertility assessments and age at menopause in subfertile women: evidence from large population studies.
abstract: BACKGROUND
  Anti-Müllerian hormone (AMH) concentration reflects ovarian aging and is argued to be a useful predictor of age at menopause (AMP). It is hypothesized that AMH falling below a critical threshold corresponds to follicle depletion, which results in menopause. With this threshold, theoretical predictions of AMP can be made. Comparisons of such predictions with observed AMP from population studies support the role for AMH as a forecaster of menopause.
  
  
  OBJECTIVE
  The objective of the study was to investigate whether previous relationships between AMH and AMP are valid using a much larger data set.
  
  
  METHODS
  AMH was measured in 27 563 women attending fertility clinics.
  
  
  METHODS
  From these data a model of age-related AMH change was constructed using a robust regression analysis. Data on AMP from subfertile women were obtained from the population-based Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect-EPIC) cohort (n = 2249). By constructing a probability distribution of age at which AMH falls below a critical threshold and fitting this to Prospect-EPIC menopausal age data using maximum likelihood, such a threshold was estimated.
  
  
  RESULTS
  The main outcome was conformity between observed and predicted AMP.
  
  
  RESULTS
  To get a distribution of AMH-predicted AMP that fit the Prospect-EPIC data, we found the critical AMH threshold should vary among women in such a way that women with low age-specific AMH would have lower thresholds, whereas women with high age-specific AMH would have higher thresholds (mean 0.075 ng/mL; interquartile range 0.038-0.15 ng/mL). Such a varying AMH threshold for menopause is a novel and biologically plausible finding. AMH became undetectable (<0.2 ng/mL) approximately 5 years before the occurrence of menopause, in line with a previous report.
  
  
  CONCLUSIONS
  The conformity of the observed and predicted distributions of AMP supports the hypothesis that declining population averages of AMH are associated with menopause, making AMH an excellent candidate biomarker for AMP prediction. Further research will help establish the accuracy of AMH levels to predict AMP within individuals.
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands. m.dolleman-2@umcutrecht.nl
authors.forename: M
authors.initials: M
authors.lastname: Dólleman
authors.forename: M J
authors.initials: MJ
authors.lastname: Faddy
authors.forename: J
authors.initials: J
authors.lastname: van Disseldorp
authors.forename: Y T
authors.initials: YT
authors.lastname: van der Schouw
authors.forename: C M
authors.initials: CM
authors.lastname: Messow
authors.forename: B
authors.initials: B
authors.lastname: Leader
authors.forename: P H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: A
authors.initials: A
authors.lastname: McConnachie
authors.forename: S M
authors.initials: SM
authors.lastname: Nelson
authors.forename: F J M
authors.initials: FJ
authors.lastname: Broekmans
mesh_terms: D000293:Adolescent; D000368:Aged; D000375:Aging; D054304:Anti-Mullerian Hormone / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000097:blood* / Q000473:pathology; D008593:Menopause / Q000097:blood*; D008875:Middle Aged; D008954:Models, Biological; D010053:Ovary / Q000473:pathology*; D047648:Perimenopause / Q000097:blood*; D011446:Prospective Studies; D012044:Regression Analysis; D014481:United States
chemical_list: D015415:Biomarkers; D054304:Anti-Mullerian Hormone