title: Back to the basics of ovarian aging: a population-based study on longitudinal anti-Müllerian hormone decline.
abstract: BACKGROUND
  Anti-Müllerian hormone (AMH) is currently used as an ovarian reserve marker for individualized fertility counseling, but very little is known of individual AMH decline in women. This study assessed whether the decline trajectory of AMH is uniform for all women, and whether baseline age-specific AMH levels remain consistently high or low during this trajectory.
  
  
  METHODS
  A total of 3326 female participants from the population-based Doetinchem Cohort Study were followed with five visits over a 20-year period. Baseline age was 40 ± 10 years with a range of 20-59 years. AMH was measured in 12,929 stored plasma samples using the picoAMH assay (AnshLabs). Decline trajectories of AMH were studied with both chronological age and reproductive age, i.e., time to menopause. Multivariable linear mixed effects models characterized the individual AMH decline trajectories.
  
  
  RESULTS
  The overall rate of AMH decline accelerated after 40 years of age. Mixed models with varying age-specific AMH levels and decline rates provided the significantly best fit to the data, indicating that the fall in AMH levels over time does not follow a fixed pattern for individual women. AMH levels remained consistent along individual trajectories of age, with an intraclass correlation coefficient (ICC) of 0.87. The ICC of 0.32 for AMH trajectories with time to menopause expressed the large variation in AMH levels at a given time before the menopause. The differences between low and high age-specific AMH levels remained distinguishable, but became increasingly smaller with increasing chronological and reproductive age.
  
  
  CONCLUSIONS
  This is the first study to characterize individual AMH decline over a long time period and broad age range. The varying AMH decline rates do not support the premise of a uniform AMH decline trajectory. Although age-specific AMH levels remain consistently high or low with increasing age, the converging trajectories and variance of AMH levels at a given time before menopause shed doubt on the added value of AMH to represent individualized reproductive age.
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. a.c.dekat@umcutrecht.nl.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. a.c.dekat@umcutrecht.nl.
authors.forename: A C
authors.initials: AC
authors.lastname: de Kat
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Y T
authors.initials: YT
authors.lastname: van der Schouw
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: M J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.affiliation: National Institute for Public Health and the Environment, Antonie van Leeuwenhoeklaan 9, 3721 MA, Bilthoven, The Netherlands.
authors.forename: G C
authors.initials: GC
authors.lastname: Herber-Gast
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Visser
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.|National Institute for Public Health and the Environment, Antonie van Leeuwenhoeklaan 9, 3721 MA, Bilthoven, The Netherlands.
authors.forename: W M M
authors.initials: WM
authors.lastname: Verschuren
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: F J M
authors.initials: FJ
authors.lastname: Broekmans
mesh_terms: D000328:Adult; D000375:Aging; D054304:Anti-Mullerian Hormone / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005298:Fertility / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008593:Menopause / Q000378:metabolism*; D008875:Middle Aged; D006080:Ovarian Follicle / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D054304:Anti-Mullerian Hormone