Esben Thyssen Vestergaard

Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS

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DOI

  • Hanne Frederiksen, Department of Growth and Reproduction, Kobenhavns Universitet, International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC)
  • ,
  • Trine Holm Johannsen, Kobenhavns Universitet
  • ,
  • Stine Ehlern Andersen, Department of Growth and Reproduction, Kobenhavns Universitet
  • ,
  • Jakob Albrethsen, Kobenhavns Universitet
  • ,
  • Selma Kløve Landersoe, Kobenhavns Universitet
  • ,
  • Jørgen Holm Petersen, Kobenhavns Universitet
  • ,
  • Anders Nyboe Andersen, Kobenhavns Universitet
  • ,
  • Esben Thyssen Vestergaard
  • Mia Elbek Schorring
  • ,
  • Allan Linneberg, Kobenhavns Universitet
  • ,
  • Katharina M. Main, Kobenhavns Universitet
  • ,
  • Anna Maria Andersson, Kobenhavns Universitet
  • ,
  • Anders Juul, Department of Growth and Reproduction, Kobenhavns Universitet, International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC)

CONTEXT: The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low concentrations. OBJECTIVE: To establish sex-specific reference ranges for estrone (E1) and estradiol (E2) throughout life and to evaluate sex-differences using the state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of E1, E2, and estriol (E3). DESIGN: LC-MS/MS method development and construction of estrogen reference ranges. SETTINGS: Population-based cross-sectional cohorts from the greater Copenhagen and Aarhus areas. PARTICIPANTS: Healthy participants aged 3 months to 61 years (n = 1838). RESULTS: An isotope diluted LC-MS/MS method was developed and validated for measurements of serum E1, E2, and E3. Limits of detections (LODs) were 3 pmol/L (E1), 4 pmol/L (E2), and 12 pmol/L (E3), respectively. This sensitive method made it possible to differentiate between male and female concentration levels of E1 and E2 in children. In girls, E2 levels ranged from <LOD to 100 pmol/L during mini-puberty, whereas it was ≤20 pmol/L during childhood. E1 and E2 increased with age and pubertal breast stage and varied during the menstrual cycle; E1 was lower than E2 in girls and premenopausal women, and higher than E2 in postmenopausal women. In boys, E1 and E2 increased with age and pubertal stage, whereas little changes with age were observed in men. High E3 concentrations were confirmed in pregnant women. CONCLUSION: Reference ranges of simultaneous quantification of E1 and E2 by this novel specific and highly sensitive LC-MS/MS method provide an invaluable tool in clinical practice and in future research studies.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume105
Issue3
Pages (from-to)754-768
Number of pages15
ISSN0021-972X
DOIs
Publication statusPublished - 2020

    Research areas

  • childhood, estradiol, estrone, LC-MS/MS, menopause, menstrual cycle, mini-puberty, pubertal development, reference range

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