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

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...

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Autores principales: Frederiksen, Hanne, Johannsen, Trine Holm, Andersen, Stine Ehlern, Albrethsen, Jakob, Landersoe, Selma Kløve, Petersen, Jørgen Holm, Andersen, Anders Nyboe, Vestergaard, Esben Thyssen, Schorring, Mia Elbek, Linneberg, Allan, Main, Katharina M, Andersson, Anna-Maria, Juul, Anders
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007877/
https://www.ncbi.nlm.nih.gov/pubmed/31720688
http://dx.doi.org/10.1210/clinem/dgz196
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author Frederiksen, Hanne
Johannsen, Trine Holm
Andersen, Stine Ehlern
Albrethsen, Jakob
Landersoe, Selma Kløve
Petersen, Jørgen Holm
Andersen, Anders Nyboe
Vestergaard, Esben Thyssen
Schorring, Mia Elbek
Linneberg, Allan
Main, Katharina M
Andersson, Anna-Maria
Juul, Anders
author_facet Frederiksen, Hanne
Johannsen, Trine Holm
Andersen, Stine Ehlern
Albrethsen, Jakob
Landersoe, Selma Kløve
Petersen, Jørgen Holm
Andersen, Anders Nyboe
Vestergaard, Esben Thyssen
Schorring, Mia Elbek
Linneberg, Allan
Main, Katharina M
Andersson, Anna-Maria
Juul, Anders
author_sort Frederiksen, Hanne
collection PubMed
description 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.
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spelling pubmed-70078772020-02-12 Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS Frederiksen, Hanne Johannsen, Trine Holm Andersen, Stine Ehlern Albrethsen, Jakob Landersoe, Selma Kløve Petersen, Jørgen Holm Andersen, Anders Nyboe Vestergaard, Esben Thyssen Schorring, Mia Elbek Linneberg, Allan Main, Katharina M Andersson, Anna-Maria Juul, Anders J Clin Endocrinol Metab Clinical Research Articles 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. Oxford University Press 2019-11-13 /pmc/articles/PMC7007877/ /pubmed/31720688 http://dx.doi.org/10.1210/clinem/dgz196 Text en © Endocrine Society 2019. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Research Articles
Frederiksen, Hanne
Johannsen, Trine Holm
Andersen, Stine Ehlern
Albrethsen, Jakob
Landersoe, Selma Kløve
Petersen, Jørgen Holm
Andersen, Anders Nyboe
Vestergaard, Esben Thyssen
Schorring, Mia Elbek
Linneberg, Allan
Main, Katharina M
Andersson, Anna-Maria
Juul, Anders
Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS
title Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS
title_full Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS
title_fullStr Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS
title_full_unstemmed Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS
title_short Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS
title_sort sex-specific estrogen levels and reference intervals from infancy to late adulthood determined by lc-ms/ms
topic Clinical Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007877/
https://www.ncbi.nlm.nih.gov/pubmed/31720688
http://dx.doi.org/10.1210/clinem/dgz196
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