Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS
Abstract 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-diff...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism Jg. 105; H. 3; S. 754 - 768 |
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| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
US
Oxford University Press
01.03.2020
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| ISSN: | 0021-972X, 1945-7197, 1945-7197 |
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| Abstract | Abstract
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. |
|---|---|
| AbstractList | 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. The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low concentrations.CONTEXTThe lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low concentrations.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).OBJECTIVETo 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).LC-MS/MS method development and construction of estrogen reference ranges.DESIGNLC-MS/MS method development and construction of estrogen reference ranges.Population-based cross-sectional cohorts from the greater Copenhagen and Aarhus areas.SETTINGSPopulation-based cross-sectional cohorts from the greater Copenhagen and Aarhus areas.Healthy participants aged 3 months to 61 years (n = 1838).PARTICIPANTSHealthy participants aged 3 months to 61 years (n = 1838).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.RESULTSAn 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.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.CONCLUSIONReference 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. Abstract 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. 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 [less than or equal to]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 confrmed 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. (J Clin Endocrinol Metab 105: 754-768, 2020) Key Words: estradiol, estrone, reference range, LC-MS/MS, mini-puberty, childhood, pubertal development, menstrual cycle, menopause The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low concentrations. 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). LC-MS/MS method development and construction of estrogen reference ranges. Population-based cross-sectional cohorts from the greater Copenhagen and Aarhus areas. Healthy participants aged 3 months to 61 years (n = 1838). 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. 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. |
| Audience | Academic |
| Author | Andersen, Stine Ehlern Albrethsen, Jakob Vestergaard, Esben Thyssen Landersoe, Selma Kløve Andersson, Anna-Maria Andersen, Anders Nyboe Linneberg, Allan Main, Katharina M Schorring, Mia Elbek Petersen, Jørgen Holm Juul, Anders Johannsen, Trine Holm Frederiksen, Hanne |
| AuthorAffiliation | 5 Paediatrics and Adolescent Medicine, Aarhus University Hospital , Aahus, Denmark 3 The Fertility Clinic, Rigshospitalet, University of Copenhagen , Copenhagen, Denmark 1 Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen , Copenhagen, Denmark 7 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark 6 Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, University of Copenhagen , Copenhagen, Denmark 2 International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen , Copenhagen, Denmark 4 Department of Biostatistics, University of Copenhagen , Copenhagen, Denmark |
| AuthorAffiliation_xml | – name: 5 Paediatrics and Adolescent Medicine, Aarhus University Hospital , Aahus, Denmark – name: 7 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark – name: 3 The Fertility Clinic, Rigshospitalet, University of Copenhagen , Copenhagen, Denmark – name: 2 International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen , Copenhagen, Denmark – name: 1 Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen , Copenhagen, Denmark – name: 4 Department of Biostatistics, University of Copenhagen , Copenhagen, Denmark – name: 6 Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, University of Copenhagen , Copenhagen, Denmark |
| Author_xml | – sequence: 1 givenname: Hanne orcidid: 0000-0002-3180-9879 surname: Frederiksen fullname: Frederiksen, Hanne email: hanne.frederiksen@regionh.dk organization: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark – sequence: 2 givenname: Trine Holm orcidid: 0000-0002-3303-5352 surname: Johannsen fullname: Johannsen, Trine Holm organization: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark – sequence: 3 givenname: Stine Ehlern surname: Andersen fullname: Andersen, Stine Ehlern organization: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark – sequence: 4 givenname: Jakob surname: Albrethsen fullname: Albrethsen, Jakob organization: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark – sequence: 5 givenname: Selma Kløve surname: Landersoe fullname: Landersoe, Selma Kløve organization: The Fertility Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark – sequence: 6 givenname: Jørgen Holm surname: Petersen fullname: Petersen, Jørgen Holm organization: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark – sequence: 7 givenname: Anders Nyboe surname: Andersen fullname: Andersen, Anders Nyboe organization: The Fertility Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark – sequence: 8 givenname: Esben Thyssen surname: Vestergaard fullname: Vestergaard, Esben Thyssen organization: Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aahus, Denmark – sequence: 9 givenname: Mia Elbek surname: Schorring fullname: Schorring, Mia Elbek organization: Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aahus, Denmark – sequence: 10 givenname: Allan surname: Linneberg fullname: Linneberg, Allan organization: Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark – sequence: 11 givenname: Katharina M surname: Main fullname: Main, Katharina M organization: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark – sequence: 12 givenname: Anna-Maria surname: Andersson fullname: Andersson, Anna-Maria organization: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark – sequence: 13 givenname: Anders orcidid: 0000-0002-0534-4350 surname: Juul fullname: Juul, Anders organization: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31720688$$D View this record in MEDLINE/PubMed |
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| Copyright_xml | – notice: Endocrine Society 2019. 2019 – notice: Endocrine Society 2019. – notice: COPYRIGHT 2020 Oxford University Press – notice: Endocrine Society 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| DOI | 10.1210/clinem/dgz196 |
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The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low... The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low concentrations. To... Context: The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low... Context The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low... The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low... |
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| SubjectTerms | 17β-Estradiol Age Breast Children Clinical s Estrogen Estrone Human physical development Liquid chromatography Mass spectrometry Mass spectroscopy Menstrual cycle Metabolites Physiological research Post-menopause Puberty Testing |
| Title | Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS |
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