Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men

Claes Ohlsson, Maria E. Nilsson, Åsa Tivesten, Henrik Ryberg, Dan Mellström, Magnus K. Karlsson, Östen Ljunggren, Fernand Labrie, Eric S. Orwoll, David M. Lee, Stephen R. Pye, Terence W. O'Neill, Joseph D. Finn, Judith E. Adams, Kate A. Ward, Steven Boonen, G. Bártfai, Felipe F. Casanueva, Gianni Forti, Aleksander GiwercmanThang S. Han, Ilpo T. Huhtaniemi, Krzysztof Kula, Michael E J Lean, Neil Pendleton, Margus Punab, Dirk Vanderschueren, Frederick C W Wu, Liesbeth Vandenput, Luisa Petrone, Giovanni Corona, Herman Borghs, Jolanta Slowikowska-Hilczer, Renata Walczak-Jedrzejowska, Alan Silman, Philip Steer, Mary Lage, Ana I. Castro, I. Földesi, I. Fejes, Paul Korrovitz, Min Jiang

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Context: Immunoassay-based techniques, routinely used to measure serum estradiol (E2), are known to have reduced specificity, especially at lower concentrations,whencompared with the gold standard technique of mass spectrometry (MS). Different measurement techniques may be responsible for the conflicting results of associations between serum E2 and clinical phenotypes in men. Objective: Our objective was to compare immunoassay and MS measurements of E2 levels in men and evaluate associations with clinical phenotypes. Design and Setting: Middle-aged and older male subjects participating in the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2599), MrOS US (n = 688), and the European Male Aging Study (n = 2908) were included. Main Outcome Measures: Immunoassay and MS measurements of serum E2 were compared and related to bone mineral density (BMD; measured by dual energy x-ray absorptiometry) and ankle-brachial index. Results: Within each cohort, serum E2 levels obtained by immunoassay and MS correlated moderately (Spearman rank correlation coefficient rS 0.53-0.76). Serum C-reactive protein (CRP) levels associated significantly (albeit to a low extent, rS = 0.29) with immunoassay E2 but not with MS E2 levels. Similar associations of immunoassay E2 and MS E2 were seen with lumbar spine and total hip BMD, independent of serum CRP. However, immunoassay E2, but not MS E2, associated inversely with ankle-brachial index, and this correlation was lost after adjustment for CRP. Conclusions: Our findings suggest interference in the immunoassay E2 analyses, possibly by CRP or a CRP-associated factor. Although associations with BMD remain unaffected, this might imply for a reevaluation of previous association studies between immunoassay E2 levels and inflammation-related outcomes.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number6
DOIs
Publication statusPublished - Jun 2013

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Immunoassay
Mass spectrometry
Estradiol
Mass Spectrometry
C-Reactive Protein
Serum
Ankle Brachial Index
Blood Proteins
Phenotype
Clinical Studies
Osteoporotic Fractures
Minerals
Bone
Nonparametric Statistics
Aging of materials
Sweden
Bone Density
Hip
X rays
Spine

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

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Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men. / Ohlsson, Claes; Nilsson, Maria E.; Tivesten, Åsa; Ryberg, Henrik; Mellström, Dan; Karlsson, Magnus K.; Ljunggren, Östen; Labrie, Fernand; Orwoll, Eric S.; Lee, David M.; Pye, Stephen R.; O'Neill, Terence W.; Finn, Joseph D.; Adams, Judith E.; Ward, Kate A.; Boonen, Steven; Bártfai, G.; Casanueva, Felipe F.; Forti, Gianni; Giwercman, Aleksander; Han, Thang S.; Huhtaniemi, Ilpo T.; Kula, Krzysztof; Lean, Michael E J; Pendleton, Neil; Punab, Margus; Vanderschueren, Dirk; Wu, Frederick C W; Vandenput, Liesbeth; Petrone, Luisa; Corona, Giovanni; Borghs, Herman; Slowikowska-Hilczer, Jolanta; Walczak-Jedrzejowska, Renata; Silman, Alan; Steer, Philip; Lage, Mary; Castro, Ana I.; Földesi, I.; Fejes, I.; Korrovitz, Paul; Jiang, Min.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 6, 06.2013.

Research output: Contribution to journalArticle

Ohlsson, C, Nilsson, ME, Tivesten, Å, Ryberg, H, Mellström, D, Karlsson, MK, Ljunggren, Ö, Labrie, F, Orwoll, ES, Lee, DM, Pye, SR, O'Neill, TW, Finn, JD, Adams, JE, Ward, KA, Boonen, S, Bártfai, G, Casanueva, FF, Forti, G, Giwercman, A, Han, TS, Huhtaniemi, IT, Kula, K, Lean, MEJ, Pendleton, N, Punab, M, Vanderschueren, D, Wu, FCW, Vandenput, L, Petrone, L, Corona, G, Borghs, H, Slowikowska-Hilczer, J, Walczak-Jedrzejowska, R, Silman, A, Steer, P, Lage, M, Castro, AI, Földesi, I, Fejes, I, Korrovitz, P & Jiang, M 2013, 'Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men', Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 6. https://doi.org/10.1210/jc.2012-3861
Ohlsson, Claes ; Nilsson, Maria E. ; Tivesten, Åsa ; Ryberg, Henrik ; Mellström, Dan ; Karlsson, Magnus K. ; Ljunggren, Östen ; Labrie, Fernand ; Orwoll, Eric S. ; Lee, David M. ; Pye, Stephen R. ; O'Neill, Terence W. ; Finn, Joseph D. ; Adams, Judith E. ; Ward, Kate A. ; Boonen, Steven ; Bártfai, G. ; Casanueva, Felipe F. ; Forti, Gianni ; Giwercman, Aleksander ; Han, Thang S. ; Huhtaniemi, Ilpo T. ; Kula, Krzysztof ; Lean, Michael E J ; Pendleton, Neil ; Punab, Margus ; Vanderschueren, Dirk ; Wu, Frederick C W ; Vandenput, Liesbeth ; Petrone, Luisa ; Corona, Giovanni ; Borghs, Herman ; Slowikowska-Hilczer, Jolanta ; Walczak-Jedrzejowska, Renata ; Silman, Alan ; Steer, Philip ; Lage, Mary ; Castro, Ana I. ; Földesi, I. ; Fejes, I. ; Korrovitz, Paul ; Jiang, Min. / Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men. In: Journal of Clinical Endocrinology and Metabolism. 2013 ; Vol. 98, No. 6.
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abstract = "Context: Immunoassay-based techniques, routinely used to measure serum estradiol (E2), are known to have reduced specificity, especially at lower concentrations,whencompared with the gold standard technique of mass spectrometry (MS). Different measurement techniques may be responsible for the conflicting results of associations between serum E2 and clinical phenotypes in men. Objective: Our objective was to compare immunoassay and MS measurements of E2 levels in men and evaluate associations with clinical phenotypes. Design and Setting: Middle-aged and older male subjects participating in the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2599), MrOS US (n = 688), and the European Male Aging Study (n = 2908) were included. Main Outcome Measures: Immunoassay and MS measurements of serum E2 were compared and related to bone mineral density (BMD; measured by dual energy x-ray absorptiometry) and ankle-brachial index. Results: Within each cohort, serum E2 levels obtained by immunoassay and MS correlated moderately (Spearman rank correlation coefficient rS 0.53-0.76). Serum C-reactive protein (CRP) levels associated significantly (albeit to a low extent, rS = 0.29) with immunoassay E2 but not with MS E2 levels. Similar associations of immunoassay E2 and MS E2 were seen with lumbar spine and total hip BMD, independent of serum CRP. However, immunoassay E2, but not MS E2, associated inversely with ankle-brachial index, and this correlation was lost after adjustment for CRP. Conclusions: Our findings suggest interference in the immunoassay E2 analyses, possibly by CRP or a CRP-associated factor. Although associations with BMD remain unaffected, this might imply for a reevaluation of previous association studies between immunoassay E2 levels and inflammation-related outcomes.",
author = "Claes Ohlsson and Nilsson, {Maria E.} and {\AA}sa Tivesten and Henrik Ryberg and Dan Mellstr{\"o}m and Karlsson, {Magnus K.} and {\"O}sten Ljunggren and Fernand Labrie and Orwoll, {Eric S.} and Lee, {David M.} and Pye, {Stephen R.} and O'Neill, {Terence W.} and Finn, {Joseph D.} and Adams, {Judith E.} and Ward, {Kate A.} and Steven Boonen and G. B{\'a}rtfai and Casanueva, {Felipe F.} and Gianni Forti and Aleksander Giwercman and Han, {Thang S.} and Huhtaniemi, {Ilpo T.} and Krzysztof Kula and Lean, {Michael E J} and Neil Pendleton and Margus Punab and Dirk Vanderschueren and Wu, {Frederick C W} and Liesbeth Vandenput and Luisa Petrone and Giovanni Corona and Herman Borghs and Jolanta Slowikowska-Hilczer and Renata Walczak-Jedrzejowska and Alan Silman and Philip Steer and Mary Lage and Castro, {Ana I.} and I. F{\"o}ldesi and I. Fejes and Paul Korrovitz and Min Jiang",
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T1 - Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men

AU - Ohlsson, Claes

AU - Nilsson, Maria E.

AU - Tivesten, Åsa

AU - Ryberg, Henrik

AU - Mellström, Dan

AU - Karlsson, Magnus K.

AU - Ljunggren, Östen

AU - Labrie, Fernand

AU - Orwoll, Eric S.

AU - Lee, David M.

AU - Pye, Stephen R.

AU - O'Neill, Terence W.

AU - Finn, Joseph D.

AU - Adams, Judith E.

AU - Ward, Kate A.

AU - Boonen, Steven

AU - Bártfai, G.

AU - Casanueva, Felipe F.

AU - Forti, Gianni

AU - Giwercman, Aleksander

AU - Han, Thang S.

AU - Huhtaniemi, Ilpo T.

AU - Kula, Krzysztof

AU - Lean, Michael E J

AU - Pendleton, Neil

AU - Punab, Margus

AU - Vanderschueren, Dirk

AU - Wu, Frederick C W

AU - Vandenput, Liesbeth

AU - Petrone, Luisa

AU - Corona, Giovanni

AU - Borghs, Herman

AU - Slowikowska-Hilczer, Jolanta

AU - Walczak-Jedrzejowska, Renata

AU - Silman, Alan

AU - Steer, Philip

AU - Lage, Mary

AU - Castro, Ana I.

AU - Földesi, I.

AU - Fejes, I.

AU - Korrovitz, Paul

AU - Jiang, Min

PY - 2013/6

Y1 - 2013/6

N2 - Context: Immunoassay-based techniques, routinely used to measure serum estradiol (E2), are known to have reduced specificity, especially at lower concentrations,whencompared with the gold standard technique of mass spectrometry (MS). Different measurement techniques may be responsible for the conflicting results of associations between serum E2 and clinical phenotypes in men. Objective: Our objective was to compare immunoassay and MS measurements of E2 levels in men and evaluate associations with clinical phenotypes. Design and Setting: Middle-aged and older male subjects participating in the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2599), MrOS US (n = 688), and the European Male Aging Study (n = 2908) were included. Main Outcome Measures: Immunoassay and MS measurements of serum E2 were compared and related to bone mineral density (BMD; measured by dual energy x-ray absorptiometry) and ankle-brachial index. Results: Within each cohort, serum E2 levels obtained by immunoassay and MS correlated moderately (Spearman rank correlation coefficient rS 0.53-0.76). Serum C-reactive protein (CRP) levels associated significantly (albeit to a low extent, rS = 0.29) with immunoassay E2 but not with MS E2 levels. Similar associations of immunoassay E2 and MS E2 were seen with lumbar spine and total hip BMD, independent of serum CRP. However, immunoassay E2, but not MS E2, associated inversely with ankle-brachial index, and this correlation was lost after adjustment for CRP. Conclusions: Our findings suggest interference in the immunoassay E2 analyses, possibly by CRP or a CRP-associated factor. Although associations with BMD remain unaffected, this might imply for a reevaluation of previous association studies between immunoassay E2 levels and inflammation-related outcomes.

AB - Context: Immunoassay-based techniques, routinely used to measure serum estradiol (E2), are known to have reduced specificity, especially at lower concentrations,whencompared with the gold standard technique of mass spectrometry (MS). Different measurement techniques may be responsible for the conflicting results of associations between serum E2 and clinical phenotypes in men. Objective: Our objective was to compare immunoassay and MS measurements of E2 levels in men and evaluate associations with clinical phenotypes. Design and Setting: Middle-aged and older male subjects participating in the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2599), MrOS US (n = 688), and the European Male Aging Study (n = 2908) were included. Main Outcome Measures: Immunoassay and MS measurements of serum E2 were compared and related to bone mineral density (BMD; measured by dual energy x-ray absorptiometry) and ankle-brachial index. Results: Within each cohort, serum E2 levels obtained by immunoassay and MS correlated moderately (Spearman rank correlation coefficient rS 0.53-0.76). Serum C-reactive protein (CRP) levels associated significantly (albeit to a low extent, rS = 0.29) with immunoassay E2 but not with MS E2 levels. Similar associations of immunoassay E2 and MS E2 were seen with lumbar spine and total hip BMD, independent of serum CRP. However, immunoassay E2, but not MS E2, associated inversely with ankle-brachial index, and this correlation was lost after adjustment for CRP. Conclusions: Our findings suggest interference in the immunoassay E2 analyses, possibly by CRP or a CRP-associated factor. Although associations with BMD remain unaffected, this might imply for a reevaluation of previous association studies between immunoassay E2 levels and inflammation-related outcomes.

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