Britton Trabert1, Xia Xu2, Roni T Falk3, Chantal Guillemette4, Frank Z Stanczyk5, Katherine A McGlynn3. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. Electronic address: britton.trabert@nih.gov. 2. Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA. 3. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. 4. Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec (CHUQ) Research Center, Laval University, Québec, Canada. 5. Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Abstract
BACKGROUND: Valid and precise measures of androgen concentrations are needed for etiologic studies of hormonally-related cancers. We developed a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with two sample preparations to measure 11 androgens, including adrenal and gonadal androgenic precursors and their 5α-reduced metabolites. METHODS: Androgen levels were measured in serum from 20 healthy volunteers (5 men, 10 premenopausal women, 5 postmenopausal women). Two blinded, randomized aliquots per individual were assayed in each of three batches. A fourth batch of samples was measured at an external laboratory using comparable methodology to measure 9 of the 11 androgens. Coefficients of variation (CV) and intraclass correlation coefficients (ICC) were calculated from the individual components of variance. Comparability of 9 androgens across laboratories was assessed using Spearman ranked correlations, Deming regression and bias plots. RESULTS: The laboratory CVs were <5% and ICCs were uniformly high (>95%) for all androgens measured across sex/menopausal status groups. Spearman ranked correlations for 9 hormones measured in the comparison laboratory were high (>0.85), suggesting good agreement. CONCLUSION: Our high-performance LC-MS/MS assays of 11 androgens, including adrenal and gonadal androgenic precursors and their 5α-reduced metabolites demonstrated excellent laboratory reproducibility, and good comparability with an established method that measured 9 of the 11 hormones tested. The serum androgen metabolite assays are suitable for use in epidemiologic research. Published by Elsevier Ltd.
BACKGROUND: Valid and precise measures of androgen concentrations are needed for etiologic studies of hormonally-related cancers. We developed a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with two sample preparations to measure 11 androgens, including adrenal and gonadal androgenic precursors and their 5α-reduced metabolites. METHODS: Androgen levels were measured in serum from 20 healthy volunteers (5 men, 10 premenopausal women, 5 postmenopausal women). Two blinded, randomized aliquots per individual were assayed in each of three batches. A fourth batch of samples was measured at an external laboratory using comparable methodology to measure 9 of the 11 androgens. Coefficients of variation (CV) and intraclass correlation coefficients (ICC) were calculated from the individual components of variance. Comparability of 9 androgens across laboratories was assessed using Spearman ranked correlations, Deming regression and bias plots. RESULTS: The laboratory CVs were <5% and ICCs were uniformly high (>95%) for all androgens measured across sex/menopausal status groups. Spearman ranked correlations for 9 hormones measured in the comparison laboratory were high (>0.85), suggesting good agreement. CONCLUSION: Our high-performance LC-MS/MS assays of 11 androgens, including adrenal and gonadal androgenic precursors and their 5α-reduced metabolites demonstrated excellent laboratory reproducibility, and good comparability with an established method that measured 9 of the 11 hormones tested. The serum androgen metabolite assays are suitable for use in epidemiologic research. Published by Elsevier Ltd.
Entities:
Keywords:
Endogenous hormones; Liquid chromatography tandem mass spectrometry; Metabolites; Reproducibility; Serum androgen assay
Authors: Kim N Danforth; A Heather Eliassen; Shelley S Tworoger; Stacey A Missmer; Robert L Barbieri; Bernard A Rosner; Graham A Colditz; Susan E Hankinson Journal: Int J Cancer Date: 2010-01-01 Impact factor: 7.396
Authors: Xia Xu; John M Roman; Haleem J Issaq; Larry K Keefer; Timothy D Veenstra; Regina G Ziegler Journal: Anal Chem Date: 2007-09-12 Impact factor: 6.986
Authors: Hannah Oh; Robert A Wild; JoAnn E Manson; Jennifer W Bea; Aladdin H Shadyab; Ruth M Pfeiffer; Nazmus Saquib; Lisa Underland; Garnet L Anderson; Xia Xu; Britton Trabert Journal: Cancer Epidemiol Biomarkers Prev Date: 2021-08-26 Impact factor: 4.090
Authors: Hannah Oh; Nazmus Saquib; Heather M Ochs-Balcom; Ruth M Pfeiffer; Phyllis A Richey; Aladdin H Shadyab; Robert A Wild; Lisa Underland; Garnet L Anderson; Xia Xu; Britton Trabert Journal: Cancer Epidemiol Biomarkers Prev Date: 2021-10-18 Impact factor: 4.090
Authors: Lauren M Hurwitz; Aladdin H Shadyab; Fred K Tabung; Garnet L Anderson; Nazmus Saquib; Robert B Wallace; Robert A Wild; Ruth M Pfeiffer; Xia Xu; Britton Trabert Journal: Cancer Prev Res (Phila) Date: 2022-03-01
Authors: Kara A Michels; Louise A Brinton; Nicolas Wentzensen; Kathy Pan; Chu Chen; Garnet L Anderson; Ruth M Pfeiffer; Xia Xu; Thomas E Rohan; Britton Trabert Journal: JNCI Cancer Spectr Date: 2019-04-25
Authors: Britton Trabert; Kara A Michels; Garnet L Anderson; Louise A Brinton; Roni T Falk; Ashley M Geczik; Holly R Harris; Kathy Pan; Ruth M Pfeiffer; Lihong Qi; Thomas Rohan; Nicolas Wentzensen; Xia Xu Journal: Int J Cancer Date: 2019-02-15 Impact factor: 7.316
Authors: Douglas A Gibson; Ioannis Simitsidellis; Olympia Kelepouri; Hilary O D Critchley; Philippa T K Saunders Journal: Fertil Steril Date: 2018-02-15 Impact factor: 7.329
Authors: David C Brooks; John S Coon V; Cihangir M Ercan; Xia Xu; Hongxin Dong; Jon E Levine; Serdar E Bulun; Hong Zhao Journal: Endocrinology Date: 2020-10-01 Impact factor: 4.736