TY - JOUR
T1 - Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the United States and Europe
AU - Travison, Thomas G.
AU - Vesper, Hubert W.
AU - Orwoll, Eric
AU - Wu, Frederick
AU - Kaufman, Jean Marc
AU - Wang, Ying
AU - Lapauw, Bruno
AU - Fiers, Tom
AU - Matsumoto, Alvin M.
AU - Bhasin, Shalender
N1 - Publisher Copyright:
Copyright © 2017 Endocrine Society.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Background: Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men. Objective: To establish harmonized reference ranges for total testosterone in men that can be applied across laboratories by cross-calibrating assays to a reference method and standard. Population: The 9054 community-dwelling men in cohort studies in the United States and Europe: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; and Male Sibling Study of Osteoporosis. Methods: Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method at Centers for Disease Control and Prevention (CDC). Generalized additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values. Normalizing equations, generated using Passing-Bablok regression, were used to generate harmonized values, which were used to derive standardized, age-specific reference ranges. Results: Harmonization procedure reduced intercohort variation between testosterone measurements in men of similar ages. In healthy nonobese men, 19 to 39 years, harmonized 2.5th, 5th, 50th, 95th, and 97.5th percentile values were 264, 303, 531, 852, and 916 ng/dL, respectively. Age-specific harmonized testosterone concentrations in nonobese men were similar across cohorts and greater than in all men. Conclusion: Harmonized normal range in a healthy nonobese population of European and American men, 19 to 39 years, is 264 to 916 ng/dL. A substantial proportion of intercohort variation in testosterone levels is due to assay differences. These data demonstrate the feasibility of generating harmonized reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator.
AB - Background: Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men. Objective: To establish harmonized reference ranges for total testosterone in men that can be applied across laboratories by cross-calibrating assays to a reference method and standard. Population: The 9054 community-dwelling men in cohort studies in the United States and Europe: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; and Male Sibling Study of Osteoporosis. Methods: Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method at Centers for Disease Control and Prevention (CDC). Generalized additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values. Normalizing equations, generated using Passing-Bablok regression, were used to generate harmonized values, which were used to derive standardized, age-specific reference ranges. Results: Harmonization procedure reduced intercohort variation between testosterone measurements in men of similar ages. In healthy nonobese men, 19 to 39 years, harmonized 2.5th, 5th, 50th, 95th, and 97.5th percentile values were 264, 303, 531, 852, and 916 ng/dL, respectively. Age-specific harmonized testosterone concentrations in nonobese men were similar across cohorts and greater than in all men. Conclusion: Harmonized normal range in a healthy nonobese population of European and American men, 19 to 39 years, is 264 to 916 ng/dL. A substantial proportion of intercohort variation in testosterone levels is due to assay differences. These data demonstrate the feasibility of generating harmonized reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator.
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U2 - 10.1210/jc.2016-2935
DO - 10.1210/jc.2016-2935
M3 - Article
C2 - 28324103
AN - SCOPUS:85017297289
SN - 0021-972X
VL - 102
SP - 1161
EP - 1173
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -