Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the framingham heart study and applied to three geographically distinct cohorts

Shalender Bhasin, Michael Pencina, Guneet Kaur Jasuja, Thomas G. Travison, Andrea Coviello, Eric Orwoll, Patty Y. Wang, Carrie Nielson, Frederick Wu, Abdelouahid Tajar, Fernand Labrie, Hubert Vesper, Anqi Zhang, Jagadish Ulloor, Ravinder Singh, Ralph D'Agostino, Ramachandran S. Vasan

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Abstract

Context: Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men. Methods: TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study. Results: In a reference sample of 456 men, mean (SD), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes. Conclusion: Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

Original languageEnglish (US)
Pages (from-to)2430-2439
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number8
DOIs
StatePublished - Aug 2011

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Liquid chromatography
Tandem Mass Spectrometry
Liquid Chromatography
Mass spectrometry
Testosterone
Reference Values
Medical problems
Aging of materials
Stairs
Osteoporotic Fractures

ASJC Scopus subject areas

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

Cite this

Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the framingham heart study and applied to three geographically distinct cohorts. / Bhasin, Shalender; Pencina, Michael; Jasuja, Guneet Kaur; Travison, Thomas G.; Coviello, Andrea; Orwoll, Eric; Wang, Patty Y.; Nielson, Carrie; Wu, Frederick; Tajar, Abdelouahid; Labrie, Fernand; Vesper, Hubert; Zhang, Anqi; Ulloor, Jagadish; Singh, Ravinder; D'Agostino, Ralph; Vasan, Ramachandran S.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 8, 08.2011, p. 2430-2439.

Research output: Contribution to journalArticle

Bhasin, Shalender ; Pencina, Michael ; Jasuja, Guneet Kaur ; Travison, Thomas G. ; Coviello, Andrea ; Orwoll, Eric ; Wang, Patty Y. ; Nielson, Carrie ; Wu, Frederick ; Tajar, Abdelouahid ; Labrie, Fernand ; Vesper, Hubert ; Zhang, Anqi ; Ulloor, Jagadish ; Singh, Ravinder ; D'Agostino, Ralph ; Vasan, Ramachandran S. / Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the framingham heart study and applied to three geographically distinct cohorts. In: Journal of Clinical Endocrinology and Metabolism. 2011 ; Vol. 96, No. 8. pp. 2430-2439.
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abstract = "Context: Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men. Methods: TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study. Results: In a reference sample of 456 men, mean (SD), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes. Conclusion: Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.",
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AU - Bhasin, Shalender

AU - Pencina, Michael

AU - Jasuja, Guneet Kaur

AU - Travison, Thomas G.

AU - Coviello, Andrea

AU - Orwoll, Eric

AU - Wang, Patty Y.

AU - Nielson, Carrie

AU - Wu, Frederick

AU - Tajar, Abdelouahid

AU - Labrie, Fernand

AU - Vesper, Hubert

AU - Zhang, Anqi

AU - Ulloor, Jagadish

AU - Singh, Ravinder

AU - D'Agostino, Ralph

AU - Vasan, Ramachandran S.

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N2 - Context: Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men. Methods: TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study. Results: In a reference sample of 456 men, mean (SD), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes. Conclusion: Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

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