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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
Open accessAbstract
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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“Multiple studies attempted to establish a reference range to achieve generally accepted values for total T in young men, ending in diverse intervals for all different cohorts [174–177].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [177]
In the citing paper
“Finally, for both measured and calculated free T, reference ranges may not be universally valid. Depending on the method to assess free T as well as characteristics of the cohort, different intervals may be generated [177, 229].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [177]
In the citing paper
“Numerous studies have consistently identified age-dependent decreases in T.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [38]
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Metadata
- Authors
- Bhasin, S., Pencina, M., Jasuja, G. K., Travison, T. G., Coviello, A., Orwoll, E., Wang, P. Y., Nielson, C., Wu, F., Tajar, A., Labrie, F., Vesper, H., Zhang, A., Ulloor, J., Singh, R., D'Agostino, R., & Vasan, R. S.
- Affiliations
- Boston University (US)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2011-08
- Volume
- 96
- Issue
- 8
- Pages
- 2430-2439
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3146796
- OpenAlex
- W2165100613
- Cited by
- 355
- References
- 54
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 11 · 2023: 18 · 2022: 32 · 2021: 21 · 2020: 22 · 2019: 28 · 2018: 29 · 2017: 20 · 2016: 34 · 2015: 30 · 2014: 32 · 2013: 36 · 2012: 19
- FWCI
- 23.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- National Institutes of Health (n01hc25195-41-0-1, 5p30ag031679-15)
- National Institute on Aging (R01AG031206, 5 P30 AG031679, U01AG018197, U01AG027810, P30-AG031679)
- National Heart, Lung, and Blood Institute (N01‐HC25195, N01-HC-025195)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (U01AR045583, U01AR045580, U01AR045632, U01AR045654, U01AR045614, U01AR045647)
- National Center for Research Resources (UL1RR024140)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Health Professions › Medical Laboratory Technology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- testosterone, reference values, androgen deficiency, free testosterone, total testosterone, physical dysfunction, sexual dysfunction, diabetes mellitus, frailty, young men, community sample
- MeSH terms
- Adult, Chemistry, Clinical, Chromatography, Liquid, Humans, Hypogonadism, Male, Massachusetts, Reference Values, Residence Characteristics, Risk Factors, Testosterone, Cohort Studies, Prevalence, Tandem Mass Spectrometry, Young Adult
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