Analog-Based Free Testosterone Test Results Linked to Total Testosterone Concentrations, Not Free Testosterone Concentrations
Abstract
Background: Analog-based free testosterone test results, sex hormone binding globulin (SHBG) concentrations, and total testosterone concentrations are somehow related. This study used new experiments to clarify these relationships. Methods: An analog-based free testosterone immunoassay and a total testosterone immunoassay were applied to well-defined fractions of serum testosterone. First, they were applied to the 2 fractions (retentate and dialysate) of normal male serum obtained by equilibrium dialysis. Second, they were applied to covaried concentrations of SHBG and total testosterone. Third, they were applied to decreasing concentrations of SHBG and protein-bound testosterone, offset by increasing concentrations of protein-free testosterone, while total testosterone was held constant. Results: The analog-based free testosterone assay and the total testosterone assay detected and reported serum testosterone test results from serum retentate, whereas neither assay detected the free testosterone in serum dialysate. Test results reported by the analog-based free testosterone assay followed varied concentrations of SHBG and total testosterone. When total testosterone was held constant, however, analog-based free testosterone test results did not follow varied concentrations of serum proteins or of free testosterone. Conclusion: An analog-based free testosterone immunoassay reported free testosterone test results that were related to total testosterone concentrations under varied experimental conditions. This alleged free testosterone assay did not detect serum free testosterone (the test results it reported were nonspecific) and should not be used for this purpose.
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Analog-based immunoassays do not detect nor quantify free T.
“Comparative studies of this analog-based immunoassay and ED confirmed that this technique does not detect nor quantify free T and that is should, therefore, not be used as an assay for free T [205, 207, 208].”
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 [205]
Analog-based immunoassays have inadequate accuracy, bias, and dependency on T rather than free T.
“Nevertheless, inadequate accuracy, bias and dependency on T rather than free T are major drawbacks in this analog-based assays [204–206].”
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 [205]
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“It has also been asserted that they are proportional to total testosterone concentrations (1, 7 , 8). This led us to question whether these analogbased free testosterone test results are more closely related to the concentrations of total testosterone or SHBG.”
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- Authors
- Fritz, K. S., McKean, A. J. S., Nelson, J. C., & Wilcox, R. B.
- Affiliations
- Loma Linda University (US)
- Loma Linda University Medical Center (US)
- Corresponding author
- Wilcox, R Bruce
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-03-01
- Volume
- 54
- Issue
- 3
- Pages
- 512-516
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2116313303
- Cited by
- 58
- References
- 5
- Citations by year
- 2026: 2 · 2025: 2 · 2022: 2 · 2021: 7 · 2020: 2 · 2019: 2 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 5 · 2013: 5 · 2012: 3
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- free testosterone, total testosterone, sex hormone-binding globulin, equilibrium dialysis, immunoassay validation
- MeSH terms
- Adult, Dialysis, Humans, Immunoassay, Male, Middle Aged, Protein Binding, Sex Hormone-Binding Globulin, Testosterone
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