The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Predictive accuracy and sources of variability in calculated free testosterone estimates
Abstract
Background: Serum free testosterone (FT) concentrations are commonly requested, but because reference FT methods are too laborious various calculational algorithms for FT based on total testosterone (TT) and sex hormone-binding globulin (SHBG) are frequently used. This study provides the first large-scale evaluation of the predictive accuracy and sources of variability for different FT formulae compared with direct laboratory measurements. Methods: Using a large data-set of direct FT measurements by centrifugal ultrafiltration, the predictive accuracy of five different formulas for cFT (four existing plus a new formula) is evaluated in 3975 consecutive blood samples. In a second data-set of 124 samples from a reference panel of healthy eugonadal young men, we estimate the relative influence of the five algorithms and eight different TT and two SHBG assays including all available commercial total TT and SHBG assays together with a gas chromatography/mass spectrometry T reference method. Results: cFT formulae show wide discrepancies with equilibrium-binding algorithms showing systematic overestimation relative to direct FT measurements, whereas two empirical cFT methods were more concordant. Variations between commercially available TT immunoassays have a strong impact on calculation of FT with TT assays contributing 82.2% of overall variance compared with 13.7% for the cFT algorithms and 4.1% for the SHBG assays. Conclusions: If FT measurements are requested and direct measurement impractical, cFT formulae using TT and SHBG immunoassays provide an approximation to direct FT measurement that is strongly dependent on the TT, cFT formula used and, to a lesser extent, SHBG immunoassays.
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“Empirical models exploiting bootstrap regression methods on cohort datasets comprise the third and last category [214, 215].”
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 [215]
In the citing paper
“A wide spectrum of algorithms for free T exists, which can broadly be divided into three categories (Table 6).”
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 [215]
In the citing paper
“Results of adult males have confirmed similar findings, with genetic contribution towards T variability of 42–65%.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [47]
In the citing paper
“One study, which obtained saliva-based fT assessments in 783 male twins, demonstrated significant decreases in fT following waking from sleep, with 32–39% of the total decline occurring within 30 minutes of waking.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [47]
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Metadata
- Authors
- Sartorius, G., Ly, L. P., Sikaris, K., McLachlan, R., & Handelsman, D. J.
- Affiliations
- The University of Sydney (AU)
- The University of Melbourne (AU)
- Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia
- Corresponding author
- Handelsman, David J
- Venue
- Annals of Clinical Biochemistry: International Journal of Laboratory Medicine
- Publisher
- SAGE Publications
- Published
- 2009-01-22
- Volume
- 46
- Issue
- 2
- Pages
- 137-143
- ISSN
- 0004-5632 (ISSN-L)
- 1758-1001
- OpenAlex
- W2042309501
- Cited by
- 175
- References
- 39
- Citations by year
- 2025: 8 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 12 · 2020: 5 · 2019: 8 · 2018: 16 · 2017: 16 · 2016: 10 · 2015: 16 · 2014: 12 · 2013: 9 · 2012: 16
- FWCI
- 11.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Clinical Biochemistry International Journal of Laboratory Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- Johnson and Johnson
- 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 › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- free testosterone, total testosterone, sex hormone-binding globulin, prediction accuracy, assay variability, centrifugal ultrafiltration, eugonadal men
- MeSH terms
- Humans, Male, Middle Aged, Testosterone
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