A mathematical comparison of techniques to predict biologically available testosterone in a cohort of 1072 men
Abstract
OBJECTIVE: In the absence of widely available measures of determining free and/or bioavailable testosterone (BioT) physicians may use formulae such as the free androgen index (FAI) to estimate free testosterone. We compared the efficacy of calculated markers of androgen status in predicting serum BioT and hypogonadism. DESIGN: Total testosterone (TT), sex hormone binding globulin (SHBG) and BioT were determined in a large cohort of men. Comparison of calculated androgen levels was performed following endocrine assessment. METHODS: TT and SHBG were determined by ELISA, and BioT was determined by ammonium sulphate precipitation. From these data we calculated FAI and free testosterone using two other published formulae - FTnw (free testosterone as calculated by the method of Nanjeee and Wheeler) and FTv (free testosterone as calculated by the method of Vermeulen). A novel formula was derived to calculate BioT from given levels of TT and SHBG (BTcalculated). The ability of the methods (FAI, FTnw, FTv, BTcalc) to predict BioT were compared using regression analysis. The ability of these markers of androgen status to predict biochemical hypogonadism was compared using area under receiver operator curve (auROC). RESULTS: The equation derived from our data was the best predictor of BioT (R(2)=0.73, P<0.0001) although TT was also a good marker (R(2)=0.68, P=0.0001). In the determination of hypogonadism, of all currently available formulae none were better that the TT (auROC: TT=0.93, FAI=0.72, FTnw=0.91, FTv=0.88) although when TT is borderline (7.5<TT<12 nmol/l) estimates of free testosterone are superior to TT alone (auROC: TT=0.63, FAI=0.74, FTnw=0.75 and FTv=0.75). CONCLUSIONS: TT is the best marker of hypogonadism and BioT, when TT is borderline calculated indices of free testosterone or BioT are useful and may help confirm hypogonadism.
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Overall variability was only minimally influenced by the calculated free testosterone algorithm used (14%), while different total testosterone and SHBG assays accounted for 82% and 4% of observed variance, respectively.
“Of interest, overall variability was only minimally influenced by the calculated fT algorithm utilized (14% of variability), while the different TT and SHBG assays accounted for 82% and 4% of observed variance, respectively.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [107]
In the largest study evaluating predictive accuracy of free testosterone calculations, Sartorius and colleagues concluded that empirical methods (Ly, Sartorius) are most concordant, while other estimations (Vermeulen, Nanjee and Wheeler, Sodergard) overestimate the true value.
“In the largest study evaluating predictive accuracy of fT calculations, Sartorius and colleagues concluded that empirical methods (Ly, Sartorius) of calculated fT are most concordant, with other estimations (Vermeulen, Nanjee and Wheeler, Sodergard) resulting in overestimation of the true value.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [107]
The type of assay used for testosterone assessment should be reported, with greater variability among non-mass-spectrometry total testosterone samples, particularly at lower levels, and systematic overestimation from non-empirically calculated free testosterone measurements.
“The type of assay utilized for T assessment should be reported, with greater variability noted among non-MS TT samples (particularly at lower levels) and systematic overestimation resulting from non-empirically calculated fT measurements.107”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [107]
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- Authors
- Morris, P., Malkin, C., Channer, K., & Jones, T.
- Affiliations
- Royal Hallamshire Hospital (GB)
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-08-01
- Volume
- 151
- Issue
- 2
- Pages
- 241-249
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2097009096
- Cited by
- 122
- References
- 19
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 7 · 2015: 2 · 2014: 9 · 2013: 6 · 2012: 7
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- bioavailable testosterone, free testosterone, total testosterone, sex hormone-binding globulin, free androgen index, hypogonadism, androgen status
- MeSH terms
- Humans, Hypogonadism, Male, Models, Biological, Predictive Value of Tests, Regression Analysis, Sensitivity and Specificity, Sex Hormone-Binding Globulin, Testosterone, Cohort Studies, Biomarkers
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