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Predictive accuracy and sources of variability in calculated free testosterone estimates
Gideon Sartorius1, Lam P Ly, Ken Sikaris
1Andrology Department, Concord Hospital, NSW, Australia.
Calculating free testosterone (FT) using total testosterone (TT) and sex hormone-binding globulin (SHBG) formulas provides an approximation when direct measurement is impractical. The accuracy of calculated FT heavily depends on the TT assay and the specific formula used.
Area of Science:
- Endocrinology
- Clinical Chemistry
- Laboratory Medicine
Background:
- Direct measurement of serum free testosterone (FT) is often impractical due to laborious methods.
- Calculational algorithms using total testosterone (TT) and sex hormone-binding globulin (SHBG) are frequently employed as alternatives.
- This study evaluates the predictive accuracy and variability of different FT calculation formulas.
Purpose of the Study:
- To assess the predictive accuracy of five different calculated FT (cFT) formulas against direct FT measurements.
- To identify sources of variability in cFT calculations using various TT and SHBG assays.
- To compare existing and a novel cFT formula.
Main Methods:
- Evaluated five cFT formulas using direct FT measurements from 3975 blood samples via centrifugal ultrafiltration.
- Assessed the influence of eight TT and two SHBG assays on cFT calculations in 124 samples from healthy men.
- Utilized gas chromatography/mass spectrometry as a reference method for TT.
Main Results:
- Equilibrium-binding algorithms for cFT showed systematic overestimation compared to direct FT measurements.
- Two empirical cFT methods demonstrated better concordance with direct measurements.
- Variations in TT immunoassays significantly impacted cFT calculations, contributing 82.2% of the overall variance.
Conclusions:
- Calculated FT formulas offer an approximation when direct measurement is not feasible.
- The accuracy of cFT is highly dependent on the chosen TT assay and the specific cFT formula.
- SHBG immunoassays also influence cFT results, though to a lesser extent than TT assays.
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