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bioRxiv · 10.64898/2026.05.23.727352

Scaled Testosterone: A Novel Metric to Calibrate Serum Testosterone and SHBG in Men

Handelsman, D. J.·Wittert, G. A.·Yeap, B. B.·Muir, C. M.·Flicker, L.·Tang Fui, M. N.·Grossmann, M.
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Abstract

ObjectivesLow serum testosterone (T) in men with obesity suggesting T deficiency may be misinterpreted by confounding changes in serum SHBG, Ts circulating carrier protein. Measuring or calculating "free" testosterone (FT) concentrations to define a low T is problematic as cFT is not a valid analytical variable lacking certified standard, quality control or reference range. We developed a novel metric, Scaled Testosterone (ST), comparing standardized serum T (LCMS) and SHBG without invoking hypothetical serum T fractions. MethodsSerum T and SHBG in men (n=10,027) pooled from three population-based studies in Australia were expressed as standardized (Z) scores (ZT, ZSHBG) and their difference ST = ZT-ZSHBG. ST was evaluated in a clinical trial of 51 men with severe obesity undergoing 1 year of diet-induced weight loss. ResultsZT and ZSHBG displayed linear correlation (r=0.44, 10-11) with ST approximating zero (-0.33 {+/-}2.14 SD). In non-obese men with low serum T suggestive of organic hypogonadism displayed very low ST indicating ST can evaluate whether a low serum T is proportionate to a concomitant serum SHBG. In men with obesity, low pre-treatment serum T and SHBG both increased during diet-induced weight loss with no change in serum LH while ST which remained within standard limits at each time. ConclusionsThe low serum T in men with obesity may better be considered as the pseudo-hypogonadism of obesity comprising low serum T with proportionately low serum SHBG in the presence of normal serum LH {+/-} FSH serving as a tissue androgen sensor.

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Handelsman, D. J., Wittert, G. A., Yeap, B. B., Muir, C. M., Flicker, L., Tang Fui, M. N., Grossmann, M.. 2026-05-27. Scaled Testosterone: A Novel Metric to Calibrate Serum Testosterone and SHBG in Men. https://doi.org/10.64898/2026.05.23.727352

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