Scaled Testosterone: A Novel Metric to Calibrate Serum Testosterone and SHBG in Men
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Objectives
Low serum testosterone (T) in men with obesity suggesting T deficiency may be misinterpreted by confounding changes in serum SHBG, T’s 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.
Methods
Serum 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.
Results
ZT 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.
Conclusions
The 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.
