Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Scaled Testosterone: A Novel Metric to Calibrate Serum Testosterone and SHBG in Men (142375)

David J Handelsman 1 2 , Gary A Wittert 3 4 , Bu B Yeap 5 6 , Christopher M Muir 2 , Leon Flicker 6 , Mark Ng Tang Fui 7 , Mathis Grossmann 7
  1. ANZAC Research Institute, Sydney, NSW, Australia
  2. Andrology, Concord Hospital, Sydney
  3. Freemasons Centre for Male Health and Wellbeing, Adelaide University, Adelaide, South Australia, Australia
  4. South Australian Health and Medical Research Institute , Adelaide, South Australia, Australia
  5. Department of Endocrinology and Diabetes, , Fiona Stanley Hospital, Perth, Western Australia, Australia
  6. Medical School, University of Western Australia, Perth, Western Australia, Australia
  7. Medicine, University of Melbourne Austin Health, , Melbourne, Victoria, Australia

Objectives: Low serum testosterone (T) in men with obesity may suggest T deficiency but may simply be the product of lower serum SHBG, T’s circulating carrier protein. Measuring or calculating “free” testosterone (FT) concentrations to is problematic as cFT is not a valid analytical variable lacking certified standard, quality control or reference range and aims to measure the unmeasurable. Therefore we developed a novel metric, Scaled Testosterone (ST), comparing standardized serum T (LCMS) and SHBG without invoking unmeasurable hypothetical tissue T concentrations to define androgen status in men with obesity.

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 as scaled testosterone (ST). ST was evaluated in a clinical trial of 51 severely obese men undergoing 1 year of diet-induced weight loss.

Results:In the population, ZT and ZSHBG displayed linear correlation (r=0.33, 10-9) with ST approximating zero (-0.33 ± 2.14 SD) as well as in each category of BMI. In non-obese men with low serum T suggesting organic hypogonadism ST was very low confirming ST can differentiate between T deficiency and low blood T not due to T deficiency. in obese men, the low serum T was proportionate to the low serum SHBG accompanied by unchanged serum LH/FSH reflect eugonadal state. In obese men, low pre-treatment serum T and SHBG both increased during diet-induced weight loss with no change in serum LH with ST remaining within 95% confidence limits at each time.  

Conclusions: The low serum T in men with obesity does not constitute testosterone deficiency and is best 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.