(O-19) Age and obesity as independent and cumulative determinants of the testosterone/sex-hormone biding globulin index: a multivariate and cluster-based analysis with artificial sample expansion

Abstract Introduction The testosterone/SHBG ratio (TT/SHBG) is an emerging marker of androgenic activity and metabolic health. However, the individual roles of age and obesity on TT, SHBG, and this index remain underexplored. We aimed to assess the separate and combined effects of age and BMI on TT, SHBG, and TT/SHBG in clinical practice using real-world data with sample amplification via bootstrapping. We also sought to identify clinical phenotypes through cluster analysis. Methods Cross-sectional data from 96 men included anthropometric, clinical, and hormonal parameters. TT/SHBG was calculated using morning TT and SHBG levels. Multivariate linear regression assessed the independent effects of age and BMI on TT, SHBG, and TT/SHBG. The sample was expanded 20-fold via bootstrap to enhance statistical power. K-means clustering (K = 3) was applied using age, BMI, and TT/SHBG. Results Age was independently associated with increased SHBG (β = +0.42 nmol/L/year; p < 0.001) and lower TT/SHBG (β = –0.25; p < 0.001). BMI was negatively associated with TT (β = –1.07 ng/dL per unit; p = 0.021) and TT/SHBG (β = –0.13; p = 0.006). Cluster analysis revealed three phenotypes: A = Young, lean, low comorbidity, optimal hormones; B = Older, obese, high comorbidity, worst profile; C = Older, overweight, intermediate profile. Conclusion Age and obesity independently and additively impair the TT/SHBG index via distinct mechanisms: SHBG elevation with age and TT suppression with obesity. Weight gain may biologically accelerate androgenic aging, reinforcing the importance of early hormonal screening in obese men. Financing No conflict.