Keele Research Repository

Introduction. The age-related fall in male testosterone levels can have clinical consequences. The concentration of serum free testosterone, the putative bioactive moiety, is mediated by carrier proteins especially sex hormone binding globulin (SHBG).

Aim. We consider the nature of hormone binding to carriers with new insights into determining calculated free testosterone levels and review how SHBG and testosterone influence age-related mortality.

Methods. Where possible we focused on recent literature describing binding of testosterone to carrier proteins or, associations between age, SHBG, testosterone and mortality. We then used logistic regression to study the impact of SHBG and total testosterone on age-related mortality in men with type 2 diabetes (T2DM).

Main outcome measure. The association between mortality and age and SHBG and / or total testosterone was determined in a cohort of 364 men with T2DM leading to a graphical display of the impact of SHBG / testosterone levels on age-related mortality.

Results. Low total testosterone and high SHBG are independently associated with increased all-cause mortality. Our analyses support these findings showing that men with T2DM and a combination of total
testosterone<12nmol/l and SHBG>35nmol/l (odds ratio (OR): 3.05, 95% CI: 1.43-6.53, p=0.004) demonstrated an increased risk of mortality, independent of age (OR: 1.08, 95% CI: 1.06-1.11, p<0.001). We graphically demonstrated that the risk combination altered the relationship between age and mortality.

Conclusions. Until free testosterone is precisely, accurately and conveniently measured, calculated values may provide useful even if somewhat inaccurate estimates. We also suggest that SHBG and testosterone assays are standardised to allow establishment of diagnostic and treatment thresholds. While it is possible the association in men with T2DM, between the combination of SHBG and total
testosterone and age related mortality is driven by free hormone levels, it is so far, unproven.