The association of obesity with sex hormone-binding globulin is stronger than the association with ageing - implications for the interpretation of total testosterone measurements

Objective Total testosterone concentrations are influenced by sex hormone-binding globulin (SHBG) concentrations, which are decreased by obesity and increased with ageing. Therefore, we sought to understand and compare the associations of ageing and obesity with SHBG. Design We performed a retrospective, cross-sectional analysis of the associations of obesity and age on SHBG and testosterone measurements in men being evaluated for hypogonadism. Patients, Measurements and Analysis A total of 3671 men who underwent laboratory testing for testosterone deficiency from the Veterans Administration Puget Sound Health Care System from 1997 through 2007 was included. Univariate and multivariate linear regression modelling of the associations between age and body mass index (BMI) and SHBG was performed. Results Obesity was associated with a significantly lower SHBG [beta = -1.26 (95% CI -1.14, -1.38) nmol/l] per unit increase in BMI. In contrast, ageing was associated with a significantly increased SHBG [beta = 0.46 (95% CI 0.39, 0.53) nmol/l per year] (P < 0.001 for both effects). The association of obesity with lower SHBG was two to three times larger than the association of ageing with increased SHBG in both univariate and multivariate modelling. On average, obese men (BMI > 30 kg/m(2)) had significantly lower SHBG and total testosterone concentrations than nonobese men [(mean +/- SD) SHBG: 36 +/- 22 vs 50 +/- 27 nmol/l and total testosterone: 10.5 +/- 5.4 nmol/l vs 14.1 +/- 7.4 nmol/l; (P < 0.001 for both comparisons)], but calculated free testosterone concentrations did not differ between obese and nonobese men. Conclusions We found that the association between obesity and lowered SHBG is greater than the association of ageing with increased SHBG. These competing effects may impact total testosterone measurements for the diagnosis of low testosterone, particularly in obese men.