Immunological and mass spectrometric assays of SHBG: Consistent and inconsistent metabolic associations in healthy men

Context: SHBG concentrations correlate inconsistently with metabolic parameters. Hypothesis: SHBG assay platforms contribute to nonuniformities according to the literature. Design: The design of the study was a noninterventional quantification of SHBG by two immunoand two mass spectrometric assays and abdominal visceral fat by computed tomography scan. Setting: The study was conducted at the Center for Translational Science Activities. Participants: Healthy men (n = 120) aged 18-80 years with a body mass index of 20-43 kg/m2 participated I the study. Outcomes: Outcomes of the study included a correlation of log SHBG with age, metabolic surrogates [body mass index, albumin, glucose, insulin, abdominal (total and visceral) fat, homeostasis model assessment insulin resistance index], sex steroids (estrone, 17β-estradiol, T, and dihydrotestosterone by mass spectrometry), and adipocytokines (IL-1β, IL-6, IL-8, IL-10 and IL-12, TNF-α, and adiponectin). Results: By univariate regression, age (P < 10-4), dihydrotestosterone (P < 10-4), T (P ≤ .00022), and adiponectin (P ≤ .0084) were positive correlates, and insulin and homeostasis model assessment insulin resistance index were negative correlates (P ≤ .0060) of SHBG in all four assays. Stepwise multivariate analysis unveiled that age and T together could explain 38.1%-52.5% of the statistical variance in SHBG in all assays (P < 10-11). Multivariate regression without sex steroids unveiled that age (P < 10-5) and insulin (P < 10-3) are jointly associated with SHBG levels in the four assays with overall R2 = 0.215-0.293 and P < 10-6. In one immunological SHBG assay each, abdominal visceral fat and adiponectin were weak multivariates also. Conclusion: Immunological and mass spectrometric SHBG assays yield both consistent and inconsistent correlations with key metabolic variables in healthy men, thereby potentially explaining earlier inconsistencies in the literature. (J Clin Endocrinol Metab 99: 184-193, 2014).