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 immuno- and 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.