Associations of Fatty Liver Disease and Other Factors Affecting Serum SHBG Concentrations: A Population Based Study on 1657 Subjects

Abstract

Sex hormone binding globulin (SHBG) is a glycoprotein expressed predominantly in the hepatocytes. It regulates the transport of sex steroid hormones in the blood stream to their target tissues. The expression of the SHBG gene is subject to multifactorial regulation including hormonal, metabolic, and nutritional aspects. Against this background, we investigated the effect of fatty liver and metabolic syndrome, together with other parameters, on serum SHBG concentrations in a population-based cohort in Germany. This cross-sectional study included 870 women and 787 men (average age 42.3±12.8 years), who underwent ultrasound screening for fatty liver in addition to providing a complete medical history and undergoing physical and laboratory examination. Fatty liver was diagnosed on ultrasound criteria in 159 women (18.3%) and 287 men (36.5%). Fatty liver was shown to exert a significant influence on serum SHBG concentrations in men and in premenopausal women. Men with grade 1 fatty liver had a 1.96-fold increased risk (95%-confidence interval=1.28-3.02; p=0.0022) and postmenopausal women with grade 1 fatty liver a 2.4-fold risk (95%-confidence interval=1.11-5.27; p=0.0267) for low SHBG concentrations. Among metabolic parameters, HDL-C represented as affecting factor in men (p=0.0058) and premenopausal women (p=0.0002), while cholesterol only showed an association in premenopausal women (p=0.0439) and triglyceride in postmenopausal women (p=0.0436). No association of concentrations of SHBG and metabolic syndrome was observed. Age, BMI and waist-to-hip ratio also influence the SHBG concentration. Based on these findings, we conclude that fat accumulation in the liver influences SHBG concentrations in men and premenopausal women.

Association Between Endogenous Sex Hormones and Liver Fat in a Multiethnic Study of Atherosclerosis

“…Our results that lower levels of sex hormone binding globulin are associated with NAFLD men and postmenopausal women are consistent with small prior studies, 22, 23 although the association was marginal in our study, and was largely explained by adjusting for the insulin sensitivity index. Another small study in hospital based patients and controls reported an association between low levels of DHEA and NAFLD, 24 but this study did not present sex-specific analysis.…”

“…22, 23 Another study reported an association between low levels of DHEA and NAFLD. 24 However, no associations with estradiol or testosterone have been reported in US population based studies.…”

Increased prevalence of polycystic ovary syndrome in premenopausal women with nonalcoholic fatty liver disease

“…In our cohort, women with NAFLD were more obese and had more pronounced abdominal adiposity, were more insulin resistant and had an abnormal lipid profile compared to women without NAFLD in agreement with existing data (1, 4, 11, 12, 13). Moreover, participating women with NAFLD had decreased SHBG levels and increased FAI values compared to women without NAFLD in agreement with our previous work (20) and another study (34). Interestingly, the association of decreased SHBG levels and increased FAI values with NAFLD has been also reported in postmenopausal women with biopsy proven NAFLD (35).…”

The biomarker sex hormone-binding globulin – From established applications to emerging trends in clinical medicine

“…In line with the information given in the section on SHBG, METS and T2DM cross-sectional as well as caseecontrol studies demonstrated that nonalcoholic fatty liver disease is associated with low SHBG concentrations. The relationship is independent of other known risk factors and can be observed in randomly chosen populations as well as in T2DM patients [58,59]. With respect to hereditary disorders, heterozygotes for the C282Y polymorphism of the hereditary hemochromatosis gene exhibit higher SHBG serum levels [60].…”