Cross-sectional association between testosterone, sex hormone-binding globulin and metabolic syndrome: The Healthy Twin Study

2017 ◽  
Vol 87 (5) ◽  
pp. 523-531 ◽  
Author(s):  
Heesun Moon ◽  
Inyoung Choi ◽  
Somi Kim ◽  
Hyeonyoung Ko ◽  
Jinyoung Shin ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Twin Study ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Cross Sectional

Abstract 020: Testosterone, Sex Hormone-binding Globulin and the Metabolic Syndrome: An Individual Participant Data Meta-analysis of 20 Observational Studies Involving 12,811 Men

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Judith S Brand ◽  
Maroeska M Rovers ◽  
Yvonne T van der Schouw ◽  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Observational Studies ◽  
Meta Analysis ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Individual Participant Data ◽  
Hormone Binding ◽  
Cross Sectional ◽  
Individual Participant

Background: The role of testosterone in metabolic syndrome (MetS) etiology is receiving increasing attention, given the overlap of testosterone deficiency and MetS in ageing men. We conducted an individual participant data (IPD) meta-analysis to examine this association in a uniform way and to produce more precise estimates of risk overall and in certain subgroups. Methods: Individual participant data of 20 observational studies including 12,811 men (mean age: 58.6 ± 15.6 years) were pooled and cross-sectional as well as prospective associations between total testosterone (TT), sex hormone-binding globulin (SHBG), free testosterone (FT) and MetS were assessed. We calculated odds ratios (ORs) and hazard ratios (HRs) by study-specific quartiles of sex hormones using mixed effects models (with random effects at the study level) and tested for effect modification by age and body mass index (BMI). Results: Cross-sectional analyses revealed that men with low concentrations of TT, SHBG or FT were more likely to have MetS. ORs for the lowest versus highest quartile were 4.56 (95% CI 4.02-5.16) for TT, 5.26 (95% CI 4.49-6.17) for SHBG and 2.18 (95% CI 1.88-2.53) for FT. Associations were attenuated but remained significant after adjustment for BMI and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)). Prospective analyses yielded similar results, but of smaller magnitude (HRs for the lowest versus highest quartile were 2.00 (95% CI 1.57-2.56) for TT, 2.71 (95% CI 1.99-3.70) for SHBG and 1.41 (95% CI 1.04-1.92) for FT). Stratified analyses revealed significant interactions by age and BMI, such that associations were strongest in young and nonobese men. Sex hormone concentrations decreased gradually with increasing number of MetS components and, for single components, were most strongly associated with abdominal obesity and hypertriglyceridemia. Conclusion: This meta-analysis of pooled individual data shows a robust, dose-response relationship of testosterone and SHBG concentrations with prevalent and incident MetS in men. The strong associations with abdominal obesity and hypertriglyceridemia provide insight into the underlying biological mechanisms.

scholarly journals Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: the Health in Men Study

2008 ◽  
Vol 158 (6) ◽  
pp. 785-792 ◽  
Author(s):  
S A Paul Chubb ◽  
Zoë Hyde ◽  
Osvaldo P Almeida ◽  
Leon Flicker ◽  
Paul E Norman ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Free Testosterone ◽  
Older Men ◽  
Community Dwelling ◽  
Sex Hormone ◽  
Mass Action ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Hormone Binding ◽  
Cross Sectional

BackgroundReduced circulating testosterone and sex hormone-binding globulin (SHBG) are implicated as risk factors for metabolic syndrome. As SHBG increases with age while testosterone declines, we examined the relative contributions of SHBG and testosterone to the risk of metabolic syndrome in older men.MethodsWe conducted a cross-sectional study of 2502 community-dwelling men aged ≥70 years without known diabetes. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) criteria. Early morning fasting sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations.ResultsThere were 602 men with metabolic syndrome (24.1%). The risk of metabolic syndrome increased for total testosterone <20 nmol/l, SHBG <50 nmol/l and free testosterone <300 pmol/l. In univariate analyses SHBG was associated with all five components of metabolic syndrome, total testosterone was associated with all except hypertension, and free testosterone was associated only with waist circumference and triglycerides. In multivariate analysis, both total testosterone and especially SHBG remained associated with metabolic syndrome, with odds ratios of 1.34 (95% confidence interval (CI): 1.18–1.52) and 1.77 (95% CI: 1.53–2.06) respectively. Men with hypogonadotrophic hypogonadism (total testosterone <8 nmol/l, LH ≤12 IU/l) had the highest prevalence of metabolic syndrome (53%,P<0.001).ConclusionsLower SHBG is more strongly associated with metabolic syndrome than lower total testosterone in community-dwelling older men. SHBG may be the primary driver of these relationships, possibly reflecting its relationship with insulin sensitivity. Further studies should examine whether measures that raise SHBG protect against the development of metabolic syndrome in older men.

scholarly journals The relationship between components of metabolic syndrome and plasma level of sex hormone-binding globulin

2019 ◽  
Vol 29 (2) ◽  
Author(s):  
Amin Alinezhad ◽  
Fatemeh Jafari
Keyword(s):  
Metabolic Syndrome ◽  
Plasma Level ◽  
Lipid Profiles ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Metabolic Abnormalities ◽  
Hormone Binding ◽  
Men And Women ◽  
Shbg Level ◽  
The Relationship

Plasma concentration of sex hormone-binding globulin (SHBG), as an androgen binding protein, is impressed by many physiological and environmental factors. Recent studies have shown that plasma level of SHBG is related to some components of metabolic syndrome (MetS); however, in contrast, few articles failed to show any associations between SHBG and MetS. So, this study was conducted to investigate the relationship between Components of Metabolic Syndrome and Plasma Level of Sex Hormone-Binding Globulin. In this study, after measuring the plasma level of SHBG in 84 individuals, the relation between MetS and the plasma level of SHBG was investigated. After evaluating the plasma level of SHBG and metabolic abnormalities in men and women, we investigated the factors which mentioned above in two groups including patients with and without MetS. Also, the metabolic abnormalities which evaluated in this study including plasma level of 25-hydroxyvitamin D, serum uric acid (SUA), Albumin, lipid profiles and etc. according to five components of MetS. Our result shows that SHBG could contributed to some laboratory parameters such as LDL-C (P<0.05), total cholesterol (P<0.05), triglycerides (P<0.05) and etc. in men, but not in women. On the other hand, we observed that concentration of SHBG is higher in patients with MetS (P<0.05); however, results from our experiment showed that there is no relation between lower level of SHBG and five components of MetS such as central obesity, raised fasting plasma glucose (FPG) (P>0.05), reduced HDL-C (P>0.05), raised triglycerides (P>0.05) and raised blood pressure (P>0.05) in both men and women. There is a significant association between SHBG and Log-Hip Circumference (P<0.05), Non-HDL-C (P<0.05) and Log-25(OH)D (P<0.05) was seen in this cross-section study in both men and women. Results obtained from our study suggest that SHBG is not a powerful enough factor to use as a predictor of MetS alone and there is no association between plasma level of SHBG and development of five components of MetS, however, lower SHBG level may contributed to lipid profiles.

scholarly journals Human sex hormone-binding globulin does not provide metabolic protection against diet-induced obesity and dysglycemia in mice

2018 ◽  
Vol 7 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Yael Sofer ◽  
Nava Nevo ◽  
Michal Vechoropoulos ◽  
Gabi Shefer ◽  
Etty Osher ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fasting Blood Glucose ◽  
Serum Triglyceride ◽  
Tolerance Test ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Wild Type ◽  
Diet Induced Obesity ◽  
Increased Risk

Background Sex hormone-binding globulin (SHBG) is the main transporter of sex hormones in most vertebrates. Low SHBG levels have been linked to increased risk for diabetes and metabolic syndrome. Polymorphisms of the SHBG gene linked to low SHBG protein levels also strongly predicted increased risk of type 2 diabetes, thus raising the possibility that SHBG may play a role in the pathogenesis of insulin resistance and diabetes. Aim To examine whether expression of human SHBG in mice may ameliorate the development of diabetes and metabolic syndrome in response to a high-fat diet (HFD). Methods Transgene mice expressing a human SHBG transgene (SHBG+) (N = 10/11; males/females) and their wild type littermates (N = 12/8; males/females) were fed HFD for 4.5 months. Results HFD induced comparable obesity in control and SHBG+ mice. Male transgenes had higher muscle mass after 2–3.5 months HFD (0.43 ± 0.028 (n = 4) vs 0.38 ± 0.053 g (n = 7), P = 0.05). Fasting blood glucose, as well as insulin or HOMA-IR, was not different in transgenic vs wild-type males after 4–5 months HFD. Female transgenes had higher fasting glucose (152 ± 29 (n = 7) vs 115 ± 27 mg/dL, P = 0.01 (n = 8)), but mean insulin and HOMA-IR were not different. Likewise, insulin tolerance test and intra-peritoneal glucose tolerance test (GTT) were not different. Finally, SHBG+ mice were not different from controls in terms of liver enzymes, serum triglyceride levels and blood pressure. Conclusion In mice with diet-induced obesity, human SHBG did not protect against development of obesity or dysglycemia.

scholarly journals Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Hiroki Yamazaki ◽  
Akifumi Kushiyama ◽  
Hideyuki Sakoda ◽  
Midori Fujishiro ◽  
Takeshi Yamamotoya ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Protective Effect ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Lipid Degradation ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
20 Nm

Sex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and a low serum level correlates with a risk for metabolic syndrome including diabetes, obesity, and cardiovascular events. However, the underlying molecular mechanism(s) linking SHBG and metabolic syndrome remains unknown. In this study, using adipocytes and macrophages, we focused on the in vitro effects of SHBG on inflammation as well as lipid metabolism. Incubation with 20 nM SHBG markedly suppressed lipopolysaccharide- (LPS-) induced inflammatory cytokines, such as MCP-1, TNFα, and IL-6 in adipocytes and macrophages, along with phosphorylations of JNK and ERK. Anti-inflammatory effects were also observed in 3T3-L1 adipocytes cocultured with LPS-stimulated macrophages. In addition, SHBG treatment for 18 hrs or longer significantly induced the lipid degradation of differentiated 3T3-L1 cells, with alterations in its corresponding gene and protein levels. Notably, these effects of SHBG were not altered by coaddition of large amounts of testosterone or estradiol. In conclusion, SHBG suppresses inflammation and lipid accumulation in macrophages and adipocytes, which might be among the mechanisms underlying the protective effect of SHBG, that is, its actions which reduce the incidence of metabolic syndrome.

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