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Sex hormone-binding globulin, but not testosterone, is associated prospectively and independently with incident metabolic syndrome in men: the framingham heart study.

Bhasin S, Jasjua GK, Pencina M, D'Agostino R, Coviello AD, Vasan RS, Travison TG - Diabetes Care (2011)

Bottom Line: SHBG, but not testosterone or free testosterone, was significantly associated with metabolic syndrome after adjusting for age, smoking, BMI, and insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR]).These findings were confirmed in a validation sample.Longitudinally, SHBG at examination 7, but not testosterone or free testosterone, was associated with incident metabolic syndrome at examination 8 after adjusting for age, smoking, BMI, and HOMA-IR.

View Article: PubMed Central - PubMed

Affiliation: Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, MA, USA. bhasin@bu.edu

ABSTRACT

Objective: The association between total testosterone and metabolic syndrome has prompted speculation that low testosterone contributes to the pathophysiology of metabolic syndrome in men. We determined whether testosterone or sex hormone-binding globulin (SHBG) is independently associated with the risk of metabolic syndrome.

Research design and methods: Cross-sectional relationships of hormone levels with metabolic syndrome were assessed in a sample of men in generation 2 of the Framingham Heart Study (FHS) who did not receive testosterone or androgen-deprivation therapy (n = 1,625) and confirmed in a validation sample of men in FHS generation 3 (n = 1,912). Hormone levels in generation 2 examination 7 were related prospectively to incident metabolic syndrome 6.6 years later at examination 8. Testosterone was measured using liquid chromatography-tandem mass spectrometry, SHBG was measured by immunofluorometric assay, and free testosterone was calculated. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS Cross-sectionally, testosterone and SHBG were more strongly associated with metabolic syndrome than free testosterone in the training sample. SHBG, but not testosterone or free testosterone, was significantly associated with metabolic syndrome after adjusting for age, smoking, BMI, and insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR]). These findings were confirmed in a validation sample. Longitudinally, SHBG at examination 7, but not testosterone or free testosterone, was associated with incident metabolic syndrome at examination 8 after adjusting for age, smoking, BMI, and HOMA-IR. Multivariable analyses suggested that age, BMI, and insulin sensitivity independently affect SHBG and testosterone levels and the risk of metabolic syndrome and its components.

Conclusions: SHBG, but not testosterone, is independently associated with the risk of metabolic syndrome. These data do not reveal an independent prospective relationship between testosterone and metabolic syndrome in men.

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Related in: MedlinePlus

A: Odds ratios expressing the association between hormone quartiles and the metabolic syndrome. For each measure (total testosterone, free testosterone, and SHBG) the highest quartile (Q4) is the reference group with which the other three quartiles (Q1, Q2, and Q3) are compared. Moving left to right, panels express estimates obtained from models with successive inclusions of variables listed in the title for each panel. The bars that do not intersect with the dotted line corresponding to the odds ratio of 1 are statistically significant. B: Odds ratios quantifying the association between low SHBG and components of the metabolic system, by FHS cohort. Line segments read left to right track change in the estimated effect with addition of successive covariates to multivariate models. The bars that do not intersect with the dotted line corresponding to the odds ratio of 1 are statistically significant. TT, total testosterone.
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Figure 2: A: Odds ratios expressing the association between hormone quartiles and the metabolic syndrome. For each measure (total testosterone, free testosterone, and SHBG) the highest quartile (Q4) is the reference group with which the other three quartiles (Q1, Q2, and Q3) are compared. Moving left to right, panels express estimates obtained from models with successive inclusions of variables listed in the title for each panel. The bars that do not intersect with the dotted line corresponding to the odds ratio of 1 are statistically significant. B: Odds ratios quantifying the association between low SHBG and components of the metabolic system, by FHS cohort. Line segments read left to right track change in the estimated effect with addition of successive covariates to multivariate models. The bars that do not intersect with the dotted line corresponding to the odds ratio of 1 are statistically significant. TT, total testosterone.

Mentions: In cross-sectional analyses of the original sample, total as well as free testosterone levels were significantly negatively associated with the risk of metabolic syndrome after adjusting for age and smoking; the association of metabolic syndrome was stronger with total than with free testosterone (Table 2). For each SD decrease in total and free testosterone levels, the odds of prevalent metabolic syndrome were increased by 83 and 25%, respectively, after adjusting for age and smoking (Table 2). The men in the lowest quartile of total testosterone had 4.5 times the odds of having prevalent metabolic syndrome than men in the highest quartile (P < 0.0001) (Fig. 2A) (Supplementary Table 1). The men in the lowest quartile of free testosterone had 1.9 times the odds of having metabolic syndrome than those in the highest quartile (P < 0.0001).


Sex hormone-binding globulin, but not testosterone, is associated prospectively and independently with incident metabolic syndrome in men: the framingham heart study.

Bhasin S, Jasjua GK, Pencina M, D'Agostino R, Coviello AD, Vasan RS, Travison TG - Diabetes Care (2011)

A: Odds ratios expressing the association between hormone quartiles and the metabolic syndrome. For each measure (total testosterone, free testosterone, and SHBG) the highest quartile (Q4) is the reference group with which the other three quartiles (Q1, Q2, and Q3) are compared. Moving left to right, panels express estimates obtained from models with successive inclusions of variables listed in the title for each panel. The bars that do not intersect with the dotted line corresponding to the odds ratio of 1 are statistically significant. B: Odds ratios quantifying the association between low SHBG and components of the metabolic system, by FHS cohort. Line segments read left to right track change in the estimated effect with addition of successive covariates to multivariate models. The bars that do not intersect with the dotted line corresponding to the odds ratio of 1 are statistically significant. TT, total testosterone.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198304&req=5

Figure 2: A: Odds ratios expressing the association between hormone quartiles and the metabolic syndrome. For each measure (total testosterone, free testosterone, and SHBG) the highest quartile (Q4) is the reference group with which the other three quartiles (Q1, Q2, and Q3) are compared. Moving left to right, panels express estimates obtained from models with successive inclusions of variables listed in the title for each panel. The bars that do not intersect with the dotted line corresponding to the odds ratio of 1 are statistically significant. B: Odds ratios quantifying the association between low SHBG and components of the metabolic system, by FHS cohort. Line segments read left to right track change in the estimated effect with addition of successive covariates to multivariate models. The bars that do not intersect with the dotted line corresponding to the odds ratio of 1 are statistically significant. TT, total testosterone.
Mentions: In cross-sectional analyses of the original sample, total as well as free testosterone levels were significantly negatively associated with the risk of metabolic syndrome after adjusting for age and smoking; the association of metabolic syndrome was stronger with total than with free testosterone (Table 2). For each SD decrease in total and free testosterone levels, the odds of prevalent metabolic syndrome were increased by 83 and 25%, respectively, after adjusting for age and smoking (Table 2). The men in the lowest quartile of total testosterone had 4.5 times the odds of having prevalent metabolic syndrome than men in the highest quartile (P < 0.0001) (Fig. 2A) (Supplementary Table 1). The men in the lowest quartile of free testosterone had 1.9 times the odds of having metabolic syndrome than those in the highest quartile (P < 0.0001).

Bottom Line: SHBG, but not testosterone or free testosterone, was significantly associated with metabolic syndrome after adjusting for age, smoking, BMI, and insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR]).These findings were confirmed in a validation sample.Longitudinally, SHBG at examination 7, but not testosterone or free testosterone, was associated with incident metabolic syndrome at examination 8 after adjusting for age, smoking, BMI, and HOMA-IR.

View Article: PubMed Central - PubMed

Affiliation: Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, MA, USA. bhasin@bu.edu

ABSTRACT

Objective: The association between total testosterone and metabolic syndrome has prompted speculation that low testosterone contributes to the pathophysiology of metabolic syndrome in men. We determined whether testosterone or sex hormone-binding globulin (SHBG) is independently associated with the risk of metabolic syndrome.

Research design and methods: Cross-sectional relationships of hormone levels with metabolic syndrome were assessed in a sample of men in generation 2 of the Framingham Heart Study (FHS) who did not receive testosterone or androgen-deprivation therapy (n = 1,625) and confirmed in a validation sample of men in FHS generation 3 (n = 1,912). Hormone levels in generation 2 examination 7 were related prospectively to incident metabolic syndrome 6.6 years later at examination 8. Testosterone was measured using liquid chromatography-tandem mass spectrometry, SHBG was measured by immunofluorometric assay, and free testosterone was calculated. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS Cross-sectionally, testosterone and SHBG were more strongly associated with metabolic syndrome than free testosterone in the training sample. SHBG, but not testosterone or free testosterone, was significantly associated with metabolic syndrome after adjusting for age, smoking, BMI, and insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR]). These findings were confirmed in a validation sample. Longitudinally, SHBG at examination 7, but not testosterone or free testosterone, was associated with incident metabolic syndrome at examination 8 after adjusting for age, smoking, BMI, and HOMA-IR. Multivariable analyses suggested that age, BMI, and insulin sensitivity independently affect SHBG and testosterone levels and the risk of metabolic syndrome and its components.

Conclusions: SHBG, but not testosterone, is independently associated with the risk of metabolic syndrome. These data do not reveal an independent prospective relationship between testosterone and metabolic syndrome in men.

Show MeSH
Related in: MedlinePlus