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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

Strobe diagram illustrating the selection of the generation 2 cross-sectional and longitudinal samples and the generation 3 cross-sectional validation sample. (A high-quality color representation of this figure is available in the online issue.)
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Figure 1: Strobe diagram illustrating the selection of the generation 2 cross-sectional and longitudinal samples and the generation 3 cross-sectional validation sample. (A high-quality color representation of this figure is available in the online issue.)

Mentions: In 1971, the offspring of the original FHS participants and the spouses of the offspring (FHS generation 2) were enrolled into the Framingham Offspring Study (16) and have since completed eight examinations at 4- to 8-year intervals. Generation 2 men who attended examination 7 (1998–2001) were eligible for inclusion in cross-sectional analyses (n = 1,625). The validation sample included children of the offspring cohort (generation 3) who attended examination 1 (n = 1,912). Men receiving testosterone or androgen-deprivation therapy for prostate cancer and those missing testosterone or data necessary for defining metabolic syndrome were excluded, resulting in a sample size of 1,407 subjects for the cross-sectional analyses of the training sample and 1,887 subjects for the validation sample (Fig. 1).


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)

Strobe diagram illustrating the selection of the generation 2 cross-sectional and longitudinal samples and the generation 3 cross-sectional validation sample. (A high-quality color representation of this figure is available in the online issue.)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Strobe diagram illustrating the selection of the generation 2 cross-sectional and longitudinal samples and the generation 3 cross-sectional validation sample. (A high-quality color representation of this figure is available in the online issue.)
Mentions: In 1971, the offspring of the original FHS participants and the spouses of the offspring (FHS generation 2) were enrolled into the Framingham Offspring Study (16) and have since completed eight examinations at 4- to 8-year intervals. Generation 2 men who attended examination 7 (1998–2001) were eligible for inclusion in cross-sectional analyses (n = 1,625). The validation sample included children of the offspring cohort (generation 3) who attended examination 1 (n = 1,912). Men receiving testosterone or androgen-deprivation therapy for prostate cancer and those missing testosterone or data necessary for defining metabolic syndrome were excluded, resulting in a sample size of 1,407 subjects for the cross-sectional analyses of the training sample and 1,887 subjects for the validation sample (Fig. 1).

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