Testosterone, sex hormone-binding globulin and the metabolic syndrome in men

An individual participant data meta-analysis of observational studies

Judith S. Brand, Maroeska M. Rovers, Bu B. Yeap, Harald J. Schneider, Tomi Pekka Tuomainen, Robin Haring, Giovanni Corona, Altan Onat, Marcello Maggio, Claude Bouchard, Peter C Y Tong, Richard Y T Chen, Masahiro Akishita, Jourik A. Gietema, Marie Hélène Gannagé-Yared, Anna Lena Undeń, Aarno Hautanen, Nicolai P. Goncharov, Philip Kumanov, S. A Paul Chubb & 9 others Osvaldo P. Almeida, Hans Ulrich Wittchen, Jens Klotsche, Henri Wallaschofski, Henry Völzke, Jussi Kauhanen, Jukka T. Salonen, Luigi Ferrucci, Yvonne T. Van Der Schouw

Research output: Contribution to journalArticle

Abstract

Background: Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably. Objectives: We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components. Data sources: Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE. Study Eligibility Criteria: Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men. Methods: We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied. Results: Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension. Conclusions: Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.

Original languageEnglish (US)
Article numbere100409
JournalPLoS One
Volume9
Issue number7
DOIs
StatePublished - Jul 14 2014
Externally publishedYes

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Sex Hormone-Binding Globulin
metabolic syndrome
observational studies
Metadata
meta-analysis
testosterone
Observational Studies
Testosterone
Meta-Analysis
body mass index
Body Mass Index
odds ratio
sex hormone-binding globulin
Hazards
Odds Ratio
hypertriglyceridemia
Abdominal Obesity
Hypertriglyceridemia
Information Storage and Retrieval
hyperglycemia

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Brand, J. S., Rovers, M. M., Yeap, B. B., Schneider, H. J., Tuomainen, T. P., Haring, R., ... Van Der Schouw, Y. T. (2014). Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: An individual participant data meta-analysis of observational studies. PLoS One, 9(7), [e100409]. https://doi.org/10.1371/journal.pone.0100409

Testosterone, sex hormone-binding globulin and the metabolic syndrome in men : An individual participant data meta-analysis of observational studies. / Brand, Judith S.; Rovers, Maroeska M.; Yeap, Bu B.; Schneider, Harald J.; Tuomainen, Tomi Pekka; Haring, Robin; Corona, Giovanni; Onat, Altan; Maggio, Marcello; Bouchard, Claude; Tong, Peter C Y; Chen, Richard Y T; Akishita, Masahiro; Gietema, Jourik A.; Gannagé-Yared, Marie Hélène; Undeń, Anna Lena; Hautanen, Aarno; Goncharov, Nicolai P.; Kumanov, Philip; Chubb, S. A Paul; Almeida, Osvaldo P.; Wittchen, Hans Ulrich; Klotsche, Jens; Wallaschofski, Henri; Völzke, Henry; Kauhanen, Jussi; Salonen, Jukka T.; Ferrucci, Luigi; Van Der Schouw, Yvonne T.

In: PLoS One, Vol. 9, No. 7, e100409, 14.07.2014.

Research output: Contribution to journalArticle

Brand, JS, Rovers, MM, Yeap, BB, Schneider, HJ, Tuomainen, TP, Haring, R, Corona, G, Onat, A, Maggio, M, Bouchard, C, Tong, PCY, Chen, RYT, Akishita, M, Gietema, JA, Gannagé-Yared, MH, Undeń, AL, Hautanen, A, Goncharov, NP, Kumanov, P, Chubb, SAP, Almeida, OP, Wittchen, HU, Klotsche, J, Wallaschofski, H, Völzke, H, Kauhanen, J, Salonen, JT, Ferrucci, L & Van Der Schouw, YT 2014, 'Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: An individual participant data meta-analysis of observational studies', PLoS One, vol. 9, no. 7, e100409. https://doi.org/10.1371/journal.pone.0100409
Brand, Judith S. ; Rovers, Maroeska M. ; Yeap, Bu B. ; Schneider, Harald J. ; Tuomainen, Tomi Pekka ; Haring, Robin ; Corona, Giovanni ; Onat, Altan ; Maggio, Marcello ; Bouchard, Claude ; Tong, Peter C Y ; Chen, Richard Y T ; Akishita, Masahiro ; Gietema, Jourik A. ; Gannagé-Yared, Marie Hélène ; Undeń, Anna Lena ; Hautanen, Aarno ; Goncharov, Nicolai P. ; Kumanov, Philip ; Chubb, S. A Paul ; Almeida, Osvaldo P. ; Wittchen, Hans Ulrich ; Klotsche, Jens ; Wallaschofski, Henri ; Völzke, Henry ; Kauhanen, Jussi ; Salonen, Jukka T. ; Ferrucci, Luigi ; Van Der Schouw, Yvonne T. / Testosterone, sex hormone-binding globulin and the metabolic syndrome in men : An individual participant data meta-analysis of observational studies. In: PLoS One. 2014 ; Vol. 9, No. 7.
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abstract = "Background: Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably. Objectives: We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components. Data sources: Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE. Study Eligibility Criteria: Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men. Methods: We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied. Results: Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95{\%} CI 1.60-1.77), 1.73 (95{\%} CI 1.62-1.85) and 1.46 (95{\%} CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95{\%} CI 1.16-1.36), 1.44 (95{\%} 1.30-1.60) and 1.14 (95{\%} 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension. Conclusions: Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.",
author = "Brand, {Judith S.} and Rovers, {Maroeska M.} and Yeap, {Bu B.} and Schneider, {Harald J.} and Tuomainen, {Tomi Pekka} and Robin Haring and Giovanni Corona and Altan Onat and Marcello Maggio and Claude Bouchard and Tong, {Peter C Y} and Chen, {Richard Y T} and Masahiro Akishita and Gietema, {Jourik A.} and Gannag{\'e}-Yared, {Marie H{\'e}l{\`e}ne} and Undeń, {Anna Lena} and Aarno Hautanen and Goncharov, {Nicolai P.} and Philip Kumanov and Chubb, {S. A Paul} and Almeida, {Osvaldo P.} and Wittchen, {Hans Ulrich} and Jens Klotsche and Henri Wallaschofski and Henry V{\"o}lzke and Jussi Kauhanen and Salonen, {Jukka T.} and Luigi Ferrucci and {Van Der Schouw}, {Yvonne T.}",
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T1 - Testosterone, sex hormone-binding globulin and the metabolic syndrome in men

T2 - An individual participant data meta-analysis of observational studies

AU - Brand, Judith S.

AU - Rovers, Maroeska M.

AU - Yeap, Bu B.

AU - Schneider, Harald J.

AU - Tuomainen, Tomi Pekka

AU - Haring, Robin

AU - Corona, Giovanni

AU - Onat, Altan

AU - Maggio, Marcello

AU - Bouchard, Claude

AU - Tong, Peter C Y

AU - Chen, Richard Y T

AU - Akishita, Masahiro

AU - Gietema, Jourik A.

AU - Gannagé-Yared, Marie Hélène

AU - Undeń, Anna Lena

AU - Hautanen, Aarno

AU - Goncharov, Nicolai P.

AU - Kumanov, Philip

AU - Chubb, S. A Paul

AU - Almeida, Osvaldo P.

AU - Wittchen, Hans Ulrich

AU - Klotsche, Jens

AU - Wallaschofski, Henri

AU - Völzke, Henry

AU - Kauhanen, Jussi

AU - Salonen, Jukka T.

AU - Ferrucci, Luigi

AU - Van Der Schouw, Yvonne T.

PY - 2014/7/14

Y1 - 2014/7/14

N2 - Background: Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably. Objectives: We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components. Data sources: Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE. Study Eligibility Criteria: Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men. Methods: We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied. Results: Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension. Conclusions: Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.

AB - Background: Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably. Objectives: We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components. Data sources: Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE. Study Eligibility Criteria: Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men. Methods: We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied. Results: Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension. Conclusions: Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.

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