Testosterone, sex hormone-binding globulin and the metabolic syndrome: A systematic review and meta-analysis of observational studies

Brand, J. S.; van der Tweel, I.; Grobbee, D. E.; Emmelot-Vonk, M. H.; van der Schouw, Y. T.

doi:10.1093/ije/dyq158

Cited by 334Hormonal and reproductive studiesDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

Testosterone, sex hormone-binding globulin and the metabolic syndrome: A systematic review and meta-analysis of observational studies

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Brand, J. S., van der Tweel, I., Grobbee, D. E., Emmelot-Vonk, M. H., van der Schouw, Y. T.·2011·International Journal of Epidemiology

DOI 10.1093/ije/dyq158

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Abstract

BACKGROUND: Accumulating evidence suggests a sex-dependent role of circulating testosterone in the metabolic syndrome (MetS). METHODS: We conducted a meta-analysis of observational studies (PubMed and EMBASE-1 May 2010) relating MetS to determinants of testosterone status [total testosterone (TT), free testosterone (FT) and sex hormone-binding globulin (SHBG)]. RESULTS: A total of 52 studies were identified, comprising 22 043 men and 7839 women and presenting relative risk (RR) estimates or hormone levels for subjects with and without MetS. Endogenous TT and FT levels were lower in men with MetS [TT mean difference = -2.64 nmol/l, 95% confidence interval (CI) -2.95 to -2.32; FT standardized mean difference = -0.26 pmol/l, 95% CI -0.39 to -0.13] and higher in women with MetS (TT mean difference = 0.14 nmol/l, 95% CI 0.07-0.20; FT standardized mean difference = 0.52 pmol/l, 95% CI 0.33-0.71) compared with those without. Similarly, men with higher TT levels had a lower MetS risk (RR estimate = 0.38, 95% CI 0.28-0.50) whereas higher TT levels increased the risk of MetS in women (RR estimate = 1.68, 95% CI 1.15-2.45). In both sexes, higher SHBG levels were associated with a reduced risk (men: RR estimate = 0.29, 95% CI 0.21-0.41; women: RR estimate = 0.30, 95% CI 0.21-0.42). CONCLUSION: This meta-analysis supports the presence of a sex-dependent association between testosterone and MetS: TT and FT levels are lower in men with MetS, whereas they are higher in women with MetS. There are no indications for a sex-specific association between SHBG and MetS. In both men and women, MetS is associated with lower SHBG levels.

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Numerous estimating equations have been described, including bioavailable testosterone, free androgen index, and free testosterone index (Vermeulen method), with results suggesting high correlations with direct assays.
“Numerous estimating equations have been described in the literature including bioavailable T (non-SHBG bound T), free androgen index (FAI; 100T/SHBG), and free T index (Vermeulen method), among others, with results suggesting high correlations to direct assays.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [103]
In the largest study evaluating predictive accuracy of free testosterone calculations, Sartorius and colleagues concluded that empirical methods (Ly, Sartorius) are most concordant, while other estimations (Vermeulen, Nanjee and Wheeler, Sodergard) overestimate the true value.
“In the largest study evaluating predictive accuracy of fT calculations, Sartorius and colleagues concluded that empirical methods (Ly, Sartorius) of calculated fT are most concordant, with other estimations (Vermeulen, Nanjee and Wheeler, Sodergard) resulting in overestimation of the true value.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [103]

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Untitled work
Alberti (1998) · doi:10.1002/(sici)1096-9136(199807)15:7

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Authors: Brand, J. S., van der Tweel, I., Grobbee, D. E., Emmelot-Vonk, M. H., & van der Schouw, Y. T.
Affiliations: University Medical Center Utrecht (NL)
ORCID: Brand, J. S.
Grobbee, D. E.
Venue: International Journal of Epidemiology
Publisher: Oxford University Press (OUP)
Published: 2010-09-24
Volume: 40
Issue: 1
Pages: 189-207
ISSN: 0300-5771 (ISSN-L)
1464-3685
DOI: 10.1093/ije/dyq158
OpenAlex: W2116785242
Cited by: 334
References: 119
Citations by year: 2026: 9 · 2025: 12 · 2024: 20 · 2023: 22 · 2022: 9 · 2021: 21 · 2020: 20 · 2019: 22 · 2018: 23 · 2017: 23 · 2016: 22 · 2015: 30 · 2014: 22 · 2013: 31 · 2012: 24
FWCI: 3.55
Type: journal article
Language: en
Open access: green
hal.science
Licence: other-oa
Locations: International Journal of Epidemiology (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
HighWire Press Open Archive (submittedVersion)
Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: testosterone, sex hormone-binding globulin, metabolic syndrome, free testosterone, sex differences, men, women, androgen status
MeSH terms: Female, Humans, Male, Sex Factors, Sex Hormone-Binding Globulin, Testosterone, Metabolic Syndrome

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Testosterone, sex hormone-binding globulin and the metabolic syndrome: A systematic review and meta-analysis of observational studies

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