Low Sex Hormone-Binding Globulin, Total Testosterone, and Symptomatic Androgen Deficiency Are Associated with Development of the Metabolic Syndrome in Nonobese Men

Kupelian, Varant; Page, Stephanie T.; Araujo, Andre B.; Travison, Thomas G.; Bremner, William J.; McKinlay, John B.

doi:10.1210/jc.2005-1326

Cited by 561Hormonal and reproductive studiesDiabetes, Cardiovascular Risks, and LipoproteinsAdrenal Hormones and Disorders

Low Sex Hormone-Binding Globulin, Total Testosterone, and Symptomatic Androgen Deficiency Are Associated with Development of the Metabolic Syndrome in Nonobese Men

Kupelian, Varant, Page, Stephanie T., Araujo, Andre B., Travison, Thomas G., Bremner, William J., McKinlay, John B.·2006·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2005-1326

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Abstract

Background: The metabolic syndrome (MetS), characterized by central obesity, lipid and insulin dysregulation, and hypertension, is a precursor state for cardiovascular disease. The purpose of this analysis was to determine whether low serum sex hormone levels or clinical androgen deficiency (AD) predict the development of MetS. Methods: Data were obtained from the Massachusetts Male Aging Study, a population-based prospective cohort of 1709 men observed at three time points (T1, 1987–1989; T2, 1995–1997; T3, 2002–2004). MetS was defined using a modification of the ATP III guidelines. Clinical AD was defined using a combination of testosterone levels and clinical signs and symptoms. The association between MetS and sex hormone levels or clinical AD was assessed using relative risks (RR), and 95% confidence intervals (95% CI) were estimated using Poisson regression models. Results: Analysis was conducted in 950 men without MetS at T1. Lower levels of total testosterone and SHBG were predictive of MetS, particularly among men with a body mass index (BMI) below 25 kg/m2 with adjusted RRs for a decrease in 1 sd of 1.41 (95% CI, 1.06–1.87) and 1.65 (95% CI, 1.12–2.42). Results were similar for the AD and MetS association, with RRs of 2.51 (95% CI, 1.12–5.65) among men with a BMI less than 25 compared with an RR of 1.22 (95% CI, 0.66–2.24) in men with a BMI of 25 or greater. Conclusions: Low serum SHBG, low total testosterone, and clinical AD are associated with increased risk of developing MetS over time, particularly in nonoverweight, middle-aged men (BMI, <25). Together, these results suggest that low SHBG and/or AD may provide early warning signs for cardiovascular risk and an opportunity for early intervention in nonobese men.

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Low levels of SHBG seem to be predictive of developing METS at an older age.
“In line with these findings, low levels of SHBG seem to be predictive of developing METS at an older age [135, 136].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [136]

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Self-citation

Authors: Kupelian, V., Page, S. T., Araujo, A. B., Travison, T. G., Bremner, W. J., & McKinlay, J. B.
Affiliations: New England Research Institutes (US)
University of Washington (US)
New England Research Institutes (V.K., A.B.A., T.G.T., J.B.M.), Watertown, Massachusetts 02472
Corresponding author: McKinlay, John B.
ORCID: Kupelian, Varant
Page, Stephanie T.
Travison, Thomas G.
Bremner, William J.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2006-03-01
Volume: 91
Issue: 3
Pages: 843-850
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2005-1326
OpenAlex: W2155165820
Cited by: 561
References: 47
Citations by year: 2026: 4 · 2025: 7 · 2024: 9 · 2023: 11 · 2022: 15 · 2021: 11 · 2020: 16 · 2019: 20 · 2018: 25 · 2017: 24 · 2016: 18 · 2015: 27 · 2014: 29 · 2013: 39 · 2012: 51
FWCI: 40.50
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: World Health Organization
National Institute on Aging (AG 04763, K23AG027238)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 51345, R01DK044995, DK44995, R01DK051345)
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 › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: metabolic syndrome, sex hormone-binding globulin, total testosterone, androgen deficiency, cardiovascular risk, middle-aged men, body mass index, Massachusetts Male Aging Study, risk prediction
MeSH terms: Adult, Aged, Androgens, Body Weight, Cardiovascular Diseases, Humans, Male, Massachusetts, Middle Aged, Reference Values, Sex Hormone-Binding Globulin, Socioeconomic Factors, Testosterone, Cohort Studies, Metabolic Syndrome

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Low Sex Hormone-Binding Globulin, Total Testosterone, and Symptomatic Androgen Deficiency Are Associated with Development of the Metabolic Syndrome in Nonobese Men

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