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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
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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“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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Metadata
- 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.
- 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
- 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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