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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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