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Sex Hormone–Binding Globulin Levels in Young Men Are Associated With Nonalcoholic Fatty Liver Disease in Midlife
Open accessAbstract
INTRODUCTION: Cross-sectional data note lower levels of testosterone and sex hormone–binding globulin (SHBG) levels in men with nonalcoholic fatty liver disease (NAFLD). Whether sex hormone levels in young men are predictive of later risk of NAFLD is not known. METHODS: Among men in the prospective population-based multicenter Coronary Artery Risk Development in Young Adults study (mean age 50; n = 837), we assessed whether testosterone and SHBG levels measured at study year 10 (median age 35 years) were associated with prevalent NAFLD at study year 25. NAFLD was defined using noncontrast abdominal computed tomography (CT) scan after excluding other causes of hepatic steatosis. The association of testosterone and SHBG with prevalent NAFLD was assessed by logistic regression. RESULTS: Total testosterone levels in young men were inversely associated with subsequent prevalent NAFLD on unadjusted analysis (odds ratio [OR] 0.64, 95% confidence interval 0.53–0.7, P < 0.001), although no longer significant after adjustment for year 10 metabolic covariates as well as change in metabolic covariates from years 10 to 25 (OR 0.99, 95% confidence interval 0.76–1.27). In contrast, there was a significant inverse association of SHBG with prevalent NAFLD, independent of testosterone and metabolic covariates (OR 0.68, OR 0.51–0.92, P = 0.013). On formal mediation testing, visceral adiposity was found to explain ∼41.0% (95% confidence interval 27%–73%) of the association of lower SHBG with prevalent NAFLD. CONCLUSIONS: Lower levels of SHBG in young men are associated with increase in prevalent NAFLD in middle age, independent of comprehensive metabolic risk factors. SHBG may provide a novel marker of NAFLD risk in young men.
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“For SHBG on the other hand, subjects of both sexes with NAFLD showed lower values compared to non-affected subjects, with a stronger inverse association in women than in men.”
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 [141]
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“Regarding calculated free T, literature remains undecided describing either an inverse, positive or no association with NAFLD [140–143].”
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 [141]
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“In fact, men with higher total T have a reduced risk of developing NAFLD, while the opposite association was seen for women [139–141].”
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 [141]
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“Moreover, for both sexes, odds ratios showed a reduced risk of NAFLD with higher SHBG levels [139, 141].”
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 [141]
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Sorted by citations
Hutchison, A. L., Tavaglione, F., Romeo, S., & Charlton, M. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.08.030 · Cited by 250
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Metadata
- Authors
- Sarkar, M., VanWagner, L. B., Terry, J. G., Carr, J. J., Rinella, M., Schreiner, P. J., Lewis, C. E., Terrault, N., & Cohort, F. T. C. A. R. D. I. Y. A. (.
- Affiliations
- University of California, San Francisco (US)
- Northwestern University (US)
- Vanderbilt University Medical Center (US)
- University of Minnesota (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Sarkar, Monika
- ORCID
- Venue
- American Journal of Gastroenterology
- Published
- 2019-02-04
- Volume
- 114
- Issue
- 5
- Pages
- 758-763
- ISSN
- 0002-9270 (ISSN-L)
- 1572-0241
- PMC
- PMC6599461
- OpenAlex
- W2912989251
- Cited by
- 37
- References
- 4
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 9 · 2021: 3 · 2020: 2 · 2019: 5
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hc48048-58-0-1, n01hc48047-55-0-1, n01hc48049-61-0-1)
- National Heart, Lung, and Blood Institute (HHSN268201300028C, HHS-N2-68201300029C, HHSN268201300027C, N01 HC048048, HHSN268200900041C, N01-HC-048049, HHSN268201300026C, HHS-N2-68201300025C, K23HL136891, N01 HC048047, R01HL098445, R01HL065611)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK111944, P30DK026743)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- sex hormone-binding globulin, non-alcoholic fatty liver disease, testosterone, young men, NAFLD risk prediction, visceral fat, hepatic steatosis, metabolic risk factors, mediation analysis
- MeSH terms
- Adult, Humans, Male, Middle Aged, Prospective Studies, Radiography, Abdominal, Risk Factors, Sex Hormone-Binding Globulin, Testosterone, Tomography, X-Ray Computed, United States, Biomarkers, Prevalence, Intra-Abdominal Fat, Non-alcoholic Fatty Liver Disease
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- Sarkar, M., VanWagner, L. B., Terry, J. G., Carr, J. J., Rinella, M., Schreiner, P. J., Lewis, C. E., Terrault, N., & Cohort, F. T. C. A. R. D. I. Y. A. (. (2019). Sex Hormone–Binding Globulin Levels in Young Men Are Associated With Nonalcoholic Fatty Liver Disease in Midlife. American Journal of Gastroenterology. https://doi.org/10.14309/ajg.0000000000000138
