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The association of sex steroid hormone concentrations with non‐alcoholic fatty liver disease and liver enzymes in US men
Open accessAbstract
Background & Aims: This study aimed to analyse the association of sex hormone levels with liver enzyme levels and non‐alcoholic fatty liver disease (NAFLD) in a nationally representative sample of men. Methods: A total of 919 men from the US National Health and Nutrition Examination Study (NHANES) III were included in this cross‐sectional analysis of data from 1988 to 1991. We used existing data on serum total and free testosterone, total and free estradiol, androstanediol glucuronide (AAG) and sex steroid‐binding globulin (SHBG), and estimated their associations with aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and NAFLD, as determined using ultrasound, after adjusting for possible confounders including age, race, smoking, alcohol, physical activity, waist circumference and steroid hormones. Results: Lower total testosterone (TT) and higher free estradiol were associated with higher odds of NAFLD after adjusting for confounders including the other sex hormones. Lower TT was associated with higher odds of elevated AST, but not ALT. Free testosterone, total estradiol, SHBG and AAG were not associated with NAFLD or liver enzymes. Conclusions: This study supports an inverse association between TT concentration and NAFLD in men independent of other sex hormones (SHBG, AAG and estradiol) and known risk factors, such as obesity, age and lifestyle. Exploration of whether TT might be a non‐invasive marker for NAFLD diagnosis is warranted.
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Regarding calculated free T, literature remains undecided describing either an inverse, positive or no association with NAFLD.
“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 [140]
The Abstract Results report no association between free testosterone and NAFLD after adjustment, while the Results describe decreasing hepatic steatosis across free-testosterone quartiles after adjustment for age and race. These findings support the no-association and inverse possibilities, but this paper does not report a positive association for free testosterone or establish the full three-way characterization of the literature. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMen with higher total T have a reduced risk of developing NAFLD, while the opposite association was seen for women.
“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 [140]
The Introduction reports that higher total testosterone was associated with reduced odds of NAFLD in men and the opposite association in women, citing a meta-analysis whose women were mostly postmenopausal. The Discussion describes this paper’s finding as lower odds of *prevalent* NAFLD in men and says its cross-sectional design cannot establish a causal association; therefore, it does not show a reduced risk of developing NAFLD. (LLM, conf=0.87)
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Cited by
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Hutchison, A. L., Tavaglione, F., Romeo, S., & Charlton, M. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.08.030 · Cited by 250
Cherubini, A., Ostadreza, M., Jamialahmadi, O., Pelusi, S., Rrapaj, E., Casirati, E., Passignani, G., Norouziesfahani, M., Sinopoli, E., Baselli, G., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02553-8 · Cited by 136
Narinx, N., David, K., Walravens, J., Vermeersch, P., Claessens, F., Fiers, T., Lapauw, B., Antonio, L., & Vanderschueren, D. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04562-1 · Cited by 96
Metadata
- Authors
- Phan, H., Richard, A., Lazo, M., Nelson, W. G., Denmeade, S. R., Groopman, J., Kanarek, N., Platz, E. A., & Rohrmann, S.
- Affiliations
- University of Zurich (CH)
- Johns Hopkins University (US)
- Corresponding author
- Rohrmann, Sabine
- ORCID
- Venue
- Liver International
- Publisher
- Wiley
- Published
- 2021-01-19
- Volume
- 41
- Issue
- 2
- Pages
- 300-310
- ISSN
- 0106-9543 (ISSN-L)
- 1478-3223
- 1478-3231
- PMC
- PMC10115140
- OpenAlex
- W3082636066
- Cited by
- 45
- References
- 0
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 12 · 2022: 11 · 2021: 5
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Liver International (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Johns Hopkins University
- 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
- non-alcoholic fatty liver disease, sex hormones, total testosterone, free estradiol, sex hormone-binding globulin, androstanediol glucuronide, liver enzymes, aspartate aminotransferase, alanine aminotransferase, men
- MeSH terms
- Cross-Sectional Studies, Humans, Male, Nutrition Surveys, Gonadal Steroid Hormones, Testosterone, Non-alcoholic Fatty Liver Disease
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