Abstract
Purpose
To study the association between testosterone and non-alcoholic fatty liver disease (NAFLD) since prior studies have reported inconsistent results.
Methods
A retrospective analysis was performed including obese men who underwent a liver biopsy and a metabolic and hepatological work-up. Free testosterone (CFT) was calculated by the Vermeulen equation. The association between total testosterone (total T) and CFT on the one hand and NAFLD and fibrosis on the other hand was investigated and corrected for biasing factors such as metabolic parameters.
Results
In total, 134 men (mean age 45 ± 12 years, median BMI 39.6 (25.0–64.9) kg/m²) were included. The level of total T and CFT did not significantly differ between NAFL and NASH and the stages of steatosis and ballooning. CFT was significantly lower in a higher stage of fibrosis (p = 0.013), not seen for total T and not persisting after controlling for the influence of BMI, HDL cholesterol and HOMA-IR. A higher stage of lobular inflammation was associated with a lower level of total T (p = 0.033), not seen for CFT and not persisting after controlling for the influence of visceral adipose tissue surface and HOMA-IR.
Conclusions
This is the second largest study investigating the association between testosterone and biopsy-proven NAFLD. No significant association between testosterone levels and NAFLD, and the different histological subgroups or fibrosis was seen. The lower level of CFT in a higher stage of fibrosis and the association between total T and lobular inflammation was driven by poor metabolic parameters.
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Data availability
All datasets generated during and/or analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.
Abbreviations
- NAFLD:
-
non-alcoholic fatty liver disease
- NAFL:
-
non-alcoholic fatty liver
- NASH:
-
non-alcoholic steatohepatitis
- VAT:
-
visceral adipose tissue surface on CT scan
- SHBG:
-
sex hormone binding globulin
- OE:
-
oestradiol
- total T:
-
total testosterone
- SAT:
-
subcutaneous adipose tissue surface on CT scan
- AHT:
-
arterial hypertension
- HOMA-IR:
-
homeostatic model assessment of insulin resistance
- LH:
-
luteinizing hormone
- FSH:
-
follicle stimulating hormone
- CFT:
-
calculated free testosterone
- FT:
-
free testosterone
- BMI:
-
body mass index
- HDL:
-
high-density lipoprotein
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Funding
The work has been supported by the HEPADIP Consortium (Hepatic and adipose tissue and functions in the metabolic syndrome) supported by the European Commission as an Integrated Project under the 6th Framework Program (Contract LSHM-CT-2005-018734).
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E.D., C.D.B. and L.V.G. contributed to the design and implementation of the research. A.V. and K.V.D. collected the data. C.D.H. wrote the manuscript. All authors discussed the results and contributed to the final manuscript.
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Informed consent was obtained from all individual participants included in the study.
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Every patient underwent a metabolic and hepatological work-up approved by the Ethics Committee of the Antwerp University Hospital (reference 6/25/125, Belgian registration number B30020071389).
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De Herdt, C., De Block, C., Francque, S. et al. A cross-sectional analysis of the association between testosterone and biopsy-proven non-alcoholic fatty liver disease in men with obesity. Endocrine 80, 54–63 (2023). https://doi.org/10.1007/s12020-022-03245-y
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DOI: https://doi.org/10.1007/s12020-022-03245-y