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A cross-sectional analysis of the association between testosterone and biopsy-proven non-alcoholic fatty liver disease in men with obesity

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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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Authors and Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Carlien De Herdt.

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The authors declare no competing interests.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Ethics

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

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