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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations
Ross Apostolov, Emily Gianatti, Darren Wong, Numan Kutaiba, Paul Gow, Mathis Grossmann, Marie Sinclair
Ross Apostolov, Darren Wong, Paul Gow, Marie Sinclair, Department of Gastroenterology and Liver Transplant Unit, Austin Health, Heidelberg 3084, VIC, Australia
Ross Apostolov, Paul Gow, Mathis Grossmann, Marie Sinclair, Department of Medicine, University of Melbourne, Parkville 3010, VIC, Australia
Emily Gianatti, Department of Endocrinology, Fiona Stanley Hospital, Murdoch 6150, WA, Australia
Numan Kutaiba, Department of Radiology, Austin Health, Heidelberg 3084, VIC, Australia
Mathis Grossmann, Department of Endocrinology, Austin Health, Heidelberg 3084, VIC, Australia
Author contributions: Apostolov R, Gow P, Grossmann M and Sinclair M designed the research; Apostolov R, Gianatti E and Kutaiba N were involved in data acquisition; Kutaiba N interpreted and analysed radiological data; Apostolov R, Wong D and Sinclair M drafted the manuscript; Gianatti E, Wong D, Kutaiba N, Gow P, Grossmann M and Sinclair M revised the manuscript for important intellectual content; all authors read and approved the final manuscript.
Institutional review board statement: Human Research Ethics Committee, Research Ethics Unit, Level 8 HSB - Room 8322, Austin Hospital.
Informed consent statement: There are no conflicts of interest to report.
Conflict-of-interest statement: Apostolov R, Darren Wong and Numan Kutaiba have no conflicts of interest to declare. Emily Gianatti, Paul Gow and Marie Sinclair have received financial support for research from Bayer Pharma AG more than five years ago. Mathis Grossmann has received research funding from Bayer Pharma AG, Otzuka and speaker’s honoraria from Besins Health Care and Novartis.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ross Apostolov, MBBS, Academic Fellow, Staff Physician, Department of Gastroenterology and Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg 3084, VIC, Australia. ross.apostolov1@gmail.com
Received: September 24, 2021
Peer-review started: September 24, 2021
First decision: November 7, 2021
Revised: November 17, 2021
Accepted: April 2, 2022
Article in press: April 2, 2022
Published online: April 27, 2022
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in people with diabetes with no available treatment.
AIM
To explore the effect of testosterone treatment on liver. Testosterone therapy improves insulin resistance and reduces total body fat, but its impact on the liver remains poorly studied.
METHODS
This secondary analysis of a 40 wk, randomised, double-blinded, placebo-controlled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging (MRI).
RESULTS
Of 88 patients enrolled in the index study, 39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo. All patients had > 5% hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD. Median liver fat at baseline was 15.0% (IQR 11.5%-21.1%) in the testosterone and 18.4% (15.0%-28.9%) in the placebo group. Median ALT was 34units/L (26-38) in the testosterone and 32units/L (25-52) in the placebo group. At week 40, patients receiving testosterone had a median reduction in absolute liver fat of 3.5% (IQR 2.9%-6.4%) compared with an increase of 1.2% in the placebo arm (between-group difference 4.7% P < 0.001). After controlling for baseline liver fat, testosterone therapy was associated with a relative reduction in liver fat of 38.3% (95% confidence interval 25.4%-49.0%, P < 0.001).
CONCLUSION
Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone. Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.
Core Tip: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disease with no current effective treatment. This study demonstrates a reduction in hepatic steatosis in men with type 2 diabetes and low testosterone who received testosterone therapy as part of a randomised controlled trial and provides justification for larger scale studies to assess the effects of testosterone therapy as a treatment for NAFLD.
