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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
ARTICLE HIGHLIGHTS
Research background
Testosterone levels are commonly low in men with type 2 diabetes and most men with type 2 diabetes have hepatic steatosis from non-alcoholic fatty liver disease (NAFLD). Animal models show that low testosterone states from castration results in hepatic steatosis and that testosterone replacement improves hepatic steatosis.
Research motivation
Hepatic steatosis occurs in NAFLD which currently has no readily available effective treatment. This study was conducted to provide rationale for future prospective studies of testosterone therapy for NAFLD.
Research objectives
To evaluate the effect of testosterone therapy on liver fat fraction as measured by magnetic resonance imaging (MRI) in a cohort of diabetic men with lowered testosterone levels. We further aimed to determine other factors associated with changes in liver fat in this population.
Research methods
We performed a secondary analysis of a previous 40 wk, randomised, double-blinded, placebo-controlled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone levels. Liver fat as determined by MRI scan before and after therapy was analyzed in addition to blood tests and body composition scans.
Research results
Patients who received testosterone therapy had an absolute reduction of liver fat fraction by 3.5% and patients who received placebo had an absolute increase in liver fat fraction by 1.2%, with a between group difference of 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% (P < 0.001).
Research conclusions
Testosterone therapy was associated with a reduction in hepatic steatosis in a cohort of men with type 2 diabetes and lowered serum testosterone levels.
Research perspectives
This study provides rationale for future prospective clinical trials of testosterone therapy for the treatment of NAFLD focusing on liver related endpoints.
