Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2020; 11(3): 66-77
Published online Mar 15, 2020. doi: 10.4239/wjd.v11.i3.66
Effects of gender-affirming hormone therapy on insulin resistance and body composition in transgender individuals: A systematic review
Cassandra Spanos, Ingrid Bretherton, Jeffrey D Zajac, Ada S Cheung
Cassandra Spanos, Ingrid Bretherton, Jeffrey D Zajac, Ada S Cheung, Trans Medical Research Group, Department of Medicine (Austin Health), University of Melbourne, Victoria 3084, Australia
Author contributions: Cheung AS designed the research; Spanos C performed the research; Spanos C, Bretherton I and Cheung AS analyzed the data; Spanos C wrote the paper; Bretherton I, Cheung AS and Zajac JD supervised the paper; all authors read and approved the final manuscript.
Supported by Australian Government National Health and Medical Research Council, No. APP1143333; Endocrine Society of Australia; Austin Medical Research Foundation; Viertel Charitable Foundation Clinical Investigator Award, No. VIERCI2017009; Royal Australasian College of Physicians Vincent Fairfax Family Foundation.
Conflict-of-interest statement: All the authors declare that they have no competing interests.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ada S Cheung, MBBS, FRACP, PhD, Senior Research Fellow, Department of Endocrinology, Austin Health, The University of Melbourne, 145 Studley Road, Heidelberg, Victoria 3084, Australia. adac@unimelb.edu.au
Received: October 31, 2019
Peer-review started: October 31, 2019
First decision: December 4, 2019
Revised: January 3, 2020
Accepted: January 19, 2020
Article in press: January 19, 2020
Published online: March 15, 2020
Processing time: 119 Days and 21.8 Hours
Abstract
BACKGROUND

Transgender individuals receiving masculinising or feminising gender-affirming hormone therapy with testosterone or estradiol respectively, are at increased risk of adverse cardiovascular outcomes, including myocardial infarction and stroke. This may be related to the effects of testosterone or estradiol therapy on body composition, fat distribution, and insulin resistance but the effect of gender-affirming hormone therapy on these cardiovascular risk factors has not been extensively examined.

AIM

To evaluate the impact of gender-affirming hormone therapy on body composition and insulin resistance in transgender individuals, to guide clinicians in minimising cardiovascular risk.

METHODS

We performed a review of the literature based on PRISMA guidelines. MEDLINE, Embase and PsycINFO databases were searched for studies examining body composition, insulin resistance or body fat distribution in transgender individuals aged over 18 years on established gender-affirming hormone therapy. Studies were selected for full-text analysis if they investigated transgender individuals on any type of gender-affirming hormone therapy and reported effects on lean mass, fat mass or insulin resistance.

RESULTS

The search strategy identified 221 studies. After exclusion of studies that did not meet inclusion criteria, 26 were included (2 cross-sectional, 21 prospective-uncontrolled and 3 prospective-controlled). Evidence in transgender men suggests that testosterone therapy increases lean mass, decreases fat mass and has no impact on insulin resistance. Evidence in transgender women suggests that feminising hormone therapy (estradiol, with or without anti-androgen agents) decreases lean mass, increases fat mass, and may worsen insulin resistance. Changes to body composition were consistent across almost all studies: Transgender men on testosterone gained lean mass and lost fat mass, and transgender women on oestrogen experienced the reverse. No study directly contradicted these trends, though several small studies of short duration reported no changes. Results for insulin resistance are less consistent and uncertain. There is a paucity of prospective controlled research, and existing prospective evidence is limited by small sample sizes, short follow up periods, and young cohorts of participants.

CONCLUSION

Further research is required to further characterise the impact of gender-affirming hormone therapy on body composition and insulin resistance in the medium-long term. Until further evidence is available, clinicians should aim to minimise risk by monitoring cardiovascular risk markers regularly in their patients and encouraging healthy lifestyle modifications.

Keywords: Transgender persons; Insulin resistance; Body composition; Gender dysphoria; Metabolic syndrome

Core tip: Evidence in transgender men suggests that testosterone therapy increases lean mass, decreases fat mass and has no impact on insulin resistance. Evidence in transgender women suggests that feminising hormone therapy (estradiol, with or without anti-androgen agents) decreases lean mass, increases fat mass, and may worsen insulin resistance. There is a paucity of prospective controlled research, and existing prospective evidence is limited by small sample sizes, short follow up periods, and young cohorts of participants. Until further evidence is available, clinicians should aim to minimise risk by monitoring cardiovascular risk markers regularly in their patients and encouraging healthy lifestyle modifications.