Systematic Reviews
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Methodol. Nov 20, 2022; 12(6): 465-475
Published online Nov 20, 2022. doi: 10.5662/wjm.v12.i6.465
Impact of gender-affirming hormone therapy on the development of COVID-19 infections and associated complications: A systematic review
Jennifer J Ferraro, Allie Reynolds, Sylvia Edoigiawerie, Michelle Y Seu, Sydney R Horen, Amir Aminzada, Alireza Hamidian Jahromi
Jennifer J Ferraro, Michelle Y Seu, Sydney R Horen, Amir Aminzada, Department of Surgery, Division of Plastic and Reconstructive Surgery, Rush University Medical Center, Chicago, IL 60612, United States
Allie Reynolds, Undergraduate Studies, Princeton University, Princeton, NJ 08544, United States
Sylvia Edoigiawerie, Medical School, The University of Chicago Pritzker School of Medicine, Chicago, IL 60637, United States
Alireza Hamidian Jahromi, Division of Plastic and Reconstructive Surgery, Temple University Health System, Philadelphia, PA 19140, United States
Author contributions: Hamidian Jahromi A contributed to conceptualization and manuscript editing; Ferraro JJ, Reynolds A, Edoigiawerie S, Seu MY, Horen SR, Aminzada A contributed to writing, statistical analysis, and manuscript editing; All authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare that they have no conflicting interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Alireza Hamidian Jahromi, MD, Doctor, Division of Plastic and Reconstructive Surgery, Temple University Health System, 3401 N Broad St., Philadelphia, PA 19140, United States. alirezahamidian@yahoo.com
Received: April 11, 2022
Peer-review started: April 11, 2022
First decision: June 27, 2022
Revised: July 14, 2022
Accepted: October 5, 2022
Article in press: October 5, 2022
Published online: November 20, 2022
Abstract
BACKGROUND

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can produce a wide range of clinical manifestations from asymptomatic to life-threatening. Various researchers have worked to elucidate the pathogenic mechanisms underlying these variable presentations. Differences in individual responses to systemic inflammation and coagulopathy appear to be modulated by several factors, including sex steroid hormones. Transgender men or non-binary individuals who undergo gender-affirming hormone therapy (GAHT) are a unique population of interest for exploring the androgen-mediated coronavirus disease 2019 (COVID-19) hypothesis. As the search for reliable and effective COVID-19 treatments continues, understanding the risks and benefits of GAHT may mitigate COVID-19 related morbidity and mortality in this patient population.

AIM

To investigate the potential role of GAHT in the development of COVID-19 infections and complications.

METHODS

This systematic review implemented an algorithmic approach using PRISMA guidelines. PubMed, Scopus, Google Scholar top 100 results, and archives of Plastic and Reconstructive Surgery was on January 12, 2022 using the key words “gender” AND “hormone” AND “therapy” AND “COVID-19” as well as associated terms. Non-English articles, articles published prior to 2019 (prior to COVID-19), and manuscripts in the form of reviews, commentaries, or letters were excluded. References of the selected publications were screened as well.

RESULTS

The database search resulted in the final inclusion of 14 studies related to GAHT COVID-19. Of the included studies, only two studies directly involved and reported on COVID-19 in transgender patients. Several clinical trials looked at the relationship between testosterone, estrogen, and progesterone in COVID-19 infected cis-gender men and women. It has been proposed that androgens may facilitate initial COVID-19 infection, however, once this occurs, testosterone may have a protective effect. Multiple clinical studies have shown that low baseline testosterone levels in men with COVID-19 are associated with worsening outcomes. The role of female sex hormones, including estrogen and progesterone have also been proposed as potential protective factors in COVID-19 infection. This was exemplified in multiple studies investigating different outcomes in pre- and post-menopausal women as well as those taking hormone replacement therapy. Two studies related specifically to transgender patients and GAHT found that estrogen and progesterone could help protect men against COVID-19, and that testosterone hormone therapy may increase the risk of contracting COVID-19.

CONCLUSION

Few studies were found related to the role of GAHT in COVID-19 infections. Additional research is necessary to enhance our understanding of this relationship and provide better care for transgender patients.

Keywords: COVID-19, Transgender, Gender-affirming hormone therapy, Gender affirmation, Testosterone, Estrogen

Core Tip: Severe acute respiratory syndrome coronavirus 2 can produce a wide range of clinical manifestations from asymptomatic to life-threatening. Differences in individual responses to systemic inflammation and coagulopathy appear to be modulated by several factors, including sex steroid hormones. Androgens may facilitate initial coronavirus disease 2019 (COVID-19) infection, however, once this occurs, testosterone may have a protective effect. The role of estrogen and progesterone has also been proposed as potential protective factors in COVID-19 infection. Few studies have investigated the role of gender-affirming hormone therapy in COVID-19 infections. Additional research is necessary to enhance our understanding of this relationship and provide better care for transgender patients.