Impact of gender-affirming hormone therapy on the development of COVID-19 infections and associated complications: A systematic review

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.