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

Table 1 Laboratory studies

Ref.	Study type	Focus	Results
Youn et al[37]	In vitro cell line treatment	Investigated potential protective effects of estrogen on endothelial cells against oxidative stress induced by IL-6 and by SARS-COV-2 spike protein (S protein)	17B-Estradiol reversed S protein induced activation of NADPH oxidase isoform 2 (NOX2) and ACE-2 dependent ROS production, as well as ACE2 upregulation and induction of pro-inflammatory gene monocyte chemoattractant protein-1 (MCP-1) in endothelial cells, effectively attenuating endothelial dysfunction completely
			Implications: Estrogen inhibits initial viral response and attenuation of cytokine storm induced endothelial dysfunction, especially in men and post-menopausal women. Data supports hypothesis that estrogen may be used to alleviate viral infection and cytokine storm-induced endothelial dysfunction, a critical mediator of ARDS/multi-organ failure. Thus, attenuating disease progression, severity and mortality
Samuel et al[42]	In vitro stem cell lines and high throughput drug screens	Established a screening strategy to identify drugs that reduce ACE2 levels in human embryonic stem cell (hESC)-derived cardiac cells and lung organoids. Target analysis of hit compounds revealed androgen signaling as a key modulator of ACE2 levels	Inhibitors of 5-alpha reductase, which dampen androgen signaling reduced ACE2 levels in target cells; Treatment with antiandrogenic drugs reduced ACE2 expression and protected hESC-derived lung organoids against COVID-19 infection; Study also found that clinical data on COVID-19 patients with prostate cancer, which is associated with elevated androgen levels, are significant risk factors and that genetic variants that are associated with higher androgen levels are associated with higher diseases severity