Objective: Female sex hormones have a pro-inflammatory effect, which may help to minimize inflammation. Estrogen's immunoregulatory properties play a significant role in the bi-directional neuroendocrine-immune activity in females. As a result, sex hormones can play a role in men's high mortality rate from coronavirus-2019 (COVID-19). It is aimed to clarify the role of 17-estradiol (E2) in the battle against COVID-19. Materials and methods: Until April 2021, a study on PubMed was performed. COVID-19, 17-estradiol (E2), immunoregulatory properties, pregnancy, menopausal symptoms, hormonal therapy, ER/ expression on immune cells, and mortality were some of the concepts used in the search. Results: Regulation of pro-inflammatory immune processes against COVID-19 appears to be associated with increased immune function (pro-inflammatory), anti-inflammatory regulation, and antiviral defense. Women with a severe coronavirus infection had higher serum IgG antibody levels than men, and their IgG production was faster in the early stages of infection. 17-estradiol (E2) levels of blood will increase by 100-fold during pregnancy. COVID-19 in pregnant women had a 15-fold lower mortality rate than other women. While menopause replacement therapy (MRT) for pre/post-menopausal women and its effectiveness in reducing COVID-19 infection is debatable. Conclusion: MRT may be considered as a viable treatment option for pre/post-menopause women with coronavirus, referring to the fact that sex hormones reduce inflammatory responses and modulate ACE2 expression. The task's difficulty and achieving the desired outcome seem to be challenging.

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