Tehran University of Medical Sciences Journal of Family and Reproductive Health 1735-8949 15 3 2021 09 07 150 159 Farideh Zafari Zangeneh Vali-e-Asr Reproductive Health Research Center, Tehran University of Medical Sciences, Tehran, Iran Maryam Sarmast Shoushtari Chemical and Environmental Engineering Department, Engineering Faculty, Malaysia Putra university, Selangor, Malaysia 2021 05 16 2021 09 11 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.   https://jfrh.tums.ac.ir/index.php/jfrh/article/view/1787 https://jfrh.tums.ac.ir/index.php/jfrh/article/download/1787/576