Premenopausal and postmenopausal women during the COVID-19 pandemic.

The current global COVID-19 mortality rate is estimated to be around 3.4%; however, it is dependent on age, sex, and comorbidities. Epidemiological evidence shows gender disparities in COVID-19 severity and fatality, with non-menopausal females having milder severity and better outcomes than age-matched males. However, the difference vanishes when comparing postmenopausal women with age-matched men. It has been suggested that, to some extent, this is due to the protective role of female hormones, such as anti-Müllerian hormone and oestradiol (E2), in non-menopausal women. Oestrogens have been hypothesized to be crucial in modulating viral infection and the progression of the disease via an action on immune/inflammatory responses and angiotensin-converting enzyme type 2 expression. Hence, the most likely explanation is that, because the levels of oestrogen in females after menopause decrease, oestrogen no longer offers a beneficial effect as seen in younger females. The COVID-19 pandemic has highlighted the serious negative effects arising from the state of E2 deficiency. Therefore, hormone replacement therapy gains further support as the damaging effect of the decline in ovarian function affects many biological systems, and recently with the COVID-19 pandemic, oestrogen's vital role within the immune system has become quite clear. However, additional clinical investigations regarding hormone replacement therapy are urgently needed to further verify the protective and therapeutic effects of E2 on menopausal women with COVID-19.