1Menstruation: a possible independent health promoter, aging and COVID-19.

Women live longer than men. Cardiovascular disorders, cancers, and serious infectious conditions are less common among women than men. Recent data also indicate that women, particularly before menopause, are less susceptible to severe COVID-19, a viral infection hitting less-healthy individuals. The superiority of women regarding health has not been completely understood and partly been explained by estradiol beneficial effects on the microenvironment of the body, notably cytokine network. Estradiol cycles are aligned with menstruation cycles, a challenge for distinguishing their individual effects on human health. Large-scale, long-term studies indicate that hysterectomy, particularly at younger ages, is associated with an increased risk of mortality, cancer, or heart disorders. The underlying mechanisms for the increased risk in hysterectomized women are hard to be investigated in animal models since only a few primates menstruate. However, blood exchange models could resemble menstruation and provide some insight into possible beneficial effects of menstruation. Sera from animal models (neutral blood exchange) and also humans that have undergone therapeutic plasma exchange enhance the proliferation of progenitor cells in the culture and contain lower levels of proinflammatory factors. If menstruation resembles a blood exchange model, it can contribute to a healthier cytokine network in women. Consequently, menstruation, independently from estradiol health beneficial effects, can contribute to greater longevity and protection against certain disorders, e.g., COVID-19, in women. Investigation of COVID-19 rate/severity in hysterectomized women will provide insight into the possible beneficial effects of menstruation in COVID-19.