26.04.2020
Prevention and therapy of COVID-19 via exogenous estrogen treatment for both male and female patients
Therapeutic Infectiology
Suba Z et al
J Pharm Pharm Sci
Main result
According to the data in the literature, the infection rate and the mortality rate for COVID-19 are age-related (14.8% for patients over 80 years old vs 1.3% for patients between 50 and 59 years old, Chinese CDC data with a difference in virus sensitivity and mortality rate in male subjects compared to female subjects for all age groups.
Studies in mice infected with the SARS-CoV virus show that androgen deficiency (after gonadectomy or treatment with anti-androgens) does not modify morbidity or mortality, whereas estrogen depletion (after ovariectomy or treatment with estrogen receptor antagonists) is correlated with a significant increase in morbidity and mortality.
A Chinese study found that out of 399 patients, those with at least one comorbidity had a 79% increased risk of needing intensive care. Among the most common comorbidities were found: metabolic syndrome and type 2 diabetes.
Insulin resistance inhibits the signaling of estrogen receptors in men and women, type 2 diabetes inhibits the immune response, the resolution of inflammation, and repair of tissue damage by estrogens.
Thanks to experimental manipulations of estrogen receptors, their role in the immune response against viral pulmonary infections have been demonstrated: in phase 1 immune response, estrogens increase the number and activation of leukocytes and myeloid cells. Estrogens activate ERs in monocytes, macrophages, and neutrophils by inducing the production of pro-inflammatory cytokines (IL-12 and TNF alpha), chemokines (CCL2), interferon types I and III.
In animal mouse models, the estrogen-mediated immune response is identical in both sexes, but at 72 hours after infection, in females, the high concentration of estrogens silences the cytokine storm and eliminates inflammatory exudate, which does not occur in male or female mice after oophorectomy.
Among the possible estrogen preparations, Premarin (natural estrogen used for the hormonal treatment of menopause) has been shown to have protective effects on thromboembolism, cardiovascular disease, dyslipidemia and osteoporosis without side effects. A study has shown that Premarin is associated with a 23% reduction in the incidence of breast cancer after 19 years of use and a 44% reduction in mortality from breast cancer.
Studies in mice infected with the SARS-CoV virus show that androgen deficiency (after gonadectomy or treatment with anti-androgens) does not modify morbidity or mortality, whereas estrogen depletion (after ovariectomy or treatment with estrogen receptor antagonists) is correlated with a significant increase in morbidity and mortality.
A Chinese study found that out of 399 patients, those with at least one comorbidity had a 79% increased risk of needing intensive care. Among the most common comorbidities were found: metabolic syndrome and type 2 diabetes.
Insulin resistance inhibits the signaling of estrogen receptors in men and women, type 2 diabetes inhibits the immune response, the resolution of inflammation, and repair of tissue damage by estrogens.
Thanks to experimental manipulations of estrogen receptors, their role in the immune response against viral pulmonary infections have been demonstrated: in phase 1 immune response, estrogens increase the number and activation of leukocytes and myeloid cells. Estrogens activate ERs in monocytes, macrophages, and neutrophils by inducing the production of pro-inflammatory cytokines (IL-12 and TNF alpha), chemokines (CCL2), interferon types I and III.
In animal mouse models, the estrogen-mediated immune response is identical in both sexes, but at 72 hours after infection, in females, the high concentration of estrogens silences the cytokine storm and eliminates inflammatory exudate, which does not occur in male or female mice after oophorectomy.
Among the possible estrogen preparations, Premarin (natural estrogen used for the hormonal treatment of menopause) has been shown to have protective effects on thromboembolism, cardiovascular disease, dyslipidemia and osteoporosis without side effects. A study has shown that Premarin is associated with a 23% reduction in the incidence of breast cancer after 19 years of use and a 44% reduction in mortality from breast cancer.
Takeaways
In this review of the literature, epidemiological data and data from animal models show that activation of ER by estrogens leads to a protective immune activity against viral respiratory infections.
The reduction in REs activation leads to an excessive inflammatory response and respiratory distress in men and women, while the estrogen-RE-aromatase circuit activated by estrogen treatment promotes the reduction of viral titer, inflammatory response and repair of tissue damage.
The authors propose the use of Premarin (a natural estrogen used for the hormonal treatment of menopause) as a medicine to prevent viral respiratory infections in sensitive patients.
The reduction in REs activation leads to an excessive inflammatory response and respiratory distress in men and women, while the estrogen-RE-aromatase circuit activated by estrogen treatment promotes the reduction of viral titer, inflammatory response and repair of tissue damage.
The authors propose the use of Premarin (a natural estrogen used for the hormonal treatment of menopause) as a medicine to prevent viral respiratory infections in sensitive patients.
Strength of evidence Weak
Weak :
1) non-exhaustive narrative review of the literature
2) considered only experimental studies carried out exclusively on animal models"
Objectives
Emphasize the crucial role of estrogen receptors (ERs) in the innate and adaptive immune response processes in viral respiratory infections in men and women.
Method
Narrative literature review (not systematic)
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