COVID-19 och könshormoner
- The severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2) infection and the climacteric woman
Peter Chedraui , Faustino R Pérez-López. Climacteric. 2020 Dec;23(6):525-527.
The severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2) infection has affected millions of individuals worldwide, causing high mortality rates and severe physical sequelae, with a negative impact on society, economy, health care, lifestyle and personal relationships. Studies have confirmed this infection has sex and age differences in terms of disease severity and immune response, with a particular relationship with the anti-Müllerian hormone, a marker of aging, and estradiol, a marker of ovarian function. Postmenopausal women seem to present a more severe infection as compared to premenopausal ones. Estradiol protects the vascular system, mediating with the renin-angiotensin-aldosterone system, whereas testosterone enhances the levels of angiotensin-converting enzyme and the transmembrane protease serine-type 2, thus delaying viral clearance in men as compared to women. This new infection will stay among us, transforming our social, economic and daily lifestyle, and hence medical and health care as well as the use of menopause hormone therapy will need redefining, considering both preventive and curative
perspectives.
- Evidence for treatment with estradiol for women with SARS-CoV-2 infection. Ute Seeland, Flaminia Coluzzi, Maurizio Simmaco, Cameron Mura, Philip E Bourne. BMC Med. 2020 Nov 25;18(1):369.
Background: Given that an individual's age and gender are strongly predictive of coronavirus disease 2019 (COVID-19) outcomes, do such factors imply anything about preferable therapeutic options? Methods: An analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in 5-year age strata, revealed age-dependent sex differences. In particular, we surveyed the effects of systemic hormone administration in women. The primary outcome for estradiol therapy was death. Odds ratios (ORs) and Kaplan-Meier survival curves were analyzed for 37,086 COVID-19 women in two age groups: pre- (15-49 years) and peri-/post-menopausal (>50 years).
Results:
The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is higher in women than men (by about + 15%) and, in contrast, the fatality rate is higher in men (about + 50%). Interestingly, the relationships between these quantities are linked to age: pre-adolescent girls and boys had the same risk of infection and fatality rate, while adult premenopausal women had a significantly higher risk of infection than men in the same 5-year age
stratum (about 16,000 vs. 12,000 cases). This ratio changed again in peri- and postmenopausal women, with infection susceptibility converging with men. While fatality rates increased continuously with age for both sexes, at 50 years, there was a steeper increase for men. Thus far, these types of intricacies have been largely neglected. Because the hormone 17ß-estradiol influences expression of the human angiotensin-converting enzyme 2 (ACE2) protein, which plays a role in SARS-CoV-2 cellular entry, propensity score matching was performed for the women´s sub-cohort, comparing users vs. non-users of estradiol. This retrospective study of hormone therapy in female COVID-19 patients shows that the fatality risk for women > 50 years receiving estradiol therapy (user group) is reduced by more than 50%; the OR was 0.33, 95% CI [0.18, 0.62] and the hazard ratio (HR) was 0.29, 95% CI [0.11,0.76]. For younger, pre-menopausal women (15-49 years), the risk of COVID-19 fatality is the same irrespective of estradiol treatment, probably because of higher endogenous estradiol levels.
Conclusions: As of this writing, still no effective drug treatment is available for COVID-19; since estradiol shows such a strong improvement regarding fatality in COVID-19, we suggest prospective studies on the potentially more broadly protective roles of this naturally occurring hormone.
- Sex Hormones and Novel Corona Virus Infectious Disease (COVID-19). Rasha A Al-Lami, Randall J Urban, Elena Volpi, Ammar M A Algburi, Jacques Baillargeon. Mayo Clin Proc. 2020 Aug;95(8):1710-1714.
Given the rapid spread of the coronavirus disease 2019 (COVID-19) pandemic and its overwhelming effect on health care systems and the global economy, innovative therapeutic strategies are urgently needed. The proposed primary culprit of COVID-19 is the intense inflammatory response-an augmented immune response and cytokine storm-severely damaging the lung tissue and rendering some patients' conditions severe enough to require assisted
ventilation. Sex differences in the response to inflammation have been documented and can be attributed, at least in part, to sex steroid hormones. Moreover, age-associated decreases in sex steroid hormones, namely, estrogen and testosterone, may mediate proinflammatory increases in older adults that could increase their risk of COVID-19 adverse outcomes. Sex hormones can mitigate the inflammation response and might provide promising therapeutic potential for patients with COVID-19. In this article, we explore the possible anti-inflammatory effects of estrogen and testosterone and the anabolic effect of testosterone, with particular attention to the potential therapeutic role of hormone replacement therapy in older men and women with COVID-19.
Full text:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256539/pdf/main.pdf
- Potential Influence of Menstrual Status and Sex Hormones on female SARS-CoV-2 Infection: A Cross-sectional Study from Multicentre in Wuhan, China. Ding T, Zhang J, Wang T, Cui P, Chen Z, Jiang J, Zhou S, Dai J, Wang B, Yuan S, Ma W, et al. Clin Infect Dis. 2020 Jul 22.
Background: Recent studies indicated that females have a lower morbidity, severe cases rate, mortality and better outcome than those of male. However, it remained to be addressed why this was the case.
Methods and findings: To find the factors that potentially protect females from COVID-19, we recruited all confirmed patients hospitalized at three branches of Tongji Hospital (n=1902) from January 28 to March 8, 2020, and analyzed the correlation between menstrual status (n=509，including 68 from Mobile Cabin Hospital)/female hormones (n=78)/ cytokines related to immunity and inflammation(n=263), and the severity/clinical outcomes in female patients under 60 years of age.Non-menopausal female patients had milder severity and better outcome compared with age-matched men (p<0.01/p<0.01). Menopausal patients had longer hospitalization times than non-menopausal patients ( hazard ratio [HR], 1.91; 95% confidence interval [CI], 1.06-3.46，p= 0.033). Both anti-müllerian hormone (AMH) and estradiol (E2) showed a negative correlation with severity of infection (AHR=0.146/0.304, 95%CI = [0.026-0.824]/[0.092-1.001], p=0.029/0.05). E2 levels were negatively correlated with IL-2R, IL-6, IL-8 and TNFα in luteal phase (Pearson Correlation=-0.592, -0.558, -0.545, -0.623; p=0.033, 0.048, 0.054, 0.023), and with C3 in follicular phase (Pearson Correlation=-0.651; p=0.030).
Conclusion: Menopause is an independent risk factor for female COVID-19 patients. AMH and E2 are potential protective factors, negatively correlated with COVID-19's severity, among which E2 is attributed to its regulation of cytokines related to immunity and inflammation. Hormone supplement might be a potential therapy for COVID-19 patients.
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The gendered impact of coronavirus disease (COVID-19): do estrogens play a role?Grandi G, Facchinetti F, Bitzer J. Eur J Contracept Reprod Health Care. 2020 May 29:1-2.
https://doi.org/10.1080/13625187.2020.1766017
- Managing thromboembolic risk with menopausal hormone therapy and hormonal contraception in the COVID-19 pandemic: Recommendations from the Spanish Menopause Society.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200366/
- FSRH CEU clinical advice to support provision of effective contraception during the COVID-19 outbreak 20 March 2020.
- Joint RCOG, BSGE and BGCS guidance for the management of abnormal uterine bleeding in the evolving Coronavirus (COVID-19) pandemic.
- COVID-19 FAQs for Obstetrician–Gynecologists, Gynecology (ACOG)
https://www.acog.org/clinical-information/physician-faqs/covid19-faqs-for-ob-gyns-gynecology
- A Multi-hospital Study in Wuhan, China：Protective Effects of Non-menopause and Female Hormones on SARS-CoV-2 infection (preprint, has not been peer-reviewed).
https://www.medrxiv.org/content/10.1101/2020.03.26.20043943v1