Role of short-term estradiol supplementation in symptomatic postmenopausal COVID-19 females: A randomized controlled trial

Seth, Shikha; Sharma, Ritu; Mishra, Pinky; Solanki, Hariom Kumar; Singh, Manpreet; Singh, Manisha

doi:10.4103/jmh.jmh_57_21

Cited by 10 publications

(10 citation statements)

References 30 publications

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“…The same study reported a similar Covid‐19 fatality risk for younger (premenopausal) women, irrespective of ERT; this probably reflects their higher endogenous estradiol (Seeland et al, 2020 ). Additionally, a small randomized trial ( n = 40) in hospitalized Covid‐19 postmenopausal females treated with oral estradiol supplementation (2 mg per day for 7 days) found faster recovery, while its small size ( n = 40) did not allow to identify a reduction in Covid‐19 fatalities (Seth et al, 2021 ). Larger cohorts are definitely required to assess the potential of prescribing estradiol to Covid‐19 patients.…”

Section: Discussionmentioning

confidence: 99%

Estradiol reduces ACE2 and TMPRSS2 mRNA levels in A549 human lung epithelial cells

Baristaite

Genevieve

2022

Drug Development Research

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Epidemiologic studies suggest slightly higher risk of severe Covid‐19 symptoms and fatalities following SARS‐CoV‐2 infection in men compared with women from similar age groups. This bias was suggested to reflect differences in the male and female immune system regulation, driven by different sex hormone levels in men and women, in particular, higher plasma estradiol in women. SARS‐CoV‐2 infects respiratory tract epithelial cells by binding to their cell membrane ACE2, followed by priming for cell entry by the host cell membrane serine protease TMPRSS2. The cell protease FURIN facilitates cell exit of mature SARS‐CoV‐2 virions. Our study examined the effects of in vitro treatment of A549 human lung epithelial cells with 17‐β‐estradiol on mRNA expression of genes coding for these proteins. Treatment of A549 human lung epithelial cells with 17‐β‐estradiol reduced the cellular mRNA levels of ACE2 and TMPRSS2 mRNA, while not affecting FURIN expression. Our findings suggest that 17‐β‐estradiol may reduce SARS‐CoV‐2 infection of lung epithelial cells, which may in part explain the reduced incidence of severe Covid‐19 and fatalities among women compared with men of similar age. Studies into the molecular pathways by which 17‐β‐estradiol reduces ACE2 and TMPRSS2 mRNA expression in lung epithelial cells are needed for assessing its potential protective value against severe Covid‐19.

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Section: Discussionmentioning

confidence: 99%

Estradiol reduces ACE2 and TMPRSS2 mRNA levels in A549 human lung epithelial cells

Baristaite

Genevieve

2022

Drug Development Research

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“…In an open-label randomized controlled trial, it was shown that the use of estradiol valerate (2 mg per day for 7 days) with the standard care in estrogen-deficient postmenopausal women infected with mild and moderate COVID-19 caused a significant decrease in the D-dimer, lactate dehydrogenase (LDH), interleukin (IL)-6, and CRP on day 5 of the intervention [29]. In addition to this study, it has been shown that the use of oral contraceptive pills in 18-45-year-old women infected with COVID-19 significantly reduced the hospital attendance and had a significantly lower predicted COVID-19 [30].…”

Section: Discussionmentioning

confidence: 99%

Effect of Norelgestromin and Ethinylestradiol in Transdermal Patches on the Clinical Outcomes and Biochemical Parameters of COVID-19 Patients: A Clinical Trial Pilot Study

et al. 2022

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The disease caused by SARS-CoV-2 is still considered a global pandemic. Transdermal patches (TP) with immunoregulators such as estrogen and progesterone compounds could be a feasible option to treat COVID-19 because of their accessibility and relative safety. The objective of the current study was to evaluate the additional treatment with norelgestromin and ethinylestradiol in TP on the clinical and biochemical evolution of COVID-19 patients. The present is a clinical-trial pilot study that included subjects diagnosed with COVID-19, randomized into two groups; the experimental Evra® TP (norelgestromin 6 mg and ethinylestradiol 0.60 mg) was administered such that it was applied on arrival and replaced at day 8 and day 15. The control continued with the conventional COVID-19 treatment protocol. A blood sample was taken each week in order to evaluate relevant biochemical parameters, clinical signs, and evolution. In total, 44 subjects participated in this study, 30 in the experimental group and 14 in the control group. Both groups were homogeneous in terms of age and comorbidities. The experimental group had a significantly lower hospital stay (p = 0.01), high flow supplemental oxygen (p = 0.001), mechanical ventilation (p = 0.003), and intubation (p = 0.01), and the oxygen saturation significantly increased (p = 0.01) in comparison with control group when patients were exposed to room air. A decrease in ferritin (p < 0.05) was observed, with no significant increase in ESR (p > 0.05), D dimer (p > 0.05) and platelets (p > 0.05) in an auto-controlled analysis in the experimental group. Norelgestromin and ethinylestradiol TP could be a safe and effective treatment for moderate and severe COVID-19 patients.

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“…As E2 administration is being considered as a supportive therapy in Covid-19 treatment [ 25 , 26 ] it may be of interest that E2 also influences the circadian system, which in turn regulates the expression of hundreds of clock-controlled genes. The finding that ACE2 and TMPRSS2 mRNA exerted a low-amplitude rhythm in animals exposed to E2 brings up the idea that the daily pattern in their expression can be modified under conditions of rhythmic E2 administration.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown that in women above 50 years of age, EHT reduced the risk of fatality from Covid-19 by more than 50% [ 25 ]. Similarly, short-term oral administration of E2 decreased the time to viral clearance in Covid-19 patients [ 26 ]. Although ACE2 levels were not monitored in these studies, it has been demonstrated previously that E2 treatment increased ACE2 activity in the plasma [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of 17β-estradiol on the daily pattern of ACE2, ADAM17, TMPRSS2 and estradiol receptor transcription in the lungs and colon of male rats

Herichová

Jendrisková²,

Pidíková³

et al. 2022

PLoS ONE

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Covid-19 progression shows sex-dependent features. It is hypothesized that a better Covid-19 survival rate in females can be attributed to the presence of higher 17β-estradiol (E2) levels in women than in men. Virus SARS-CoV-2 is enabled to enter the cell with the use of angiotensin converting enzyme 2 (ACE2). The expression of several renin-angiotensin system components has been shown to exert a rhythmic pattern, and a role of the circadian system in their regulation has been implicated. Therefore, the aim of the study is to elucidate possible interference between E2 signalling and the circadian system in the regulation of the expression of ACE2 mRNA and functionally related molecules. E2 was administered at a dosage of 40 μg/kg/day for 7 days to male Wistar rats, and sampling of the lungs and colon was performed during a 24-h cycle. The daily pattern of expression of molecules facilitating SARS-CoV-2 entry into the cell, clock genes and E2 receptors was analysed. As a consequence of E2 administration, a rhythm in ACE2 and TMPRSS2 mRNA expression was observed in the lungs but not in the colon. ADAM17 mRNA expression showed a pronounced rhythmic pattern in both tissues that was not influenced by E2 treatment. ESR1 mRNA expression exerted a rhythmic pattern, which was diminished by E2 treatment. The influence of E2 administration on ESR2 and GPER1 mRNA expression was greater in the lungs than in the colon as a significant rhythm in ESR2 and GPER1 mRNA expression appeared only in the lungs after E2 treatment. E2 administration also increased the amplitude of bmal1 expression in the lungs, which implicates altered functioning of peripheral oscillators in response to E2 treatment. The daily pattern of components of the SARS-CoV-2 entrance pathway and their responsiveness to E2 should be considered in the timing of pharmacological therapy for Covid-19.

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Role of short-term estradiol supplementation in symptomatic postmenopausal COVID-19 females: A randomized controlled trial

Cited by 10 publications

References 30 publications

Estradiol reduces ACE2 and TMPRSS2 mRNA levels in A549 human lung epithelial cells

Estradiol reduces ACE2 and TMPRSS2 mRNA levels in A549 human lung epithelial cells

Effect of Norelgestromin and Ethinylestradiol in Transdermal Patches on the Clinical Outcomes and Biochemical Parameters of COVID-19 Patients: A Clinical Trial Pilot Study

Effect of 17β-estradiol on the daily pattern of ACE2, ADAM17, TMPRSS2 and estradiol receptor transcription in the lungs and colon of male rats

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