Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients

Study Overview
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Brief Summary
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The goal of this randomized placebo-controlled study is to investigate the short-term effects of transdermal estrogen therapy on postmenopausal women with COVID-19 disease. The main question[s] it aims to answer are: the clinical outcomes with adding estrogen treatment to conventional therapy of Covid-19 disease the biochemical outcomes with adding estrogen treatment to conventional therapy of Covid-19 disease All participants received favipiravir for a week according to the national guidelines published by the Health Ministry of Turkish Republic at that time. As an intervention, transdermal estradiol patch (7.8 mg patch/week) was applied for 14 days on the upper buttock of the patients in experimental arm. As a placebo, hydrogel patch (adhesive hydrogel patch/week) was applied to the female patients for 14 days. Researchers compared experimental and control groups to see if the impact of adding estrogen on the clinical course of Covid-19 disease

Detailed Description
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The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, morbidity and mortality from Covid-19 disease were higher among men compared to women. This is caused by the differences in immunological response and viral pathogenesis between men and women. It is theoretically assumed that estrogen has a positive impact on female COVID-19 patients. In this randomized placebo-controlled study, we aimed to investigate the short-term effects of transdermal estrogen therapy on postmenopausal women with COVID-19 disease. Female patients diagnosed with Covid-19 disease were examined and only postmenopausal women were included into the study. The COVID-19 diagnosis was made with a positive reverse transcription-polymerase chain reaction (RT-PCR) test given with nasal and oral swabs. All participants received favipiravir for a week according to the national guidelines published by the Health Ministry of Turkish Republic at that time. As an intervention, transdermal estradiol patch (7.8 mg patch/week) was applied for 14 days on the upper buttock of the patients in experimental arm. As a placebo, hydrogel patch (adhesive hydrogel patch/week) was applied to the female patients for 14 days. Our primary outcome was to achieve better clinical and biochemical outcomes with adding estrogen treatment to conventional therapy of Covid-19 disease. The epidemiological and clinical data, the results of biochemical analysis, the information regarding the treatment and outcomes and serum estradiol levels were determined.

Official Title
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Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients: A Randomized Placebo-Controlled Study

Conditions
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COVID-19, Hormone Replacement Therapy

Intervention / Treatment
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* Drug: Climara 0.1Mg/24Hr Transdermal System
* Other: Hydrogel patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients diagnosed with Covid-19 disease Postmenopausal women (who had 12 months of amenorrhea after their final menstrual period) Positive reverse transcription-polymerase chain reaction (RT-PCR) test given with nasal and oral swabs Exclusion Criteria: Negative RT-PCR test Female patients at reproductive stage

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>All patients were treated with favipiravir for a week. At the same time, the patients in this arm received Estradiol patch (Climara 7.8 mg patch/week, Bayer, Germany) for 14 days. | Drug: Climara 0.1Mg/24Hr Transdermal System<br>* Transdermal estradiol patch is used.<br>|
| Placebo Comparator: Placebo<br>All patients were treated with favipiravir for a week. At the same time, the patients in this arm received Hydrogel patch (Adhesive Hydrogel patch/week, Rebul Pharmacy, Turkey) for 14 days. | Other: Hydrogel patch<br>* Adhesive Hydrogel patch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of disease progression for mild cases | Proportion of patients who are hospitalised in 15 days | 15 days | 
| Evidence of disease progression for moderate and severe cases | Proportion of patients who required mechanical ventilation or died within 15 days | 15 days | 
| Kidney function tests | change of urea(mg/dL), creatinine(mg/dL) and uric acid (mg/dL) levels with estrogen and hydrogel patch application | 15 days | 
| Platelet | change of platelets in total blood count (*10^3/μL) with estrogen and hydrogel patch application | 15 days | 
| Markers of coagulation | change of fibrinogen (mg/dL) and D-dimer (mg/L) with estrogen and hydrogel patch application | 15 days | 
| Marker of inflammation | change of C-reactive protein (mg/L) levels within 15 days | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum E2 levels | change of serum E2 levels with estrogen and hydrogel patch application | 15 days | 
| rate of death | comparison of rate of death in each arm | 15 days | 
| rate of complications | comparison of rate of complications in each arm | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid-19, hormone replacement therapy