{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:10:27Z","timestamp":1789150227003,"version":"build-2803163510"},"reference-count":34,"publisher":"JMIR Publications Inc.","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JMIR Res Protoc"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Early epidemiological studies suggested that pre- and postmenopausal women receiving estrogen therapy were less likely to develop severe disease or die from COVID-19 infection. Potential mechanisms include estrogen-mediated immunomodulation and 17\u03b2-estradiol\u2013induced downregulation of angiotensin-converting enzyme type 2 (ACE2), the cellular receptor for SARS-CoV-2.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n This study aimed to evaluate the feasibility, safety, and preliminary efficacy of transdermal 17\u03b2-estradiol as an adjunctive treatment for COVID-19 in men and postmenopausal women.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We designed and conducted a randomized controlled trial comparing 17\u03b2-estradiol transdermal gel plus standard care with standard care alone in adults with confirmed COVID-19. Initial ethics and funding approvals were obtained in March 2021. Owing to changes in the epidemiology of COVID-19 in Qatar and revisions to national quarantine policies, protocol amendments were required before recruitment commenced in February 2022. The treatment duration was reduced from 10 to 7 days due to changes in national quarantine guidelines. Recruitment and follow-up were conducted between February 2022 and June 2022.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Recruitment was substantially lower than anticipated because widespread COVID-19 vaccination, declining disease severity, and revised national quarantine policies markedly reduced the number of eligible hospitalized patients. Consequently, the planned sample size was not achieved, and the study was terminated in June 2022. A total of 29 men with mild COVID-19 were enrolled, with 44.8% (n=13) randomized to standard care and 55.2% (n=16) to transdermal 17\u03b2-estradiol plus standard care. The intervention was well tolerated, with no adverse safety signals or thromboembolic events reported.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Although the study was underpowered to assess efficacy because recruitment targets were not achieved, it showed that transdermal 17\u03b2-estradiol was well tolerated, with no major safety concerns among enrolled participants. The experience also provided important operational lessons for conducting clinical trials during rapidly evolving pandemics. Adequately powered studies are required to determine whether transdermal estrogen has therapeutic potential against COVID-19, other ACE2-mediated coronavirus infections, or potentially other severe viral illnesses.<\/jats:p>\n <\/jats:sec>","DOI":"10.2196\/81541","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:44:12Z","timestamp":1789148652000},"page":"e81541-e81541","source":"Crossref","is-referenced-by-count":0,"title":["Transdermal 17\u03b2-Estradiol for the Treatment of COVID-19: Protocol of an Early Terminated Phase 2 Randomized Controlled 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