{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:28:06Z","timestamp":1790504886674,"version":"4.1.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (\n                    <jats:ext-link>clinicaltrials.gov<\/jats:ext-link>\n                    number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale &amp;lt;3) were administered proxalutamide 200 mg\/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo,\n                    <jats:italic>P<\/jats:italic>\n                    &amp;lt; 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03\u20130.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2021.668698","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T02:47:44Z","timestamp":1626662864000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":35,"title":["RETRACTED: Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial"],"prefix":"10.3389","volume":"8","author":[{"given":"John","family":"McCoy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Goren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1vio Adsuara","family":"Cadegiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Va\u00f1o-Galv\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Kovacevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirna","family":"Situm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney","family":"Sinclair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Tosti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrija","family":"Stanimirovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edinete","family":"Dorner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirce Costa","family":"Onety","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Ariel","family":"Zimerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Gustavo","family":"Wambier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2021450118","DOI":"10.1073\/pnas.2021450118","article-title":"Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2","volume":"118","author":"Qiao","year":"2020","journal-title":"Proc Natl Acad Sci USA."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1009212","DOI":"10.1371\/journal.ppat.1009212","article-title":"Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2","volume":"17","author":"Ou","year":"2021","journal-title":"PLOS Pathog."},{"key":"B3","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.stem.2020.11.009","article-title":"Androgen signaling regulates SARS-CoV-2 receptor levels and is associated with severe COVID-19 symptoms in men","volume":"27","author":"Samuel","year":"2020","journal-title":"Cell Stem Cell."},{"key":"B4","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.jaad.2020.04.032","article-title":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated","volume":"83","author":"Wambier","year":"2020","journal-title":"J Am Acad Dermatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e453","DOI":"10.1016\/j.jaad.2020.07.099","article-title":"Androgenetic alopecia in COVID-19: compared to age-matched epidemiologic studies and hospital outcomes with or without the Gabrin sign","volume":"83","author":"Wambier","year":"2020","journal-title":"J Am Acad Dermatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1016\/j.jaad.2020.07.062","article-title":"Male balding is a major risk factor for severe COVID-19","volume":"68","author":"Lee","year":"2020","journal-title":"J Am Acad Dermatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1111\/exd.14220","article-title":"Alopecia and gray hair are associated with COVID-19 severity","volume":"29","author":"Ramos","year":"2020","journal-title":"Exp Dermatol."},{"key":"B8","first-page":"37","article-title":"Alopecia and severity of COVID-19: a cross-sectional study in Peru","volume":"29","author":"Salazar Arenas","year":"2021","journal-title":"Le Infez Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/j.annonc.2020.04.479","article-title":"Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532)","volume":"31","author":"Montopoli","year":"2020","journal-title":"Ann Oncol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.1111\/jdv.16953","article-title":"Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men","volume":"35","author":"Goren","year":"2021","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e243","DOI":"10.1111\/jdv.17021","article-title":"5-alpha-reductase inhibitors are associated with reduced frequency of COVID-19 symptoms in males with androgenetic alopecia","volume":"35","author":"McCoy","year":"2021","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e13047","DOI":"10.7759\/cureus.13047","article-title":"Early antiandrogen therapy with dutasteride reduces viral shedding, inflammatory responses, and time-to-remission in males with COVID-19: a randomized, double-blind, placebo-controlled interventional trial (EAT-DUTA AndroCoV Trial - Biochemical)","volume":"13","author":"Cadegiani","year":"2021","journal-title":"Cureus."},{"key":"B13","doi-asserted-by":"publisher","first-page":"232","DOI":"10.47176\/mjiri.35.30","article-title":"Finasteride in hospitalized adult males with COVID-19: A risk factor for severity of the disease or an adjunct treatment: A randomized controlled clinical trial TT","volume":"35","author":"Zarehoseinzade","year":"2021","journal-title":"MJIRI."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1007\/s10637-020-00901-w","article-title":"Metabolomic profiling to evaluate the efficacy of proxalutamide, a novel androgen receptor antagonist, in prostate cancer cells","volume":"38","author":"Qu","year":"2020","journal-title":"Invest New Drugs."},{"key":"B15","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1126\/science.1168175","article-title":"Development of a second-generation antiandrogen for treatment of advanced prostate cancer","volume":"324","author":"Tran","year":"2009","journal-title":"Science."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e13492","DOI":"10.7759\/cureus.13492","article-title":"Proxalutamide significantly accelerates viral clearance and reduces time to clinical remission in patients with mild to moderate COVID-19: results from a randomized, double-blinded, placebo-controlled trial","volume":"13","author":"Cadegiani","year":"2021","journal-title":"Cureus"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2020.25.49.2000790","article-title":"Epidemiological characteristics of COVID-19 cases in Italy and estimates of the reproductive numbers one month into the epidemic","volume":"25","author":"Riccardo","year":"2020","journal-title":"medRxiv."},{"key":"B18","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1590\/S0365-05962012000400012","article-title":"Brazilian blood donation eligibility criteria for dermatologic patients","volume":"87","author":"Wambier","year":"2012","journal-title":"An Bras Dermatol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2021.03.084","article-title":"Response to \u201cReply to effectiveness of dutasteride in a large series of patients with FFA in real clinical practice","author":"Pindado-Ortega","year":"2021","journal-title":"J Am Acad Dermatol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ejca.2020.04.013","article-title":"Preclinical profile and phase I clinical trial of a novel androgen receptor antagonist GT0918 in castration-resistant prostate cancer","volume":"134","author":"Zhou","year":"2020","journal-title":"Eur J Cancer."},{"key":"B21","doi-asserted-by":"publisher","first-page":"241572","DOI":"10.1136\/bcr-2021-241572","article-title":"Potential risk for developing severe COVID-19 disease among anabolic steroid users","volume":"14","author":"Cadegiani","year":"2021","journal-title":"BMJ Case Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and Is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1101\/2020.09.13.295691","article-title":"Ambroxol hydrochloride inhibits the interaction between severe acute respiratory syndrome coronavirus 2 spike protein's receptor binding domain and recombinant human ACE2","author":"Olaleye","year":"2020","journal-title":"bioRxiv Prepr Serv Biol [preprint]"},{"key":"B24","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1038\/s41467-021-21171-x","article-title":"Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide","volume":"12","author":"Li","year":"2021","journal-title":"Nat Commun."},{"key":"B25","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1242\/jcs.02786","article-title":"Androgens modulate the inflammatory response during acute wound healing","volume":"119","author":"Gilliver","year":"2006","journal-title":"J Cell Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1152\/japplphysiol.00012.2008","article-title":"Flutamide protects against trauma-hemorrhage-induced liver injury via attenuation of the inflammatory response, oxidative stress, and apopotosis","volume":"105","author":"Kan","year":"2008","journal-title":"J Appl Physiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/1471-2407-9-92","article-title":"Androgen deprivation modulates the inflammatory response induced by irradiation","volume":"9","author":"Wu","year":"2009","journal-title":"BMC Cancer."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-030-55617-4_1","article-title":"Interleukin-6 function and targeting in prostate cancer","volume":"1290","author":"Culig","year":"2021","journal-title":"Adv Exp Med Biol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1101\/2021.04.19.21255441","article-title":"Early treatment with nitazoxanide prevents worsening of mild and moderate COVID-19 and subsequent hospitalization","author":"Rossignol","year":"2021","journal-title":"medRxiv [preprint]."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2003725","DOI":"10.1183\/13993003.03725-2020","article-title":"Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial","volume":"14","author":"Rocco","year":"2021","journal-title":"Eur Respir J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3176","DOI":"10.1002\/jmv.26880","article-title":"Effect of a combination of nitazoxanide, ribavirin, and ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-19","volume":"93","author":"Elalfy","year":"2021","journal-title":"J Med Virol."}],"updated-by":[{"DOI":"10.3389\/fmed.2021.831449","type":"expression_of_concern","label":"Expression of concern","source":"retraction-watch","updated":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"record-id":"37574"},{"DOI":"10.3389\/fmed.2022.964099","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"record-id":"37573"},{"DOI":"10.3389\/fmed.2021.831449","type":"expression_of_concern","label":"Expression of concern","source":"publisher","updated":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000}},{"DOI":"10.3389\/fmed.2022.964099","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000}}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.668698\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T09:23:08Z","timestamp":1712136188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.668698\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,19]]},"references-count":31,"alternative-id":["10.3389\/fmed.2021.668698"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.668698","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-135303\/v4","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-135303\/v3","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-135303\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-135303\/v1","asserted-by":"object"}]},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,19]]},"article-number":"668698"}}