Abstract: medRxiv preprint doi: https://doi.org/10.1101/2020.04.20.20068056; this version posted September 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Impact of anti-androgen therapies on COVID-19 susceptibility: a case-control study in male population from two COVID-19 regional centers of Lombardy (Italy) Massimo Lazzeri, MD-PhD1*, Stefano Duga, PhD1,2*, Elena Azzolini, MD1, Vittorio Fasulo, MD1, Nicolò Buffi, MD1-2, Alberto Saita, MD1, The Humanitas COVID-19 Task Force1, The Humanitas Gavazzeni COVID-19 Task Force3, Rodolfo Hurle, MD1, Alessandro Nobili, MD4, Maurizio Cecconi, MD-PhD1,2, Paolo Casale, MD1, Rosanna Asselta, PhD1,2 1 Humanitas Clinical and Research Center – IRCCS –, via Manzoni 56, 20089 Rozzano (Mi) – Italy 2 Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele – Milan, Italy 3 Humanitas Gavazzeni-Castelli, Bergamo, Italy 4 Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri, 2 , 20156, Milan *Equally contributed Short title: 5ARIs and the risk of COVID-19 Keywords: COVID-19, 5-alpha reductase inhibitors, androgens, sex. Manuscript word count: 1200 Corresponding Authors: Massimo Lazzeri, MD, PhD Department of Urology Istituto Clinico Humanitas IRCCS Via Manzoni 56 (20089) Rozzano – Milan (Italy) Email: massimo.lazzeri@humanitas.it Stefano Duga, PhD Department of Biological Sciences Humanitas University Via Rita Levi Montalcini 4 (20090) Pieve Emanuele - Milan (Italy) Email: stefano.duga@hunimed.eu NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.04.20.20068056; this version posted September 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . KEY POINTS Question: May treatment of benign prostatic hyperplasia with 5-alpha reductase inhibitors (5ARIs) impact on COVID-19-related hospitalization risk? Findings: In this case-control study, which compared 943 adult males hospitalized for COVID-19 with age-matched men from Lombardy (all beneficiaries of the Regional Health Service), the proportion of patients aged >55 years, who were exposed to 5ARIs (dutasteride, finasteride), was significantly lower (5.57%) than that of the general male population (8.14%) (p=0.0083, 95%CI=0.75-3.97%). Meaning: The use of 5ARIs was associated with a potential reduced risk of hospitalization for COVID-19 in men older than >55 years. This suggests the opportunity to test whether antiandrogen therapies can prevent the transition from paucisymptomatic SARS-CoV-2 infection to overt pulmonary disease. medRxiv preprint doi: https://doi.org/10.1101/2020.04.20.20068056; this version posted September 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . ABSTRACT Importance: There are gender differences in vulnerability to the Coronavirus..