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)
Authors: Lazzeri Massimo , Duga Stefano , Azzolini Elena , Fasulo Vittorio , Buffi Nicolò , Saita Alberto ,   The Humanitas COVID-19 Task Force,   The Humanitas Gavazzeni COVID-19 Task Force, Hurle Rodolfo , Nobili Alessandro , Cecconi Maurizio , Casale Paolo , Asselta Rosanna 
Published: April 2020

ABSTRACTImportanceThere are gender differences in vulnerability to the Coronavirus disease 2019 (COVID-19), with men experiencing more severe disease at any age. The use of anti-androgen drugs, like 5-alpha reductase inhibitors (5ARIs), could protect from severe pulmonary disease.ObjectiveTo determine whether men who received 5ARIs for benign prostatic hyperplasia (BPH) have a lower risk of hospitalization for COVID-19.DesignThis is a case-control study on patients hospitalized for COVID-19 (cases), matched to beneficiaries of the Lombardy Regional Health Service (controls).SettingData were collected by two high-volume COVID-19 regional centres of Lombardy (Italy) from 1st March to 24th April 2020.ParticipantsConsecutive patients positive for SARS-CoV-2 virus according to the WHO guidance, who required hospitalization.ExposureBPH treatment with 5ARIs (finasteride/dutasteride) in the last six months.Main Outcome(s) and Measure(s)The primary outcome was to compare the prevalence of male patients chronically exposed to 5ARIs, who required hospitalization for COVID-19, with the one of age-matched males in Lombardy.ResultsOverall, 1,432 COVID-19 patients were included. Among the 943 males, 45 (4.77%) patients were exposed to chronic 5ARI therapy. COVID-19 patients aged >55 years under 5ARI treatment were significantly less than expected on the basis of the prevalence of 5ARI treatment among age-matched controls (5.57 vs. 8.14%; p=0.0083, 95%CI=0.75-3.97%). This disproportion was even higher for men aged >65 (7.14 vs. 12.31%; p=0.0001, 95%CI=2.83-6.97%).Eighteen 5ARIs-patients died; the mean age of men who died was higher than those who did not: 75.98±9.29 vs. 64.78±13.57 (p<0.001). Cox regression and multivariable models did not show any correlation between the exposure to 5ARIs and protection against ICU admission or death: HR=0.79 (95%CI=0.54-1.15; p=0.22) and OR=1.23 (95%CI=0.81-1.87; p=0.33), respectively.Conclusions and RelevanceIn this case-control study the use of 5ARIs was less frequent among patients hospitalized for COVID-19 than among controls, suggesting that men exposed to 5ARIs might be less vulnerable to severe COVID-19. This observation further supports the idea to test in randomized clinical trials whether anti-androgen therapies can prevent the transition from paucisymptomatic SARS-CoV-2 infection to overt pulmonary disease.KEY POINTSQuestionMay treatment of benign prostatic hyperplasia with 5-alpha reductase inhibitors (5ARIs) impact on COVID-19-related hospitalization risk?FindingsIn 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%).MeaningThe 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 anti-androgen therapies can prevent the transition from paucisymptomatic SARS-CoV-2 infection to overt pulmonary disease.