Impact of anti-androgenic therapies on COVID-19: an observational study in male population from a COVID-19 regional centre of Lombardy (Italy)

Lazzeri, Massimo; Duga, Stefano; Azzolini, Elena; Fasulo, Vittorio; Buffi, Nicolo; Saita, Alberto; Force, - The Humanitas COVID-19 Task; Force, - The Humanitas Gavazzeni COVID-19 Task; Hurle, Rodolfo; Nobili, Alessandro; Cecconi, Maurizio; Casale, Paolo; Asselta, Rosanna

Importance: There 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. Objective: To determine whether men who received 5ARIs for benign prostatic hyperplasia (BPH) have a lower risk of hospitalization for COVID-19. Design: This is a case-control study on patients hospitalized for COVID-19 (cases), matched to beneficiaries of the Lombardy Regional Health Service (controls). Setting: Data were collected by two high-volume COVID-19 regional centres of Lombardy (Italy) from 1st March to 24th April 2020. Participants: Consecutive patients positive for SARS-CoV-2 virus according to the WHO guidance, who required hospitalization. Exposure: BPH 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. Results: Overall, 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 Relevance: In 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.