A population-level analysis of the protective effects of androgen deprivation therapy against COVID-19 disease incidence and severity

ABSTRACT Importance The incidence and severity of coronavirus disease 19 (COVID-19) is higher in men. Sex hormones potentially offer one explanation for differences by sex. Objective To determine whether men exposed to androgen deprivation therapy (ADT) have lower incidence and severity of COVID-19. Design We conducted an observational study of male Veterans treated in the Veterans Health Administration from February 15th to July 15th, 2020. We developed a propensity score model to predict the likelihood to undergo Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing. We performed multivariable logistic regression modeling adjusted with inverse probability weighting to examine the relationship between ADT and COVID-19 incidence. We conducted logistic regression analysis among COVID-19 patients to test the association between ADT and COVID-19 severity. Setting The U.S. Department of Veterans Affairs Participants The study sample consisted of 6,250,417 male Veterans who were alive as of February 15, 2020. Exposure Exposure to ADT was defined as having any prescription for a luteinizing hormone releasing hormone analogue or an antiandrogen in the six months prior to the index date. Main Outcomes and Measures To assess incidence, we used a binary variable indicating any positive reverse transcriptase polymerase chain reaction SARS-CoV-2 test result through July 15, 2020. To measure severity, we constructed a binary variable indicating whether a patient was admitted to the intensive care unit, placed on mechanical ventilation, or dead in the 60 days following a positive test up to July 15, 2020. Results We identified 246,087 patients who had been tested for SARS-CoV-2, of whom 3,057 were exposed to ADT, and 36,096 patients with cancer and no ADT exposure. Of these, 295 ADT patients and 2,427 other cancer patients had COVID-19 illness. In the primary, propensity-weighted comparison of ADT patients to cancer patients not on ADT, ADT was associated with decreased likelihood of testing positive for SARS-CoV-2 (adjusted OR, 0.88 [95% CI, 0.81-0.95]; p=0.001). ADT was associated with fewer severe COVID-19 outcomes (OR 0.72 [95% CI 0.53-0.96]; p=0.03). Conclusions and Relevance ADT is associated with reduced incidence and severity of COVID-19 amongst male Veterans. Repurposing of drugs that modulate androgen production and/or action may represent viable potential treatments for COVID-19. KEY POINTS Question Does androgen deprivation therapy (ADT) lower incidence and severity of COVID-19? Findings In this observational study of male Veterans treated in the Veterans Healthcare System, ADT was associated with decreased likelihood of testing positive for SARS-CoV-2 (adjusted OR, 0.88 [95% CI, 0.81-0.95]; p=0.001). ADT was also associated with fewer severe COVID-19 outcomes (OR 0.72 [95% CI 0.53-0.96]; p=0.03). Meaning The use of androgen deprivation therapy may be protective against SARS-CoV-2 infection and modulate severity of COVID-19 outcomes.