A population-level analysis of the protective effects of androgen deprivation therapy against COVID-19 disease incidence and severity
Authors: Lee Kyung Min , Heberer Kent , Gao Anthony , Becker Daniel J , Loeb Stacy , Makarov Danil V. , Gulanski Barbara , DuVall Scott L , Aslan Mihaela , Lee Jennifer , Hauger Richard , Shih Mei-Chiung , Lynch Julie , Rettig Matthew 
Published: May 2021

ABSTRACTImportanceThe incidence and severity of coronavirus disease 19 (COVID-19) is higher in men. Sex hormones potentially offer one explanation for differences by sex.ObjectiveTo determine whether men exposed to androgen deprivation therapy (ADT) have lower incidence and severity of COVID-19.DesignWe 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.SettingThe U.S. Department of Veterans AffairsParticipantsThe study sample consisted of 6,250,417 male Veterans who were alive as of February 15, 2020.ExposureExposure 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 MeasuresTo 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.ResultsWe 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 RelevanceADT 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 POINTSQuestionDoes androgen deprivation therapy (ADT) lower incidence and severity of COVID-19?FindingsIn 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).MeaningThe use of androgen deprivation therapy may be protective against SARS-CoV-2 infection and modulate severity of COVID-19 outcomes.