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A Population-Level Analysis of the Protective Effects of Androgen Deprivation Therapy Against COVID-19 Disease Incidence and Severity.

Lee KM, Heberer K, Gao A, Becker DJ, Loeb S, Makarov DV, Gulanski B, DuVall SL, Aslan M, Lee J, Shih MC, Lynch JA, Hauger RL, Rettig M. A Population-Level Analysis of the Protective Effects of Androgen Deprivation Therapy Against COVID-19 Disease Incidence and Severity. Frontiers in medicine. 2022 May 4; 9:774773.

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BACKGROUND: The incidence and severity of coronavirus disease 19 (COVID-19) is substantially higher in men. Sex hormones may be a potential mechanism for differences in COVID-19 outcome in men and women. We hypothesized that men treated with androgen deprivation therapy (ADT) have lower incidence and severity of COVID-19. METHODS: 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. RESULTS: We identified a large cohort of 246,087 VA male patients who had been tested for SARS-CoV-2, of whom 3,057 men were exposed to ADT, and 36,096 men with cancer without ADT. Of these, 295 ADT patients and 2,427 cancer patients not on ADT had severe 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]; = 0.001). Furthermore, ADT was associated with fewer severe COVID-19 outcomes (OR 0.72 [95% CI 0.53-0.96]; = 0.03). CONCLUSION: ADT is associated with reduced incidence and severity of COVID-19 amongst male Veterans. Testosterone and androgen receptor signaling may confer increased risk for SARS-CoV-2 infection and contribute to severe COVID-19 pathophysiology in men.

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