A Population-Level Analysis of the Protective Effects of Androgen Deprivation Therapy Against COVID-19 Disease Incidence and Severity
Kyung Min Lee, Kent Heberer, Anthony Gao, Daniel J Becker, Stacy Loeb, Danil V Makarov, Barbara Gulanski, Scott L Duvall, Mihaela Aslan, Jennifer Lee, Mei-Chiung Shih, Julie A Lynch, Richard L Hauger, Matthew Rettig
Frontiers in Medicine, doi:10.3389/fmed.2022.774773
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]; p = 0.001).
Rules of Behavior for Access and Use of Data from VHA Vital Status File. The data are not publicly available. Further inquiries can be directed to the corresponding author.
ETHICS STATEMENT The studies involving human participants were reviewed and approved by the VA Central Institutional Review Board. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
AUTHOR CONTRIBUTIONS
SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmed.
2022.774773/full#supplementary-material Author Disclaimer: The views expressed are those of the authors and do not necessarily represent the views or policy of the Department of Veterans Affairs or the United States Government. Conflict of Interest: SL reports equity in Gilead Sciences, Inc. SD reports research grants from the following for-profit organizations outside this submitted work: Alnylam Pharmaceuticals Inc., AbbVie Inc., Astellas Pharma Inc., AstraZeneca Pharmaceuticals LP, Biodesix, Inc., Boehringer Ingelheim International GmbH, Celgene Corporation, Eli Lilly and Company, Genentech Inc., Gilead Sciences Inc., GlaxoSmithKline PLC, Innocrin Pharmaceuticals Inc., Janssen Pharmaceuticals, Inc., Kantar Health, Myriad Genetic Laboratories, Inc., Novartis International AG, and Parexel International Corporation through the University of Utah or Western..
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'abstract': '<jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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]; <jats:italic>p</jats:italic> = 0.001). Furthermore, ADT was associated '
'with fewer severe COVID-19 outcomes (OR 0.72 [95% CI 0.53–0.96]; <jats:italic>p</jats:italic> '
'= 0.03).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>',
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