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. 2022 May 4:9:774773.
doi: 10.3389/fmed.2022.774773. eCollection 2022.

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

Kyung Min Lee  1   2 , Kent Heberer  3   4 , Anthony Gao  1   2 , Daniel J Becker  5   6 , Stacy Loeb  5   7 , Danil V Makarov  5   7 , Barbara Gulanski  8   9 , Scott L DuVall  1   2 , Mihaela Aslan  8   9 , Jennifer Lee  3   4 , Mei-Chiung Shih  3   10 , Julie A Lynch  1   2 , Richard L Hauger  11   12 , Matthew Rettig  13   14
Affiliations

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

Kyung Min Lee et al. Front Med (Lausanne). .

Abstract

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). Furthermore, ADT was associated with fewer severe COVID-19 outcomes (OR 0.72 [95% CI 0.53-0.96]; p = 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.

Keywords: COVID-19 incidence; COVID-19 severity; Veterans Health Administration; androgen deprivation therapy; prostate cancer.

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Conflict of interest statement

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 Institute for Veteran Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Consort diagram for the selection of patients for the model for the propensity to be tested for SARS-CoV-2. Curved arrows indicate excluded patients.
See this image and copyright information in PMC

Comment in

  • Urological Oncology: Prostate Cancer.
    Taneja SS. Taneja SS. J Urol. 2022 Dec;208(6):1349-1351. doi: 10.1097/JU.0000000000002950. Epub 2022 Nov 9. J Urol. 2022. PMID: 36349923 No abstract available.

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