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

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

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

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.

Article activity feed

  1. Version published to 10.3389/fmed.2022.774773
  2. ScreenIT

    SciScore for 10.1101/2021.05.10.21255146: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: 19 This study was approved by the VA Central Institutional Review Board.
    Sex as a biological variableStudy sample: The study sample consisted of all male Veterans who were alive as of February 15, 2020.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Weaknesses include the retrospective nature of the analysis and uncertainty about the underlying cause for ICU admission, mechanical ventilation, and death. While we treated VHA facility as a random effect in our severity analysis, the rapid change in treatment decisions and ability for hospitals to handle capacity at different times in the pandemic may leave confounding for patients who develop severe disease. Ongoing work in VA may provide further clarify the association between ADT and COVID-19 illness and determine the utility of ADT agents including LHRH analogs, androgen receptor antagonists, and 5-alpha reductase inhibitors. LHRH analogs achieve castrate levels of serum testosterone in virtually all patients, although the LHRH antagonist, degarelix, is the only FDA-approved LHRH analog that rapidly suppresses serum testosterone concentrations. A randomized, double-blind, placebo-controlled, multicenter VA trial entitled, “Hormonal Intervention for the Treatment of Veterans with COVID-19 Requiring Hospitalization (HITCH)” (Clinicaltrials.gov identifier NCT04397718), is prospectively testing the hypothesis that ADT with the LHRH antagonist, degarelix, reduces the severity of COVID-19 illness defined by a composite of ongoing hospitalization, intubation, or death within 15 days of randomization. The VA Million Veteran Program MVP035 COVID-19 Disease Mechanisms study is investigating the role of TMPRSS2 and other androgen-regulated genes in COVID-19 severity. Several other...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04397718RecruitingHormonal Intervention for the Treatment in Veterans With COV…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.05.10.21255146v1 on medRxiv