Is Androgen Deprivation Therapy Protective Against COVID-19 in Men?

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Is Androgen Deprivation Therapy Protective Against COVID-19 in Men?

Based on reports all over the world, men appear to be more likely to contract COVID-19 and to die of severe infection than women. Find out how androgen-deprivation therapy appears to affect those risks, adding information to why men might have disproportionately bad outcomes.

BELLINZONA, SWITZERLAND – That a drug commonly prescribed to treat prostate cancer might be somewhat protective against COVID-19 adds evidence to observations as to why men might fare worse when infected.

The study published in Annals of Oncology reports that men being treated for prostate cancer with androgen-deprivation therapies (ADT) were less likely to develop the coronavirus COVID-19 and to have less-severe cases if they got it.

https://doi.org/10.1016/j.annonc.2020.04.479

Lead researcher Andrea Alimonti, MD, from the Università della Svizzera Italiana and colleagues focused on 4,532 men infected with COVID-19, of which 9.5% (430) had cancer and 2.6% (118) had prostate cancer. Researchers determined that male cancer patients had a 1.8-fold increased risk of COVID-19 infection out of the whole male population and developed more severe disease.

Looking only at prostate cancer patients in the Veneto region of Italy, however, the study team found that only four out of 5,273 men on ADT developed COVID-19 infection and none of them died. This compared to 37,161 men with prostate cancer who were not receiving ADT, of whom 114 developed COVID-19 and 18 died. Among 79,661 patients with other types of cancer, 312 developed COVID-19 and 57 died.

"Patients with prostate cancer receiving androgen-deprivation therapies had a significant four-fold reduced risk of COVID-19 infections compared to patients who did not receive ADT,” Alimonti explained. “An even greater difference was found when we compared prostate cancer patients receiving ADT to patients with any other type of cancer; there was a more than five-fold reduction in risk of infection among the prostate cancer patients on ADT.”

Background information in the report points out that cell entry of SARS-CoV-2 depends on binding of the viral spike (S) proteins to ACE2 and on S protein priming by TMPRSS2 and that inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections.

“Intriguingly, TMPRSS2 is an androgen-regulated gene that is upregulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene,” according to the authors. “First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections.”

Looking at patients in Veneto on April 1, 2020, researchers write that males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females.

The study notes that, of the 2.4 million men in Veneto, 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. They add,  “"Comparing the total number of SARS-CoV-2 positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared to patients who did not receive ADT (OR 4.05; 95% CI 1.55-10.59). A greater difference was found comparing prostate cancer patients receiving ADT to patients with any other type of cancer (OR 5.17; 95% CI 2.02-13.40).”

"This is the first paper to suggest a link between ADT and COVID-19. We collected data from a large population of patients infected by the coronavirus and have found that those being treated with ADT for prostate cancer are protected, even though all patients with cancer have a greater risk of COVID-19 infection than non-cancer patients,” Alimonti emphasized.

Researchers raise the possibility that, based on their findings, even if men did not have prostate cancer, those who are at high risk of developing COVID-19 could take ADT for a limited period of time to prevent infection, while those who become infected could take ADT to reduce the severity of the symptoms. Fabrice André, MD, PhD, Director of Research at the Institut Gustave Roussy in Villejuif, France, and editor-in-chief of Annals of Oncology cautions, however, that more research is needed before those recommendations can be made.

"We decided to publish this study because it provides a rationale to evaluate the efficacy of ADT prospectively in patients infected with COVID-19,” he said. “Nevertheless, the study does not provide a definitive conclusion about the role of ADT in patients infected with COVID-19, and this class of drugs should not be used for this purpose until prospective trials have confirmed its efficacy.".

Alimonti.seconded the call for more research, adding, "I hope that our findings inspire other clinicians to carry out clinical trials using transient ADT in men infected with COVID-19, in addition to other experimental therapies. Although these data need to be further validated in additional large cohorts of patients with COVID-19, they provide an answer to the hypothesis that androgen levels can facilitate coronavirus infections and increase the severity of symptoms, as has been seen in male patients."

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