In a new study, researchers found that lowering testosterone could lessen the severity of COVID-19 disease by preventing the new coronavirus from entering lung cells.
The finding supports the idea to treat COVID-19 by reducing testosterone.
The research was conducted by a team at Columbia University Irving Medical Center.
Using existing data on the effects of hundreds of drugs on human cells, the researchers sought to identify compounds that can regulate the expression of genes that encode key viral entry proteins.
Their work showed that TMPRSS2 represented the most promising viral entry protein to target and that lowering testosterone would be the best available option for lowering the expression of TMPRSS2.
The team found the new coronavirus cannot enter cells without the help of the TMPRSS2 proteins on our lung cells.
This analysis suggests that decreasing testosterone will lower TMPRSS2, interfere with viral entry, and reduce the severity or duration of COVID-19.
In the analyses, which also looked for drugs that could target other proteins used by the virus, TMPRSS2 really stood out as the best opportunity to treat patients, according to the team.
Other drugs that lower testosterone may be suitable for less severe cases
For the current trial, the researchers chose degarelix to lower testosterone because it quickly and completely eliminates the hormone from the bloodstream.
The trial is restricted to COVID-19 patients with serious illness but who are not in intensive care at the time of enrollment.
The researchers think eliminating testosterone production is too extreme for patients with mild disease, and may not be effective for severely ill patients on ventilators and with organ failure, as some of those issues may be driven by the patient’s immune response, not the virus.
If the testosterone-lowering strategy works in patients in the current trial, other anti-androgen agents that reduce but do not eliminate androgen signaling may be an option for patients with milder COVID-19 disease.
Increasing estrogen also may reduce TMPRSS2 levels, but because increasing estrogen causes TMPRSS2 levels to briefly spike before levels ultimately decline, the possibility that estrogen could be linked to a transient increase in expression of TMPRSS2 suggested that, at least in men, reducing testosterone would be the better therapeutic option.
If lowering testosterone works in hospitalized men, the team says related approaches will also be tested in women and other points in the disease course.
Estrogen or progesterone also may be tested if raising estrogen levels in women doesn’t cause TMPRSS2 to spike.
The study raises the possibility that the severity of COVID-19 disease could be linked to levels of TMPRSS2.
A recent study by other researchers reports that the lung cells of men have more TMPRSS2 levels and that TMPRSS2 levels are greater in older individuals compared with younger people.
TMPRSS2 levels also vary widely among individuals. Most people have low levels of TMPRSS2, the researchers found, but a few have extremely high levels and older people are more likely than younger people to have extremely high levels.
Based on these findings, a clinical trial to test the effect of reducing testosterone in COVID-19 patients is set to begin at three Veterans Affairs hospitals in New York City, Los Angeles, and the Seattle region.
One researcher of the study is David Goldstein, PhD, the director of the Institute for Genomic Medicine at Columbia University Irving Medical Center.
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