Men have roughly twice the risk of developing severe disease and dying from COVID-19 than women. Scientists say this is in part because women mount stronger immune reactions to the disease’s microbial cause: the infamous coronavirus called SARS-CoV-2.
Now research with prostate cancer patients points to another possible explanation, which is that the male sex hormone testosterone helps SARS-Cov-2 get into and infect human cells.
SARS-CoV-2 initiates infections by first latching onto its human cell receptor. But it can only pass into a cell with the aid of a second protein called TMPRSS2. Testosterone regulates TMPRSS2, such that levels of the hormone and the protein rise and fall together in tandem. If testosterone levels are depressed, scientists speculate, then TMPRSS2 levels might also be so low that the novel coronavirus is blocked at the gates.
At least five clinical trials are now investigating if drugs acting on testosterone and its own receptor “could either prevent or cure COVID-19 symptoms,” said Dr. Andrea Alimonti from the University of Lugano in Bellanzona, Switzerland.
Positive results from one study
During a recent study, Alimonti’s team reviewed data from 42,434 men who were being treated for prostate cancer in the Veneto region of Italy. Among them, 5,273 were getting androgen deprivation therapies (ADT) that suppress testosterone. (The hormone fuels prostate tumors, so ADT is for some men a mainstay of treatment.) According to that investigation, coronavirus infection rates in the ADT-treated men were four times lower than they were in men who were not getting ADT. The researchers acknowledged the need for more study, but proposed that ADT “could be used transiently in men affected by SARS-CoV-2.”
And negative results from another
Other scientists are skeptical. Dr. Eric Klein, a urologist at the Cleveland Clinic Lerner College of Medicine, argues that testosterone may not regulate TMPRSS2 in the lungs as it does in the prostate. Suppressing the hormone, he says, might therefore have little consequence for preventing SARS-CoV-2 respiratory symptoms. In a recent study of 1,779 men with prostate cancer, Klein and his colleagues generated evidence showing that ADT did not protect from COVID-19. The paper is currently in press at the Journal of Urology and has not yet been published.
Still, Klein stopped short of dismissing the possibility that ADT could be therapeutically useful in treating COVID-19. “Definitive answers will only come from the results of ongoing clinical trials using various forms of ADT in COVID-19 patients,” he said.
Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org, agrees. “These studies — some positive and some negative — add to the complexities of fully understanding what affects coronavirus infectivity,” he says. “It is likely to be multi-factorial, and in some patients, testosterone levels may play a role. Pending results from large-scale clinical studies, however, no definitive recommendations about altering testosterone levels for COVID-19 treatment can be made.”
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