Doctors Are Testing Whether Estrogen Could Help Men Fight COVID-19

More men than women have fallen severely ill or died from COVID-19, and now two clinical trials will probe whether sex hormone differences might explain the trend, The New York Times reported.

Since the COVID-19 pandemic first emerged in China, men around the world have been more likely to require intensive medical care or die from the disease than women, according to the Times report. For instance, men make up about 75% of the COVID-19 patients in intensive care or on ventilators at Cedars-Sinai Medical Center in Los Angeles, Dr. Sara Ghandehari, a pulmonologist and intensive care physician, told the Times. And as of early April, infected men in New York City were dying at about twice the rate of infected women, according to NPR.

The trend may be related to the high prevalence of heart and lung conditions in men, who also generally smoke cigarettes, consume alcohol and are exposed to outdoor air pollution at higher rates than women, Sarah Hawkes, professor of global public health at University College London, told NPR on an episode of Morning Edition. In addition to these factors, though, "there's quite a lot of good evidence that ... female immune systems are essentially a lot stronger," she added.

The sex hormones estrogen and progesterone, which women produce in larger quantities than men, help to regulate the female immune system and may grant women special resistance against infections and harmful immune system responses, the Times reported. With that in mind, scientists at Cedars-Sinai and the Renaissance School of Medicine at Stony Brook University plan to treat small groups of COVID-19 patients with the hormones, to see if they make a difference.

"We may not understand exactly how estrogen works [to counteract COVID-19], but maybe we can see how the patient does," Dr. Sharon Nachman, the principal investigator of the Stony Brook University trial, told the Times.

The Stony Brook trial will include 110 patients with confirmed or presumed cases of COVID-19 who develop at least one serious symptom, such as high fever, shortness of breath or pneumonia, but do not yet require mechanical breathing support through intubation, according to ClinicalTrials.gov. All men ages 18 and older may enter the trial, as well as women ages 55 and older (women's estrogen levels tend to decline after menopause.) Half the participants will be treated with an estrogen patch placed on their skin for one week, while the other half will receive standard medical care.

Previous research suggests that extra estrogen could help clear the virus from the body, as well as support repair of damaged tissues once the COVID-19 infection begins to subside, Nachman said.

Participants in the Cedars-Sinai trial will receive progesterone, rather than estrogen, as progesterone may have anti-inflammatory properties and could prevent the onset of a so-called cytokine storm, wherein inflammatory chemical signals go haywire and damage the body, Ghandehari told the Times. The study will include 40 hospitalized men with mild to moderate COVID-19 infections. Half of those men will receive two shots of progesterone a day for five days. Both the estrogen and progesterone trials will monitor the severity of patients' illnesses through time, comparing the treated groups with the untreated groups.

Both trials bank on the idea that heightened levels of estrogen and progesterone may help the body fight COVID-19 infection, but not all the data supports that notion, Sabra Klein, who studies sex differences in viral infections and vaccination responses at the Johns Hopkins Bloomberg School of Public Health, told the Times.

"Older men are still disproportionately affected" by COVID-19 compared with older women, whose hormone levels dip dramatically following menopause, she said. "That suggests to me it's got to be something genetic, or something else, that's not just hormonal," she said. That said, infusions of estrogen and progesterone may still modulate the male immune system in a beneficial way, Klein added.

"You could get a beneficial effect in both men and women," she said. "But if women are better at recovery at 93 years old, I doubt it's hormones."

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