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While men have been shown to have greater risk of COVID-19 illness compared with women, a new study shows that the lower the testosterone level in men, the higher the likelihood of severe COVID-19 disease.
"During the pandemic, there has been a prevailing notion that testosterone is bad," senior author Abhinav Diwan, MD, a professor of medicine at Washington University School of Medicine in St. Louis, said in a statement.
"But we found the opposite in men," he said.
"If a man had low testosterone when he first came to the hospital, his risk of having severe COVID-19 — meaning his risk of requiring intensive care or dying — was much higher compared with men who had more circulating testosterone."
Testosterone in the Very Ill
For the study, published this week in JAMA Network Open, Diwan and his colleagues looked at 152 patients, including 90 men and 62 women, who were treated for COVID-19 between March and May 2020 at Barnes-Jewish Hospital in St. Louis. Of those patients, 143 were hospitalized for COVID-19.
Among 66 men in the group who had severe COVID-19, median testosterone levels on the day of admission and at day 3 were about 65% to 85% lower than in the 24 men who had milder disease.
And overall, the vast majority — 89% — of the COVID-19-infected men, including those with mild disease, showed testosterone levels below what's considered to be the normal range when they were admitted to hospital.
The men in the current study with severe COVID-19 had average blood levels of testosterone of just 53 ng/dL when they entered hospital. Any testosterone level of 250 ng/dL or below is considered 'low' in adult men.
By day 3 of hospitalization, their average testosterone levels dropped even further — to only 19 ng/dL.
Also, the testosterone level among men who were admitted to ICU was 49 ng/dL, versus 142 ng/dL among men who did not placed in ICU.
In general, the lowest testosterone levels were associated with the highest risks of requiring mechanical ventilation, ICU admission or of dying.
"The groups of men who were getting sicker were known to have lower testosterone across the board," said study author Sandeep Dhindsa, MD, an endocrinologist at Saint Louis University.
"We also found that those men with COVID-19 who were not severely ill initially, but had low testosterone levels, were likely to need intensive care or intubation over the next 2 or 3 days. Lower testosterone levels seemed to predict which patients were likely to become very ill over the next few days."
Hormone Effect Seen Among Men Only
The scientists looked at other hormones but found that only levels of testosterone were linked with COVID-19 disease severity in men. Among women, there were no differences in any hormone levels according to COVID-19 disease severity, including levels of testosterone (women have small amounts of testosterone), or estrogen.
The testosterone concentrations in men with severe disease were not affected by other known risk factors for COVID-19 severity, including age, body mass index, underlying conditions such as diabetes or heart disease, smoking and race.
However, the low testosterone levels did significantly track with signs of inflammation.
Importantly, however, the results don't necessarily prove that lack of testosterone is causing more severe cases of COVID-19, the researchers said.
They note that testosterone concentrations are known to drop by as much as 50% when men are admitted to the hospital, even for routine elective surgeries.
Drops in testosterone are also normal after traumatic brain injury and heart attack.
To further test the relationship between testosterone and COVID-19, the researchers are now focusing on the hormone's effects on long-term symptoms of COVID-19.
"We are now investigating whether there is an association between sex hormones and cardiovascular outcomes in 'long COVID-19', when the symptoms linger over many months," said Diwan, a cardiologist.
In the meantime, the results should give pause for researchers studying whether hormonal treatment may help fight COVID-19. For example, one study was looking at giving estrogen to men with COVID-19.
"These data suggest caution should be practiced with approaches that antagonize testosterone signaling or supplement estrogen to treat men with severe COVID-19," the authors stress.
"Our study results suggest that, unlike the common presumption, testosterone may not be a propagator of COVID-19 severity in either gender," they conclude. "On the contrary, it may be protective in men."
JAMA Network Open: "Association of Circulating Sex Hormones With Inflammation and Disease Severity in Patients With COVID-19."
Washington University School of Medicine in St. Louis: "For men, low testosterone means high risk of severe COVID-19."
Sandeep Dhindsa, MD, endocrinologist, Saint Louis University.
Abhinav Diwan, MD, professor of medicine, Washington University School of Medicine in St. Louis.