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Why men are more likely to die of Covid — US study shows testosterone levels are key

Study published in JAMA Network Open journal urges caution against ongoing clinical trials probing hormonal therapies as a treatment for men with Covid.

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New Delhi: A new US study could finally help answer why men are more likely to die from Covid-19 than women.

The study, by researchers from the Washington University School of Medicine in St Louis, Missouri, revealed that men with low testosterone levels are more likely to require intensive care.

However, the study, published in the journal JAMA Network Open Tuesday, does not prove that severe Covid is caused by low testosterone. Instead, the researchers establish a link between severity of the disease and low levels of the sex hormone, and urge caution against ongoing clinical trials that are investigating hormonal therapies — which block or lower testosterone or increase oestrogen — as a treatment for men with Covid.

“During the pandemic, there has been a prevailing notion that testosterone is bad,” Abhinav Diwan, a professor of medicine at the university, said in a statement.

“But we found the opposite in men. 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. And if testosterone levels dropped further during hospitalisation, the risk increased,” Diwan added.

Also read: How use of antibiotics for Covid patients is worsening India’s drug resistance crisis

The study

For the study, researchers measured several hormones in blood samples from 90 men and 62 women, who came to Barnes-Jewish Hospital in St Louis with symptoms of Covid-19 or confirmed cases of the illness. Of these, 143 were hospitalised.

The researchers measured hormone levels after three, seven, 14 and 28 days — depending on how long the patient was hospitalised.

In addition to testosterone, the researchers also measured levels of oestradiol, a form of oestrogen produced by the body, and IGF-1 — an important growth hormone that is similar to insulin and plays a role in maintaining muscle mass.

Among men, only testosterone levels were linked to Covid-19 severity. At hospital admission, men with severe Covid had average testosterone levels of 53 nanograms per decilitre, and men with less severe disease had average levels of 151 nanograms per decilitre.

A blood testosterone level of 250 nanograms per decilitre or less is considered low testosterone in adult men.

By day three, the average testosterone level of the most severely ill men was only 19 nanograms per decilitre.

The researchers also found that those with the lowest levels of testosterone in the blood were at highest risk of going on a ventilator, needed intensive care or were dying.

Thirty-seven patients, 25 of whom were men, died over the course of the study.

Meanwhile, no such link between levels of any hormone and disease severity was found among women.

Also read: Moderna vaccine effective in 12-17 year-olds, could become 2nd shot approved for teens in US

Other risk factors for Covid also related to low testosterone

The researchers also pointed out that other factors known to increase the risk of severe Covid-19, including advanced age, obesity and diabetes, were also associated with lower testosterone.

The team found that lower testosterone levels in men also correlated with higher levels of inflammation and an increase in the activation of genes that allow the body to carry out the functions of circulating sex hormones inside the cells.

This means that the body could be adapting to less testosterone circulating in the bloodstream by increasing its ability to detect and use the hormone. However, the researchers don’t yet know what effect this adaptation would have on Covid patients.

The study adds to the growing body of research that demonstrates a link between low testosterone and Covid-19 severity.

Another study from Italy, published this month, also reached similar conclusions. An analysis of 48 male Covid patients in the study concluded that low testosterone was a predictor of disease severity.

Diwan’s team will now study whether testosterone therapy could benefit Covid patients.

Men at higher risk of developing severe Covid

Throughout the pandemic, scientists have observed that men are more likely to suffer from severe disease and die of Covid than women.

For instance, an analysis of 31,11,714 global cases of Covid, published in the journal Nature Communications in December 2020, showed that while there is no difference in infectivity between the two sexes, men are three times more likely to require intensive care than women.

Initially, the theory was that hormonal differences between men and women may make the latter more susceptible to severe disease.

Studies hypothesised that oestrogen probably helped protect women from Covid. As a result, some clinical trials were also launched to study if oestrogen therapy could help treat Covid patients.

However, this is probably not true, since the St Louis study now suggests that for men, low testosterone levels in the blood may be linked to more severe disease.

(Edited by Rachel John)

Also read: Why health experts are wary of Bharat Biotech’s Covid vaccine trials on children


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