Low Testosterone may be a Risk Factor for Severe COVID

Testosterone molecule
Model of a testosterone molecule. Source: Wikimedia CC0

Among men with COVID, those with low testosterone levels are more likely to become seriously ill and be hospitalised than men with normal levels of the hormone, according to a study which appears in JAMA Network Open.

Analysis of data for 723 men who tested positive for COVID, mostly in 2020 before vaccines were available, indicated that low testosterone is an independent risk factor for COVID hospitalisation, similar to diabetes, heart disease and chronic lung disease.

They found that men with low testosterone who developed COVID were 2.4 times more likely to require hospitalisation than men with hormone levels in the normal range. Further, men who were once diagnosed with low testosterone but successfully treated with hormone replacement therapy were no more likely to be hospitalised for COVID than men whose testosterone levels had always tested in the normal range.

The findings, by researchers from the Washington University School of Medicine in St. Louis and Saint Louis University School of Medicine, suggest that treating men with low testosterone may help protect them against severe disease and reduce the burden on hospitals during COVID waves.

“It is very likely that COVID is here to stay,” said co-senior author Abhinav Diwan, MD, a professor of medicine at Washington University. “Hospitalizations with COVID are still a problem and will continue to be a problem because the virus keeps evolving new variants that escape immunization-based immunity. Low testosterone is very common; up to a third of men over 30 have it. Our study draws attention to this important risk factor and the need to address it as a strategy to lower hospitalisations.”

Prof Diwan and co-senior author Sandeep Dhindsa, MD, an endocrinologist at Saint Louis University, had previously shown that men hospitalised with COVID have abnormally low testosterone levels. However, severe illness or traumatic injury can cause a temporary drop in hormone levels, so causation cannot be proved in data from men already hospitalised with COVID. Data were needed for men with chronically low testosterone before COVID infection.

Profs Diwan, Dhindsa and colleagues identified 723 men whose testosterone levels had been measured between Jan. 1, 2017, and Dec. 31, 2021, and who had documented cases of COVID in 2020 or 2021. In some cases, testosterone levels were measured after the patient recovered from COVID. Since low testosterone is a chronic condition, men who tested low a few months after recovering from COVID probably had low levels before as well, Prof Dhindsa said.

The researchers identified 427 men with normal testosterone levels, 116 with low levels, and 180 who previously had low levels but were being successfully treated, meaning that they were on hormone replacement therapy and their testosterone levels were in the normal range at the time they developed COVID.

“Low testosterone turned out to be a risk factor for hospitalisation from COVID, and treatment of low testosterone helped to negate that risk,” Prof Dhindsa said. “The risk really takes off below a level of 200 nanograms per decilitre, with the normal range being 300 to 1000 nanograms per decilitre. This is independent of all other risk factors that we looked at: age, obesity or other health conditions. But those people who were on therapy, their risk was normal.”

Men with low testosterone levels can experience sexual dysfunction, depressed mood, irritability, difficulty with concentration and memory, fatigue, loss of muscular strength and a reduced sense of well-being overall. When a man’s quality of life is clearly diminished, he is typically treated with testosterone replacement therapy. When the symptoms are mild, though, doctors and patients may hesitate to treat.

The two main concerns related to testosterone therapy are an increased risk of prostate cancer and heart disease. Testosterone is well known to boost prostate cancer, but for heart disease, the evidence for risk is more ambiguous. A large clinical trial on the relationship between heart health and testosterone supplementation is expected to be completed soon.

“In the meantime, our study would suggest that it would be prudent to look at testosterone levels, especially in people who have symptoms of low testosterone, and then individualise care,” said Prof Diwan, whose specialty is cardiology. “If they are at really high risk of cardiovascular events, then the doctor could engage the patient in a discussion of the pros and cons of hormone replacement therapy, and perhaps lowering the risk of COVID hospitalisation could be on the list of potential benefits.”

Since this study is observational, it only suggests that boosting testosterone levels may help men avoid severe COVID, Diwan cautioned. A clinical trial would be needed to demonstrate conclusively whether such a strategy works.

Source: Washington University School of Medicine