Severe COVID-19 in men linked to low testosterone levels

A new study tracking testosterone levels in hospitalized COVID-19 patients has found a link between low levels of the hormone in men and severe disease outcomes. The research offers important clues as to why men seem to be at greater risk of death from coronavirus compared to women.

Very early in the pandemic, one of the first epidemiological observations to come out of China was that men seemed to be suffering from more severe illness than women. A large meta-analysis published late in 2020 confirmed those early suspicions. While there was no difference in general COVID-19 infection rates between men and women, men were nearly three times more likely to need intensive care treatment and were at greater risk of death.

One early hypothesis to explain this strange gender bias in disease severity suggested testosterone increased one’s risk of hospitalization and death. This was based on the knowledge that testosterone can dampen one’s immune response, so it seemed reasonable to suspect high testosterone levels were responsible for worse disease outcomes in men. There were even clinical trials testing drugs that lower testosterone as a treatment for COVID-19 patients.

However, by the end of 2020 researchers began to suspect we had the COVID-19 testosterone relationship backwards. A new study is offering the most robust insights on the subject to date, looking at circulating testosterone levels in 142 COVID-19 patients and reporting low testosterone levels are strongly linked to worse disease outcomes in men.

The researchers measured testosterone levels at the time of admission, and several other points during hospitalization. As male patients became more severely ill, their testosterone levels continued to drop. In fact, low testosterone levels could effectively predict which patients would decline over the subsequent days.

“During the pandemic, there has been a prevailing notion that testosterone is bad,” says Abhinav Diwan, senior author on the new study. “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 hospitalization, the risk increased.”

Around 60 women were included in the study and there was no association between female testosterone levels and COVID-19 severity.

A major limitation in the research so far is that these studies linking low testosterone and COVID-19 severity have all initially measured hormone levels at the point of hospital admission. So it is unclear whether these men had low testosterone levels prior to viral infection, or whether these concentrations rapidly drop as the disease progresses.

Diwan is calling for more research on the topic to help answer this and other questions, including whether testosterone replacement therapy could help men in the recovery process after acute illness. In the short term, the researchers urge caution in subjects undergoing hormone treatments involving reduced testosterone levels.

“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,” adds Diwan. “We also are interested in whether men recovering from COVID-19, including those with long COVID-19, may benefit from testosterone therapy. This therapy has been used in men with low levels of sex hormones, so it may be worth investigating whether a similar approach can help male COVID-19 survivors with their rehabilitation.”

The new research was published in JAMA Network Open.

Source: Washington University School of Medicine in St. Louis

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