From the Journals

Androgens may explain male vulnerability to COVID-19


 

As the COVID-19 pandemic has swept across the world, a striking difference has been seen between the sexes. But why are men so much more susceptible to severe outcomes from COVID-19 than women?

Suspicions naturally turn to the sex hormones, and there have been suggestions that estrogen may be protective against COVID-19 in females and/or that androgens worsen COVID-19 outcomes in males.

New data supporting the androgen theory come from a study in Italy.

These researchers found that patients with prostate cancer being treated with androgen deprivation therapy (ADT) were less likely to become infected with COVID-19 and die from the disease than other groups, including other patients with cancer.

The findings suggest that androgens somehow make the virus more virulent and that this exacerbates the severity of disease in men, they say. They also speculate that ADT may be protective against COVID-19.

The study was published online May 7 in Annals of Oncology.

The team analyzed data from 68 hospitals in the Veneto region, one of the areas in Italy most severely affected by the COVID-19 pandemic.

They found data on 9280 patients with laboratory-confirmed SARS-CoV-2 infection — of whom 4532 were males.

Women in the region were actually slightly more likely to be infected with COVID-19 than men, 56% vs 44%, the researchers point out.

However, men were more prone to develop more severe forms of the disease: 60% of men vs 40% of women required hospitalization, rising to 78% of men vs 22% of women who required intensive care. Also, more men died than women (62% vs 38%).

The team then turned their focus onto patients with cancer.

Of the entire male population of Veneto, those with cancer had an almost twofold higher risk of becoming infected with COVID-19 than men without cancer (P < .0001).

However, when the team looked specifically at men with prostate cancer in the region, they found “strikingly, only 4 out of 5273 patients receiving ADT developed SARS-CoV-2 infection and none of these patients died.”

This compared to 37,161 men with prostate cancer who were not receiving ADT, among whom 114 men developed COVID-19 and 18 died.

Among another 79,661 patients in the Veneto region with cancer other than prostate cancer, 312 developed COVID-19 and 57 died.

“This is the first paper to suggest a link between ADT and COVID-19,” commented lead author Andrea Alimonti, MD, PhD, Università della Svizzera Italiana in Lugano, Switzerland.

“Patients with prostate cancer receiving ADT had a significant fourfold reduced risk of COVID-19 infections compared to patients who did not receive ADT. An even greater difference (fivefold reduction in risk) was found when we compared prostate cancer patients receiving ADT to patients with any other type of cancer,” he said.

The finding raises “the hypothesis that androgen levels can facilitate coronavirus infections and increase the severity of symptoms, as has been seen in male patients,” he said.

“These data are very interesting and raise a fascinating hypothesis,” said Richard Martin, PhD, professor of clinical epidemiology at the University of Bristol, UK, commenting about the study. “But they do need independent validation in other large population-wide datasets...with appropriate statistical analysis including adjustment for important risk factors for SARS-CoV-2.”

He noted that the Italian study results were not adjusted for potential confounders, for example, age, body mass index, and cardiometabolic comorbidities, that are strong risk factors for SARS-CoV-2. In addition, men taking ADT may have been more likely to self-isolate and so be at reduced risk of getting the infection, he suggested.

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