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Because of the widespread pandemic of COVID-19 all over the world, there were striking differences between sexes. But why are men more susceptible to severe COVID-19 outcomes than women?
Doubt naturally goes to sex hormones, and estrogen Protective against COVID-19 in women, and androgens can exacerbate the consequences of COVID-19 in men.
The new data supporting androgen theory comes from studies in Italy.
These researchers Prostate cancer Patients treated with androgen deprivation therapy (ADT) were less likely to be infected with COVID-19 and less likely to die of the disease than other groups, including other cancer patients.
Findings suggest that androgens somehow make the virus more toxic, which exacerbates the severity of the disease in men. They also speculate that ADT may be protective against COVID-19.
Research Published online May 7 Oncology records.
The team analyzed data from 68 hospitals in the Veneto region, one of the regions of Italy most severely affected by the COVID-19 epidemic.
They found data on 9280 patients with SARS-CoV-2 infection confirmed in the laboratory. 4532 of them were men.
Researchers point out that women in the region are actually slightly more likely to be infected with COVID-19 than men, 56% vs. 44%.
However, men were more likely to develop more severe illness: 60% of men vs. 40% of women needed hospitalization, rising to 78% of men requiring intensive care vs. 22% of women . More women died than men (62% vs 38%).
The team then focused on cancer patients.
Among Veneto’s total male population, those with cancer were almost twice as likely to have COVID-19 as those without cancer (P <.0001).
But when the team looked specifically at men with prostate cancer, “surprisingly, only four of the 5273 patients who had ADT developed SARS-CoV-2 infections, and none of these patients I didn’t die. “
Of the 37,161 men with prostate cancer who did not receive ADT, 114 men developed COVID-19 and 18 died.
Of another 79,661 patients with cancers other than prostate cancer in the Veneto region, 312 developed COVID-19 and 57 died.
“This is the first paper proposing a link between ADT and COVID-19,” commented lead author Dr. Andrea Alimonti, MD, and Svizzera Italiana University in Lugano, Switzerland.
“Prostate cancer patients who received ADT had a four-fold reduced risk of COVID-19 infection compared to those who did not. ADT patients with prostate cancer and other types of cancer “He said.
The finding raises the hypothesis that androgen levels may promote coronavirus infection and increase the severity of symptoms, as seen in male patients, “he said.
“These data are very interesting and make interesting hypotheses,” said Dr. Richard Martin, Professor of Clinical Epidemiology at the University of Bristol, UK. Comment on the survey. “However, independent validation is required on other large population-wide datasets with appropriate statistical analysis, including adjustments for significant risk factors for SARS-CoV-2.”
He said the results of the Italian study were not adjusted for potential confounding factors, such as age, body mass index, and cardiometabolic comorbidities, which are strong risk factors for SARS-CoV-2. In addition, he suggested that men taking ADT are more likely to be self-isolated, which may reduce their risk of becoming infected.
How do androgens interact with viruses?
Alimonti and colleagues provide mechanistic explanations of how androgens interact with viruses.
Coronavirus gains entry into human cells by binding the viral spike (S) protein to ACE2 and priming the S protein by TMPRSS2. TMPRSS2, a member of a family of proteins called type II transmembrane serine proteases, is involved in many processes, including cancer and viral infection, they explain.
“Interestingly, TMPRSS2 is an androgen-regulated gene upregulated in prostate cancer that supports tumor progression,” they point out.
There is also evidence that the same androgen receptor regulates TMPRSS2 expression in non-prostate tissues including lung.
“[This] The authors may explain that men are more susceptible to developing SARS-CoV-2 severe infections than women, “the authors speculate.
ADT is known to lower TMPRSS2 levels, suggesting that androgen receptor antagonists “can be used to block or reduce the severity of SARS-CoV-2 infection in male patients.”
They go further and suggest that men without prostate cancer who are at high risk for COVID-19 can take ADT to prevent infection.
For men infected with COVID-19, ADT may also help reduce the severity of symptoms, they add.
Considering that the effects of androgen receptor antagonists are reversible, “the risk of side effects from long-term administration is because patients who are affected by SARS-CoV-2 can use it transiently (for example, 1 month) Are alleviated, “the authors say. suggest.
Another theory: are estrogens protective?
Another theory that explains the male / female difference in severe COVID-19 is that the female hormone estrogen may be protective.
“People have to stop putting estrogen in their” female hormone box. ” Because it’s a molecule we all use as humans, not women, “said Dr. Sharon Nackman. Medscape Medical News.
“Seeing estrogen as having potentially important immune effects is part of thinking outside the box,” she said.
Nachman is a Vice Dean of Research at the Renaissance School of Medicine at Stony Brook University in New York and works with the surgeon professor Antonios Gasparis, MD at the same center.
They are investigating the use of transdermal estrogen patches in COVID-19 patients in a randomized, placebo-controlled trial. They are looking for patients in the emergency department who show signs and symptoms of COVID-19 and enroll in the study if they are interested.
“We’re also testing everyone, but instead of waiting for the results to come back, we start taking patients on admission,” Nackman explained.
The main purpose of this study was to evaluate whether transdermal patches applied to the skin for 7 days could reduce the need for intubation in men and women infected with COVID-19 compared to standard care. is.
The product is the same disposable transdermal Estradiol patch(Klimala, 25 cm2, Bayer) Prescription for post-menopausal women and used at the same dose known to be safe.
After the patch is removed, the patient will carefully follow the symptoms over the next 45 days to see if the patch reduced the severity of the symptoms.
Nakman would have wanted to enroll patients before they had overt symptoms, which she said was not possible in medical centers with symptomatic patients. Medscape Medical News.
However, even my medical center knows that the odds are higher for male COVID-19 patients. Something is needed to alleviate the severity of this patient group.
Since they were developing a protocol for the current study, the team decided to see who was in the ICU on one study day.
Answer: Mainly male. Male intubation and mortality in the ICU during the day was approximately 80%, compared to only 20% in women.
“We have a horrible new pathogen that is a pandemic, and perhaps we all get it, it’s a matter of when and how ill we get,” Nackman said.
Alimonti and co-authors have not reported similar financial relationships as Goulder and Nachman.
Anne Oncol. Published May 7, 2020 Online. Full text
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