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The Role of Hormones in Treating COVID and Immune Response

Across the world, why are men so much more susceptible to severe outcomes from COVID-19 than women? It has been suggested that estrogen may be protective against COVID-19 in females and/or that androgens (like testosterone) worsen COVID-19 outcomes in men. Androgen sensitivity would explain severe cases in female patients who present with metabolic syndrome or polycystic ovary syndrome (PCOS) or who are using birth control methods with progestogen hormones that bind to an androgen receptor. 

The first biological step required to cause infection by the SARS-CoV-2 virus (which causes COVID) is priming of the spike proteins by an androgen-regulated gene. This has led researchers to speculate that ADT (Androgen Deprivation Therapy) may be protective against COVID-19 in male patients. Data was analyzed from 9280 patients with laboratory-confirmed COVID-19 infection in 68 hospitals in the Italian region hardest hit by COVID. Men were more prone to develop severe forms of the disease: 60% of men vs 40% of women required hospitalization, and 78% of men vs 22% of women required intensive care. More men died than women (62% vs 38%). Patients with prostate cancer being treated with ADT were significantly less likely to become infected with COVID-19 and die from the disease than other groups. For men who do become infected with COVID-19, ADT might also help reduce symptom severity. ADT involves the use of medications that temporarily target androgen activity, such as androgen receptor inhibitors (flutamide, bicalutamide) and 5-alpha reductase inhibitors (finasteride). 

Hormones such as estrogens, progesterone, and testosterone can bind to spikes on the virus which may interfere with attachment of the virus to stressed cells. These substances may be helpful as anti-COVID-19 agents for people with a high risk of cell stress like the elderly, cancer patients, and front-line medical staff.

Doctors at the Renaissance School of Medicine, Stony Brook University, New York are conducting a randomized trial to determine if the use of a transdermal estrogen patch for 7 days in patients with COVID-19 might reduce the need for intubation in men and women infected with COVID-19. They are recruiting male and female patients who present to their emergency department with signs and symptoms of COVID-19. 

In many of the sickest patients with COVID-19, their blood has very high levels of immune system proteins called cytokines. “Cytokine storm” is an overactive immune response to a viral infection and is one of the most devastating complications of COVID-19 infections, where the body starts to attack its own cells and tissues rather than just fighting off the virus. Cytokine storms are known to happen in autoimmune diseases, during certain kinds of cancer treatment, and can be triggered by infections like the flu. One study of patients who died of H1N1 influenza, for example, found that 81% had features of a cytokine storm.

Researchers have looked at the anti-inflammatory properties of progesterone based on a significant amount of data describing how progesterone affects immune response.  “There’s a striking difference between the number of men and women in the intensive care unit, and men are clearly doing worse,” said Dr. Sara Ghandehari, a pulmonologist and ICU physician at Cedars-Sinai in Los Angeles who is the principal investigator for a new progesterone study. Pregnant women, who are usually immunocompromised but have high levels of estrogen and progesterone, tend to have mild courses of COVID-19. Ghandehari’s study will assess the use of a short course of progesterone therapy in hospitalized men diagnosed with the novel coronavirus.

For the reasons discussed above, it is essential that women continue their hormone therapy and that the hormonal status of both men and women is optimized to potentially reduce their risk of serious consequences of COVID-19.

 

References

References are available upon request.


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