If you’re like me, you’ve been refreshing the news every day trying to find more information on COVID-19. After all, life changed in March; the global pandemic and its associated impact have led to social distancing, job losses, and health anxieties. As the situation continues to evolve, more and more has been discovered about those experiencing severe COVID-19 reactions. The viral infection seems to disproportionately affect those with certain comorbidities, the African-American community, and men.
But why are men experiencing worse outcomes than women? Well, says Medscape, it might have to do with sex hormones called androgens.
Androgens vs. Estrogen
According to HelloClue, androgens are hormones that assist with reproductive development, metabolism, insulin sensitivity, and body composition. Some studies even suggest that androgens impact cardiovascular health, bone density, and moods.
Androgens are produced in the adrenal gland or, in women, in the ovaries. That’s right! Although many people view androgens as a male hormone, especially as the most well-known androgen is testosterone, androgens are present in both men and women. In men, testosterone and androstenedione shape the development of male features and traits. For women, androgens are converted into estrogen.
Estrogen contributes to female sexual development. It is produced in the ovaries, fat cells, and adrenal gland. Estrogen encourages female puberty, but also plays a role in bone health, blood clotting, and skin and tissue function.
COVID-19 & Patient Impact
Researchers questioned why men seemed to experience more severe symptoms, and worse outcomes resulting from COVID-19. To begin their study, they sourced data from 68 Italian hospitals in an area heavily hit by the virus. Out of 9,280 patients with COVID-19, 48.8% (4532) were male. So, although women may be more likely to contract COVID-19, it is less likely that the condition will be fatal.
However, out of these initial patients, 60% of men required hospitalization compared to 40% of women. In intensive care, the number was even more radically split: 78% men compared to 22% women. Fatalities consisted of 62% men versus 38% women.
Next, researchers wanted to see if these results were replicated in patients with cancer. Men with cancer were 2x as likely to contract COVID-19 than those without cancer. But they discovered something unusual: patients with prostate cancer undergoing androgen deprivation therapy (ADT) were actually much less likely to contract or die from COVID-19.
Androgen Deprivation Therapy (ADT)
According to the American Cancer Society, androgen deprivation therapy (also called androgen suppression therapy or hormone therapy) works to reduce the level of androgens in the body. An excess of androgens causes cancer cells to grow. ADT works to reduce the androgens being made in the testicles, prostate, or adrenal glands. This slows the growth of cancer. ADT is a good option for patients whose cancer is recurrent or who cannot have other treatment.
Androgens and COVID-19
Going back to the researchers, they examined 5,273 patients with prostate cancer who were receiving ADT. Out of the 5,273, only four patients contracted COVID-19, with no fatalities.
In a population of 37,161 patients with prostate cancer not receiving ADT, 114 patients contracted COVID-19, with 18 fatalities. Out of 79,661 other patients with cancer, 312 contracted COVID-19, with 57 fatalities.
Their findings suggest that reducing androgen levels can also reduce the chance of contracting COVID-19, experiencing extreme side effects, or dying.
The research team believes that COVID-19 binds to proteins like ACE2 and TMPRSS2. TMPRSS2 is genetically regulated by androgen and can stimulate tumor growth. So ADT reduces androgen levels, stopping the expression of TMPRSS2 and leading to less inflammation and respiratory problems.
However, other researchers note that additional research needs to be performed to see if these results are replicated. Additionally, this study did not take into account patient age, weight, comorbidities, or self-isolation.
Estrogen Protection
Another consideration is that estrogen might strengthen the immune system and protect against negative COVID-19 reactions. Dr. Sharon Nachman, MD, wants to see if estrogen therapy can help patients of all genders:
“because it’s a molecule that we all use as humans, it’s not just women.”
Nachman and her research team are testing whether estrogen can reduce the negative impact of COVID-19. They provided patients with COVID-19 with either a placebo or a transdermal (applied through the skin) estrogen patch. Currently, the patch being used is Climara, normally prescribed for postmenopausal women.
In this study, patients wear the patch for one week. First, researchers will determine whether this prevents patients with COVID-19 from needing intubation or ventilation. Next, they will track the patients for 45 days to see whether it reduced symptom severity for men and women, or which patients estrogen was most effective in treating (if any).
Before developing this study, Nachman looked at the numbers from her own emergency room and intensive care: 80% of the fatalities were men.
Read the full findings in Annals of Oncology.
