Hormones and Covid (#185)

The world is experiencing a pandemic from COVID-19. So research is looking at every which way various physiologic states might be protective or increase vulnerability. Across the world males seem more susceptible, compared to women (especially premenopausal women) to getting COVID. Once they get it, they are more susceptible to severe outcomes as well as fatalities, once again compared to younger women. It has been suggested that estrogen may be protective against COVID-19 in females and/or that androgens (like testosterone) worsen COVID-19 in men. As of this date, there are three studies being done giving males and menopausal females "estrogen" and/or "progesterone" replacement as it "may" be protective against COVID-19. In This Show You will Hear About Estrogen Is estrogen protective against COVID? Estrogen signals are critical in both innate and adaptive immune responses as well as in tissue repairing processes during respiratory virus infection. Estrogens can regulate the expression of angiotensin-converting enzyme 2 (ACE2), a key component for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry. So estrogen may play a role as a protective COVID “gate-keeper”. The paper that discusses this is: Estrogen regulates the expression of SARS-CoV-2 receptor ACE2 in differentiated airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2020;318(6):L1280-L1281. doi:10.1152/ajplung.00153.2020 In animal experiments, estrogen treatment silences the inflammatory reactions and decreases virus titers leading to improved survival rate. One article even said stated in it abstract, “Premarin (commercial patented estrogen from horse’s urine) is capable of stopping the COVID-19 pandemic.” (Prevention and therapy of COVID-19 via exogenous estrogen treatment for both male and female patients. J Pharm Pharm Sci. 2020;23(1):75-85. doi:10.18433/jpps31069) Estrogen (and progesterone) 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 in 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 older women infected with COVID-19. What About Progesterone? Many of the sickest patients with COVID-19 have high levels of immune system proteins called cytokines in their blood. “Cytokine storm” is an overactive immune response to a viral infection and is one of the most devastating complications of COVID-19 infections. Cytokine storms are known to happen in autoimmune diseases. 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. Pregnant women, who usually have high levels of progesterone, tend to have milder courses of COVID-19. A new study will assess the use of a short course of progesterone therapy in hospitalized men diagnosed with the novel coronavirus. What About Androgens? In January, one of the first publications on those sickened by the novel coronavirus in Wuhan, China, reported that three out of every four hospitalized patients were male. But many men in China smoke while women don’t, so it wasn’t completely known if androgens (male hormones) were the issue, or smoking. But data from around the world have since confirmed that men face a greater risk of severe illness and death from COVID-19 than women. Androgens—male hormones such as testosterone—appear to boost the virus’ ability to get inside cells. Preliminary observations from Spain suggest that a disproportionate number of men with male pattern baldness—which is linked to a powerful androgen—end up in hospitals with COVID-19. Epidemiological data from around the world have confirmed the early reports of male vulnerability. In Lombardy in Italy, for example, men comprised 82% of 1591 patients admitted to intensive care units (ICUs) from 20 February to 18 March, according to a JAMA paper. And male mortality exceeded that of women in every adult age group in another JAMA study of 5700 New York City patients hospitalized with COVID-19. Several studies link baldness to higher risk of COVID and more severe cases. Baldness is associated with higher levels of the most aggressive metabolites of testosterone (DHT). Two small studies have reported that men with male pattern baldness are overrepresented among hospitalized COVID-19 patients.   A paper by Markus Hoffmann of the Leibniz Institute for Primate Research and colleagues in CELL, sent a lightning bolt through scientific community. This work showed Covid can gain entry into the body more easily by the action of an enzyme called TMPRSS2, a membrane-bound enzyme. The enzyme cleaves the “spike” protein on the coronavirus’ surface, allowing the virus to fuse with the host cell’s membrane and get inside the cell. Male hormones turn this enzyme on. In the prostate, TMPRSS2 is produced when male hormones bind to the androgen receptor. Researchers haven’t established if androgens control TMPRSS2 in the lungs as they have in the prostate. But Andrea Alimonti, head of molecular oncology at Università della Svizzera italiana, looked at data on more than 42,000 men with prostate cancer in Italy. He and colleagues found that patients on androgen-deprivation therapy (ADT)—drugs that slash levels of testosterone—were only one-quarter as likely to contract COVID-19 as men with prostate cancer not on ADT. Men on ADT were also less likely to be hospitalized and to die. In one Italian study, men with prostate cancer who received drugs that suppress androgens were much less likely to be infected with COVID. Prostate cancer researcher Catherine Marshall of Johns Hopkins University is preparing a trial of bicalutamide, an older, inexpensive androgen receptor blocker, in 20 patients hospitalized within 3 days after they tested positive for COVID-19. Women are being included in the trial, she adds, because they have androgens, too, although at lower levels than men. What You will Learn Overall Estrogens help heal acute lung injury. Progesterone tamps down inflammatory cytokines. Androgens might help the virus’s spike protein take grip inside the body. But does this mean high androgens compared to healthy normal levels? We don’t know yet. Drugs ( finasteride and dutasteride) that block the conversion of testosterone to DHT, the most powerful form of testosterone, seem to reduce ACE2 levels in healthy human lung alveolar cells. 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 that include the use of hormones that bind to an androgen receptor (such as levonorgestrel and norethisterone). There is a lot we don’t know, but in this show you will hear the latest about the link between hormones and COVID!