In late March, hair research specialists Andy Goren and Carlos Wambier published an article titled “What Does Androgenetic Alopecia (Male Pattern Baldness) Have To Do with COVID-19?.” In it, they explained that men with androgen receptors with a higher sensitivity were more likely to have severe COVID infections, and thus more likely to die from the virus. Put simply, those with a higher likelihood of going bald also faced a higher likelihood of getting sicker from the coronavirus.
“We said, you know what? There’s something in COVID that’s actually linked to the androgen receptor — the main factor that makes men more vulnerable to have baldness and the receptor of the male hormones,” says Wambier. Goren explains to think of it like this: A virus has to enter a cell, where it makes copies of itself. But in order to get into the cell, it needs some help. “If you look at the picture of coronavirus, you see these little spikes, those are called spike protein,” he tells me. “They need to be cleaved or cut off in order for the virus to penetrate the cell.”
To prime that spike protein, or to activate it, the virus needs TMPRSS2 — the same protease (that is, an enzyme that helps catalyze the breakdown of proteins) that’s also on your lung cells. “And so what happens is that the TMPRSS2 is regulated by androgens,” says Goren. In other words, the higher androgen sensitivity a person has, the more TMPRSS2 the body will create. “Which means the virus is going to have an easier time entering into your lung cells,” says Goren. “When I researched, I found out that the TMPRSS2 requires androgen receptors,” he says. “So that’s why I made a hypothesis that androgenetic alopecia was related to COVID.”
Back in March, the link between a genetic predisposition for increased androgen sensitivity and therefore being at higher risk of dying from COVID-19 was nothing more than a theory. “After we found the link, it was incredible because we were looking at pictures of health-care workers that died because of COVID-19 all over the world,” says Wambier. “It was, ‘Oh this director of this hospital, bald. Then this very young man who died, bald, and then, oh, this here, bald, bald, bald.’ Then with the death of American Dr. Frank Gabrin, we saw the news of the first emergency department doctor that died in the U.S., and he was another bald man.”
By that point, Goren and Wambier were already starting to collect data from a 41-person study that had been conducted in Spain by Dr. Sergio Vano Galvan, at a hospital with which Goren is an affiliate. “We have some friends in Spain who are dermatologists specializing in hair,” says Wambier. “They were working in the COVID zones even before the actual outbreak here in the U.S. So we did a pilot study; we looked at the patients there in the single hospital and then we found that baldness was very common in the patients who were admitted.” This, Goren adds, was the first observable evidence they had confirming their theory.
When I ask Goren how they can be sure of attributing the severe COVID-19 infection to an androgen sensitivity that leads to baldness, rather than age — another major factor for severe coronavirus infections — he tells me that 80 percent of the men who were hospitalized (average age 60) that were a part of their pilot study were bald. “We all know that some men go bald, and of course as you get older, more of them are bald,” he says. “But at the age of 60, 80 percent of all men aren’t bald. In a similar group of men from the same ethnicity in Spain, you would expect between 30 percent to 50 percent to be bald.” Which obviously is significantly lower than the 80 percent of men in their pilot study who had severe COVID infections and who were also bald. “That’s why we kept publishing on this,” he says.
Then, in late April, after the results from their first study in Spain had come in, Goren and Wambier — knowing what they do about androgen sensitivity — predicted in a separate paper that African-American males have a higher chance of dying from COVID-19 because of their genetic predisposition to androgen sensitivity. “There’s no doubt that socioeconomic conditions do predispose African Americans to COVID as well, like less access to care, but the problem becomes worse because they have a genetic predisposition,” says Goren. Which, again, is confirmed by the data, considering African Americans are dying from COVID at alarming rates. “In Louisiana, African Americans accounted for 70 percent of COVID-19 deaths, while comprising 33 percent of the population,” per a Medpage Today report. If the results of yet another Spanish study prove Goren and Wambier’s theory to be true, they plan on applying for an immediate FDA approval of a genetic test to measure androgen sensitivity in men. “We’ll be able to know, based on a genetic test, a male patient’s genetic predisposition for a severe COVID infection.”
But determining a person’s sensitivity to a severe COVID infection was just the first step. Soon after their initial results had come in, Wambier and Goren also connected with researchers in Italy who were examining the link between men with enlarged prostates and a higher likelihood of dying from COVID. “They’re very familiar with TMPRSS2,” says Goren, “because 50 percent of prostate cancer patients have this over-expressed as well. And so they knew a lot about it and then it hit them, ‘Maybe like prostate cancer, it’s also androgen-mediated.’ And [the researchers in Italy] are very familiar with that, because the treatments for prostate cancer are anti-androgens.”
Goren tells me that the men in that study who had already been taking anti-androgens to mitigate their prostate cancer were found to be four times less likely to be infected with COVID, “compared with men of the same age not taking antiandrogens.”
Naturally, the pair began to conduct their own study, testing anti-androgens as a way to prevent severe COVID-19 infection for balding men over the age of 50. “We’re looking at 400 male health-care workers in Spain and Brazil, all of whom have been taking Dutasteride, the anti-androgen with probably the least side effects,” says Goren.
In that study, for which Goren and Wambier are waiting the data to be analyzed, they split the men into two groups. “There’s a prophylactic trial [a drug trial for preventative medication] for patients who are SARS-CoV-2 negative, meaning they’re not diagnosed right now with SARS-CoV-2,” says Goren. “We put them on an anti-androgen, specifically Dutasteride, which already millions of men use for enlarged prostate. And you would take that for two weeks, because it takes about two weeks to reduce the androgens in your body using Dutasteride.” After two weeks, the participants were tested again to measure their androgen levels. “Our idea is that, by reducing androgens, we’ll reduce [TMPRSS2], which is going to prevent the SARS-CoV-2 from entering your lungs.”
Yet another uniquely male vulnerability to COVID-19, according to Wambier, is having higher levels of IL6 (inflammatory cytokine) expression throughout their body, which leads to higher androgen sensitivity. “There’s this link between DHT, which is the hormone that’s the strongest male hormone — DHT, and IL6,” he says. “They work together. So if someone has more of DHT, they produce more of IL6.” Previous studies have shown that IL6 triggers the miniaturization of hair, says Wambier. “DHT causes hair thinning because of many factors,” he explains. “One known factor is the increased release of IL-6 that directly acts on the ‘matrix’ of the hair, disturbing the normal growth.” Which again, results in balding.
To that end, Wambier also warns that, based on what they’re seeing, it’s likely that men who have taken testosterone supplements may also be increasing their risk of severe COVID infections. “Although we don’t know yet if they have indeed higher risk to become infected, we know that the virus enters the cells because of the TMPRSS2 protease, which is produced by male hormones,” he says.
Goren, however, cautions that it’s too early to be sure. “If you’re concerned about hearing all this about testosterone supplements, you should see your doctor if you want to start or stop medications,” he says. “There’s a chance that supplementing with testosterone isn’t a good idea, but it’s not a foregone conclusion that you should stop. You should see your doctor and discuss with them.”
As for why so much of Goren and Wambier’s research is focused solely on men, Goren — whose life’s work has actually been more focused on women’s hair loss — explains that it’s because the drugs they’re testing have a teratogenic effect. “They can give defects in childbirth,” he says. But the main reason is that they simply didn’t see the same association with regard to balding women and more severe COVID infections in any of their studies. “Specifically, androgens might not express themselves in the same way in women as in men,” says Goren. “And also, women are much more complicated in genetic makeup, because they have two X chromosomes.”
When I ask Goren why they haven’t tested their theory here in the U.S., he tells me that they do have a proposal for clinical trials on 400 men over the age of 45 who work in the meat-packing industry in Colorado. However, he says that, “in the United States, the infection rate isn’t high enough right now to actually get a good study,” so they’ve had to look elsewhere. Even among health-care workers, the infection rate in the U.S. is “0.5 percent,” according to Becker’s Hospital Review.
But what’s interesting about the meatpacking industry, Goren says, is that the rate of infection amongst their workers is “about 20 percent within the same plant.” Which is roughly five times higher than the rest of rural America and nearly twice as high as the national average.
The other reason, Goren says, is that researchers are struggling to find groups of patients in the U.S. to test on who haven’t already been exposed to Hydroxychloroquine. After the president began touting the drug as a potential cure for COVID, it basically “log jammed the system in the U.S. for trying to find patients that could be studied with a different drug,” says Goren.
That could be a major issue, says Goren, since there are very few prophylactic studies going on. “There’s still no HIV vaccine,” he says. “Like HIV, there may never be a vaccine for COVID. A prophylactic treatment may turn out to be the only solution.”
Nonetheless, Goren and Wambier’s research is very promising. If their trials further confirm their theory, prophylactics like dutasteride are an inexpensive medication (a one-month supply currently costs around $20) that could save thousands of lives. But until then, it may be time to add “balding” to the list of pre-existing conditions that puts people at greater risk of a severe COVID infection.
Andrew Fiouzi
Andrew Fiouzi is a staff writer at MEL.
