May COVID-19 updates: From spironolactone to estrogen to GnRH antagonists

Disclaimer: I am not a medical professional and this is not medical advice. Our understanding of the pandemic is evolving rapidly; this information may be superseded by later and more conclusive findings. This article was last updated on May 31, 2020.

Is it just me, or is this pandemic getting… transier?

In March, I reported on unsubstantiated claims circulating in beauty magazines that spironolactone, used as an acne treatment for cis women and a testosterone blocker for trans women, could increase the likelihood of contracting the novel coronavirus or worsen the severity of COVID-19. Several medical organizations soon clarified that any risk here appears to be theoretical and is not cause for discontinuing spironolactone, and other doctors have even suggested that it could have a beneficial effect in treating the disease; one study in Turkey is comparing a five-day course of 200mg of spironolactone to placebo in the treatment of acute respiratory distress.

April saw the arrival of a pet theory among transphobes that the greater likelihood of death from COVID-19 experienced by men compared to women was specifically due to sex chromosomes, implying that trans women would experience a predisposition similar to cis men. This notion met an unceremonious demise when numerous researchers pointed out that levels of sex hormones may instead play a key role in disease severity, with doctors in Los Angeles and Long Island going so far as to conduct trials of estrogen or progesterone treatment in cis men and postmenopausal cis women with COVID-19.

So what would May hold – a big reveal that COVID-19 is disproportionately killing trans women after all? Quite the opposite: Veterans Affairs hospitals across the country are now conducting a UCLA-led study on whether the GnRH antagonist degarelix can treat COVID-19 in men. Unlike the GnRH agonists typically used as puberty blockers which create an initial spike of sex hormones due to overstimulation before this is suppressed, GnRH antagonists rapidly black the production of sex hormones. Degarelix has been used as a one-time initial treatment for trans women and trans men in Sweden, reducing sex hormones to “castrate levels” within 24 hours. This experimental treatment is based on the observation that cellular expression of the protein TMPRSS2, which is required for the SARS-CoV-2 virus to enter cells, is regulated by testosterone and could be decreased by lowering testosterone levels:

“The new coronavirus cannot enter cells without the help of the TMPRSS2 proteins on our lung cells,” Goldstein says. “Our analysis suggests that decreasing testosterone will lower TMPRSS2, interfere with viral entry, and reduce the severity or duration of COVID-19.”

In the analyses, which also looked for drugs that could target other proteins used by the virus, “TMPRSS2 really stood out as the best opportunity to treat patients,” Goldstein says.

The leader of the study further stated that if this is shown to be an effective treatment, other antiandrogens could potentially be used for COVID-19 as well.

As of this writing, these are all still unconfirmed hypotheses; trials of all these medications are ongoing, results may not be reported for some time, and those results may ultimately show no effect or even a harmful effect on COVID-19 severity. But right now, the medications used by trans people seem to have found an unexpected application. Let’s hope that these elements of biological sex turn out to be something that can be reconfigured for the benefit of even more of the population. ■