Covid and Anti-Androgens

Proxalutamide: Hospitalization rate in male covid patients reduced by 91% (McCoy et al)

Published: June 24, 2021

Anti-androgens have shown promising results in Brazilian randomized controlled trials.

Note: No medical advice. Patients are asked to consult a doctor.

Back in April 2020, it was discovered that SARS-CoV-2 relies on the cellular TMPRSS2 protease as a co-receptor to gain entry into cells. The cellular expression of TMPRSS2 is driven by androgens (i.e. male sexual hormones), which may help explain why covid tends to be more severe in males compared to females and also more severe in adults compared to children.

TMPRSS2 can be targeted directly (e.g. by bromhexine and camostat), or indirectly, by using anti-androgen drugs. Bromhexine, a prescription-free cough medication, has shown promising results in several small trials and is already part of the SPR covid early treatment protocol.

In addition, it was noticed early on – during the first wave in Italy – that men receiving anti-androgen therapy – typically used against prostate cancer or hair loss – were at a much lower age-adjusted risk of severe covid and hospitalization. It was also found that anti-androgen drugs influence not only the TMPRSS2 co-receptor, but even the ACE2 main receptor used by SARS-CoV-2.

Recently, a series of multi-center, randomized, double-blinded and placebo-controlled trials by a Brazilian group found that investigational anti-androgen drug proxalutamide reduced hospitalization rates in male outpatients by 91% (see chart above); reduced mortality in hospitalized patients (male and female) by 78% (see chart below); and achieved a significantly faster viral clearance.

It should be noted that so far, these studies have been published in non-major journals (one of them is currently a pre-print), and that the Chinese manufacturer of proxalutamide, as well as the Brazilian research group, have been criticized for potential conflicts of interest and other issues.

Nevertheless, if these results get confirmed by other groups using other anti-androgen drugs, health authorities and doctors treating high-risk patients, especially in regions with a low vaccination rate or if faced with vaccine breakthrough cases, may want to consider this option. Ideally, such questions should have been answered already a year – and millions of deaths — ago.

See also: Why coronavirus hits men harder: sex hormones offer clues (Science, June 2020)

Related: The German Association of Pharmaceutical Research Companies (VFA) has recently published a detailed overview of existing and potential anti-covid therapeutics, including anti-viral, cardiovascular, immuno-modulatory, and pulmonary drugs.

Figure: Survival rate (A) and hospital discharge rate (B) in patients treated with proxalutamide.

Proxalutamide: Survival rate and hospital discharge rate (Cadegiani et al)

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