Philip Neustrom
Anti-androgens are a proposed COVID-19 therapeutic. Anti-androgens are drugs that either block the binding of ligands at the androgen receptor (e.g. bicalutamide) or block the production of androgens in the body (e.g. dutasteride).
Possible mechanism of benefit in COVID-19
One proposed mechanism of benefit for anti-androgens in COVID-19 is by modulating the expression of serine protease TMPRSS2. In "SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor," it was shown that SARS-CoV-2 cell entry depends on TMPRSS2. TMPRSS2 may be regulated by androgens and estrogens.
Overview articles on potential mechanisms
- The role of androgens in COVID-19
- Androgen sensitivity in COVID‐19 and antiandrogens: Prospective data are still needed
- Estrogen and Androgen Receptor Inhibitors: Unexpected Allies in the Fight Against COVID-19
- The pivotal role of TMPRSS2 in coronavirus disease 2019 and prostate cancer
- TMPRSS2 and COVID-19: Serendipity or Opportunity for Intervention?
- Androgen Signaling Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men
Clinical trial results
N=588 double-blind, randomized controlled trial of proxalutamide in Brazil reported a > 90% reduction in mortality in hospitalized COVID-19 patients in an early press release:
The preliminary analysis conducted on March 9, 2021 was based on 294 patients (56.8% male) inthe Proxalutamide arm and 296 patients (57.8% male) in the control arm. According to the results on day 14, the mortality in Proxalutamide arm was 11(3.7%), compared to 141 (47.6%) in control arm, demonstrating a reduced mortality risk of 92%. The number of new mechanical ventilation (MV) and/ordeath in Proxalutamide arm was 13 (4.4%), compared to 156 (52.7%) in control arm, reducing mortality risk by 92%; and median hospital length stay (days) in Proxalutamide arm was 5, while it was 14 in control arm, which means Proxalutamide shortened hospital stay by 9 days.
Observational studies
- Anti‐androgens may protect against severe COVID‐19 outcomes: results from a prospective cohort study of 77 hospitalized men
- Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The “Gabrin sign”
- Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532)
- Androgen Signaling Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men
Possibly contradictory to androgen-driven hypothesis:
In vitro & vivo animal studies
- Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19
- Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2
List of clinical trials
- Enzalutamide Treatment in COVID-19 (COVIDENZA)
- Randomized Open Label Phase II Study to Evaluate the Efficacy of Enzalutamide in High Risk Male Outpatients With COVID-19
- EAT-DUTA AndroCoV Trial
- Bicalutamide to Block TMPRSS2 in Males With COVID-19 Infection
- Camostat With Bicalutamide for COVID-19 (COMBO)
- Proxalutamide Treatment for Hospitalized COVID-19 Patients
- Anti-Androgen Treatment for COVID-19
