Do Anti-androgens Have Potential as Therapeutics for COVID-19?
Mauvais-Jarvis et al.,
Do Anti-androgens Have Potential as Therapeutics for COVID-19?,
Endocrinology, doi:10.1210/endocr/bqab114 (Review)
Review of research related to the potential benefits of anti-androgrens for COVID-19.
Mauvais-Jarvis et al., 5 Jun 2021, peer-reviewed, 1 author.
Abstract: Endocrinology, 2021, Vol. 162, No. 8, 1–4
doi:10.1210/endocr/bqab114
Perspective
Perspective
Franck Mauvais-Jarvis1,2,3
1
Department of Medicine, Section of Endocrinology, Tulane University School of Medicine, New Orleans,
LA, USA; 2Tulane Center of Excellence in Sex-Based Biology & Medicine, New Orleans, LA, USA; and
3
Southeast Louisiana VA Medical Center, New Orleans, LA, USA
ORCiD number: 0000-0002-0874-0754 (F. Mauvais-Jarvis).
Received: 29 April 2021; Editorial Decision: 1 June 2021; First Published Online: 5 June 2021; Corrected and Typeset:
7 July 2021.
Abstract
Coronavirus disease 2019 (COVID-19) is characterized by a gender disparity in severity,
with men exhibiting higher hospitalization and mortality rates than women. Severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19,
infects cells following recognition and attachment of the viral spike glycoprotein to the
angiotensin-converting enzyme 2 transmembrane protein, followed by spike protein
cleavage and activation by cell surface transmembrane protease serine 2 (TMPRSS2).
In prostate cancer cells, androgen acting on the androgen receptor increases TMPRSS2
expression, which has led to the hypothesis that androgen-dependent expression of
TMPRSS2 in the lung may increase men’s susceptibility to severe COVID-19 and that, accordingly, suppressing androgen production or action may mitigate COVID-19 severity by
reducing SARS-CoV-2 amplification. Several ongoing clinical trials are testing the ability
of androgen deprivation therapies or anti-androgens to mitigate COVID-19. This perspective discusses clinical and molecular advances on the rapidly evolving field of androgen
receptor (AR) action on cell surface transmembrane protease serine 2 (TMPRSS2) expression and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection,
and the potential effect of anti-androgens on coronavirus disease 2019 (COVID-19) severity in male patients. It discusses limitations of current studies and offers insight for
future directions.
Key Words: androgens, testosterone, TMPRSS2, ACE2, SARS-CoV-2, COVID-19, sex differences
As of June 2021, with over 170 000 000 confirmed cases of
COVID-19 worldwide, the percentage of confirmed cases is
equal among men and women. However, among more than
3 500 000 deaths globally, for every 10 female confirmed cases
that have died from COVID-19, there are 15 males (https://
globalhealth5050.org/the-sex-gender-and-covid-19-project/
the-data-tracker/). Several mechanisms have been proposed to explain this relative female protection from severe
COVID-19 outcomes, with the most likely being related to
women’s more robust immune response to viruses (1).
SARS-CoV-2 entry and infection of cells is mediated by
recognition and attachment of the viral spike glycoprotein
ISSN Online 1945-7170
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
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https://academic.oup.com/endo 1
Do Anti-androgens Have Potential as
Therapeutics for COVID-19?
2
evidence indicates that ADT prevents COVID-19 infection
or mitigates COVID-19 severity. Thus, several randomized
clinical trials (RCTs) have begun to test the efficacy of ADT
in the general population of male COVID-19 patients. The
most interesting to..
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