key: cord-0982301-wb3mnfqv
authors: Ianhez, Mayra; Ramos, Paulo Müller; Goren, Andy; Miot, Hélio Amante
title: Androgen sensitivity in COVID‐19 and antiandrogens: prospective data are still needed
date: 2020-08-09
journal: Dermatol Ther
DOI: 10.1111/dth.14166
sha: 853d8a1c568e177424f413531211ac783586adf7
doc_id: 982301
cord_uid: wb3mnfqv

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Men are disproportionately affected by COVID-19 and have an increased risk of ICU admittance as well as mortality. In contrast, prepubescents appear to be largely protected from COVID-19 severe symptoms 1 . The androgen receptor regulates the transcription of the transmembrane protease, serine 2 (TMPRSS2), and angiotensin converting enzyme 2 (ACE2) which are required for the COVID-19 infectivity; thus, raising the hypothesis of androgen sensitivity as a risk factor 2,3 . The recent association of androgenetic alopecia (AGA) with COVID-19 severity strengthens the androgen theory 2 . Testosterone levels are low not only in prepubescents but also in elderly men 4 and recent observations point out that disease severity may be best correlated with specific gene loci, rather than ACE2 or TMPRSS2 receptors 5 . Furthermore, serum androgens do not always correlate with tissue androgens or androgen mediated disease. For example, AGA and prostate cancer can be exacerbated by elevated tissue androgen in genetically predisposed patients 6 .

In order to elucidate the effect of androgens on COVID-19 outcomes, some epidemiological studies were conducted. Since TMPRSS2 are expressed in the lungs, the use of antiandrogens or androgen-depleting therapies (ADT), currently used for prostate cancer, represent an appealing target for prevention or treatment of COVID-19 4 . An Italian study compared infectivity and outcomes of COVID-19 in prostate cancer patients treated with or without ADT (androgen deprivation therapies). The study concluded that ADT was associated with reduced risk of infection and with reduced COVID-19 disease burden 7 ; however, to-date, no large epidemiological study attempted to evaluate the potential protective role of diverse antiandrogens in COVID-19 infection.

To gather large scale data, we performed a population survey through In addition, TMPRSS2 also plays a role in infectivity of influenza 8 . Disease burden due to the influenza-A virus is often higher in men, but fatality following exposure to pathogenic influenza-A is higher in women and men before puberty 9 .

Moreover, the variability between outcomes in men and women could also be due to anatomical and immunological differences 9 .

Even though our survey could not establish an association between antiandrogen therapy and prophylaxis of COVID-19 infection or severity, the hypothesis remains to be confirmed. Not all antiandrogens have the same potency (e.g, androgen deprivation therapy for prostate cancer compared with finasteride for androgenetic alopecia in men); thus, different medications and equivalent dosages must be carefully evaluated. The elucidation of the role of testosterone towards COVID-19 infection turns out to be an urgent need. Many candidates could be potential drugs such as androgen receptor inhibitors, steroidogenesis inhibitors and 5-alpha reductase inhibitors 2 . To date, there are six trials with antiandrogen therapies registered in clinicaltrials.gov. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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