key: cord-0852635-fw45zydb
authors: La Vignera, Sandro; Cannarella, Rossella; Condorelli, Rosita A.; Torre, Francesco; Aversa, Antonio; Calogero, Aldo E.
title: SARS-CoV-2: the endocrinological protective clinical model derived from patients with prostate cancer
date: 2020-07-11
journal: Ther Adv Endocrinol Metab
DOI: 10.1177/2042018820942385
sha: 3af294ef15cafee323cb3f88f52bca4ed7222d11
doc_id: 852635
cord_uid: fw45zydb

nan

As researchers clinically and scientifically engaged in the management of male hypogonadism, we read with interest a recent article entitled 'Androgendeprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (n = 4532)' 1 , published in the Annals of Oncology, that suggests a possible role for androgen-deprivation therapy (ADT) in male patients with Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection.

In a cross-sectional, population-based study performed on 4532 male patients with SARS-CoV-2 infection from Veneto (Italy), the authors reported an impressively low frequency of SARS-CoV-2 infection (4/5273) in patients with prostate cancer on ADT, with no deaths. Also, among all infected patients, those receiving ADT for prostate cancer had around a four-fold lower risk of SARS-CoV-2 infection compared with those not on ADT, thus suggesting prognostic implications of the androgenic status in these patients. As an explanatory mechanism, the authors focused on the androgenmodulated expression of the TMPRSS2 protein, which is involved in SARS-CoV-2 cellular infection by promoting the fusion of viral and cellular membranes. In particular, since androgens trigger the expression of TMPRSS2, ADT might interfere with SARS-CoV-2 entry into the host cells by enhancing its downregulation. 1 This study confirms clinically the 'androgen hypothesis' that we recently advanced by analyzing the in vitro evidence on SARS-CoV-2 infection. 2 Beyond TMPRSS2, the ACE2 protein is also very likely involved in the modulation of sex-specific SARS-CoV-2 mortality. ACE2 is the ligand of the viral spike protein that plays a relevant role in the mechanisms by which SARS-CoV-2 penetrates cells. 3 ACE2 is expressed in several tissues, such as the alveolar cells, myocardium, or Leydig cells. A low ACE2 expression could hypothetically deter SARS-CoV-2 penetration into the host cells. Also, ACE2 is highly expressed in the myocardium of spontaneously hypertensive male mice compared with female mice. 4 Interestingly, its expression decreases significantly after orchiectomy, thus suggesting that androgens sustain ACE2 protein expression. 2 This additional mechanism may explain the lower severity of SARS-CoV-2 infection in patients with prostate cancer under ADT 1 and leads to a possible beneficial consideration for the management of SARS-CoV-2 infection.

First, testosterone (T) [or luteinizing hormone (LH)/human chorionic gonadotropin] discontinuation should be considered in hypogonadal patients with SARS-CoV-2 infection, 2 and ADT could be temporarily counseled to male patients at high risk (e.g. patients with high venous thromboembolic risk). 2 Second, it would be appropriate to assess the gonadal function upon ADT discontinuation. Recent findings point to the possible risk that male patients infected with SARS-CoV-2 may develop hypogonadism. In 81 infected male patients of reproductive age, SARS-CoV-2 led to a significant increase in serum LH levels and LH/T ratio, indicating an early stage Leydig cell dysfunction. 5 Third, male hypogonadism occurs in 2-15% of elderly patients (40-79 years). 6 The evaluation of SARS-CoV-2 infection in male untreated hypogonadal patients would be relevant in further confirming the androgen influence on this disease. Finally, hypogonadism, ADT, and T replacement SARS-CoV-2: the endocrinological protective clinical model derived from patients with prostate cancer

Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (n= 4532). Ann Oncol. Epub ahead of print 6

Sex-specific SARS-CoV-2 mortality: among hormone-modulated ACE2 expression, risk of venous thromboembolism and hypovitaminosis D

Does the direct renin inhibitor have a role to play in attenuating severity of the outbreak coronavirus disease 2019 (COVID-19)?

Sex hormones promote opposite effects on ACE and ACE2 activity, hypertrophy and cardiac contractility in spontaneously hypertensive rats

Effect of SARS-CoV-2 infection upon male gonadal function: a single center-based study

Characteristics of androgen deficiency in lateonset hypogonadism: results from the European Male Aging Study (EMAS)

The authors declare that there is no conflict of interest.

The authors received no financial support for the research, authorship, and/or publication of this article.

Sandro La Vignera https://orcid.org/0000-0002-7113-2372 Rossella Cannarella https://orcid.org/0000-0003-4599-8487