Men more at risk of Covid-19: the important role of androgens

Les hommes plus à risque de Covid-19: le rôle important des androgènes

Recent studies suggest that androgens or male sex hormones such as testosterone, promote the entry of the sars coronavirus in cells, which could explain why men are more affected by the Covid-19 than women.

From the beginning of the pandemic Covid-19, it was quickly noted that the men were much more affected by the severe forms of the disease than women. This difference in susceptibility according to gender is particularly striking in Lombardy (Italy) : the analysis of 1591 patients admitted to the intensive care unit of 20 February and 18 march revealed that men accounted for no less than 82 % of the patients (1). The men are not only more affected by the COVID-19, but they are also more at risk of dying of complications of the disease : a study in New York showed that the mortality rate of hospitalized patients was higher in men than in women, and this, in all age groups (2).

Involvement of androgens

The immune system of women is higher than men, and it is likely that this factor contributes to the difference of susceptibility in the face of infection by the coronavirus observed between the two sexes. However, recent observations suggest that the male sex hormones (androgens) might also play an important role. For example, a study conducted in Spain reported that men with male pattern baldness accounted for a disproportionate share of hospitalized patients because of the Covid-19 : a census of 122 patients hospitalized in 3 schools of Madrid has revealed that 79 % of men treated for the disease were hairless, while the proportion of normal baldness for men of the same age is approximately 40 % (3). Another study (41 patients) arrived at similar results, with 71 % of patients who were bald. Since baldness is associated with high levels of dihydrotestosterone, an active metabolite of testosterone, so it is possible that androgens increase the risk of infection by the coronavirus and/or accelerates the development of complications of the Covid-19. Moreover, the analysis of blood levels of androgens in patients with the Covid-19 has shown that a high amount of androgens was associated with a significant increase in the risk of severe complications of the disease, including cardiac injury (4).

Prostate Cancer

Another indication of the potential role of androgens comes from studies conducted among men with prostate cancer. The growth of this cancer is stimulated by androgens (testosterone and dihydrotestosterone) and a therapeutic approach common is to reduce the levels of these androgens with drugs that block the production of these hormones (analogues and / or antagonists of LHRH such as leuprolide or degarelix, for example). Italian researchers have shown that patients with prostate cancer who were treated with these drugs were 4 times less likely to be infected with the coronavirus and to develop complications of the Covid-19, suggesting again that androgens contribute to the development of this disease (5).

This association between androgens and the infection by the coronavirus is biologically plausible : to infect cells, the proteins present at the surface of the coronavirus must be cut by an enzyme called TMPRSS2 present in the cell membrane, which allows the virus to interact with the receptor ACE2, and enter the following in the cells.

Very interesting fact, it has been shown that the expression of TMPRSS2 is strongly stimulated by androgens and that mutations in this enzyme are present in a high proportion of prostate cancers. By reducing the amount of androgens, diminish, therefore, the expression of TMPRSS2 on the cell surface, which prevents the infection by the virus. Several clinical trials are in progress and should allow us to determine the therapeutic potential of the approach to androgen deprivation for the treatment of the Covid-19 (6).

(1) Grasselli G et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA 2020; 323:1574-1581.

(2) Richardson S, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020; 323: 2052-2059.

(3) Wambier CG, et al. Androgenetic alopecia present in the majority of hospitalized COVID-19 patients – The “Gabrin Sign”. J. Am. Acad. Dermatol., published may 21, 2020.

(4) Ghazizadeh Z, et al. Androgen regulates SARS-CoV-2 receptor levels and is associated with severe COVID-19 symptoms in men. bioRxiv, submitted on may 12, 2020.

(5) Montopoli M, et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Annals Oncol., published on may 6, 2020.

(6) Wadman M. Sex hormones signal why virus hits men harder. Science 2020; 368 : 1038-1039.

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