Androgen Hormone Levels Linked to Increased Risk and Severity of COVID-19

Between hope and despair
The lower rate of severe COVID-19 infection in women and children may be because of their lower androgen receptor expression.

Androgen hormone levels may increase the risk and severity of coronavirus 19 (COVID-19) infection in patients, according to research in a letter to the editor published in Dermatologic Therapy.

One of the most confounding aspects of the global coronavirus (SARS-CoV-2/COVID-19) pandemic has been why symptoms are so severe for some patients yet milder for many others. The study researchers hypothesized that the same male hormones that cause hair loss, androgens, are linked to the vulnerability of patients to SARS-CoV-2.

The researchers cite several pieces of evidence for the possible implication of androgens, specifically the androgen receptor (AR), in COVID‐19 infection severity. They noted that children seem extremely resistant as the rate of severe cases in pre‐pubescent children was exceptionally low at 0.6%. This may be because AR expression is low prior to pubertal maturation. Similarly, the lower rate of severe COVID‐19 infection in women may be credited to lower AR expression. Epidemiologic studies have reported a disproportionately low rate of severe cases in women compared with men, 42% and 58%, respectively. Also, molecular mechanistic evidence demonstrates that SARS‐CoV‐2 cell entry depends on priming of a viral spike surface protein by transmembrane protease serine 2 (TMPRSS2) present in the host. It is well established that TMPRSS2 expression is associated with an increase in AR expression. Therefore, the authors noted, it would be useful and informative to investigate the epidemiology of COVID‐19 patients who are predisposed to either lower or higher AR expression, such as, men with androgenetic alopecia, benign prostatic hyperplasia, or women with polycystic ovary syndrome. AR activation can be reduced by several classes of drugs including androgen synthesis inhibitors, AR antagonists, and antigonadotropins. The analysis of AR expression in ethnic groups may also serve to predict COVID‐19 ethnic mortality differences. 

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In summary, excess activation of androgens, essentially, hormones that regulate male characteristics, is intrinsically linked to the vulnerability of patients to COVID-19. These findings provide the rationale for further studies to elucidate the role, if any, of the AR on the severity of COVID‐19 infection.

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Goren A, McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Dhurat R, et al. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy (published online April 1, 2020). Dermatol Ther.doi: 10.1111/dth.13365