Worldwide epidemiology studies have found higher number of cases of SARS-CoV-2 in men. Moreover, male gender carries a worse prognosis, especially in younger adults. Two opposing theories about androgens have been proposed to explain the gender gap.
Testosterone as a promoter of COVID-19 infection:
- Transmembrane protease serine 2 (TMPRSS2) is a cellular co-receptor required for SARS-CoV-2 viral spread. TPRSS2’s transcription is driven by androgens and is expressed in the lungs.
- Male patients have higher angiotensin-converting enzyme-2 (ACE2) receptor levels, which could be mediated by testosterone.
- A preliminary observational study has found that 71% of males hospitalized for COVID-19 had clinically significant androgenetic alopecia, reflecting androgen receptor polymorphisms.
- The effect of testosterone on the immune system is unclear in the context of COVID-19. Testosterone inhibits pro-inflammatory cytokines, which could contribute to an immunosuppressed state leading to poorer outcomes. On the other side, hypogonadism is associated with an inflammatory state that could augment to the cytokine storm.
- In mice, estrogens seemed to have a protective effect in SARS-CoV’s outcomes.
- Prepubescent boys have extremely low prevalence of severe cases.
COVID-19 infection could be associated with low testosterone:
- Since ACE2 receptors (implicated in the pathogenesis of COVID-19) are present in testis, impaired testosterone production by the virus has been hypothesized as a cause of poorer outcomes in men.
- Delayed viral clearance and long-term effects on male reproductive function will be further assessed by the PROTEGGIMI study.
- Comorbidities such as obesity and diabetes, known to predict unfavorable outcomes in COVID-19, are also associated with lower testosterone.
The role of testosterone is still poorly understood in SARS-CoV-2 but further investigation of anti-androgens as a targeted therapy is warranted.
These data come from analysis of 5 publications. The first study observed 41 Caucasian males admitted to 2 Spanish tertiary hospitals with bilateral SARS-CoV-2 pneumonia. A dermatologist diagnosed the presence or the absence as well as the severity of androgenetic alopecia. The second article is a commentary about the sex-specific SARS-CoV-2 mortality. The third study is a review about the roles of testosterone in the context of the pandemic. The fourth article is an opinion letter exposing the rationale of the ongoing PROTEGGIMI study, which is a prospective multidimensional andrological translational research project about the impact of COVID-19 in males. The fifth article is an editorial about androgens and COVID-19.
- Goren, A., Vano-Galvan, S., Wambier, C. G., et al (Apr 14th 2020). A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain – A potential clue to the role of androgens in COVID-19 severity. Journal of Cosmetic Dermatology. https://doi.org/10.1111/jocd.13443
- La Vignera, S., Cannarella, R., Condorelli, R. A., et al (Apr 22 2020). Sex-Specific SARS-CoV-2 Mortality: Among Hormone-Modulated ACE2 Expression, Risk of Venous Thromboembolism and Hypovitaminosis D. International Journal of Molecular Sciences, 21(8). https://doi.org/10.3390/ijms21082948
- Pozzilli, P., & Lenzi, A. (Apr 27th 2020). Testosterone, a key hormone in the context of COVID-19 pandemic. Metabolism: Clinical and Experimental, 108, 154252. https://doi.org/10.1016/j.metabol.2020.154252
- Salonia, A., Corona, G., Giwercman, A., et al (May 5th 2020). SARS-CoV-2, Testosterone and frailty in males (PROTEGGIMI): A multidimensional research project. Andrology. https://doi.org/10.1111/andr.12811
- Sharifi, N., & Ryan, C. J. (Apr 17th 2020). Androgen hazards with COVID-19. Endocrine-Related Cancer, 27(6), E1-e3. https://doi.org/10.1530/erc-20-0133