Why does COVID-19 kill more elderly men than women? Is there a role for testosterone?

Abstract

Background: Recent epidemiological data indicate that there may be a gender predisposition to COVID-19, with men predisposed to being most severely affected, and older men accounting for most deaths.

Objectives: Provide a review of the research literature, propose hypotheses, and therapies based on the potential link between testosterone (T) and COVID-19 induced mortality in elderly men.

Materials and methods: A search of publications in academic electronic databases, and government and public health organization web sites on T, aging, inflammation, severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) infection, and COVID-19 disease state and outcomes was performed.

Results: The link between T, the immune system, and male aging is well-established, as is the progressive decline in T levels with aging. In women, T levels drop before menopause and variably increase with advanced age. Elevated IL-6 is a characteristic biomarker of patients infected with COVID-19 and has been linked to the development of the acute respiratory distress syndrome (ARDS). Thus far, half of the admitted COVID-19 patients developed ARDS, half of these patients died, and elderly male patients have been more likely to develop ARDS and die. Low T is associated with ARDS. These data suggest that low T levels may exacerbate the severity of COVID-19 infection in elderly men. It may also stand to reason that normal T levels may offer some protection against COVID-19. SARS-CoV-2 binds to the angiotensin-converting enzyme 2, present in high levels in the testis.

Conclusion: At present, it is not known whether low T levels in aging hypogonadal males create a permissive environment for severe responses to COVID-19 infection or if the virus inhibits androgen formation. Given the preponderance of COVID-19 related mortality in elderly males, additional testing for gonadal function and treatment with T may be merited.

Keywords: SARS-CoV-2; acute respiratory distress syndrome; aging; inflammation; testis; testosterone replacement therapy.