Testosterone Target Therapy: Focus on Immune Response, Controversies, and Clinical Implications in Patients with COVID-19 Infection

The document from January 1, 2021, explored the complex role of testosterone in the immune response to COVID-19, particularly in elderly male patients. It suggested that while low testosterone levels might protect against initial infection by enhancing immune function and inhibiting TMPRSS2, they could also worsen the clinical course in advanced infection by intensifying the cytokine storm. The paper presented clinical data indicating that lower testosterone levels were significantly associated with poor outcomes in male COVID-19 patients, such as higher risks of ARDS, invasive oxygenation, and ICU admission. For instance, ARDS patients had notably lower testosterone levels, and higher serum testosterone was linked to a lower risk of invasive oxygenation. Additionally, a study of 221 male patients showed a negative correlation between lower baseline serum total testosterone levels and ICU admission, with a significant decrease in testosterone levels from pre-COVID-19 to during infection. The document highlighted the potential of ADT in COVID-19 treatment but also cautioned its use in critically ill patients due to possible exacerbation of cytokine syndrome. It concluded that testosterone might have a dual role in COVID-19 infection and that testosterone replacement therapy could be beneficial for hypogonadal patients with COVID-19, though clinical trials are necessary to confirm this.