Androgen-deprivation therapy and SARS-Cov-2 infection: the potential double-face role of testosterone

Abstract

We read with great interest the recent articles published in Therapeutic Advances in Endocrinology and Metabolism on the role of androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) and SARS-Cov-2 infection. 1

Modeling the Contribution of Male Testosterone Levels to the Duration of Positive COVID Testing among Hospitalized Male COVID-19 Patients

“…In the early phase, the immunosuppressive action of testosterone could explain males' greater susceptibility to infection when compared to women in all age groups. When the infection has settled, in elderly males who frequently develop a severe course, lower testosterone levels related to age could result in a lower immunosuppressive effect on the cytokine storm [8]. Given the prior evidence on the role of testosterone in the clinical course of the COVID-19 disease, in this study, we hypothesized and confirmed that testosterone could also be important in the duration of viral positivity.…”

“…Previous experiences showed that low testosterone levels were independently associated with worse overall men's health and clinical COVID-19 phenotype, need for intensive care unit (ICU) treatment, and mortality [10,11,[30][31][32][33][34][35]. Moreover, an inverse correlation was found between testosterone levels and IL-6 levels [11], suggesting that testosterone could play an important role in both early and late stages of disease [8]. On the basis of these results, it has been hypothesized that testosterone may play a double-edged role in the pathogenesis of the COVID-19 disease.…”

“…Studies indicate male sex and older age to be significant risk factors for severe COVID-19 infection regardless of the geographical area and suggest that the hormonal constitution could play a role both in the susceptibility and severity of the clinical course [ 6 ]. In this context, there is evidence that testosterone can affect all cells involved in the immune response to both bacterial and viral infections, and the testosterone effect on the immune response could explain the greater susceptibility of men to infections including COVID-19 [ 7 , 8 , 9 ]. Indeed, previous clinical experiences in patients with COVID-19 infection showed that testosterone levels were significantly lower in patients with a more severe clinical course [ 10 , 11 ] suggesting a role of testosterone in the immune response to COVID-19 [ 12 , 13 , 14 ].…”

Protective Role of a TMPRSS2 Variant on Severe COVID-19 Outcome in Young Males and Elderly Women

“…Sexual hormones can be used for therapeutic purposes [ 34 , 35 ]. Quite interestingly, and in line with our results, Seeland et al reported that: “their retrospective study of hormone therapy in female COVID-19 patients shows that the fatality risk for women > 50 years receiving estradiol therapy (user group) is reduced by more than 50%; the OR was 0.33, 95% CI (0.18, 0.62) and the hazard ratio (HR) was 0.29, 95% CI (0.11,0.76).…”

Testosterone in COVID-19: Friend or Foe?

“…In this context, there is conflicting data on the role of testosterone, its measurement, supplementation, and possible augmentation in COVID-19. While there has been some evidence to suggest a possible positive effect of androgendeprivation therapy (ADT) in prostate cancer patients infected by SARS-CoV2, this has recently been called into question [2]. Conversely, there is mounting evidence that low testosterone levels might actually worsen overall outcome-hypogonadism appears to be a risk factor for a more severe clinical course in COVID-19 [3].…”