Sex Hormones and Hormone Therapy during COVID-19 Pandemic: Implications for Patients with Cancer

Abstract

The novel coronavirus disease 2019 (COVID-19) shows a wide spectrum of clinical presentations, severity, and fatality rates. The reason older patients and males show increased risk of severe disease and death remains uncertain. Sex hormones, such as estradiol, progesterone, and testosterone, might be implicated in the age-dependent and sex-specific severity of COVID-19. High testosterone levels could upregulate transmembrane serine protease 2 (TMPRSS2), facilitating the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells via angiotensin-converting enzyme 2 (ACE2). Data from patients with prostate cancer treated with androgen-deprivation therapy seem to confirm this hypothesis. Clinical studies on TMPRSS2 inhibitors, such as camostat, nafamostat, and bromhexine, are ongoing. Antiandrogens, such as bicalutamide and enzalutamide, are also under investigation. Conversely, other studies suggest that the immune modulating properties of androgens could protect from the unfavorable cytokine storm, and that low testosterone levels might be associated with a worse prognosis in patients with COVID-19. Some evidence also supports the notion that estrogens and progesterone might exert a protective effect on females, through direct antiviral activity or immune-mediated mechanisms, thus explaining the higher COVID-19 severity in post-menopausal women. In this perspective, we discuss the available evidence on sex hormones and hormone therapy in patients infected with SARS-CoV-2, and we highlight the possible implications for cancer patients, who can receive hormonal therapies during their treatment plans.

Differences in mortality of cancer patients with COVID-19 in a Brazilian cancer center

“…In the present study, differences in mortality due to COVID-19 between the sexes were not identified, as reported in other studies [9 , 11 , 19] . Sex hormones are believed to be important in the immune response; estrogen is known to act as an immune booster, but androgens need to be further investigated for their interaction with COVID-19 [38 , 39] .…”

Exploration of sex-specific and age-dependent COVID-19 fatality rate in Bangladesh population

“…Evidences suggest that male gender and aged persons are key factors connected to higher danger of severe events and death from COVID-19[ 36 , 37 ]. The enhancing mortality rate from COVID-19 for males (2.4 times) than for females is overall comparable to that originated in other coronaviruses during the past two years, including the SARS-CoV and the MERS-CoV[ 37 - 39 ].…”

An overview of Betacoronaviruses-associated severe respiratory syndromes, focusing on sex-type-specific immune responses

“…Variations in weight, body mass index, and hormonal changes (during puberty, menstrual cycles, and menopause) can be factors that lead to sexual differences in adverse reactions to antiviral drugs [81] Hence, an appropriate treatment for patients is the use of hormone therapy. Sex hormones such as testosterone, progesterone, and estradiol can be considered in these therapeutic processes ( Table 1 ) [80] , [82] , [83] .…”