Testosterone and Covid‐19: An update

Abstract

There is overwhelming evidence to suggest that male gender is at a higher risk of developing more severe Covid-19 disease and thus having poorer clinical outcomes.However, the relationship between testosterone (T) and Covid-19 remains unclear with both protective and deleterious effects on different aspects of the disease suggested. Here, we review the current epidemiological and biological evidence on the role of testosterone in the process of SARS-CoV-2 infection and in mediating Covid-19 severity, its potential to serve as a biomarker for risk stratification and discuss the possibility of T supplementation as a treatment or preventative therapy for Covid-19. K E Y W O R D Sprostate, sexual medicine, testosterone | INTRODUCTIONSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also known as Corona Virus Disease 2019 or Covid-19) exhibits differences in morbidity and mortality between sexes, with a male bias towards severe disease. [1][2][3][4] A meta-analysis of over 3 million cases globally (accumulated from 92 data sets that contained information on the total number of infections by sex, and the severity of disease as measured by admission to intensive therapy unit (ITU) and death) has shown that whilst there are no sex-based differences in the proportion of Covid-19 cases, male patients have higher odds for requiring Intensive treatment (odds ratio OR = 2.84) and death (OR = 1.39) compared to females, despite this analysis not controlling for lifestyle, comorbidities, testing method and case type (hospital vs. community). 5 This sex difference is apparent across different countries when comparing Covid-19 fatality (Figure 1). 6 Epidemiological data from the previous coronavirus epidemic of SARS-CoV (2002) also show preponderancy of poorer outcomes forThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment

“…As to other mechanisms that contribute to COVID-19 severity in men, circulating testosterone is reportedly lower in COVID-19 patients, which may parallel androgen status in older men that are at greater risk for SAR-CoV-2 disease. 5,23,[27][28][29]32,94,107,[134][135][136][137][138][139] Lower testosterone also associates with other pathologies that present greater risk of COVD-19 severity including cardiovascular disease, diabetes, and obesity in men, which may contribute to the overall severity in male COVID-19 patients. [140][141][142][143][144][145][146] Both ACE2 and TMPRSS2 are expressed in Leydig cells of the testes, the principal site for androgen synthesis, and SARS-CoV-2 infection could potentially impair the synthetic capacity to produce testosterone.…”

Men, testosterone and Covid‐19

“…Disparities in Covid-19 infections and deaths between sexes can be attributed to social, behavioral and comorbidity factors. 6 Higher percentage of smokers among men might influence gender differences in Covid-19 severity as nicotine increases the expression of TMPRSS2, potentially explaining more severe Covid-19 outcomes in smokers. 27 Women are believed to be generally more cautious, and more likely to adhere to treatments.…”

“…In general, estrogens have immune‐enhancing effects, making women generally immune‐privileged. Disparities in Covid‐19 infections and deaths between sexes can be attributed to social, behavioral and comorbidity factors 6 . Higher percentage of smokers among men might influence gender differences in Covid‐19 severity as nicotine increases the expression of TMPRSS2, potentially explaining more severe Covid‐19 outcomes in smokers 27 .…”

“…Low serum testosterone levels in men are associated with severe Covid‐19 outcomes, possibly due to lack of immunomodulatory benefits of testosterone 4 . On the other hand, androgens modulate angiotensin‐converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), 5 so concerns have been raised that higher testosterone levels could increase the occurrence of Covid‐19 manifestations and negatively affect Covid‐19 outcome by the increased expression of TMPRSS2, which is crucial for the cleavage and activation of SARS‐CoV‐2 spike protein 6,7 …”

Relationship between emotion and health: a two-way street

“…Some studies claim that low testosterone may serve as a protective factor against Coronavirus infection for men in certain situations. However, a growing body of research states otherwise, presenting evidence that low testosterone levels are associated with increased severity and mortality from Covid-19 in male patients (YASSIN, Aksam et al,2022;LANSER, Lukas et al,2021).…”