What’s Testosterone Got to Do with It? A Critical Assessment of the Contribution of Testosterone to Gender Disparities in COVID-19 Infections and Deaths

Traish, Abdulmaged M.; Morgentaler, Abraham

doi:10.1089/andro.2020.0012

Cited by 5 publications

(10 citation statements)

References 72 publications

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“…Multiple studies have demonstrated that low T is predictive of worse outcomes in COVID-19 patients, leading to an increased likelihood of ICU transfer or death. 8 , 26–31 A similar trend was observed in the previously discussed study using mice infected with SARS-CoV-1, which reported that many of the male mice had low T, a finding correlating with significant male predominance of post-infection fatalities in the study. 10 Interestingly, the hypogonadal state noted in patients with SARS-CoV-2 infection has been reported to endure long after recovery from the virus.…”

Section: Factors Accounting For Trend Of Male Predominant Severe Covi...supporting

confidence: 81%

“…Pro-inflammatory cytokines, such as interleukin (IL)-6, play a prominent role in the progression of COVID-19 and have been implicated in inducing cytokine storm related to severe respiratory illness. 8 As T has been shown to suppress the expression of such pro-inflammatory cytokines, a T deficiency could, therefore, increase patient vulnerability to severe COVID-19 outcomes by mitigating the effectiveness of one of the body's natural protective mechanisms against cytokine storm. 8 , 19 This hypothesis is supported by several animal and human subject studies that report that hypogonadism is associated with increased pro-inflammatory cytokines and that treatment with T reduces IL-1-beta, IL-6, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α).…”

Section: Factors Accounting For Trend Of Male Predominant Severe Covi...mentioning

confidence: 99%

“… 8 As T has been shown to suppress the expression of such pro-inflammatory cytokines, a T deficiency could, therefore, increase patient vulnerability to severe COVID-19 outcomes by mitigating the effectiveness of one of the body's natural protective mechanisms against cytokine storm. 8 , 19 This hypothesis is supported by several animal and human subject studies that report that hypogonadism is associated with increased pro-inflammatory cytokines and that treatment with T reduces IL-1-beta, IL-6, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). 20–24 However, the magnitude and clinical impact of T's anti-inflammatory properties remains debatable.…”

Section: Factors Accounting For Trend Of Male Predominant Severe Covi...mentioning

confidence: 99%

“… 5 , 7 Of note, developed countries such as Canada, Portugal, Finland, and Vietnam as well as 23.5% of states within the United States reported a female predominant death toll secondary to COVID-19. 8 A deeper understanding of the nature of this trend may provide important clues about the pathogenesis of SARS-CoV-2 as well as potential therapeutic drug targets and other effective treatments after infection.…”

Section: Introductionmentioning

confidence: 99%

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Examining Male Predominance of Severe COVID-19 Outcomes: A Systematic Review

Twitchell

Christensen

Hackett

et al. 2022

Androgens: Clinical Research and Therapeutics

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Although not universal, many epidemiological data sources signal that a higher proportion of males than females with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections have adverse outcomes, such as intensive care unit (ICU) admission and death. Though likely multifactorial, the various hypotheses that have been proposed as underlying factors behind this trend are related to greater smoking prevalence among males, testosterone (T) deficiency causing an inflammatory storm, androgen-driven pathogenesis of SARS-CoV-2, a protective effect of estrogen in females, and inborn errors of cytokine immunity. This review aims at examining the evidence and at assessing the likelihood that the factors being investigated are contributory to the reported trend of male predominance of severe COVID-19 cases. Sources were obtained using the PubMed database and were selected based on their relevance to one of the primary hypotheses attempting to explain the strong male sex bias of severe SARS-CoV-2 infections. Emphasis was placed on meta-analyses and population-based studies. Sources are current through February 22, 2022. A severe COVID-19 case or outcome is defined in this review as a progression of the SARS-CoV-2 virus that results in either admission to an ICU for management of symptoms and clinical stabilization or which leads to death. Although the trend of male predominance of severe COVID-19 cases is likely multifactorial, the hypothesis of T deficiency causing an inflammatory storm has support from many studies with limited conflicting evidence. An inborn error in cytokine immunity is also well supported, but it needs more studies to add support to the hypothesis. The immunologic protective effect of estrogen is supported by multiple studies, but it also has conflicting evidence. It appears less likely that the trend is caused solely by an increased prevalence of smoking among males or an androgen-driven pathogenesis, based on the extent of conflicting evidence.

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Section: Factors Accounting For Trend Of Male Predominant Severe Covi...supporting

confidence: 81%

Section: Factors Accounting For Trend Of Male Predominant Severe Covi...mentioning

confidence: 99%

Section: Factors Accounting For Trend Of Male Predominant Severe Covi...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Examining Male Predominance of Severe COVID-19 Outcomes: A Systematic Review

Twitchell

Christensen

Hackett

et al. 2022

Androgens: Clinical Research and Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Certainly, the fact that there is a gender-related distinction in COVID-19 infection, with male individuals experiencing higher morbidity and mortality rates, may in part be attributable to hormonal (androgenic) differences [ 32 , 33 ]. According to emerging but triangulating viewpoints [ 34 ▪ , 35 ], this is in part perhaps because of the manner in which COVID-19 viral spread is articulated through the mechanism of androgen receptor activation and the transcription of the transmembrane protease, serine 2 ( TMPRSS2 ) gene.…”

Section: Androgen Use and Potential Problems With Coronavirus Disease 2019mentioning

confidence: 99%

Public health concerns and increased risk of severe COVID-19 disease through androgen use

Crisp

Sims

2021

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of review Given governmental policy responses to the COVID-19 pandemic include various foci on establishing preventive measures to increase the health and constitution of populations (i.e. through renewed efforts to tackle obesity), the use of androgens in a recreational manner requires attention because of existing medical evidence related to their role in immunosuppression. Recent findings Whilst a broad body of work exists that outlines the mechanisms that underpin COVID-19 and public health responses, as well as the use of androgens in both recreational and medicinal contexts, the recent nature of the disease has left an area requiring greater investigation and clarification. There is emerging literature that highlights the potential complications that existing androgens use may bring to those infected with COVID-19, as well as the start of empirical evidence detailing this. Summary In this article, we outline the latest viewpoints and literature related to how the use of androgens may contribute to less robust immunoresponses.

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