Hypogonadism and Mortality in Aged Hospitalized Male Patients: A 5-Year Prospective Observational Study

Iglesias, Pedro; Prado, Florentino; Ridruejo, Elena; Muñoz, Angélica; Macías, M. C.; Guerrero, María Teresa; Tajada, P.; García‐Arévalo, Carmen; Díez, Julia

doi:10.1055/s-0035-1564119

Cited by 11 publications

(6 citation statements)

References 14 publications

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“…T reduction seems to be independent of LH levels, indicating a dysfunction of the hypothalamic‐pituitary‐gonadal axis 78,79 . Fifty percent of men over 65 years old hospitalized for acute illness, such as respiratory tract infection, were found to be hypogonadal and low T levels were related with in‐hospital mortality 80,81 . ARDS, a complication of severe sepsis, and sepsis‐related morbidity and mortality were shown to be more prevalent in men than in women, were linked to high IL‐6 levels and occurred in a manner independent of age and disease 82 .…”

Section: Methodsmentioning

confidence: 99%

“…78,79 Fifty percent of men over 65 years old hospitalized for acute illness, such as respiratory tract infection, were found to be hypogonadal and low T levels were related with in-hospital mortality. 80,81 ARDS, a complication of severe sepsis, and sepsis-related morbidity and mortality were shown to be more prevalent in men than in women, were linked to high IL-6 levels and occurred in a manner independent of age and disease. 82 Low T levels were reported in male patients with severe sepsis and respiratory failure 83,84 suggesting that hypogonadism may create a permissive environment for severe outcomes in men.…”

Section: Ards Aging and Tmentioning

confidence: 99%

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Why does COVID‐19 kill more elderly men than women? Is there a role for testosterone?

Papadopoulos

Samplaski

2020

Andrology

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Background Recent epidemiological data indicate that there may be a gender predisposition to COVID‐19, with men predisposed to being most severely affected, and older men accounting for most deaths. Objectives Provide a review of the research literature, propose hypotheses and therapies based on the potential link between testosterone (T) and COVID‐19 induced mortality in elderly men. Materials and Methods A search of publications in academic electronic databases, and government and public health organization web sites on T, aging, inflammation, severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS‐CoV‐2) infection, and COVID‐19 disease state and outcomes was performed. Results The link between T, the immune system and male aging is well‐established, as is the progressive decline in T levels with aging. In women, T levels drop before menopause and variably increase with advanced age. Elevated IL‐6 is a characteristic biomarker of patients infected with COVID‐19 and has been linked to the development of the acute respiratory distress syndrome (ARDS). Thus far, half of the admitted COVID‐19 patients developed ARDS, half of these patients died, and elderly male patients have been more likely to develop ARDS and die. Low T is associated with ARDS. These data suggest that low T levels may exacerbate the severity of COVID‐19 infection in elderly men. It may also stand to reason that normal T levels may offer some protection against COVID‐19. SARS‐CoV‐2 binds to the angiotensin‐converting enzyme 2, present in high levels in the testis. Conclusion At present, it is not known whether low T levels in aging hypogonadal males create a permissive environment for severe responses to COVID‐19 infection or if the virus inhibits androgen formation. Given the preponderance of COVID‐19 related mortality in elderly males, additional testing for gonadal function and treatment with T may be merited.

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Section: Methodsmentioning

confidence: 99%

Section: Ards Aging and Tmentioning

confidence: 99%

Why does COVID‐19 kill more elderly men than women? Is there a role for testosterone?

Papadopoulos

Samplaski

2020

Andrology

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“…A third possibility is that low testosterone levels may be a marker of severe illness in hospitalized patients in general irrespective of underlying diseases. In one prospective study of 150 elderly men (mean age 86 years, range 68-99) admitted to the hospital with various diseases, hypogonadism was a strong independent predictor of in-hospital and long-term (up to 5 years) total mortality (adjusted hazard ratio 3.35, 95% CI 1.53-7.23; P=0.0002) and cardiovascular mortality (adjusted hazard ratio 2.14, 95% CI 1.18-3.86; P <0.05) [18].…”

Section: Male Studiesmentioning

confidence: 97%

Clinical significance of sex hormones in COVID-19

Mikhail¹,

Wali²

2020

Front Womens Health

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Background: Sex hormones may play a role in excess male lethality from coronavirus disease-2019 .Objective: To clarify the implications of testosterone and estradiol in the course and prognosis of COVID-19 in men and women.Methods: PUBMED search until September 7, 2020. Search terms included: COVID-19, sex hormones, testosterone, estrogen, androgen-deprivation, mortality. Due to lack of randomized trials, we included retrospective trials, case series, and pre-print studies. Results:In men hospitalized with COVID-19, circulating testosterone levels are generally decreased and inversely correlated with pro-inflammatory cytokines. Low testosterone levels may be associated with severe COVID-19 and high mortality. Yet, androgen deprivation therapy as treatment of prostate cancer may be associated with decreased hospitalization and favourable clinical outcomes in COVID-19. In women hospitalized with COVID-19, high testosterone levels directly correlate with pro-inflammatory cytokines. In premenopausal women, estradiol serum levels above 70 pg/ml were associated with decreased risk of having severe COVID-19. Pre-menopausal women using combined oral contraceptives may have decreased risk of COVID-19. Conversely, post-menopausal women taking hormone replacement therapy may have increased risk. In general, pregnant women with COVID-19 seem to have similar disease course as non-pregnant women, but studies were lacking adequate control subjects.Conclusions: Preliminary data suggest that androgen deprivation therapy and estrogen could be beneficial as potential treatment of COVID-19 in men and women, respectively. However, the possible therapeutic role of these agents will be only confirmed by randomized trials.

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“… 41 Of note, hypogonadism is reported to be a strong independent predictor of all-cause mortality (HR 3.35; 95% CI 1.55–7.23; p = 0.002). 42 Multiple studies indicate that a low T hypogonadal state leads to worse outcomes in patients with acute respiratory illnesses. 41–43 Half of the males older than 65 years of age admitted to the hospital for acute illnesses such as a respiratory tract infection have been reported to have low T. 43 , 44 …”

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

confidence: 99%

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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Hypogonadism and Mortality in Aged Hospitalized Male Patients: A 5-Year Prospective Observational Study

Abstract: Hypogonadism discovered during hospitalization is associated with in-hospital and long-term mortality in elderly male patients and predicts both all-cause mortality and CV mortality in this population.

Cited by 11 publications

References 14 publications

Why does COVID‐19 kill more elderly men than women? Is there a role for testosterone?

Why does COVID‐19 kill more elderly men than women? Is there a role for testosterone?

Clinical significance of sex hormones in COVID-19

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

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