Sex hormones in SARS-CoV-2 susceptibility: key players or confounders?

Article Urology & Nephrology

A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data

Karin Welen et al.

Summary: The study suggests that antiandrogens may not have therapeutic or preventive effects in COVID-19 patients, and androgen inhibition may lead to longer hospitalizations and higher risk of death.

EUROPEAN UROLOGY (2022)

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Article Public, Environmental & Occupational Health

Sex disparities in COVID-19 outcomes in the United States: Quantifying and contextualizing variation

Ann Caroline Danielsen et al.

Summary: This paper presents the first longitudinal study of sex disparities in COVID-19 cases and mortalities across U.S. states. The results demonstrate considerable variation in the sex disparity in COVID-19 cases and mortalities over time and between states. When present, the sex disparity is modest and likely influenced by context-sensitive variables such as health behaviors, preexisting health status, occupation, race/ethnicity, and other markers of social experience.

SOCIAL SCIENCE & MEDICINE (2022)

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Article Psychology, Clinical

TransCOVID: Does Gender-Affirming Hormone Therapy Play a Role in Contracting COVID-19?

Emre Durcan et al.

Summary: This study investigated the relationship between Gender-Affirming Hormone Therapy (GAHT) and COVID-19 in individuals with Gender Dysphoria (GD). It found that individuals with female-to-male (FtM) GD who received testosterone therapy are at higher risk of contracting COVID-19 and had longer therapy duration. Clinicians following up on GAHT should be more cautious about the increased risk of COVID-19 in FtM GD patients receiving testosterone treatment.

JOURNAL OF SEX & MARITAL THERAPY (2022)

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Article Medicine, General & Internal

Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19 The HITCH Randomized Clinical Trial

Nicholas G. Nickols et al.

Summary: This randomized clinical trial aimed to determine if androgen suppression could improve clinical outcomes in men hospitalized with COVID-19. However, degarelix did not result in amelioration of COVID-19 severity.

JAMA NETWORK OPEN (2022)

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Letter Critical Care Medicine

Sex versus gender-related characteristics: which predicts clinical outcomes of acute COVID-19?

Caroline E. Gebhard et al.

INTENSIVE CARE MEDICINE (2022)

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Article Multidisciplinary Sciences

Development of an aerosol intervention for COVID-19 disease: Tolerability of soluble ACE2 (APN01) administered via nebulizer

Robert H. Shoemaker et al.

PLoS One (2022)

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Article Medicine, General & Internal

A phase 2 randomized, double-blinded, placebo-controlled, multicenter trial evaluating the efficacy and safety of raloxifene for patients with mild to moderate COVID-19

Emanuele Nicastri et al.

Summary: Raloxifene showed evidence of effect in reducing viral shedding in early mild to moderate COVID-19 patients, but did not significantly affect the need for supplemental oxygen or mechanical ventilation. The drug was well tolerated at both doses.

ECLINICALMEDICINE (2022)

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Article Primary Health Care

Mortality in COVID-19 among women on hormone replacement therapy: a retrospective cohort study

Hajira Dambha-Miller et al.

Summary: The study found an association between hormone replacement therapy (HRT) and combined oral contraceptive pill (COCP) use with all-cause mortality in COVID-19 patients. HRT use was associated with a reduced all-cause mortality rate in COVID-19 patients.

FAMILY PRACTICE (2022)

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Article Andrology

Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients

Giulia Rastrelli et al.

Summary: In male patients with SARS-CoV-2 pneumonia, lower testosterone levels are associated with poor prognosis and mortality, indicating a potential role for testosterone in determining clinical outcomes in COVID-19 patients.

ANDROLOGY (2021)

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Article Immunology

Potential Influence of Menstrual Status and Sex Hormones on Female Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Cross-sectional Multicenter Study in Wuhan, China

Ting Ding et al.

Summary: Recent studies have shown that female COVID-19 patients have lower morbidity, severe case rate, and mortality compared to males. Nonmenopausal female patients had milder severity and better outcome, while menopausal patients had longer hospitalization times. Anti-Mullerian hormone (AMH) and estradiol (E2) were negatively correlated with COVID-19 severity, with E2 regulating cytokines related to immunity and inflammation.

CLINICAL INFECTIOUS DISEASES (2021)

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Review Andrology

Worse progression of COVID-19 in men: Is testosterone a key factor?

Vito A. Giagulli et al.

Summary: Testosterone levels may affect the progression of COVID-19 in men, with low levels predisposing to endothelial dysfunction, thrombosis, and defective immune response. This can ultimately lead to impaired viral clearance and systemic inflammation, especially in critically ill individuals. Further studies are needed to confirm these findings and identify appropriate therapeutic strategies.

ANDROLOGY (2021)

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Article Virology

Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients

Ling Ma et al.

Summary: The study found that although the COVID-19 virus was not detected in the semen of male patients, there were abnormal levels of sex hormones in the COVID-19 group, with a negative correlation with white blood cell counts and C-reactive protein levels.

JOURNAL OF MEDICAL VIROLOGY (2021)

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Article Urology & Nephrology

COVID-19 Infection in Men on Testosterone Replacement Therapy

Amarnath Rambhatla et al.

Summary: The study suggests that testosterone replacement therapy (TRT) is not associated with worse clinical outcomes in men diagnosed with COVID-19.

JOURNAL OF SEXUAL MEDICINE (2021)

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Article Urology & Nephrology

Androgen Deprivation Therapy in Men with Prostate Cancer Does Not Affect Risk of Infection with SARS-CoV-2

Eric A. Klein et al.

Summary: Investigating the relationship between androgen deprivation therapy and infection rate and disease severity in prostate cancer patients, the study found that androgen deprivation therapy does not appear to be protective against SARS-CoV-2 infection.

JOURNAL OF UROLOGY (2021)

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Article Infectious Diseases

Expression and co-expression analyses of TMPRSS2, a key element in COVID-19

Francesco Piva et al.

Summary: The research analyzed TMPRSS2 expression data in the lungs, investigating factors influencing its expression and their impact on susceptibility to infection and COVID-19 prognosis. Polymorphisms affecting TMPRSS2 expression were reported, along with suggestions of ethnic groups more prone to COVID-19, and a gender-specific co-expression between TMPRSS2 and other related genes.

EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES (2021)

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Article Neurosciences

ACE-2-interacting Domain of SARS-CoV-2 (AIDS) Peptide Suppresses Inflammation to Reduce Fever and Protect Lungs and Heart in Mice: Implications for COVID-19 Therapy

Ramesh K. Paidi et al.

Summary: Research has shown that designing an AIDS peptide to interfere with the binding of SARS-CoV-2 to ACE2 can inhibit viral activity in lung cells and have a protective effect on COVID-19 symptoms.

JOURNAL OF NEUROIMMUNE PHARMACOLOGY (2021)

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Article Multidisciplinary Sciences

Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2

Yuanyuan Qiao et al.

Summary: Research has shown that androgens regulate the expression of ACE2, TMPRSS2, and AR in lung epithelial cells, affecting the risk of COVID-19 infection in males over 70 years old. The use of AR or BET antagonists can inhibit SARS-CoV-2 infection, providing support for further investigation into transcriptional inhibition for the treatment or prevention of COVID-19.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Respiratory System

ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma

Peter A. B. Wark et al.

Summary: This study found that ACE2 gene expression is associated with age and gender, and is lower in asthma patients. The expression of some genes related to SARS-CoV-2 cell entry in asthma patients is also different from other populations.

RESPIROLOGY (2021)

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Article Biochemistry & Molecular Biology

Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry

Jorge Alberto Aguilar-Pineda et al.

Summary: Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females, with mechanisms such as sex hormones and ACE2 receptor glycosylation potentially playing a role. Estrogens can disrupt interactions between ACE2 and SARS-CoV-2, reducing viral entry into cells. This sheds light on a potential mechanism by which female sex hormones may protect against severe infection and influence future COVID-19 therapies.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Critical Care Medicine

Progesterone in Addition to Standard of Care vs Standard of Care Alone in the Treatment of Men Hospitalized With Moderate to Severe COVID-19 A Randomized, Controlled Pilot Trial

Sara Ghandehari et al.

Summary: By administering subcutaneous progesterone to hypoxemic men hospitalized with moderate to severe COVID-19, it was found that progesterone at a dose of 100 mg, twice daily in addition to standard of care, can safely improve clinical outcomes and reduce the number of days on supplemental oxygen and length of hospital stay.

CHEST (2021)

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Letter Multidisciplinary Sciences

A finding of sex similarities rather than differences in COVID-19 outcomes

Heather Shattuck-Heidorn et al.

NATURE (2021)

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Letter Dermatology

Androgens and women: COVID-19 outcomes in women with acne vulgaris, polycystic ovarian syndrome, and hirsutism

Katerina Yale et al.

INTERNATIONAL JOURNAL OF DERMATOLOGY (2021)

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Article Multidisciplinary Sciences

A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells

Matthew Mahoney et al.

Summary: A novel TMPRSS2 inhibitor, MM3122, has shown exceptional potency in inhibiting viral entry and reducing cytopathic effects, with promising potential as a treatment for COVID-19. This compound, discovered using SBDD, exhibits unique structural features and excellent pharmacokinetic properties, making it a strong candidate for in vivo efficacy evaluation.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Biochemistry & Molecular Biology

Attributes and predictors of long COVID

Carole H. Sudre et al.

Summary: Reports on long-lasting COVID-19 symptoms, known as 'long COVID', are increasing. Analysis of data from over 4,000 COVID-19 cases revealed that long COVID is more common in older individuals, those with higher body mass index, and females. Experiencing more than five symptoms in the first week of illness was associated with long COVID. A simple model showed promise in distinguishing between short and long COVID cases early in the disease.

NATURE MEDICINE (2021)

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Article Biochemistry & Molecular Biology

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Christoph Muus et al.

Summary: Our study reveals that cell-type-specific expression patterns of ACE2, TMPRSS2, and CTSL are associated with the pathogenesis of COVID-19. Factors such as age, sex, and smoking status are linked to the expression of viral entry genes in respiratory cell populations, suggesting potential therapeutic targets for intervention. The integrated analysis of single-cell and single-nucleus transcriptomics studies highlights coexpression patterns of SARS-CoV-2 viral entry genes across different human tissues.

NATURE MEDICINE (2021)

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Article Multidisciplinary Sciences

Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide

Fei Li et al.

Summary: Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cells, however, such antiviral efficacy was lacking in human lung cells and organoids.

NATURE COMMUNICATIONS (2021)

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Article Medicine, General & Internal

Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

Markus Hoffmann et al.

Summary: The study demonstrates that Camostat mesylate and its metabolite GBPA can block the spread of SARS-CoV-2 in human lung tissue, and the related protease inhibitor Nafamostat mesylate exhibits enhanced antiviral activity.

EBIOMEDICINE (2021)

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Article Multidisciplinary Sciences

Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury

Susan Bengs et al.

Summary: An analysis on mouse models found that sex hormones, age, and cardiovascular disease can impact the expression of ACE-2 and TMPRSS-2, but they do not alter the expression of these proteins in the respiratory tract. This suggests that the observed sex differences in ACE-2 and TMPRSS-2 protein expression in mice may not explain the higher disease burden of COVID-19 among men.

SCIENTIFIC REPORTS (2021)

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Article Multidisciplinary Sciences

Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19

Qu Deng et al.

Summary: The study suggests a potential role of androgen in SARS-CoV-2 infection by regulating ACE2 and TMPRSS2 transcription. Camostat, a TMPRSS2 inhibitor, blocks the cleavage of SARS-CoV-2 Spike protein, providing evidence of TMPRSS2's direct role in viral fusion to host cells. Androgen-deprivation, anti-androgens, or camostat attenuate SARS-CoV-2 cellular entry, highlighting the importance of TMPRSS2 inhibitors and androgen-deprivation therapy in preventing COVID-19 progression.

ISCIENCE (2021)

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Article Medicine, General & Internal

Acute estradiol and progesterone therapy in hospitalised adults to reduce COVID-19 severity: a randomised control trial

Dragana Lovre et al.

Summary: This study aims to evaluate the efficacy of short-term E2 and P4 therapy in mitigating disease severity in hospitalized COVID-19 patients. The randomized, double-blind, placebo-controlled trial will assess patient improvement on the WHO scale over 28 days as the primary outcome.

BMJ OPEN (2021)

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News Item Medicine, General & Internal

Covid-19: Trial of experimental covid cure is among worst medical ethics violations in Brazil's history, says regulator

Luke Taylor

BMJ-BRITISH MEDICAL JOURNAL (2021)

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Review Physiology

The effect of estrogen in coronavirus disease 2019

Qing Ma et al.

Summary: Men have a higher risk of developing and experiencing worse outcomes from COVID-19 compared to women, with gender differences in immune system playing a critical role in shaping the immune response and pathogenesis of the disease.

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY (2021)

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Letter Oncology

Clinical outcome of SARS-CoV-2 infection in breast and ovarian cancer patients who underwent antiestrogenic therapy

M. Montopoli et al.

ANNALS OF ONCOLOGY (2021)

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Article Oncology

Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: a propensity score-based analysis

Mateus Bringel Oliveira Duarte et al.

Summary: The active use of ADT was not associated with a reduced risk of death in patients with COVID-19. There was a significant imbalance in the propensity score of patients in active and non-active ADT, with important reductions in the differences after adjustments.

INFECTIOUS AGENTS AND CANCER (2021)

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Article Medicine, General & Internal

The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis

Shu Qin Wei et al.

Summary: Infection with COVID-19 during pregnancy may lead to an increased risk of preeclampsia, preterm birth, and other adverse pregnancy outcomes. Severe cases of COVID-19 are particularly associated with higher risks of complications such as preeclampsia, preterm birth, gestational diabetes, and low birth weight.

CANADIAN MEDICAL ASSOCIATION JOURNAL (2021)

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Article Endocrinology & Metabolism

Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers

Maria Teresa Pagano et al.

Summary: This study identified sex-specific biomarkers for predicting the severity and progression of ARDS in COVID-19 patients. Some biomarkers were predictive for both males and females, while others were only predictive for one sex. Sex-specific biomarkers can help differentiate between patients who can be safely discharged and those who need respiratory monitoring.

BIOLOGY OF SEX DIFFERENCES (2021)

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Article Multidisciplinary Sciences

Sex differences in the case-fatality rates for COVID-19-A comparison of the age-related differences and consistency over seven countries

Manfred S. Green et al.

Summary: Research found that in seven countries, males consistently had higher case-fatality rates at all ages compared to females, with age group and country contributing to the variability in case-fatality rate ratios.

PLOS ONE (2021)

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Article Multidisciplinary Sciences

Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress

Atila Duque Rossi et al.

Summary: ACE2 and TMPRSS2 levels are positively correlated with age, which is strongly associated with respiratory distress. Increased ACE2 levels have a protective effect against this outcome, while the TMPRSS2/ACE2 ratio is associated with risk. In modeling COVID-19 severity, the TMPRSS2/ACE2 ratio outperforms ACE2.

SCIENTIFIC REPORTS (2021)

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Review Endocrinology & Metabolism

The Double Edge Sword of Testosterone's Role in the COVID-19 Pandemic

Johnny S. Younis et al.

Summary: COVID-19 is a complex disease involving various health and disease mechanisms. Sex hormones like estrogen and testosterone play significant roles in its pathogenesis and development, while factors such as age, gender, and ethnic background may also impact disease progression.

FRONTIERS IN ENDOCRINOLOGY (2021)

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Article Infectious Diseases

Role of testosterone in SARS-CoV-2 infection: A key pathogenic factor and a biomarker for severe pneumonia

Marta Camici et al.

Summary: The study found that male patients with severe COVID-19 had significantly lower testosterone levels compared to those with mild COVID-19. Low testosterone levels were correlated with hyperinflammatory syndrome and longer hospital stays.

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES (2021)

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Article Immunology

Intersubject Variation in ACE2 Protein Expression in Human Airway Epithelia and Its Relationship to Severe Acute Respiratory Syndrome Coronavirus 2

Kun Li et al.

Summary: The study found that variations in ACE2 protein abundance had minimal effects on viral replication and interferon response in airway epithelia infected with SARS-CoV-2, suggesting that additional host factors beyond viral receptor expression may play a role in determining COVID-19 lung disease outcomes.

JOURNAL OF INFECTIOUS DISEASES (2021)

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Article Medicine, Research & Experimental

Age and gender differences in ACE2 and TMPRSS2 expressions in oral epithelial cells

Jinfeng Peng et al.

Summary: ACE2 and TMPRSS2 were found to be co-expressed in the epithelial cells of oral tissues, with higher expression levels in the relatively elderly group. Male oral epithelial cells exhibited higher level of TMPRSS2.

JOURNAL OF TRANSLATIONAL MEDICINE (2021)

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Article Medicine, General & Internal

Sex steroid hormones are associated with mortality in COVID-19 patients Level of sex hormones in severe COVID-19

Ingeborg E. van Zeggeren et al.

Summary: In patients with severe COVID-19, lower levels of total and free testosterone were associated with mortality in men, while lower SHBG levels were associated with mortality in both men and women. Estradiol levels did not show a significant difference between deceased and surviving patients.

MEDICINE (2021)

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Article Cell Biology

Renin-angiotensin system and inflammation update

Elena Cantero-Navarro et al.

Summary: The classical view of the renin-angiotensin system highlights its role in regulating sodium balance and blood pressure, but it is now recognized that RAS also plays a crucial role in organ damage and inflammation. Angiotensin II and its receptors can promote inflammatory responses, while other RAS components may have anti-inflammatory properties. Recent research has revealed new insights into the complex interactions between RAS and inflammation, shedding light on potential therapeutic targets for kidney and heart diseases.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2021)

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Article Multidisciplinary Sciences

Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study

Ricardo Costeira et al.

Summary: The study found that menopausal women had higher rates of predicted COVID-19, while users of combined oral contraceptive pills had lower rates. Hormone replacement therapy usage did not consistently show associations with COVID-19. However, caution should be taken when interpreting the results due to certain limitations in the data collection.

PLOS ONE (2021)

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Article Medicine, Research & Experimental

Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial

Nicholas G. Nickols et al.

Summary: This randomized phase 2 clinical trial aims to investigate the efficacy of using degarelix, an LHRH antagonist, in male Veterans hospitalized due to COVID-19. The study will assess the potential of degarelix in suppressing TMPRSS2 expression in lung epithelium and improving clinical outcomes.

TRIALS (2021)

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Article Virology

SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients

Lucia Gutierrez-Chamorro et al.

Summary: The study found that soluble functional ACE2 levels increase upon SARS-CoV-2 infection in swabs and plasma of infected patients, but rapidly decrease during the course of infection alongside ACE2 gene expression. Similarly, SARS-CoV-2 infection induced the expression of inflammatory cytokines, which correlated positively with viral load.

VIRUSES-BASEL (2021)

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Article Microbiology

The TMPRSS2 Inhibitor Nafamostat Reduces SARS-CoV-2 Pulmonary Infection in Mouse Models of COVID-19

Kun Li et al.

Summary: The serine protease inhibitors camostat and nafamostat have shown potential in limiting SARS-CoV-2 infection in respiratory tract, with nafamostat exhibiting greater potency. Preclinical evidence supports the efficacy of nafamostat in treating and/or preventing COVID-19 in mice models sensitized to SARS-CoV-2 infection by introducing human ACE2.

MBIO (2021)

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Article Multidisciplinary Sciences

The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells

D. A. Leach et al.

Summary: Antiandrogen treatment reduces TMPRSS2 expression in the lung, decreasing SARS-CoV-2 viral entry and infection, supporting the potential of antiandrogens as a therapeutic approach for COVID-19.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes

Mehdi Baratchian et al.

Summary: Sex discordance in COVID-19 outcomes may not be related to TMPRSS2 but may be associated with modest changes in ACE2.

SCIENTIFIC REPORTS (2021)

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Article Medicine, General & Internal

被撤回的出版物: Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial (Publication with Expression of Concern. See vol. 8, 2022) (Retracted article. See vol. 9, 2022)

John McCoy et al.

Summary: The use of proxalutamide as an androgen receptor antagonist in men with COVID-19 has shown to significantly reduce the hospitalization rate, with a 91% reduction compared to usual care.

FRONTIERS IN MEDICINE (2021)

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Article Medicine, General & Internal

Nafamostat in hospitalized patients with moderate to severe COVID-19 pneumonia: a randomised Phase II clinical trial

Sergey Zhuravel et al.

Summary: The study found no significant difference in the time to clinical improvement between the nafamostat and standard-of-care groups for COVID-19 pneumonia patients overall, but nafamostat showed a significantly shorter time to clinical improvement in a small subgroup of high-risk patients requiring oxygen treatment.

ECLINICALMEDICINE (2021)

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Article Immunology

High estradiol and low testosterone levels are associated with critical illness in male but not in female COVID-19 patients: a retrospective cohort study

Maria Schroeder et al.

Summary: The study found significantly elevated estradiol levels and reduced testosterone levels in critically ill male COVID-19 patients compared to control cohorts. No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends towards elevated estradiol levels were observed. Furthermore, high estradiol levels in male COVID-19 patients were associated with a higher likelihood of receiving ECMO treatment.

EMERGING MICROBES & INFECTIONS (2021)

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Review Public, Environmental & Occupational Health

Sensitive to Infection but Strong in Defense-Female Sex and the Power of Oestradiol in the COVID-19 Pandemic

Louise Newson et al.

Summary: SARS-CoV2 infections are higher in premenopausal women, but the fatality rate of COVID-19 is higher in men. Estrogen may explain the higher infection risk in women, while immune-related genes on the X chromosome may confer an advantage to females. Lifestyle factors may also contribute to gender differences.

FRONTIERS IN GLOBAL WOMENS HEALTH (2021)

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Letter Biochemistry & Molecular Biology

TMPRSS2 activity may mediate sex differences in COVID-19 severity

Derick Okwan-Duodu et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Article Physiology

17β-estradiol reduces SARS-CoV-2 infection in vitro

Robertha Mariana Rodrigues Lemes et al.

Summary: COVID-19 originated from Wuhan, China, and has unprecedentedly affected the public health system, society, and economy. Estrogen has been shown to potentially protect cells against SARS-CoV-2 infection by reducing viral load and decreasing TMPRSS2 levels, offering new possibilities for further research on 17β-estradiol in human cell lines infected by SARS-CoV-2.

PHYSIOLOGICAL REPORTS (2021)

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Article Biochemistry & Molecular Biology

Obesity alters Ace2 and Tmprss2 expression in lung, trachea, and esophagus in a sex-dependent manner: Implications for COVID-19

Dylan C. Sarver et al.

Summary: Obesity may alter the expression of ACE2 and TMPRSS2 in the lower respiratory tract and esophagus, with differences in regulation of these genes by diet and sex.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2021)

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Article Respiratory System

Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma

Nazanin Zounemat Kermani et al.

Summary: Levels of ACE2 and FURIN in severe asthma patients may be associated with neutrophilic inflammation, indicating a potential for greater morbidity and mortality from SARS-CoV-2 infection.

RESPIRATORY RESEARCH (2021)

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Review Immunology

SARS-CoV-2 Infection of Airway Epithelial Cells

Gwanghui Ryu et al.

Summary: COVID-19 caused by SARS-CoV-2 is a highly contagious virus that primarily spreads through airway epithelial cells, with high viral loads in the upper respiratory tract. Host cellular receptors in these cells have been identified through single-cell RNA sequencing or immunostaining. Infected airway epithelial cells produce chemokines and cytokines to recruit inflammatory cells, while IFN signaling is crucial for host defense against the virus.

IMMUNE NETWORK (2021)

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Article Medicine, General & Internal

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang et al.

LANCET (2020)

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Article Multidisciplinary Sciences

Sexual-dimorphism in human immune system aging

Eladio J. Marquez et al.

NATURE COMMUNICATIONS (2020)

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Article Physiology

Estrogen regulates the expression of SARS-CoV-2 receptor ACE2 in differentiated airway epithelial cells

Kimberly E. Stelzig et al.

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY (2020)

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Article Oncology

Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N=4532)

M. Montopoli et al.

ANNALS OF ONCOLOGY (2020)

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Letter Microbiology

Nafamostat Mesylate Blocks Activation of SARS-CoV-2: New Treatment Option for COVID-19

Markus Hoffmann et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2020)

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Article Biochemistry & Molecular Biology

SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract

Yixuan J. Hou et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Alexandra C. Walls et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann et al.

CELL (2020)

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Editorial Material Cardiac & Cardiovascular Systems

Angiotensin Converting Enzyme 2 A Double-Edged Sword

Kaiming Wang et al.

CIRCULATION (2020)

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Article Immunology

Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19)

Kaijin Xu et al.

CLINICAL INFECTIOUS DISEASES (2020)

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Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract

Joan C. Smith et al.

DEVELOPMENTAL CELL (2020)

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Letter Urology & Nephrology

Expression of ACE2, the SARS-CoV-2 Receptor, and TMPRSS2 in Prostate Epithelial Cells

Hanbing Song et al.

EUROPEAN UROLOGY (2020)

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Letter Medicine, General & Internal

Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults

Supinda Bunyavanich et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

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Article Virology

Systematic analysis of ACE2 and TMPRSS2 expression in salivary glands reveals underlying transmission mechanism caused by SARS-CoV-2

Jukun Song et al.

JOURNAL OF MEDICAL VIROLOGY (2020)

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Letter Dermatology

A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity

Andy Goren et al.

JOURNAL OF COSMETIC DERMATOLOGY (2020)

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Letter Dermatology

Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The Gabrin sign

Carlos Gustavo Wambier et al.

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY (2020)

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Article Medicine, General & Internal

Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study

Shufa Zheng et al.

BMJ-BRITISH MEDICAL JOURNAL (2020)

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Article Microbiology

Sex-specific clinical characteristics and prognosis of coronavirus disease-19 infection in Wuhan, China: A retrospective study of 168 severe patients

Yifan Meng et al.

PLoS Pathogens (2020)

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Article Medicine, General & Internal

The gendered dimensions of COVID-19

The Lancet

LANCET (2020)

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Review Endocrinology & Metabolism

Impact of sex and gender on COVID-19 outcomes in Europe

Catherine Gebhard et al.

BIOLOGY OF SEX DIFFERENCES (2020)

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Article Infectious Diseases

Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues

Meng-Yuan Li et al.

INFECTIOUS DISEASES OF POVERTY (2020)

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Article Medicine, Research & Experimental

Airways Expression of SARS-CoV-2 Receptor, ACE2, and TMPRSS2 Is Lower in Children Than Adults and Increases with Smoking and COPD

Narjes Saheb Sharif-Askari et al.

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT (2020)

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Letter Medicine, General & Internal

Clinical Characteristics of Pregnant Women with Covid-19 in Wuhan, China

Lian Chen et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Cell Biology

Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation

Jiawei Chen et al.

AGING CELL (2020)

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Article Cell Biology

ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy

Rosanna Asselta et al.

AGING-US (2020)

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Letter Cardiac & Cardiovascular Systems

Genetic Associations With Plasma Angiotensin Converting Enzyme 2 Concentration Potential Relevance to COVID-19 Risk

Christopher P. Nelson et al.

CIRCULATION (2020)

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Letter Oncology

Does androgen deprivation therapy protect against severe complications from COVID-19?

V. G. Patel et al.

ANNALS OF ONCOLOGY (2020)

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Article Cardiac & Cardiovascular Systems

Single-cell analysis of SARS-CoV-2 receptor ACE2 and spike protein priming expression of proteases in the human heart

Hanning Liu et al.

CARDIOVASCULAR RESEARCH (2020)

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Article Infectious Diseases

Coronavirus disease 2019 in pregnancy

Xu Qiancheng et al.

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES (2020)

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Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status - United States, January 22-June 7, 2020

Sascha Ellington et al.

MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT (2020)

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Article Immunology

ACE2 Expression Is Increased in the Lungs of Patients With Comorbidities Associated With Severe COVID-19

Bruna G. G. Pinto et al.

JOURNAL OF INFECTIOUS DISEASES (2020)

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Article Physiology

Sex steroids skew ACE2 expression in human airway: a contributing factor to sex differences in COVID-19?

Rama Satyanarayana Raju Kalidhindi et al.

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY (2020)

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Article Infectious Diseases

A minimal common outcome measure set for COVID-19 clinical research

J. C. Marshall et al.

LANCET INFECTIOUS DISEASES (2020)

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Article Medicine, General & Internal

Targeting TMPRSS2 in SARS-CoV-2 Infection

Linda B. Baughn et al.

MAYO CLINIC PROCEEDINGS (2020)

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Editorial Material Endocrinology & Metabolism

Commentary: Testosterone, a key hormone in the context of COVID-19 pandemic

Paolo Pozzilli et al.

METABOLISM-CLINICAL AND EXPERIMENTAL (2020)

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Article Medicine, General & Internal

The influence of sex and gender domains on COVID-19 cases and mortality

Christina P. Tadiri et al.

CANADIAN MEDICAL ASSOCIATION JOURNAL (2020)

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The protein expression profile of ACE2 in human tissues

Feria Hikmet et al.

MOLECULAR SYSTEMS BIOLOGY (2020)

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Longitudinal analyses reveal immunological misfiring in severe COVID-19

Carolina Lucas et al.

NATURE (2020)

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Article Medicine, General & Internal

Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study

Marian Knight et al.

BMJ-BRITISH MEDICAL JOURNAL (2020)

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Article Multidisciplinary Sciences

Sex differences in immune responses that underlie COVID-19 disease outcomes

Takehiro Takahashi et al.

NATURE (2020)

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Article Multidisciplinary Sciences

Gender differences in COVID-19 attitudes and behavior: Panel evidence from eight countries

Vincenzo Galasso et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Medicine, General & Internal

Evidence for treatment with estradiol for women with SARS-CoV-2 infection

Ute Seeland et al.

BMC MEDICINE (2020)

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Article Cell & Tissue Engineering

Androgen Signaling Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men

Ryan M. Samuel et al.

CELL STEM CELL (2020)

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Article Multidisciplinary Sciences

Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

Harlan Barker et al.

PLOS ONE (2020)

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Article Multidisciplinary Sciences

ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs

Ivan T. Lee et al.

NATURE COMMUNICATIONS (2020)

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Letter Critical Care Medicine

Screening for low testosterone is needed for early identification and treatment of men at high risk of mortality from Covid-19

Simon Peter Rowland et al.

CRITICAL CARE (2020)

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Letter Critical Care Medicine

Age and sex differences in soluble ACE2 may give insights for COVID-19

Per Sward et al.

CRITICAL CARE (2020)

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Review Endocrinology & Metabolism

Sex differences in the metabolic effects of the renin-angiotensin system

Melissa C. White et al.

BIOLOGY OF SEX DIFFERENCES (2019)

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Review Immunology

Glucocorticoids, Sex Hormones, and immunity

Oxana Bereshchenko et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Review Immunology

Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection

Sapana Kadel et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Review Behavioral Sciences

Sex differences in immune responses: Hormonal effects, antagonistic selection, and evolutionary consequences

Jacob Roved et al.

HORMONES AND BEHAVIOR (2017)

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Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection

Rudragouda Channappanavar et al.

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Preliminary analysis of the association between methylation of the ACE2 promoter and essential hypertension

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Landscape of X chromosome inactivation across human tissues

Taru Tukiainen et al.

NATURE (2017)

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Sex differences in the aging pattern of renin-angiotensin system serum peptidases

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BIOLOGY OF SEX DIFFERENCES (2017)

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Review Immunology

Sex differences in immune responses

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Suppressive effects of androgens on the immune system

Abhishek Trigunaite et al.

CELLULAR IMMUNOLOGY (2015)

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Article Oncology

The Androgen-Regulated Protease TMPRSS2 Activates a Proteolytic Cascade Involving Components of the Tumor Microenvironment and Promotes Prostate Cancer Metastasis

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CANCER DISCOVERY (2014)

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Review Endocrinology & Metabolism

Update on the angiotensin converting enzyme 2-angiotensin (1-7)-Mas receptor axis: fetal programing, sex differences, and intracellular pathways

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Emerging markers in cardiovascular disease: Where does angiotensin-converting enzyme 2 fit in?

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Michael E. Baker

STEROIDS (2013)

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Selective suppression of endothelial cytokine production by progesterone receptor

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VASCULAR PHARMACOLOGY (2013)

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Angiotensin Converting Enzyme 2 Contributes to Sex Differences in the Development of Obesity Hypertension in C57BL/6 Mice

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Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications

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Genes that escape from X inactivation

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Macrophages Regulators of Sex Differences in Asthma?

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Regulation of multiple renin-angiotensin system genes by Sry

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Androgen receptor and androgen-dependent gene expression in lung

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MOLECULAR AND CELLULAR ENDOCRINOLOGY (2010)

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Article Endocrinology & Metabolism

Sex differences in renal angiotensin converting enzyme 2 (ACE2) activity are 17β-oestradiol-dependent and sex chromosome-independent

Jun Liu et al.

Biology of Sex Differences (2010)

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Article Physiology

Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia

Hong Peng Jia et al.

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY (2009)

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Article Immunology

The Influence of Age and Sex on the Cell Counts of Peripheral Blood Leukocyte Subpopulations in Chinese Rhesus Macaques

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CELLULAR & MOLECULAR IMMUNOLOGY (2009)

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Review Endocrinology & Metabolism

What does the four core genotypes mouse model tell us about sex differences in the brain and other tissues?

Arthur P. Arnold et al.

FRONTIERS IN NEUROENDOCRINOLOGY (2009)

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Article Genetics & Heredity

Stronger inflammatory/cytotoxic T-cell response in women identified by microarray analysis

A. Hewagama et al.

GENES AND IMMUNITY (2009)

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Article Geriatrics & Gerontology

The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20-100 years of age

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BIOGERONTOLOGY (2008)

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Article Biotechnology & Applied Microbiology

Personalized vaccines: the emerging field of vaccinomics

Gregory A. Poland et al.

EXPERT OPINION ON BIOLOGICAL THERAPY (2008)

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Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer

Sunita R. Setlur et al.

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2008)

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Review Immunology

Sexual dimorphism of humoral immunity with human vaccines

Ian Francis Cook

VACCINE (2008)

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Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer

SA Tomlins et al.

SCIENCE (2005)

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Article Multidisciplinary Sciences

Angiotensin-converting enzyme 2 protects from severe acute lung failure

Y Imai et al.

NATURE (2005)

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Article Oncology

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

I Hamming et al.

JOURNAL OF PATHOLOGY (2004)

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Article Immunology

Predominant type 1 CMV-specific memory T-helper response in humans: Evidence for gender differences in cytokine secretion

MC Villacres et al.

HUMAN IMMUNOLOGY (2004)

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Preliminary study on sex-related inflammatory reactions in mice infected with Schistosoma mansoni

J Boissier et al.

PARASITOLOGY RESEARCH (2003)

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Review Immunology

Evidence for the presence of immune dysfunction in chronic fatigue syndrome

BH Natelson et al.

CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY (2002)

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Review Cardiac & Cardiovascular Systems

Renin angiotensin system and gender differences in the cardiovascular system

M Fischer et al.

CARDIOVASCULAR RESEARCH (2002)

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Sex hormones in SARS-CoV-2 susceptibility: key players or confounders?

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