Sex Hormones in SARS-CoV-2 Susceptibility: Key Players or Confounders?

December 2022 in “ Nature Reviews Endocrinology ”

Nicola Lott, Caroline E. Gebhard, Susan Bengs, Ahmed Haider, Gabriela M. Kuster, Vera Regitz‐Zagrosek, Cathérine Gebhard

androgens oestrogens progesterone oestradiol testosterone estrogen estradiol

TLDR Sex hormones' effects on COVID-19 are unclear and more research is needed to understand their potential as treatment.

The review article "Sex hormones in SARS-CoV-2 susceptibility: key players or confounders?" explores the role of sex hormones, including androgens, oestrogens, and progesterone, in the regulation of virus entry receptors and the progression of COVID-19. The article indicates that there is no definitive evidence that sex-specific expression of virus entry receptors contributes to the observed sex disparities in COVID-19 outcomes. The effects of these hormones on the course of COVID-19 have yielded inconsistent results, and current data do not support the use of oestradiol or deprivation of androgens in COVID-19 treatment. The authors conclude that more research is needed to clarify the potential therapeutic value of these hormones in COVID-19.

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research Final Results of a Randomized, Placebo-Controlled, Two-Arm, Parallel Clinical Trial of Proxalutamide for Hospitalized COVID-19 Patients: A Multiregional, Joint Analysis of the Proxa-Rescue AndroCoV Trial

19 citations , December 2021 in “Cureus”

Proxalutamide improved recovery, lowered death rates, and reduced hospital stay for COVID-19 patients.

research Immunoreactivity of the SARS-CoV-2 Entry Proteins ACE-2 and TMPRSS-2 in Murine Models of Hormonal Manipulation, Aging, and Cardiac Injury

5 citations , December 2021 in “Scientific Reports”

Age affects how certain proteins involved in COVID-19 infection are expressed in mice, but sex hormones and heart injury do not.

research Impact of Androgen Deprivation Therapy on Mortality of Prostate Cancer Patients with COVID-19: A Propensity Score-Based Analysis

9 citations , November 2021 in “Infectious Agents and Cancer”

Androgen deprivation therapy doesn't lower the risk of death from COVID-19 in prostate cancer patients.

research Proxalutamide Improves Inflammatory, Immunologic, and Thrombogenic Markers in Mild-to-Moderate COVID-19 Males and Females: An Exploratory Analysis of a Randomized, Double-Blinded, Placebo-Controlled Trial Early Antiandrogen Therapy with Proxalutamide

5 citations , July 2021 in “medRxiv (Cold Spring Harbor Laboratory)”

Proxalutamide improved blood markers related to inflammation, immune response, and clotting in COVID-19 patients, potentially reducing hospitalizations.

research Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial

42 citations , July 2021 in “Frontiers in Medicine”

Proxalutamide significantly lowered hospital admissions for male COVID-19 patients compared to a placebo.

research Proxalutamide Reduces Hospitalization Rate in Mild-to-Moderate COVID-19 Female Patients: A Randomized Double-Blinded Placebo-Controlled Trial

5 citations , July 2021 in “medRxiv (Cold Spring Harbor Laboratory)”

Proxalutamide significantly lowered hospitalization rates in women with mild-to-moderate COVID-19.

research The Antiandrogen Enzalutamide Downregulates TMPRSS2 and Reduces Cellular Entry of SARS-CoV-2 in Human Lung Cells

50 citations , July 2021 in “Nature Communications”

The drug enzalutamide may reduce the ability of the virus causing COVID-19 to enter lung cells.

research The Double-Edged Sword of Testosterone’s Role in the COVID-19 Pandemic

29 citations , March 2021 in “Frontiers in Endocrinology”

Testosterone may influence COVID-19 severity and outcomes.

research Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial

41 citations , February 2021 in “Cureus”

Proxalutamide helps COVID-19 patients get rid of the virus faster and recover quicker.

research Early Antiandrogen Therapy With Dutasteride Reduces Viral Shedding, Inflammatory Responses, and Time-to-Remission in Males With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Interventional Trial

41 citations , February 2021 in “Cureus”

Dutasteride treatment in men with mild to moderate COVID-19 reduced viral shedding, inflammation, and recovery time without serious side effects.

research Testosterone Target Therapy: Focus on Immune Response, Controversies, and Clinical Implications in Patients with COVID-19 Infection

21 citations , January 2021 in “Therapeutic Advances in Endocrinology and Metabolism”

Testosterone may have a dual role in COVID-19, potentially worsening outcomes in men, and testosterone therapy could help some patients, but more research is needed.

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

139 citations , December 2020 in “Cell Stem Cell”

Male hormones affect COVID-19 severity and certain drugs targeting these hormones could help reduce the risk.

research Androgenetic Alopecia Present in the Majority of Patients Hospitalized with COVID-19: The 'Gabrin Sign'

119 citations , August 2020 in “Journal of The American Academy of Dermatology”

Most COVID-19 patients in hospitals have androgenetic alopecia, more in men, suggesting a link between androgen sensitivity and severe COVID-19 symptoms.

research 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

134 citations , July 2020 in “Journal of Cosmetic Dermatology”

Male pattern hair loss could hint at androgens affecting COVID-19 severity.