COVID-19 Outcomes in Men with Low Testosterone
NEW STUDY REVEALS STRONG CORRELATION BETWEEN LOW TESTOSTERONE AND COVID-19 MALE PATIENT CRITICAL OUTCOMES.
The majority of male patients with COVID-19 present low testosterone levels on admission to Intensive Care in Hamburg, Germany: a retrospective cohort study.
ABSTRACT
“We here show that critically ill male COVID-19 patients suffer from severe testosterone and dihydrotestosterone deficiencies. Both androgens are required to mount antiviral immune responses to combat infection in males.
Low levels of the hormone can’t control the immune response in men, but the study found that among female patients, higher levels were linked to a higher inflammatory response.
“Men with normal testosterone levels do not present a cytokine storm and thus are more likely to survive,” Professor Gülsah Gabriel from the Leibniz Institute for Experimental Virology in Hamburg, who was involved in the research, told the Daily Mail.
“Thus, low testosterone levels in men seem to be a risk factor for severe and even fatal disease outcome in men upon infection with so-called ‘cytokine inducing’ respiratory viruses,” he said.”
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide and pose a major public health burden. There is increasing evidence that men are more likely to die from SARS-CoV-2 infection than women. However, underlying factors that mediate the observed sex bias in coronavirus disease 2019 (COVID-19) remain unknown.
METHODS
In this retrospective cohort, we included COVID-19 patients who were admitted to an Intensive Care Unit at the University Hospital Hamburg-Eppendorf, Germany. We obtained demographic data of all patients who were discharged or had died by 29th April 2020. We systematically analyzed sex hormones as well as cytokine and chemokine responses in male and female patients with laboratory-confirmed SARS-CoV-2 infections upon hospital admission. We used uni- and multivariable linear regression methods to identify potential risk factors for disease severity in males and females.
FINDINGS
All enrolled patients (n=45; n=35 males and n=10 females) presented comorbidities with hypertension being the most common (45.7% in males; 40% in females), followed by cancer (35% in males; 40% in females), obesity (34.3% in males and 30% in females), type II diabetes (25.7% in males and 20% in females) and chronic heart diseases (8.6% in males and 0% in females). We detected that the vast majority of male COVID-19 patients present low testosterone (68.6%) and low dihydrotestosterone (48.6%) levels. In contrast, most female COVID-19 patients have elevated testosterone levels (60%) without alterations in dihydrotestosterone levels. Both, female and male COVID-19 patients may present elevated estradiol levels (45.7% in males and 40% in females). Disease severity defined by SOFA score correlates with elevated cytokine responses (e.g. IL-6) in males and IL-2 in females. In male COVID-19 patients, testosterone levels negatively correlate with inflammatory IL-2 and IFN-γ, whereas estradiol levels positively correlate with the inflammatory cytokine IL-6. Vice versa, in female COVID-19 patients, testosterone levels positively correlate with inflammatory cytokines (e.g. IL-6).
INTERPRETATION
We here show that critically ill male COVID-19 patients suffer from severe testosterone and dihydrotestosterone deficiencies. Both androgens are required to mount antiviral immune responses to combat infection in males.
All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. medRxiv preprint doi: https://doi.org/10.1101/2020.05.07.20073817.this version posted May 11, 2020. The copyright holder for this preprint 3 Funding. This study was funded by the German Federal Ministry of Health (to G.G.).
Maria Schroeder (MD)1,*, BerfinTuku2(MSc)*, Dominik Jarczak (MD)1, Axel Nierhaus (MD)1, Tian Bai (MSc)2, Henning Jacobsen (MSc)2, Martin Zickler (MSc)2, Zacharias Müller (BSc)2, Stephanie Stanelle-Bertram (PhD)2, Andreas Meinhardt (PhD)4, Jens Aberle (MD)5, Stefan Kluge (MD)1§, Gülsah Gabriel (PhD)2,3§
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
- Department for Viral Zoonoses-One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany;
- Institute for Virology, University for Veterinary Medicine Hannover, Hannover, Germany;
- Institute of Anatomy and Cell Biology, Justus-Liebig
- University of Giessen, Germany;
- Department of Endocrinology, Diabetology, Obesity and Lipids,
- University Medical Center Hamburg-Eppendorf, Hamburg,
