Effects of Early Testosterone Gel Administration on Physical Performance in the Critically Ill
Status:
Not yet recruiting
Trial end date:
2027-04-01
Target enrollment:
Participant gender:
Summary
Critically ill patients experience major insults that lead to increased protein catabolism.
Hypermetabolism occurs early and rapidly during the first week of critical illness to provide
amino acids for the production of energy via gluconeogenesis, and also for the synthesis of
acute phase proteins and repair of tissue damage. During acute phase, neuroendocrine and
inflammatory responses promote protein breakdown and amino acid release. Under stress
conditions, protein synthesis cannot match the increased rate of muscle proteolysis because
of a state of anabolism resistance, which limits uptake of amino acids into muscles.
Hypermetabolism results in a significant loss of lean body mass with an impact on weaning
from the ventilator and muscle recovery. Functional disability can be long term sometimes
with no full return to normal.
In critically ill patients, severe and persistent testosterone deficiency is very common and
is observed early after Intensive Care Unit (ICU) admission. This acquired hypogonadism
promotes the persistent loss of skeletal muscle protein and is related to poor outcome.
Administration of testosterone induces skeletal muscle fiber hypertrophy and decreases
protein breakdown in healthy young men. It has been repeatedly shown that testosterone
treatment enhances muscle mass and strength in hypogonadal men and women and can improve
physical performance. Testosterone administration in burned patients reduces protein
breakdown and increases protein synthesis efficiency. Oxandrolone, a synthetic testosterone
analogue, reduces body mass and nitrogen loss and accelerates healing in burned patients.
Trials in critically ill unburned patients failed to demonstrate any effect on clinical
outcome but the studies were underpowered to detect a difference.
Transdermal gel testosterone is the preferred route of administration for achieving steady
serum testosterone concentrations as compared to oral and intramuscular formulations.
Intramuscular injection induces strong fluctuations of testosterone plasma concentrations and
can cause haematoma in patients with coagulation disorders, a common condition in ICUs.
Several studies have raised the concern that testosterone administration could increase the
risk of cardiovascular disease events. However, in a recent meta-analysis, no significant
effects on cardiovascular risk were observed with either injected or transdermal testosterone
supplementation in men, and the French National Agency for Medicines (ANSM) recently reported
that drugs containing testosterone were not associated with an increased risk of
cardiovascular events.