We have previously shown that there is a steep decline in serum levels of the adrenal steroid Dehydroepiandrosterone (DHEA) after trauma, including hip fracture in older adults, which is associated with loss of muscle and reduced immune function. This is a pilot study supplementing major trauma victims and hip-fracture patients with DHEA to determine how much DHEA needs to be given to restore levels in the blood. We are also assessing effects on immune cell function (neutrophil function).
In a previous study of 100 major trauma patients with an Injury Severity Score of 16 or higher, we aimed to understand the immune and endocrine response to injury to identify factors associated with poor outcomes. The outcomes included loss of muscle, sepsis, infections, multi-organ failure and death. We measured a range of biomarkers every day for one month after injury, then monthly to 6 months with a final sampling at 1-year post-injury. Measurements included bicep muscle thickness, serum pro- and anti-inflammatory cytokines, immune cell function (neutrophil bactericidal function) and steroid hormone levels. One of the findings was that patients lost significant amounts of muscle in the first weeks after injury and that this was associated with very low levels of the androgenic steroid hormone DHEA. This hormone is not only important for muscle maintenance, but it also enhances neutrophil function and the low levels may increase susceptibility to infection.
In this study, we are testing the hypothesis that restoring serum levels of DHEA soon after trauma will reduce muscle loss and improve immune function, specifically neutrophil function. The study involved using three doses of DHEA (50, 100 and 200 mg) given orally or sublingual, the latter to see if the first-pass metabolism affects serum levels of DHEA supplements. Patients involved are young victims of major trauma, or older hip fracture patients so that we can also assess the impact of the age of the patient. Patients are given DHEA for 3 days starting at day 7 post-injury and blood samples are taken at regular intervals and levels of DHEA assessed by LC-MS. On day 3 of supplementation and prior to supplementation neutrophil bactericidal function is also assessed.