A new study suggests that giving progesterone to victims with Traumatic Brain Injury (TBI) shortly following brain injury may reduce the risk of death and the degree of disability, and appears to be safe.
According to a study by Emory University researchers, progesterone treatment for TBI has been extensively studied in laboratory animals for more than 15 years and has been shown to reduce brain swelling, prevent nerve death and improve functional outcomes.
As the results were so impressive, the research team felt it was time to take the treatment to the bedside for testing in patients who had suffered a serious brain injury.
It is estimated that 1.5 to 2 million people in the U.S. sustain a TBI each year, leading to 50,000 deaths and 80,000 new cases of long-term disability.
It is also a major cause of death and disability among children and military personnel.
Despite the enormity of the problem, scientists have failed to identify effective medications to improve outcomes following a TBI and no new medical therapies have been developed for traumatic brain injuries in over 30 years.
Although it is classed as a "sex steroid," progesterone is also a neurosteroid that exerts protective effects on human tissue.
It is naturally present in small but measurable amounts in the brains of males and females.
Laboratory studies suggest that progesterone is critical for the normal development of neurons in the brain and exerts protective effects on damaged brain tissue.
In a phase II three-year pilot study, called ProTECT ("Progesterone for Traumatic brain injury--Experimental Clinical Treatment"), the Emory researchers enrolled 100 participants who reached the emergency department within 11 hours of injury, in order to evaluate whether progesterone can be administered intravenously in a reliable way, and whether the treatment is safe to use in humans with TBI.
People enrolled in the study had a "blunt" traumatic brain injury, which typically occurs from a car accident, motorcycle crash or a fall, and lead researcher Dr. David W. Wright and colleagues randomly assigned the patients to receive an intravenous dose of progesterone or an inactive "placebo."
The death rate in the 30 days after injury was 13 percent in the progesterone group compared with 30 percent in the comparison group indicating that progesterone cut the risk of death by 57 percent.
No serious side effects were seen with the hormone or with the placebo.
Progesterone is a promising treatment because it is inexpensive, widely available and has a long track record of safe use in humans in treating other diseases.
Wright's team was able to contact 92 percent of patients who survived 30 days and saw evidence that progesterone improved the recovery of patients with moderate brain injury, however those patients with severe injury seemed to glean no benefit from the hormone.
The authors say one-year outcomes will be reported later.
The research team is now planning a large, multi-center, phase III clinical trial designed to test the effectiveness of progesterone in 1000 patients with TBI.
They also hope to study the effects of progesterone treatment in animal models of blast-related brain injury, a major cause of death among combat personnel, along with a study of progesterone treatment in pediatric brain injury which is a leading cause of death and disability in children.
Animal research at Emory and elsewhere also indicates that progesterone may limit the damage from transient and permanent ischemic stroke and the Emory researchers hope to initiate a similar pilot clinical trial to study the effectiveness of progesterone or a progesterone metabolite to treat patients with acute stroke.
The research is published in the Annals of Emergency Medicine, October 2, 2006.