Could the use of female hormones one day aid in the treatment and recovery of people who have experienced severe brain injuries?

The role that progesterone and estrogen play in brain trauma is getting a closer look by a team of researchers directed by Dr. Amy Wagner, who specializes in physical medicine and rehabilitation at University of Pittsburgh Medical Center.

Their five-year, federally funded study builds on earlier research by other investigators that shows a paradox: While progesterone and estrogen appear to be protective of brain cells, women seem to recover less successfully from severe brain trauma than men.

Marshaling protective uses of these hormones, however, could be a boon to trauma medicine. Outside of care to manage complications related to severe brain injury, such as swelling, there is limited treatment available.

"There are few interventions that we know that unequivocally decrease the effects of injury or improve recovery,'' Wagner said.

Estrogen is an antioxidant, a chemical that can help minimize the effects of secondary injury after the initial trauma. Progesterone can help decrease brain swelling.

Still, she added, an analysis of available literature "showed women performed worse than men on a majority of outcomes assessments measured."

Wagner also has some personal experience from a study she completed looking at disabilities and community integration one year after injury. "We had a whole range of people we evaluated who had mild to severe injuries," she said. "We found women were more than 2 1/2 times more likely to report more disability at one year than males."

But the problem with gender studies so far is that they deal only with gender status. "The scientific literature doesn't talk about the hormonal status. It doesn't talk about what the person's hormones were like during the person's injury. It doesn't talk about what the person's hormones were like during the recovery, and I think these are two different issues," she said.

"My working theory is that your hormonal status at the time of injury and your hormonal status during recovery both play a role in how you ultimately do from an outcome standpoint."

The team is recruiting 100 to 125 male and female patients with severe head injuries. Soon after the injury, researchers with cooperating medical staff will monitor hormone levels in spinal fluid and blood. They also will gather information on female patients important for understanding their reproductive history and hormone status.

Wagner's hope is that this study will provide enough information to help her research group and other investigators effectively design clinical trials that test the use of hormones as treatment interventions.

She also hopes these findings will highlight the importance of understanding how males and females might respond differently when designing clinical trials that target other treatment strategies aimed at minimizing injury or promoting recovery.