20 years in the making

Emory neurobiologist Donald Stein has been researching progesterone's effects on the brain in animals for 20 years. His work laid the foundation for the clinical trial.

It has taken two decades to get to a clinical phase because progesterone often is viewed as "merely a female hormone," he said.

In fact, Stein said, progesterone is a neurosteroid. It is present in high levels in pregnant women - 40 to 60 times higher than in women who are not pregnant - because it helps to keep the fetus healthy and "provides nourishment to growing nerve cells."

It works in traumatic brain injuries, Stein said, because "it's doing the same kinds of things in injury as it's doing in the development of the nervous system."

In the study, progesterone helped to reduce swelling, which causes pressure to build up as the brain pushes against the skull. Smith said he was told that his head swelled to the size of a basketball after his accident.

For the next study, researchers hope to cut down the time between injury and the patient receiving progesterone.

For the Grady trial, doctors sought consent from family members when the patients could not give it themselves.

"Because this was a safety study, it was critical to get consent," Wright said. "It did add about four or five hours for every patient."

With safety now established, Wright said he wants to, as a last resort, enroll patients without informed consent. Doctors would seek family for one to two hours before enrolling them without consent.

As Wright focuses on continuing the clinical work for traumatic brain injury, Stein now is testing progesterone's effectiveness at treating stroke in animals.

Preliminary results, he said, are promising: substantial reduction in the damaged area - the brain tissue that is dying because of a lack of blood - after a stroke if progesterone is used. ¦