Progesterone's promise

It's time to throw out the old idea of progesterone as a mere sex hormone, says Donald Stein, PhD, a neuroscientist and professor of emergency medicine at Emory University. For more than three decades, Stein has studied progesterone's role in protecting brains damaged by traumatic injury and stroke. He'll discuss this groundbreaking work at APA's 2013 Annual Convention as this year's Neil Miller lecturer in a talk titled "Sex, Brain Damage and Recovery: How Progesterone Went from the Laboratory Bench to the Patient's Bedside in Only 30 Years."

As a student in the 1960s, Stein noticed that a significant fraction of brain-injured rats recovered better than expected. His interest was piqued, but at the time few people believed that neurons could be repaired.

"I had a lot of trouble getting anyone to let me study it," he says.

He persevered. After reading anecdotal reports that women tended to recover better than men from trauma and stroke, he tested that notion in rats. Sure enough, he discovered that female animals fared better after brain injury.

Investigating further, he found that the extent of recovery was linked to the rats' estrus cycles. "When they were high in progesterone, the outcome was much better," he says.

Fast-forward several decades: More than 250 publications around the world have now demonstrated the benefits of progesterone in central-nervous-system injuries, Stein says, and he has moved his own attention from lab rats to human trials. In phase two clinical trials, a team of investigators led by Stein's close colleague David Wright, MD, director of emergency neurosciences at Emory University School of Medicine, found that administering progesterone to both men and women with severe brain injury reduced mortality by almost 60 percent with no adverse side effects (Annals of Emergency Medicine, 2007).

One perk of progesterone is that the window for treating brain-injured patients is relatively large. "In any kind of brain injury, time is brain," he says. But progesterone appears to benefit patients even eight hours after they've suffered a trauma to the brain.

This year, two large phase three trials are testing the use of progesterone in victims of moderate to severe traumatic brain injury. Meanwhile, Stein is working with clinical colleagues at Emory to plan a similar trial to study the hormone in stroke patients.

Stein is hopeful that the studies will lead to the use of progesterone as a first-line therapy for brain injuries. "There are no effective treatments for traumatic brain injury and few for strokes," he says. "It's very exciting to see this work do something good for people."

—Kirsten Weir