Can a ‘female’ sex hormone protect against the damage?
by Megan Scudellari
Corry* was late for a meeting. An educator at a rural secondary school in upstate New York, she was rushing down a hallway when she heard a voice and turned to wave to a friend. When she turned back, Corry misjudged her location and ran straight into a wall. Her face smashed into the ridged, wood trim of the wall, and her head jolted back. Corry stood motionless for a few moments, suspended in shock, then collapsed on the floor.
Co-workers ran to help and asked if they could take her to the doctor. Corry declined, saying she was fine. She wasn’t.
In fact, Corry doesn’t remember any of the preceding story. Her husband, principal of the school where she worked, told her what happened afterward. When she and I spoke over the phone, she often paused mid-sentence, and I’d hear a soft murmur in the background as her husband filled in some word or detail that Corry couldn’t recall. Piece by piece, her unbelievable story came together.
When Corry hit the wall, she broke her nose and bones in her face and sustained a traumatic brain injury (TBI). A TBI results in brain damage that can manifest cognitively and physically. It can affect how a person thinks and feels and how an individual processes language and information. It can affect walking ability, balance, and senses of sight, touch, smell, and more. TBI can even change a personality.
When Corry’s accident happened in October 2007, she thought it was “just a concussion.” At first, she felt dazed and confused and cried a lot. Then other symptoms emerged: Corry couldn’t sleep. She had constant headaches, light and noises bothered her, and she couldn’t understand her daughters’ high-pitched voices.
Her life changed dramatically. She lost the ability to read complete sentences, couldn’t do simple arithmetic, and didn’t remember how to cook, though she had raised and fed three grown daughters. “I was a very capable person before this occurred,” says Corry. “I had to re-learn everything: how to dust, where to dust, how to load the dishwasher.”
Today, Corry has improved, but still struggles with the lingering day-to-day consequences of her injury. “The girls laugh and say, ‘You can tell Mom anything in the morning, because she won’t remember it later,’” says Corry with a chuckle. She is quiet for a moment, then sighs. “Which, of course, is very sad.”
Each year in the United States, about 1.7 million experience some version of Corry’s injury, according to the US Centers for Disease Control and Prevention. Yet despite this staggering pervasiveness (see chart), many Americans may be unfamiliar with the term “brain injury” or realize that a concussion is a mild form of brain injury. Because of this, TBI is a “silent epidemic” — a devastating national problem that is rarely discussed and likely underestimated. TBI is also “silent” because you often can’t tell that a person has a brain injury just by looking at her: She may look the same on the outside but be a changed person on the inside.
The quietest group of TBI survivors, the ones you probably hear the least about, are women. In every age group, TBI rates are higher in males than females, which has led to the perception that TBI is a man’s problem. When you hear ‘brain injury’, you might think of young men engaged in high-risk behaviors, veterans with blast injuries (who are overwhelmingly male), and football players. And what clinicians know about TBI comes primarily from studies of men. For example, an overwhelming 74% of the 11,058 individuals included in the Traumatic Brain Injury Model Systems National Database, a resource for TBI researchers, are male.
But brain injury affects women — millions of them — and in ways that we are only just beginning to understand. The long-term health of women with brain injury is largely unexplored. The few existing studies suggest that, in addition to difficulties common to both sexes, women face unique challenges after TBI, including psychological, reproductive, and sexuality issues. A 2010 study, for example, found that women with brain injuries have fewer children and experience more problems after childbirth.
But despite women’s oft-overlooked role in the field of brain injury, they — and their hormones — could be the key to the first real treatment for TBI.
TBI is complex: The initial impact of a head trauma — in Corry’s case, running into a wall — is only the beginning of a brain injury. After the impact, a cascade of processes that kill brain cells goes on for hours, days, even weeks: Neurons lose their protective myelin sheaths. Inflammatory immune system cells swoop in and destroy both damaged and healthy neurons. Mitochondria sputter and fail, and toxic fluids accumulate in the brain.
The complexity of a brain injury may be the reason that 50 compounds, across 30 clinical trials in 30 years, have yielded exactly zero treatments for TBI. That’s right — no approved therapies exist to reverse or prevent brain damage caused by trauma. Not for Corry, and not for the 1.7 million people each year in the US who sustain a TBI.
“At the beginning, I was angry,” says Corry. “I’d think, ‘There’s got to be something that can be done. Don’t tell me that you don’t know what medication or therapy to give me.’”
But there is hope. The brain community swaps anecdotal examples of women recovering with greater success than men from stroke and brain trauma, though scientific studies investigating that phenomenon are generally inconclusive.
In the early 1980s, researcher Donald Stein, then at Clark University in Massachusetts, decided to put this sex-based speculation to the test. He experimented with various sex hormones in rats and found that rats flooded with progesterone, a female hormone, had better outcomes after brain injury than any of the other rats.
It turns out that progesterone, though commonly known as a ‘female’ sex hormone, is present in the brains of both men and women and protects against swelling, inflammation, and cell-damaging oxidants. It also stimulates brain cells to express growth factors after injury. Since Stein’s initial discovery, over 190 publications have found that progesterone makes a positive difference following neurological injury, according to Stein, now at Emory University.
Today, progesterone is the focus of a national clinical trial in TBI. The trial, called ProTECT III, has already enrolled 692 of 1,140 participants nationwide. Within four hours of a traumatic event, patients receive an infusion of a high dose of progesterone and continue to receive infusions for four days. The trial should conclude in 2014, says trial investigator David Wright, professor at Emory University School of Medicine in Atlanta. If it is successful, the next step is clearance from the US Food and Drug Administration to use progesterone as a legal and approved treatment for TBI. It would be the first. “A lot hinges on this trial,” Wright says. “It keeps me up at night.”
*Last name omitted for anonymity
Megan Scudellari is a freelance science journalist based in Durham, North Carolina, specializing in the life sciences. She is a correspondent for The Scientist magazine and has contributed to Scientific American, Pacific Standard, Technology Review, Nature Medicine and more. Follow her on Twitter @Scudellari.