There’s something wrong with the brain banks created to study the dangers of repeated trauma to the head: Almost all the brains donated so far belonged to men.

It’s just one example of how the study of brain trauma in women lags behind—even though women get concussions at higher rates than men in many sports and may suffer more severe and persistent symptoms.

“If concussion is the invisible injury, then females are the invisible population within that injury,” said Katherine Snedaker, a licensed clinical social worker from Norwalk, Conn., who founded the nonprofit PINK Concussions in 2013 to focus attention on the issue.

Evidence is building that the response to traumatic injury is different enough in females that they might benefit from gender-specific treatment, as they do with cardiac disease. But the data to create such guidelines simply aren’t there.

“It’s an incredible gap in our knowledge,” said Angela Colantonio, director of the Rehabilitation Science Institute at the University of Toronto. “It’s just not acceptable.”

When Colantonio examined 200 studies on prognosis after mild traumatic brain injury, she found only 7 percent separated out women. And if female athletes are overlooked, other groups vulnerable to concussion—aging women, women in prison, and domestic abuse survivors—have been nearly entirely ignored.

But a growing number of researchers are fighting to get the data they need. They’re helped by a new requirement that all research funded by the National Institutes for Health explicitly address sex and gender. They’re also buoyed by increasing public interest in the topic, including a congressional briefing on female brain injury held last June.

Meanwhile, a raft of new studies are starting to include women. A $30 million study by the Pentagon and the NCAA is currently tracking 1,288 college athletes with concussions; one-third are female.

The ‘mean girls’ phenomenon

Many studies show the female brain does appear to react differently when concussed. Female rats behave differently than males, and there are biological differences, too—females have cycling hormones, higher rates of blood flow through their brains, less myelin sheathing around nerve fibers, and more migraine headaches. All those factors might affect concussion response.

“Boys and girls—whether you’re a rat or a human—are different,” said Mayumi Prins, a neuroscientist and associate director of the UCLA Steve Tisch BrainSPORT Program, whose work is largely funded by the NIH. “It’s not some great stretch of the imagination to think there would be differences in response to disease and injury.”

The program’s director, Dr. Christopher Giza, agreed, but offered a note of caution: He said many studies that show differences in females are small, poorly controlled, and conducted by researchers (like him, he acknowledged) who may be biased toward finding results showing sex differences. Giza, who has received research funds from the NFL and is helping to guide the NCAA/Defense Department study, also notes that there have been plenty of studies showing no gender differences, though those rarely get media attention.

“It’s easy to drink your own Kool-Aid,” he said.

So, what’s the evidence for gender difference?

A 2013 study of 144 women who came to emergency room departments following concussions offers some tantalizing hints.

It showed that women who were concussed during the two weeks before their period had a slower recovery and poorer outcome one month later than those who were hurt in the two weeks after their period—or those who were taking birth control pills.

More evidence that the hormonal cycle may play a key role: Premenstrual girls and postmenopausal women have concussion outcomes similar to men, said Dr. Jeffrey Bazarian, a concussion expert at the University of Rochester who is also participating in the NCAA/Defense Department study.

Bazarian suspects blows to the head may debilitate the pituitary gland at the base of the brain. When it’s healthy, the pituitary gland stimulates the ovaries to release progesterone, which promotes both calming and brain cell growth. Damaging that output at certain times during a woman’s hormonal cycle may hit neurons particularly hard, worsening symptoms and leading to the social withdrawal many concussed athletes report.

Prins has seen such withdrawal in female rats that are concussed. And a study from another lab, aptly titled “Mean Girls,” found female rats with brain injuries were excluded from play more than injured male rats.

Another issue is neck strength. Women in general have weaker, thinner, and less stiff necks than men and are therefore less able to brace for anticipated hits. They are also more prone to migraines, which may affect electrical patterns in the brain in ways similar to concussion.

Social pressure to play down symptoms?

Even so, there’s still a big debate in the field about whether concussions are worse in females for biological reasons—or whether they just appear worse because women are more willing to disclose symptoms.

Studies show both male and females athletes are prone to lie about concussions in order to stay in games, but men do so at slightly higher rates. (One study from earlier this year showed male athletes lied about concussion 79 percent of the time while women did so 70 percent of the time.)

Snedaker would like to see more research on whether women recover more slowly—and whether they feel pressure to keep quiet about symptoms that linger for weeks or months. “When a girl says she still needs to go to the nurse four weeks after a concussion,” she said, “she gets judged as a malingerer or someone with a mental health problem.”

Alarmingly, new research shows the increased awareness about concussions is not encouraging more athletes from either gender to report their injuries, said Tracey Covassin, an associate professor and athletic trainer at Michigan State University. She was one of the first to report, in 2003, that females suffer concussions at nearly twice the rate of men playing similar sports.

Brittni Souder, 28, estimates she’s had more than 10 concussions—many while playing soccer at Hood College in Frederick, Md. The symptoms grew so bad, she had surgery to relieve pressure in her brain.

“There’s pictures of me on the field—you can see how not there I am. My eyes are like zombies,” she said.

Souder had to leave campus and finish school from home due to concussion symptoms. She’s still plagued with headaches, sensitivity to light, and an inability to concentrate that’s kept her from pursuing her goal of graduate study.

Now an assistant soccer coach at Frederick Community College and a board member of PINK Concussions—which is funded by private donors, including the NCAA—Souder is adamant about pulling her injured players from games despite their protests. She believes that repeated subconcussive hits damaged her injured brain while it was still trying to heal.

She doesn’t want her players suffering the same fate.

A plea for women to donate their brains

A looming question is whether women who suffer repeated brain trauma may be prone to developing chronic traumatic encephalopathy, or CTE. There are two reports of CTE-like damage in female brains in the medical research literature from 1990: one, a severely autistic girl who hit her head repeatedly; the other, a wife so badly abused she developed the cauliflower ears seen in boxers.

The famed brain bank at Boston University has detected CTE in 236 of 377 brains donated to the research lab.

But only four of those brains belonged to women. None had CTE.

Obtaining female brains is now one of the bank’s major goals. Soccer stars Brandi Chastain, Abby Wambach, and Megan Rapinoe are among a handful of female athletes who have pledged to donate their brains to be studied after their deaths.

Snedaker plans to donate her brain as well.

Republished with permission from STAT. This article originally appeared on November 21, 2016