Retired American soccer star Brandi Chastain recently agreed to donate her brain to concussion research after her death. Females are often an unseen part of the concussion story even though they suffer more concussions than males, have more severe symptoms and are slower to recover. Just why is not completely clear, but the deficit in knowledge is slowly beginning to change thanks to women’s advocates behind Pink Concussions. The group gathered last weekend at Georgetown University to review the science behind concussions, and also to develop recommendations on gender-specific prevention protocols and clinical practices on how best to treat females with concussions.

In comparable sports “female rates of concussions are much higher than those of their male counterparts,” says Zachary Kerr, director of the National Collegiate Athletic Association (NCAA) Injury Surveillance Program. Over a five-year period the rates per 1000 athlete-exposures were 6.3 in females versus 3.4 in males in soccer, 6.0 in females versus 3.9 in males in basketball and 3.3 in females versus 0.9 in males in baseball and softball. Only in swimming and diving did male rates (0.3) exceed those of females (0.5). Headache, dizziness and difficulty concentrating were roughly similar among both sexes, Kerr says. But among injured high school athletes, “larger portions of females are reporting sensitivity to light, sensitivity to noise, nausea and drowsiness,” he says. They were also slower to return to normal activity.

The difference between the incidence and severity of concussions between the sexes does not start at birth, because infants and young children of both sexes have similar rates and symptoms with concussions. Puberty, however, which marks a significant developmental fork in the road for males and females, also marks a divergence for concussions. With its onset, females increasingly experience higher incidence of concussions, different and more severe symptoms, and are often slower to recover from the injury. The symptoms of both sexes begin to converge again after females go through menopause, though use of hormone replacement therapy can have an effect.

It is difficult to study the direct effect of hormones on concussions because they change throughout a woman’s estrous cycle. Testosterone levels in both sexes also fluctuate throughout the day; they are best measured by drawing blood. So most of what we know comes from studies in animals, says Michigan State University kinesiologist Tracey Covassin, and the picture is mixed. Estrogen appears to be a protective factor in male rats, but in female rats, it actually exacerbated the injury, while progesterone appears to be a neuroprotective factor in animals. The menstrual cycle can be a predictor of outcomes after mild traumatic brain injury, argues Jeffrey Bazarian, an emergency medicine neurologist at the University of Rochester. “It looks like women injured during the luteal phase, the last two weeks of the cycle, do worse than women injured during the follicular phase. This may help get us thinking about why there might be a difference between the sexes,” he says. His hypothesis is that the ratio of progesterone to testosterone in a woman and abrupt changes in the levels of those hormones may be key.

“Headache is by far the most common symptom of concussion, more than 90 percent” experience it, says Tad Seifert, a Kentucky neurologist who leads the NCAA Headache Task Force. Among the overall population, migraine is about three times more common in women than men, and at midlife about a quarter of women experience migraine. Estrogen is the primary neuromodulator of headache.

“We know that when there is a drop in estrogen that occurs with ovulation and menstruation, that is a precipitant for migraine . . . It is associated with dysfunctional pain modulation,” Seifert says. “Their brains are wired just a little bit differently to respond to the insult.” Women generally have a longer recovery. Given that, Seifert suggests screening for these higher risk characteristics and maybe treating earlier and more aggressively.

Although hormones are a factor in some of these differences, they do not encompass the entire picture, which also involves the structure of the neck, blood flow in the brain, vulnerability to migraines, and social and educational factors of awareness that affect who gets diagnosed. For example, females have 50 percent less isometric neck strength, 23 percent less neck girth, and 43 percent less head-neck segment stiffness during acceleration than males, Covassin says. This less average bone and muscle support makes the head and brain more vulnerable to sudden movement and predicts risk for concussion.

It’s important to pinpoint the underlying biological causes of concussions and devise proper treatments. Concussions, especially in developing adults, may play a role in social development, according to Mayumi Prins, a neurobiologist at the University of California Los Angeles (UCLA). Work in a rat model of concussion has found evidence. “There are not only sex differences but age related sex differences, even within the adolescent time period,” Prins says. “Social interactions were different.” Concussed female animals avoided play and interaction with others. “If a normal animal can pick up that another animal has an injury and it affects their willingness to interact with them . . . this can have serious consequences during a development time period when social interaction is really key to their growth and development,” she says. Repeated concussions, without adequate time for full recovery between them, can have a compounded effect.

But it isn't all biology—social roles, expectations, and education and training also shape our recognition of and reaction to concussions. Male athletes are more likely to recognize that they have a concussion, but are less likely to disclose the condition because of loyalty to the team, and perhaps because of the lure of a professional career in sports, Covassin says. That has changed over time with education, however, and they are becoming more willing to disclose. “Females did not know it was a concussion,” she says. Part of it is that women receive less education on the matter, there are fewer and less knowledgeable coaches and trainers, and symptoms vary and are less well understood.

The Concussion Research Initiative promises to revolutionize our understanding of concussions, according to Brian Hainline, the NCAA's first medical officer. It is a joint program with the Department of Defense and the National Institutes of Health that has completed complex baseline assessments – more than 25 million data points – on 15,300 people, and so far includes 472 concussions to date, 157 of which have been females. The longitudinal cohort study will follow participants for decades, much like the still ongoing Framingham study on cardiovascular disease which began in 1948. The first reports will become public in the spring. “It is definitely going to change our perception of concussions,” Hainline says.