Accessibility Panel

Females have been underrepresented in TBI clinical trials and studies and often excluded in preclinical studies. An absence of research on females has resulted in an incomplete and perhaps inaccurate understanding of TBI in females. The discussions and presentations centered on the existing knowledge regarding sex differences in TBI research and how these differences could be incorporated into preclinical and clinical efforts in the future.

Traumatic Brain Injury (TBI) has a common and often devastating injury affecting all sexes and genders. However, whatever is known about TBI comes from preclinical and clinical studies of male subjects, leaving great gaps in the understanding of females and sex- or gender-related differences in prevention, epidemiology, neuroprotection, rehabilitation timing and therapeutics, secondary injury, and specific outcomes.

Variables such as the severity of TBI also affected whether females fared “better” or “worse” than males. It is vital to report the effect of sex and gender on all aspects of TBI across the lifespan to produce better scientific knowledge and clinical care for women and girls. It is also vital to study populations where females are more likely to be at a greater risk than males to experience a TBI, as in intimate partner violence (IPV).

The National Institutes of Health (NIH) states sex as the physiological and biological characteristics that differentiate male from female bodies (e.g., anatomy, physiology, genes, and hormones). Generally, from all pediatric age ranges (0-17 years), young males aged 0 to 4 years have the highest incidence rates, and young females have a lower incidence of TBI than young males. Generally, young males are about 2 times more likely than young females to have a TBI.

 Several factors may contribute to the sex differences in the epidemiology of TBI, such as a higher occurrence of general injury among younger males, differences in risk-taking behaviors the alteration between females and males in traditional societal roles and activities. Across all difficulties of TBI, they found that females were more likely than males to report internalizing problems, such as depression and anxiety. In contrast, males were more likely to report externalizing problems, such as substance abuse or criminal behavior.

In another study of adolescents, investigators found that aggregate concussive symptoms were higher in female athletes than in males at baseline and immediately after injury. However, the path of recovery was similar between males and females. However, there are mixed reports on sex differences in recovery times and persistent symptoms. The factors highlighted, such as injury biomechanics, frequency of symptom reporting in females, and injury rates, may be the reason for these changes.

In summary, clinical studies in children have confirmed sex differences in functional outcome, ICU length of stay, and death after pediatric TBI. Moreover, potential sex modifications were found in pediatric and adolescent concussions, with an extended recovery time in female athletes but with an advanced baseline rate of symptom reporting. These sex-based changes in adolescents could be due to systemic sex hormone differences and/or gender. 

However, preclinical and clinical studies show sex-based differences even before puberty. Failure to consider sex as a biological variable could restrict preclinical therapies and limit the value of clinical research in pediatric TBI.

Aging populations

Females 65 years and older have the highest rates of diagnosed mild TBI. Falls are the primary cause of injury, particularly among females. Aging with TBI was identified as a priority area at the first international workshop on women and TBI in 2010. Still, no systematic reviews on older adults with TBI have explicitly considered sex. Therefore, there is limited knowledge to inform sex-specific interventions and guidelines.