Traumatic brain injury (TBI) is a leading cause of death and disability and a global public health challenge. Every year more than 50 million people suffer a TBI, and it is estimated that 50% of the global population will experience at least one TBI in their lifetime. TBI affects both men and women of all ages, however there is a male bias in TBI research as women have frequently been left out of the literature despite irrefutable evidence of male and female dimorphism in several posttraumatic measures. Women uniquely experience distinct life stages marked by levels of endogenous circulating sex hormones, as well as by physiological changes that are nonexistent in men. In addition to generalized sex-specific differences, a woman's susceptibility, neurological outcomes, and treatment success may vary considerably depending upon when in her lifespan she incurred a traumatic insult. How women impacted by TBI might differ from other women as a factor of age and physiology is not well understood. Furthermore, there is a gap in the knowledge of what happens when TBI occurs in the presence of certain sex-specific and sex-nonspecific variables, such as during pregnancy, with oral contraceptive use, in athletics, in cases of addiction and nicotine consumption, during perimenopause, postmenopause, in frailty, among others. Parsing out how hormone-dependent and hormone-independent lifespan variables may influence physiological, neurodegenerative, and functional outcomes will greatly contribute to future investigative studies and direct therapeutic strategies. The goal of this review is to aggregate the knowledge of prevalence, prognosis, comorbid risk, and response of women incurring TBI at differing phases of lifespan. We strive to illuminate commonalities and disparities among female populations, and to pose important questions to highlight gaps in the field in order to further the endeavor of targeted treatment interventions in a patient-specific manner.
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