Neuroimaging and Fluid-Based Biomarkers in Sport-Related Concussion in Female Athletes: A Scoping Review

Abstract

Sport-related concussion (SRC) is a significant public health concern, warranting exploration of neuroimaging and fluid-based biomarkers as objective measures for diagnosis and prognosis. Sex differences in concussion outcomes may be influenced by the menstrual cycle, hormones, and hormonal contraceptives. Equitable representation of female athletes in emerging biomarker research is critical, but existing literature may not meet this need. This scoping review assessed neuroimaging and fluid-based biomarker research in SRC for inclusion and analysis of female athletes and to summarize female-specific and sex-difference results. Searches in MEDLINE, Scopus, Cochrane, and PsycInfo from January 2001 to July 2025 identified original research published in English and focused on SRC with neuroimaging or fluid-based biomarker assessment within 6 months after injury. Studies were then classified based on study sample sex/gender, and studies with female-specific and sex-difference results were further summarized. Literature review revealed underrepresentation of concussed female athletes in biomarker research, with over three times more concussed male athletes studied than concussed female athletes and approximately 19 times more male-only than female-only studies. Most mixed-sex studies did not explicitly investigate female-specific results. The 29 summarized reports indicate potential sex differences and different results for female athletes than those in the broader existing literature, although small sample sizes make definitive conclusions difficult. Addressing the knowledge gap in SRC in female athletes requires future biomarker research to include sufficient numbers of female athletes, analyze data to identify potential sex differences, and collect relevant data, including hormone levels and detailed menstrual cycle and hormonal contraceptive use information.