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How Sex and Gender Differences Influence Functional Recovery in Patients With Traumatic Brain Injury: A Systematic
Raffaela Maione1, Maria Grazia Maggio, Rosaria De Luca
1Author Affiliations: IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy (Maione, Maggio, De Luca, Corallo, Calapai, Quartarone, Calabrò); IRCCS San Camillo Hospital, Venice, Italy (Lago, Zago, Arcara); and University Of Padua, Padova, Italy (Lago, Arcara).
Objective:
This systematic review aimed to examine how sex differences and, when available, gender-related factors affect rehabilitation outcomes in individuals with TBI.
Design:
Systematic review registered in PROSPERO (ID: 1018531) and conducted in accordance with PRISMA guidelines and the Cochrane Handbook. We included randomized controlled trials and observational and experimental studies published in the past 5 years (2020-2025) that explicitly analyzed sex- and/or gender-related differences in response to a rehabilitation intervention after TBI.
Interventions:
Various rehabilitation programs, including conventional therapy, virtual reality, and telerehabilitation.
Main Measures:
Cognitive, motor, emotional, functional, and social outcomes, analyzed by biological sex and, when available, gender-related psychosocial traits.
Results:
Six studies met the inclusion criteria. Most findings referred to sex-based differences: female participants (sex: female) demonstrated better recovery in cognitive and social functioning, potentially linked to neuroprotective effects of estrogen and progesterone. However, they also reported higher anxiety and more persistent postconcussive symptoms. Only one study investigated gender as a social construct, suggesting that gender-related social traits, particularly those culturally associated with femininity, were associated with reduced access to rehabilitation services. A subset of studies evaluated technology-assisted interventions (e.g., virtual reality, telerehabilitation); however, sex/gender-differential effects were rarely tested, limiting firm conclusions about tailoring by sex or gender.
Conclusions:
Although current evidence predominantly concerns sex-based differences, limited data also point to a potential role of gender-related social factors. Together, these findings suggest that sex and gender may significantly shape rehabilitation outcomes after TBI. Integrating sex- and gender-sensitive strategies into clinical pathways may improve equity, enhance personalization, and optimize recovery. Standardized, gender-inclusive protocols are needed to address disparities and promote fair access to neurorehabilitation.
