Differences between Men and Women in Treatment and Outcome after Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a significant cause of disability, but little is known about sex and gender differences after TBI. We aimed to analyze the association between sex/gender, and the broad range of care pathways, treatment characteristics, and outcomes following mild and moderate/severe TBI. We performed mixed-effects regression analyses in the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, stratified for injury severity and age, and adjusted for baseline characteristics. Outcomes were various care pathway and treatment variables, and 6-month measures of functional outcome, health-related quality of life (HRQoL), post-concussion symptoms (PCS), and mental health symptoms. The study included 2862 adults (36% women) with mild (mTBI; Glasgow Coma Scale [GCS] score 13-15), and 1333 adults (26% women) with moderate/severe TBI (GCS score 3-12). Women were less likely to be admitted to the intensive care unit (ICU; odds ratios [OR] 0.6, 95% confidence interval [CI]: 0.4-0.8) following mTBI. Following moderate/severe TBI, women had a shorter median hospital stay (OR 0.7, 95% CI: 0.5-1.0). Following mTBI, women had poorer outcomes; lower Glasgow Outcome Scale Extended (GOSE; OR 1.4, 95% CI: 1.2-1.6), lower generic and disease-specific HRQoL, and more severe PCS, depression, and anxiety. Among them, women under age 45 and above age 65 years showed worse 6-month outcomes compared with men of the same age. Following moderate/severe TBI, there was no difference in GOSE (OR 0.9, 95% CI: 0.7-1.2), but women reported more severe PCS (OR 1.7, 95% CI: 1.1-2.6). Men and women differ in care pathways and outcomes following TBI. Women generally report worse 6-month outcomes, but the size of differences depend on TBI severity and age. Future studies should examine factors that explain these differences.

Association of Sex and Age With Mild Traumatic Brain Injury–Related Symptoms: A TRACK-TBI Study

“…Our finding of the vulnerability of women in the 35-to 49-year age range to chronic mTBI effects was also compatible with the results of a recent multicenter study that showed that the greater difference in women vs men with PCS after mTBI was in the 16-to 45-year age range, but we acknowledge the difference in age grouping between the studies. 8 As noted previously, psychosocial stress may contribute to greater PCS in the women aged 35 to 49 years than in younger females after TBI. 26 The contribution of psychosocial stress was also proposed by Yue et al 5 to account for the more severe PTSD symptoms reported by women aged 30 to 39 years with mTBI as compared with women aged 18 to 29 years and men of either age range in a TRACK-TBI pilot study.…”

“…Second, potential interactions of sex with age have not been studied extensively. 5,6,8 There are several reasons women at certain ages may be especially vulnerable to the consequences of mTBI. For example, circulating levels of sex hormones, which decrease in women from about 35 to 50 years of age, may moderate recovery, but the evidence for a causal linkage is preliminary.…”

The interaction of the circadian and immune system: Desynchrony as a pathological outcome to traumatic brain injury

“…Therefore, future studies may demonstrate that restoration of vasopressin levels helps remediate TBI related symptomology, including circadian disruption. Finally, research should aim to not only include both sexes, as a European cohort that analysed gender differences found women exhibit worse outcomes following TBI ( Mikolic et al, 2020 ), but also take comorbid impairments such as sleep disruption into consideration. This is an extremely important consideration given that many mTBI patients who present with insomnia showed a greater number of circadian rhythm sleep wake disorders ( Zalai et al, 2020 ).…”

Sex, Genes, and Traumatic Brain Injury (TBI): A Call for a Gender Inclusive Approach to the Study of TBI in the Lab

“…Additionally, if untreated, these long-term effects of TBI can result in increased risk of neurodegenerative diseases such as Alzheimer's disease, chronic traumatic encephalopathy, and Parkinson's disease (Lye and Shores, 2000 ; McKee et al, 2009 ; Hutson et al, 2011 ). Treatment of secondary injuries is complex, as there are a multitude of neurobiochemical and metabolic pathways that are activated across multiple time scales and can differ depending on sex (Prins et al, 2013 ; Saldanha et al, 2013 ; Rahimian et al, 2019 ; Mikolić et al, 2020 ).…”

“…Both clinical and lab studies show a clear influence of sex on TBI outcome. However, whether this is mediated by hormones, genes, or both is still under debate (Gupte et al, 2019 ; Ma et al, 2019 ; Mikolić et al, 2020 ). The majority of research focuses on factors of endogenous hormone signaling (release and reception) in natal males (Slewa-Younan et al, 2004 ; Dubal et al, 2006 ; Herson et al, 2009 ; Griesbach et al, 2015 ; Clevenger et al, 2018 ; Mollayeva et al, 2018 ; Späni et al, 2018 ; Ma et al, 2019 ).…”