Traumatic Brain Injury And Gender: What Is Known And What Is Not

Differences in Outcome in Moderate & Severe TBI

Although there is an emerging amount of work that focuses on the biochemical and hormonal differences between the male and female brain, we continue to ask the essential question: is there a difference in overall outcome between males and females? Overall, the majority of earlier studies have utilized classic broad outcome measures that have generally reported worse female outcomes; however, some more recent work has not. Data from the IMPACT study was analyzed for Glasgow Outcome Scores at 6 months following moderate-to-severe TBI, and found that age, race and education were all associated with outcome, and gender was not.^{[21,22,23,24]}

In 2000, Farace performed a meta-analysis regarding outcome and concluded that women fair worse overall. After an extensive Medline search, including 'gender' and 'sex' as keywords, they included a total of eight studies that had separately analyzed women and men with respect to outcome. Most of these studies used specific symptoms at follow-up, or return-to-work status as outcome variables. This analysis did not include age-matching criteria, which may have had an impact on results, since female gonadal hormone circulation changes from childbearing to postmenopausal age.^[25]

More recently, injury severity with respect to gender was compared by Slewa-Younan, who concluded that while controlling for mechanism of injury and speed of collision, males revealed significantly lower initial Glasgow Coma Scores and longer durations of post-traumatic amnesia than did females. Interestingly, their Glasgow Outcome Scales were the same after rehabilitation.^[26]

Ratcliff and colleagues explored this question and found that at 1 year from injury, women showed better memory and language skills, while men showed better visual analytic skills, using neuropsychological outcome measures. Interestingly, these results held true while controlling for normative data (differences between men and women without TBI).^[27]

The apparent gender differences with respect to injury, illness and outcome are not necessarily unique to TBI. In 1945, Britton and Kline studied the effect of hypoxia in rats and observed that females actually had a 40% increase in survival time than age-matched males.^[28] There are several studies that have demonstrated the decreased incidence of ischemic stroke in females, both in human work and experimental models. Rate of survival and extent of cerebral pathology, including neuronal loss, have been shown to be favorable in female rodents, following experimental ischemic stroke.^[29] In patients with subarachnoid hemorrhage, favorable outcome was shown to be significantly better for females versus males at 3-month follow up, and mortality was found to be significantly lower in one randomized clinical trial addressing the effect of tirilizad.^[30]

Cite this: Traumatic Brain Injury And Gender: What Is Known And What Is Not - Medscape - Jul 01, 2008.

Table 1. Gender-based Differences in the Effects of Chronic Stress
Data	Male	Female
Anatomical	1260 cm³ volume	1130 cm³ volume
	Larger volume of white matter	Larger volume of gray matter, higher gray:white matter ratio
	Frontal and parietal gray matter volumes correlate with IQ scores (visual-spatial)	Frontal lobe volume and Broca's area volumes correlate with IQ scores (verbal and language)
	Young males have larger volumes in the amygdala (where there are higher concentrations of androgen receptors)	Young females have larger hippocampal volumes (where there are higher concentrations of estrogen)
Neurotransmitter & neurohormonal	Synthesize serotonin at a faster rate	Higher levels of 5-hydroxytryptamine (5-HT) in the brain, and higher density of 5-HT transporter availability in the brainstem and diencephalon
		Elevated dopaminergic response to amphetamine
		Higher overall dopamine transporter density
		Female hormones may promote anxiolytic state
Animal data	At baseline, male rats demonstrated higher anxiety	Under chronic stress, female rats performed better in spatial memory, water maze proficiency and object recognition
	Decreased anxiety when exposed to the same chronic-stress environment	Increased anxiety when exposed to the same chronic-stress environment
		Female sex hormones' positive effect on brain edema, cortical lesion size and protection of the BBB
	Natural progesterone appears to positively affect outcome	Natural progesterone appears to positively affect outcome

Table 2. Outcome Differences Following Progesterone use in Traumatic Brain Injury
Male	Female
Lower initial Glasgow Coma Scores and longer durations of post-traumatic amnesia	Women fair worse overall
Glasgow Outcome Scale scores were the same after rehabilitation	Glasgow Outcome Scale scores were the same after rehabilitation
1 year from injury, better visual analytic skills	1 year from injury, better memory and language skills

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Traumatic Brain Injury And Gender: What Is Known And What Is Not

Differences in Outcome in Moderate & Severe TBI

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