Abstract
Published epidemiological studies of traumatic brain injury (TBI) of all severities consistently report higher incidence in men. Recent increases in the participation of women in sports and active military service as well as increasing awareness of the very large number of women who sustain but do not report TBI as a result of intimate partner violence (IPV) suggest that the number of women with TBI is significantly larger than previously believed. Women are also grossly under-represented in clinical and natural history studies of TBI, most of which include relatively small numbers of women, ignore the role of sex- and age-related gonadal hormone levels, and report conflicting results. The emerging picture from recent studies powered to detect effects of biological sex as well as age (as a surrogate of hormonal status) suggest young (i.e., premenopausal) women are more likely to die from TBI relative to men of the same age group, but this is reversed in the 6th and 7th decades of life, coinciding with postmenopausal status in women. New data from concussion studies in young male and female athletes extend this finding to mild TBI, since female athletes who sustained mild TBI are significantly more likely to report more symptoms than males. Studies including information on gonadal hormone status at the time of injury are still too scarce and small to draw reliable conclusions, so there is an urgent need to include biological sex and gonadal hormone status in the design and analysis of future studies of TBI.
Highlights
Traumatic brain injury is a major cause of death and disability, especially among young people, and a major public health problem throughout the world
Female TBI victims need to be queried about their hormonal status, i.e., Pre- or post-pubertal, pre- or post-menopausal and if reproductively competent, estimated stage of menstrual cycle
Both men and women can benefit from actual acute and repeated measurement of sex steroid levels, including androgens, estrogens, progesterone, in order to understand possible sex-specific impact of TBI on reproductive health and possibly provide new sex-sensitive guidelines and sex-specific hormone-based treatment targets
Summary
Traumatic brain injury is a major cause of death and disability, especially among young people, and a major public health problem throughout the world. Female and male gonadal hormones are known to exert many diverse effects on brain structure and function [reviewed in [39]] which are likely to modulate the brain response to trauma in multiple ways and may, in principle, offer sex-specific treatment targets This is an important and timely question since with the increasing involvement of women in the military [40] and in sports, including contact sports such as Rugby [41]; the number of women at risk for sustaining TBI or concussion is on the rise, while treatment algorithms are still based on the results of clinical studies with an overwhelming majority of men (70% or above), none of which resulted in an FDA approved treatment for the neurological sequelae of TBI; despite promising results from animal studies (Table 1). We offer a concise critical review of emerging data on the effect of biological sex and hormonal status on TBI incidence and outcome, highlighting some possible mechanisms
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