Abstract
Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women). Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel-based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women.
Highlights
Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, as well as in learning, emotion perception, and treatment response [1,2,3]
We investigate whether steroid hormone concentrations are linked to cerebral perfusion, and whether hormone concentrations may explain the previously reported sex differences in perfusion
Oestradiol levels were higher in women (M = 332.7 pmol/L, SD = 160.35) than in men (M = 99.73 pmol/L, SD = 40.6, p < .001), testosterone levels were higher in men (M = 17.12 nmol/L, SD = 4.72) than in women (M = 0.92 nmol/L, SD = 0.45, p < .001), and dehydroepiandrosterone sulphate (DHEAS) levels were higher in men (M = 7.78 μmol/L, SD = 4.34) than in women (M = 5.4 μmol/L, SD = 2.55) on a trend level (p = .07)
Summary
Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, as well as in learning, emotion perception, and treatment response [1,2,3]. While early childhood disorders like autism and attention-deficit/hyperactivity disorder are more prevalent in males, anxiety and depression are more prevalent in females [1], and differences in the age of onset for schizophrenia have been reported between men and women [4]. To date little is known about the cerebral mechanisms underlying these apparent differences, despite an increasing body of knowledge about differences in brain structure, function, and morphology between the sexes. One of the most widely reported findings with regard to baseline brain physiology in men and women is that of an increased rate of perfusion or cerebral blood flow in women. The underlying cause of these sex differences remains unclear and the factors modulating this sex difference in perfusion are poorly understood
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