Sex differences in human brain structure have repeatedly been described, but results are inconsistent. However, these studies hardly controlled for cycle phase of women or the use of hormonal contraceptives. Our study shows that these factors are not negligible, but have a considerable influence on human brain structure. We acquired high-resolution structural images from the brains of 14 men, 14 women, who did not use, and 14 women, who did use hormonal contraceptives. Women, who did not use hormonal contraceptives, were scanned twice, once during their early follicular and once during their mid-luteal cycle-phase. Regional gray matter volumes were compared by voxel-based morphometry. Men had larger hippocampi, parahippocampal and fusiform gyri, amygdalae and basal ganglia than women. Women showed larger gray matter volumes in the prefrontal cortex, pre- and postcentral gyri. These sex-dependent effects were modulated by menstrual cycle phases and hormonal contraceptives. We found larger volumes in the right fusiform/parahippocampal gyrus during early follicular compared to mid-luteal cycle phase. Women using hormonal contraceptives showed significantly larger prefrontal cortices, pre- and postcentral gyri, parahippocampal and fusiform gyri and temporal regions, compared to women not using contraceptives.
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