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Table 1 - Clusters with higher grey matter volumes in men compared to women. g.=gyrus. had larger regional GM volumes in the cerebellum (Fig. 2A-B, Table 1). Both naturally cycling women and contraceptive users showed larger regional GM volumes bilaterally com- pared to men in the prefrontal cortex, the pre- and postcentral gyri, the supplementary motor area and the inferior parietal lobule (Fig. 2, Table 2). This effect was most pronounced in hormonal contraceptive users. Women under hormonal contraception additionally had larger GM volumes compared to men in the cerebellum (Fig. 2, Table 2).

Table 1 - Clusters with higher grey matter volumes in men compared to women. g.=gyrus. had larger regional GM volumes in the cerebellum (Fig. 2A-B, Table 1). Both naturally cycling women and contraceptive users showed larger regional GM volumes bilaterally com- pared to men in the prefrontal cortex, the pre- and postcentral gyri, the supplementary motor area and the inferior parietal lobule (Fig. 2, Table 2). This effect was most pronounced in hormonal contraceptive users. Women under hormonal contraception additionally had larger GM volumes compared to men in the cerebellum (Fig. 2, Table 2).

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Fig. 1 - Total gray matter volume. Men had significantly higher gray matter volumes compared to women. Total gray matter volume did not differ between follicular and luteal phase in women and between women using contraceptives compared to women who did not use hormonal contraceptives. **p<0.01 compared to men, “““p<0.001 compared to men.
Fig. 1 - Total gray matter volume. Men had significantly higher gray matter volumes compared to women. Total gray matter volume did not differ between follicular and luteal phase in women and between women using contraceptives compared to women who did not use hormonal contraceptives. **p<0.01 compared to men, “““p<0.001 compared to men.
Fig. 2- Sex-dependent effects. Clusters with differing gray matter volumes in men compared to naturally cycling women during early follicular (A) or mid-luteal phase (B) and women using hormonal contraceptives (C). Gray matter volumes were larger in women compared to men bilaterally in the prefrontal cortex, the pre- and postcentral gyri and the supramarginal gyrus (showr in red). Gray matter volumes were larger in men compared to women bilaterally in the hippocampus, parahippocampal and fusiform gyri, putamen, pallidum, amygdala and temporal regions (shown in blue). Furthermore, men show larger cerebellat regions only in comparison to naturally cycling women. Sex-dependent effects were more pronounced during follicular compared to luteal phase. The female>male contrast increased with hormonal contraceptive use. Uncorrected threshold: p<0.001. Secondary FDR-corrected peak threshold: p<0.05. A comparison of regional GM volumes in women during different cycle phases has so far only been carried out by one study. Protopopescu et al. (2008) compared women during the late follicular phase to themselves during the late luteal phase. They found increased GM volumes in the lingual gyrus and hippocampus and decreased GM volumes in the superior parietal lobe, pallidum/putamen and anterior cingulate gyrus during follicular compared to luteal phase. To our knowledge no study did so far address the effects of hormonal contraceptives on brain structure. In the present study we compared GM volumes of men, women, who did not use hormonal contra- ceptives, and women, who did use hormonal contraceptives. Women, who did not use hormonal contraceptives, were compared to the other groups twice, once during the early follicular cycle phase, when estrogen and progesterone levels are both low, and once during the mid-luteal cycle phase, when estrogen and progesterone levels are both high. Thus, we address (i) the sexual dimorphism of regional GM volumes, (ii) cycle-dependent effects on regional GM volumes and (iii) the effect of hormonal contraceptives on regional GM volumes. results are inconsistent. These inconsistencies may be due to hormonal fluctuations during the menstrual cycle or use of hormonal contraceptives. Previous studies assessing sex
Fig. 2- Sex-dependent effects. Clusters with differing gray matter volumes in men compared to naturally cycling women during early follicular (A) or mid-luteal phase (B) and women using hormonal contraceptives (C). Gray matter volumes were larger in women compared to men bilaterally in the prefrontal cortex, the pre- and postcentral gyri and the supramarginal gyrus (showr in red). Gray matter volumes were larger in men compared to women bilaterally in the hippocampus, parahippocampal and fusiform gyri, putamen, pallidum, amygdala and temporal regions (shown in blue). Furthermore, men show larger cerebellat regions only in comparison to naturally cycling women. Sex-dependent effects were more pronounced during follicular compared to luteal phase. The female>male contrast increased with hormonal contraceptive use. Uncorrected threshold: p<0.001. Secondary FDR-corrected peak threshold: p<0.05. A comparison of regional GM volumes in women during different cycle phases has so far only been carried out by one study. Protopopescu et al. (2008) compared women during the late follicular phase to themselves during the late luteal phase. They found increased GM volumes in the lingual gyrus and hippocampus and decreased GM volumes in the superior parietal lobe, pallidum/putamen and anterior cingulate gyrus during follicular compared to luteal phase. To our knowledge no study did so far address the effects of hormonal contraceptives on brain structure. In the present study we compared GM volumes of men, women, who did not use hormonal contra- ceptives, and women, who did use hormonal contraceptives. Women, who did not use hormonal contraceptives, were compared to the other groups twice, once during the early follicular cycle phase, when estrogen and progesterone levels are both low, and once during the mid-luteal cycle phase, when estrogen and progesterone levels are both high. Thus, we address (i) the sexual dimorphism of regional GM volumes, (ii) cycle-dependent effects on regional GM volumes and (iii) the effect of hormonal contraceptives on regional GM volumes. results are inconsistent. These inconsistencies may be due to hormonal fluctuations during the menstrual cycle or use of hormonal contraceptives. Previous studies assessing sex
Table 2 - Clusters with higher grey matter volumes in women compared to men. g.=gyrus. from literature (e.g. Goldstein et al., 2001; Good et al., 2001; Garcia-Falgueras et al., 2006; Luders et al., 2009; Witte et al., 2009). Furthermore, we found larger volumes of the hippo- campus, parahippocampal and fusiform gyrus, putamen and pallidum in men. These sex-dependent effects are modulated by cycle phase and intake of hormonal contraceptives (Fig. 3). For the hippocampus and basal ganglia, findings derived from the literature are variable. While Garcia-Falgueras et al. (2006) report larger hippocampi in young adult women, Good et al. (2001) found larger hippocampi in men compared to women in a large sample of adults (465 subjects). However, both studies did not control for cycle phase or the use of hormonal contraceptives. volumes compared to naturally cycling women during both cycle phases, in the prefrontal cortex, the pre- and postcentral gyri, the parahippocampal and fusiform gyri and temporal regions (Fig. 4, Table 3). We did not identify brain regions with larger GM volumes in naturally cycling women compared to women using hormonal contraceptives.
Table 2 - Clusters with higher grey matter volumes in women compared to men. g.=gyrus. from literature (e.g. Goldstein et al., 2001; Good et al., 2001; Garcia-Falgueras et al., 2006; Luders et al., 2009; Witte et al., 2009). Furthermore, we found larger volumes of the hippo- campus, parahippocampal and fusiform gyrus, putamen and pallidum in men. These sex-dependent effects are modulated by cycle phase and intake of hormonal contraceptives (Fig. 3). For the hippocampus and basal ganglia, findings derived from the literature are variable. While Garcia-Falgueras et al. (2006) report larger hippocampi in young adult women, Good et al. (2001) found larger hippocampi in men compared to women in a large sample of adults (465 subjects). However, both studies did not control for cycle phase or the use of hormonal contraceptives. volumes compared to naturally cycling women during both cycle phases, in the prefrontal cortex, the pre- and postcentral gyri, the parahippocampal and fusiform gyri and temporal regions (Fig. 4, Table 3). We did not identify brain regions with larger GM volumes in naturally cycling women compared to women using hormonal contraceptives.
Fig. 3 - Cycle-dependent effects. In naturally cycling women gray matter volume were higher during early follicular phase compared to mid-luteal phase in the right fusiform/parahippocampal gyrus. Uncorrected threshold: p<0.001. Local maximum at [28, -27, -27], T=5.46, pror=0.256.
Fig. 3 - Cycle-dependent effects. In naturally cycling women gray matter volume were higher during early follicular phase compared to mid-luteal phase in the right fusiform/parahippocampal gyrus. Uncorrected threshold: p<0.001. Local maximum at [28, -27, -27], T=5.46, pror=0.256.
Fig. 4 - Effects of hormonal contraceptives. Clusters with higher gray matter volumes in women using hormonal contraceptives compared to women, who did not use hormonal contraceptives, during early follicular (A) and mid-luteal phase (B). Gray matter volumes were larger in women using hormonal contraceptives bilaterally in the prefrontal cortex, the pre- and postcentral gyri, the parahippocampal and fusiform gyri and temporal regions. The effect of hormonal contraceptive use was more pronounced in comparison to follicular phase. Uncorrected threshold: p<0.001. Secondary FDR-corrected peak threshold: p<0.05. Menstrual cycle effects on hippocampal volumes have been related to performance variations in hippocampus dependent memory (Protopopescu et al., 2008). Especially spatial working memory seems to be affected by the estrogen- decline during ovulation, as has been demonstrated in rats (Healy et al., 1999). In human fMRI studies, the fusiform and parahippocampal gyri have been implicated in spatial navi- gation abilities (Meulenbroek et al., 2004, 2010; Epstein et al., A tremendous effect of sex hormones on brain structures is further demonstrated by differences between hormonal contraceptive users and naturally cycling women (Fig. 4). These concern primarily the prefrontal cortex, pre- and postcentral gyri and inferior parietal lobule, but include weaker effects on hippocampal and parahippocampal regions. In this first investigative approach hormonal contraceptive users comprise a very heterogeneous group with respect to
Fig. 4 - Effects of hormonal contraceptives. Clusters with higher gray matter volumes in women using hormonal contraceptives compared to women, who did not use hormonal contraceptives, during early follicular (A) and mid-luteal phase (B). Gray matter volumes were larger in women using hormonal contraceptives bilaterally in the prefrontal cortex, the pre- and postcentral gyri, the parahippocampal and fusiform gyri and temporal regions. The effect of hormonal contraceptive use was more pronounced in comparison to follicular phase. Uncorrected threshold: p<0.001. Secondary FDR-corrected peak threshold: p<0.05. Menstrual cycle effects on hippocampal volumes have been related to performance variations in hippocampus dependent memory (Protopopescu et al., 2008). Especially spatial working memory seems to be affected by the estrogen- decline during ovulation, as has been demonstrated in rats (Healy et al., 1999). In human fMRI studies, the fusiform and parahippocampal gyri have been implicated in spatial navi- gation abilities (Meulenbroek et al., 2004, 2010; Epstein et al., A tremendous effect of sex hormones on brain structures is further demonstrated by differences between hormonal contraceptive users and naturally cycling women (Fig. 4). These concern primarily the prefrontal cortex, pre- and postcentral gyri and inferior parietal lobule, but include weaker effects on hippocampal and parahippocampal regions. In this first investigative approach hormonal contraceptive users comprise a very heterogeneous group with respect to
formulation, route or duration of administration. Yet for all women using hormonal contraceptives either progesterone or both estrogen and progesterone levels were enhanced to some extent in comparison to naturally cycling women. Thus, an enhancement of the “female” sex hormones leads to further enlarged GM volumes in regions with a sexual dimorphism favouring women (red clusters in Fig. 2). However, regions with a sexual dimorphism favouring men (blue clusters in Fig. 2) are hardly affected by the use of hormonal contra- ceptives. Exceptions are the right hippocampus and para- hippocampus. The weak enlarging effect of hormonal contraceptives on these regions mirrors the neuroplastic changes accompanying the hormone rise throughout the menstrual cycle. The specific roles of estrogen and progester- one need further clarification. We conclude that additionally to the organizing effects during development (e.g. Goldstein et al., 2001), sex hormones have significant acute effects on human brain structure, which may relate to variations in behaviour. Therefore both, menstrual cycle phase as well as the use of hormonal contraceptives has to be controlled when studying sex differences in human behaviour, brain structure or function.
formulation, route or duration of administration. Yet for all women using hormonal contraceptives either progesterone or both estrogen and progesterone levels were enhanced to some extent in comparison to naturally cycling women. Thus, an enhancement of the “female” sex hormones leads to further enlarged GM volumes in regions with a sexual dimorphism favouring women (red clusters in Fig. 2). However, regions with a sexual dimorphism favouring men (blue clusters in Fig. 2) are hardly affected by the use of hormonal contra- ceptives. Exceptions are the right hippocampus and para- hippocampus. The weak enlarging effect of hormonal contraceptives on these regions mirrors the neuroplastic changes accompanying the hormone rise throughout the menstrual cycle. The specific roles of estrogen and progester- one need further clarification. We conclude that additionally to the organizing effects during development (e.g. Goldstein et al., 2001), sex hormones have significant acute effects on human brain structure, which may relate to variations in behaviour. Therefore both, menstrual cycle phase as well as the use of hormonal contraceptives has to be controlled when studying sex differences in human behaviour, brain structure or function.
Related topics:
Cognitive ScienceSex DifferenceVoxel Based Morphometry
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