Sex Hormones and Gender Role Relate to Gray Matter Volumes in Sexually Dimorphic Brain Areas

The present study investigates the relationship of circulating sex hormone levels and gender role to gray matter volumes in sexually dimorphic brain areas and explores, whether these relationships are modulated by biological sex (as assigned at birth based on sexual anatomy) or oral contraceptive (OC) use. It was hypothesized that testosterone and masculinity relate positively to gray matter volumes in areas that are typically larger in men, like the hippocampus or cerebellum, while estradiol/progesterone and femininity relate positively to gray matter volumes in the frontal cortex. To that end, high resolution structural MRI scans, sex hormone levels and gender role self-assessments were obtained in a large sample 89 men, 89 naturally cycling (NC) women, and 60 OC users. Men showed larger regional gray matter volumes than women in the cerebellum and bilateral clusters spanning the putamen and parts of the hippocampi/parahippocampi and fusiform gyri. In accordance with our hypotheses, a significant positive association of testosterone to hippocampal volumes was observed in women irrespective of OC use. Participant’s self-reported femininity was significantly positively associated with gray matter volumes in the left middle frontal gyrus (MFG) in men. In addition several differences between OC-users and NC women were identified.

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title: Gender-Role Differences in Spatial Ability: A Meta-Analytic Review
abstract: Although gender-related differences in highly gender typed cognitive abilities are of considerable interest to educators and cognitive researchers alike, relatively little progress has been made in understanding the psychological processes that lead to them. Nash (1979) proposed a gender-role mediation hypothesis for such differences, with particular emphasis on spatial ability. However, changes in gender equality and gender stereotypes in the decades since merit a re-examination of whether a gender-role association still holds (Feingold 1988). A meta-analysis of 12 studies that examined gender-role identity and mental rotation performance was conducted. These included studies from the United Kingdom, Canada, Poland, Croatia, and the United States of America. The mean effect size for masculinity was r = .30 for men and r = .23 for women; no association was found between femininity and mental rotation. This effect size was slightly larger than that found previously by Signorella and Jamison (1986), and exceeds many other factors known to influence spatial ability. The implications of gender-role mediation of gender differences are discussed and future research directions are identified.

title: Reproductive toxicology. Di-n-octylphthalate.
abstract: 1 Section of Sexual Medicine, Christian-Albrechts University, Kiel, Germany, 2 Department of Neurology, Christian-Albrechts University, Kiel, Germany, 3 NeuroImage Nord, Hamburg-Kiel-Lübeck, Germany, 4 Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom, 5 Department of Neurology, University Freiburg, Freiburg, Germany, 6 Section of Neuroradiology, Department of Neurosurgery, ChristianAlbrechts University, Kiel, Germany, 7 Department of Neurosurgery, Christian-Albrechts University, Kiel, Germany

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title: Cerebral sex dimorphism and sexual orientation
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title: Increased Cortical Thickness in Male-to-Female Transsexualism.
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To investigate potential neuroanatomical variations associated with transsexualism, we compared the regional thickness of the cerebral cortex between 24 MTF transsexuals who had not yet been treated with cross-sex hormones and 24 age-matched control males.



Results revealed thicker cortices in MTF transsexuals, both within regions of the left hemisphere (i.e., frontal and orbito-frontal cortex, central sulcus, perisylvian regions, paracentral gyrus) and right hemisphere (i.e., pre-/post-central gyrus, parietal cortex, temporal cortex, precuneus, fusiform, lingual, and orbito-frontal gyrus).



These findings provide further evidence that brain anatomy is associated with gender identity, where measures in MTF transsexuals appear to be shifted away from gender-congruent men.

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abstract: The five-factor model (FFM) is a widely used taxonomy of human personality; yet its neuro anatomical basis remains unclear. This is partly because past associations between gray-matter volume and FFM were driven by different surface-based morphometry (SBM) indices (i.e. cortical thickness, surface area, cortical folding or any combination of them). To overcome this limitation, we used Free-Surfer to study how variability in SBM measures was related to the FFM in n = 507 participants from the Human Connectome Project. Neuroticism was associated with thicker cortex and smaller area and folding in prefrontal–temporal regions. Extraversion was linked to thicker pre-cuneus and smaller superior temporal cortex area. Openness was linked to thinner cortex and greater area and folding in prefrontal–parietal regions. Agreeableness was correlated to thinner prefrontal cortex and smaller fusiform gyrus area. Conscientiousness was associated with thicker cortex and smaller area and folding in prefrontal regions. These findings demonstrate that anatomical variability in prefrontal cortices is linked to individual differences in the socio-cognitive dispositions described by the FFM. Cortical thickness and surface area/folding were inversely related each others as a function of different FFM traits (neuroticism, extraversion and consciousness vs openness), which may reflect brain maturational effects that predispose or protect against psychiatric disorders.

title: Effect of four different oral contraceptives on various sex hormones and serum-binding globulins.
abstract: In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on various hormone parameters and serum-binding globulins was investigated. Four groups with 25 volunteers each (18-35 years of age) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). The study was completed by 91 subjects. Blood samples were taken after at least 12 h of fasting on Day 21-26 of the preceding control cycle and on Day 18-21 of the first, third and sixth treatment cycle. The serum concentrations of free testosterone were significantly decreased by about 40-60% in all four groups, while those of dehydroepiandrosterone sulfate (DHEAS) showed a time-dependent decrease during treatment. Except for EE/EV/DNG, which increased prolactin significantly during the third and sixth cycles, no change was observed with the EE-containing preparations. There was a significant increase in the levels of serum-binding globulins during treatment, which differed according to the composition of the OCs used. The rise in sex hormone-binding globulin (SHBG) was highest during intake of 30EE/DNG (+320%) and lowest with EE/LNG (+80%), while the effect of 20EE/DNG and EE/EV/DNG was similar (+270%). The thyroxine-binding globulin (TBG) levels increased significantly, by 50-60%, during treatment with the DNG-containing formulations, while the effect of EE/LNG was less significant (+30%). The rise in corticosteroid-binding globulin (CBG), which occurred in all groups, was most pronounced in women treated with 30EE/DNG (+90%) and least with EE/EV/DNG (+55%), indicating a strong influence of EE and no effect of the progestogen component. In all treatment groups, the frequency of intracyclic bleeding rose in the first treatment cycle and decreased thereafter. Cycle control was significantly better with 30EE/DNG or EE/LNG than with 20EE/DNG or EE/EV/DNG. There was no significant change in blood pressure, body mass index or pulse rate throughout the study. In conclusion, the DNG-containing OCs caused a higher rise in SHBG and TBG levels than the LNG-containing preparation. The effects on CBG suggest a lesser hepatic effect of 2 mg EV as compared to 20 or 30 microg EE. In contrast to EE, the use of estradiol in OCs appeared to increase prolactin release, while the cycle control was better with the OC containing 30 microg EE.

title: Oral contraceptive pill use is associated with localized decreases in cortical thickness
abstract: Oral contraceptive pills (OCs), which are used to prevent pregnancy by the majority of women in the United States, contain steroid hormones that may affect the brain's structure and function. In this investigation, we tested the hypothesis that OC use is associated with differences in brain structure using a hypothesis‐driven, surface‐based approach. In 90 women, (44 OC users, 46 naturally‐cycling women), we compared the cortical thickness of brain regions that participate in the salience network and the default mode network, as well as the volume of subcortical regions in these networks. We found that OC use was associated with significantly lower cortical thickness measurements in the lateral orbitofrontal cortex and the posterior cingulate cortex. These regions are believed to be important for responding to rewards and evaluating internal states/incoming stimuli, respectively. Further investigations are needed to determine if cortical thinning in these regions are associated with behavioral changes, and also to identify whether OC use is causally or only indirectly related to these changes in brain morphology. Hum Brain Mapp 36:2644–2654, 2015.

title: Interactive effects of culture and sex hormones on the sex role self-concept
abstract: Sex role orientation, i.e., a person's masculinity or femininity, influences cognitive and emotional performance, like biological sex. While it is now widely accepted that sex differences are modulated by the hormonal status of female participants (menstrual cycle, hormonal contraceptive use), the question, whether hormonal status and sex hormones also modulate participants sex role orientation has hardly been addressed previously. The present study assessed sex role orientation and hormonal status as well as sex hormone levels in three samples of participants from two different cultures (Northern American, Middle European). Menstrual cycle phase did not affect participant's masculinity or femininity, but had a significant impact on reference group. While women in their follicular phase (low levels of female sex hormones) determined their masculinity and femininity in reference to men, women in their luteal phase (high levels of female sex hormones) determined their masculinity and femininity in reference to women. Hormonal contraceptive users rated themselves as significantly more feminine and less masculine than naturally cycling women. Furthermore, the impact of biological sex on the factorial structure of sex role orientation as well as the relationship of estrogen to masculinity/femininity was modulated by culture. We conclude that culture and sex hormones interactively affect sex role orientation and hormonal status of participants should be controlled for when assessing masculinity and/or femininity.

title: Hormonal contraception usage is associated with altered memory for an emotional story
abstract: Substantial evidence now documents sex-related influences on the neurobiology of emotional memory. Robust sex influences exist, for example, on the amygdala's role in emotional memory formation, as well as on retention of central information (gist) and detail for an emotional event. Evidence also suggests that the well-documented effects of stress hormones on memory depend upon sex hormone levels. Since hormonal contraception alters sex hormone levels, and must by extension alter sex/stress hormone interactions in memory, we examined whether the use of hormonal contraception also alters memory for an emotional story. Two groups of healthy female subjects--one naturally cycling, one using hormonal contraception--viewed either a brief, emotionally arousing story, or a closely matched, but more emotionally neutral story. Each subject's eye movements and pupil dilation changes were recorded as they viewed the story. Additionally, saliva samples were taken throughout the experimental session to examine salivary alpha-amylase, a biomarker for norepinephrine. A surprise free recall test one week later measured story memory in all subjects. Naturally cycling women exhibited enhanced memory of story details, but not of central information (gist), in the emotional compared with neutral story conditions. In contrast, women using hormonal contraception exhibited enhanced memory of gist, but not story details, in the emotional compared with neutral story conditions. Analysis of eye movements made while watching the stories indicated that the differences in memory could not be attributed either to a differential attention focus or to the degree of arousal induced by the stories in the two groups. These findings suggest that the use of hormonal contraception alters memory for an emotional event, perhaps by altering sex/stress hormone interactions in memory formation. They also suggest that further investigation of the mnemonic effects of these very widely used treatments is warranted.

title: Hormonal contraceptives masculinize brain activation patterns in the absence of behavioral changes in two numerical tasks
abstract: The aim of the present study was to identify, whether and how oral hormonal contraceptives (OCs) alter women's number processing. Behavioral performance and brain activation patterns (BOLD-response) of 14 OC-users were evaluated during two distinct numerical tasks (number comparison, number bisection) and compared to 16 men (high testosterone), and 16 naturally cycling women, once during their follicular (low hormone levels) and once during their luteal cycle phase (high progesterone). For both tasks, reliable sex differences and menstrual cycle dependent modulation have previously been described. If progestogenic effects of the synthetic progestins contained in OC play a predominant role, OC-users should be comparable to luteal women. If androgenic effects of the synthetic steroids exert the progestogenic actions, OC-users should be comparable to men. Likewise, if neither of the above are the case, the reduction of endogenous steroids by OCs should make OC-users comparable to follicular women. Our findings suggest that OC-users resemble follicular women in their behavioral performance, but show male-like brain activation patterns during both tasks. Analysis of brain-behavior relationships suggests that OC-users differ from naturally cycling women in the way they recruit their neural resources to deal with challenges of the tasks. We conclude that OCs, which are used by 100 million women worldwide, may have profound effects on cognition that have not been recognized so far.

title: Neuroimaging supports behavioral personality assessment: Overlapping activations during reflective and impulsive risk taking
abstract: Personality assessment has been challenged by the fact that different assessment methods (implicit measures, behavioral measures and explicit rating scales) show little or no convergence in behavioral studies. In this neuroimaging study we address for the first time, whether different assessment methods rely on separate or overlapping neuronal systems. Fifty nine healthy adult participants completed two objective personality tests of risk propensity: the more implicit Balloon Analogue Risk Task (BART) and the more explicit Game of Dice Task (GDT). Significant differences in activation, as well as connectivity patterns between both tasks were observed. In both tasks, risky decisions yielded significantly stronger activations than safe decisions in the bilateral caudate, as well as the bilateral Insula. The finding of overlapping brain areas validates different assessment methods, despite their behavioral non-convergence. This suggests that neuroimaging can be an important tool of validation in the field of personality assessment.

title: Sex differences in number processing: Differential systems for subtraction and multiplication were confirmed in men, but not in women
abstract: Neuroimaging studies suggest segregated neuronal systems underlying number magnitude processing (e.g. subtraction) and arithmetic fact retrieval (e.g. multiplication). While number magnitude processing is thought to rely on the intraparietal sulcus (IPS) bilaterally, arithmetic fact retrieval is thought to rely on the left angular gyrus (AG). However, evidence from brain damaged patients and brain stimulation challenges this view and suggests considerable overlap between the systems underlying number magnitude processing and arithmetic fact retrieval. This study investigates, whether sex differences in number processing can account for these conflicting findings. A subtraction and a multiplication task were administered to 40 men and 34 women in their luteal phase during functional MRI. Replicating previous studies in men, we found the IPS to be more strongly activated during subtraction than multiplication, and the AG to be more strongly activated during multiplication than subtraction. However, no differences between the two tasks were observed in women.

title: Ratings of self and peers on sex role attributes and their relation to self-esteem and conceptions of masculinity and femininity.
abstract: Male (N = 248) and female (N = 282) subjects were given the Personal Attributes Questionnaire consisting of 55 bipolar attributes drawn from the Sex Role Stereotype Questionnaire by Rosenkrantz, Vogel, Bee, Broverman, and Broverman and were asked to rate themselves and then to compare directly the typical male and female college student. Self-ratings were divided into male-valued (stereotypically masculine attributes judged more desirable for both sexes), female-valued, and sex-specific items. Also administered was the Attitudes Toward Women Scale and a measure of social self-esteem. Correlations of the self-ratings with stereotype scores and the Attitudes Toward Women Scale were low in magnitude, suggesting that sex role expectations do not distort self-concepts. For both men and women, "femininity" on the female-valued self items and "masculinity" on the male-valued items were positively correlated, and both significantly related to self-esteem. The implications of the results for a concept of masculinity and femininity as a duality, characteristic of all individuals, and the use of the self-rating scales for measuring masculinity, femininity, and androgyny were discussed.

title: Why can't a man be more like a woman? Sex differences in Big Five personality traits across 55 cultures.
abstract: Previous research suggested that sex differences in personality traits are larger in prosperous, healthy, and egalitarian cultures in which women have more opportunities equal with those of men. In this article, the authors report cross-cultural findings in which this unintuitive result was replicated across samples from 55 nations (N = 17,637). On responses to the Big Five Inventory, women reported higher levels of neuroticism, extraversion, agreeableness, and conscientiousness than did men across most nations. These findings converge with previous studies in which different Big Five measures and more limited samples of nations were used. Overall, higher levels of human development--including long and healthy life, equal access to knowledge and education, and economic wealth--were the main nation-level predictors of larger sex differences in personality. Changes in men's personality traits appeared to be the primary cause of sex difference variation across cultures. It is proposed that heightened levels of sexual dimorphism result from personality traits of men and women being less constrained and more able to naturally diverge in developed nations. In less fortunate social and economic conditions, innate personality differences between men and women may be attenuated.

title: Testing Predictions From Personality Neuroscience
abstract: We used a new theory of the biological basis of the Big Five personality traits to generate hypotheses about the association of each trait with the volume of different brain regions. Controlling for age, sex, and whole-brain volume, results from structural magnetic resonance imaging of 116 healthy adults supported our hypotheses for four of the five traits: Extraversion, Neuroticism, Agreeableness, and Conscientiousness. Extraversion covaried with volume of medial orbitofrontal cortex, a brain region involved in processing reward information. Neuroticism covaried with volume of brain regions associated with threat, punishment, and negative affect. Agreeableness covaried with volume in regions that process information about the intentions and mental states of other individuals. Conscientiousness covaried with volume in lateral prefrontal cortex, a region involved in planning and the voluntary control of behavior. These findings support our biologically based, explanatory model of the Big Five and demonstrate the potential of personality neuroscience (i.e., the systematic study of individual differences in personality using neuroscience methods) as a discipline.

title: Correlations Between Personality and Brain Structure: A Crucial Role of Gender
abstract: Previous studies have shown that males and females differ in personality and gender differences have also been reported in brain structure. However, effects of gender on this "personality-brain" relationship are yet unknown. We therefore investigated if the neural correlates of personality differ between males and females. Whole brain voxel-based morphometry was used to investigate the influence of gender on associations between NEO FFI personality traits and gray matter volume (GMV) in a matched sample of 182 males and 182 females. In order to assess associations independent of and dependent on gender, personality-GMV relationships were tested across the entire sample and separately for males and females. There were no significant correlations between any personality scale and GMV in the analyses across the entire sample. In contrast, significant associations with GMV were detected for neuroticism, extraversion, and conscientiousness only in males. Interestingly, GMV in left precuneus/parieto-occipital sulcus correlated with all 3 traits. Thus, our results indicate that brain structure-personality relationships are highly dependent on gender, which might be attributable to hormonal interplays or differences in brain organization between males and females. Our results thus provide possible neural substrates of personality-behavior relationships and underline the important role of gender in these associations.

title: Sex Differences in the Flexibility of Sexual Orientation: A Multidimensional Retrospective Assessment
abstract: The flexibility of sexual orientation in men and women was examined by assessing self-reported change over time for three dimensions of sexual orientation (sexual fantasy, romantic attraction, and sexual behavior) across three categorical classifications of current sexual orientation (heterosexual, bisexual, and gay). The primary purpose of the study was to determine if there were sex differences in the flexibility (i.e., change over time) of sexual orientation and how such differences were manifested across different dimensions of orientation over the lifespan. Retrospective, life-long ratings of sexual orientation were made by 762 currently self-identified heterosexual, bisexual, and gay men and women, aged 36 to 60, via a self-report questionnaire. Cumulative change scores were derived for each of the three dimensions (fantasy, romantic attraction, and sexual behavior) of orientation by summing the differences between ratings over consecutive 5-year historical time periods (from age 16 to the present). Sex differences were observed for most, but not all, classification groups. There were significant sex differences in reported change in orientation over time for gays and heterosexuals, with women reporting greater change in orientation over time than did men. Bisexual men and women did not differ with respect to self-reported change in orientation.