Gender, sex and all that ‎ > ‎ What causes transsexualism? ‎ > ‎ References 5.a: Causes – Hormone exposure – Human studies An endocrine disrupting chemical, bisphenol A: could it be associated with sex differentiation in brain regarding to transsexuality? Transsexuality is characterised by a belief of having been born in a wrong body. Sexual differentiation of genitals take place in the first 2 months of pregnancy. Sexual differentiation of brain takes place in the second half of pregnancy. It is found that there is structural sex differences in the central nucleus of the bed nucleus of the stria terminalis (BSTc). Structural differences were found to be reversed in transsexual people. In humans main mechanism appears to involve a direct effect of testosterone on the developing brain. Direct effect of testosterone on developing brain in boys and lack of this effect in girls are crucial factors in the development of male and female gender identity. The origin of transsexuality is based on the fact that the differentiation of sexual organs takes place before the sexual differentiation of the brain. It was found a reversal in BSTc. In men this area is twice the size of that in women. In male-to-female transsexuals they found female BSTc. They had shown that sex reversal of the differences in the BSTc were independent of changing hormone levels in adulthood. The size of BSTc and the number of neurons match the gender that transsexuals feel they belong to, not the sex of their sexual organs. An endocrine disrupting chemical (EDC), bisphenol A (BPA), acts as oestrogen mimic compund. BPA may affect sexual differentiation of brain and cause reversal of differentiation in male to female transsexual as female brain. Brain expresses the oestrogen receptors and other hormone receptors making it a potential target for EDC. Transsexuality presume a combination of a genetic background and an early effect on interaction of sex hormones with developing brain during critical foetal period. We hypothesize that exposure to BPA may be a cause for transsexualism. Author/-s: Banu Sarer Yurekli; Nilufer Ozdemir Kutbay; Fusun Saygili Publication: Endocrine Abstracts, 2015 Web link: http://www.endocrine-abstracts.org/ea/0037/ea0037EP208.htm Early androgen exposure and human gender development During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This approach has recently begun to be used, with some promising results relating testosterone during the first few months of postnatal life to later gender-typical play behavior. In replicating and extending these findings, it may be important to assess testosterone when it is maximal (months 1 to 2 postnatal) and to take advantage of the increased reliability afforded by repeated sampling. Author/-s: Melissa Hines; Mihaela Constantinescu; Debra Spencer Publication: Biology of Sex Differences, 2015 Web link: http://www.bsd-journal.com/content/pdf/s13293-015-0022-1.pdf Gender identity development in children with heightened prenatal androgen exposure Understanding how gender identity develops has important theoretical implications for typically developing populations and clinical implications for those with gender variability or dysphoria (e.g. low contentment with one’s assigned gender) and practical implications for the assignment and management of gender in children born with ambiguous sex/genitalia. While chromosomal females exposed to heightened levels of androgens prenatally consistently express later masculinised/defeminised gendered behaviour, the relationship between prenatal androgen exposure and gender identity development (masculinisation/defeminisation and feelings associated with this) is less consistent. Between-group differences in gender identity, gendered behaviour, gender typicality, gender contentedness, and felt pressure for gender conformity were examined in a sample of children (age 7 – 11) with congenital adrenal hyperplasia (CAH; 23 males, 26 females) together with unaffected siblings (19 males, 29 females). Analyses reveal reduced gender typicality and gender contentedness in girls with CAH together with reduced female gender identity and increased cross-sex gendered behaviour. Bootstrapping mediation analysis examining gender typicality, gender contentedness, and gendered behaviour as mediators between prenatal androgen exposure typicality and gender identity revealed two important relationships: (1) gendered behaviour mediated the relationship between prenatal androgen exposure typicality and gender identity and, (2) this mediation was moderated by gender typicality and gender contentedness. These findings suggest that, for girls with CAH, the increased expression of cross-sex gendered behaviour contributes to the development of desires to be the other sex and that this relationship may depend upon feelings of gender typicality and contentedness. Author/-s: Miranda L. Abild Publication: Dissertation, Department of Psychology, University of Cambridge, 2015 Web link: http://mlabild.webs.com/MPhil%20FINAL%20(revised%20-%20for%20print)%20(1).pdf Gendered Development How does human behavior come to be gendered, and how do gendered behaviors change or remain stable over time? Although men and women, as well as girls and boys, are largely similar psychologically and behaviorally, there are some areas of gender difference. These include gender identity; sexual orientation; childhood play behaviors, such as toy, playmate, and activity preferences; personality characteristics, such as aggression and empathy; and some specific spatial, mathematical, and verbal abilities. The incidence of many psychiatric disorders also differs by sex. These gender differences appear to result from numerous factors and their interactions. These include genetic information on the sex chromosomes; concentrations of gonadal steroids, particularly testosterone, before and shortly after birth; socialization by parents, peers, teachers, and strangers; and cognitive developmental processes. Gender identity also is a mechanism for acquiring gendered behavior; based on this identity, children self-socialize gendered behavior. These factors have been shown to act individually to influence gendered outcomes. They are also likely to interact with one another to shape gender development, but little research has investigated these interactions. An understanding of gendered development is important for addressing differences between the sexes in social roles and economic status, and should also be relevant to understanding and ameliorating psychiatric disorders that differ by gender. A complete understanding will probably require developmental systems approaches to understanding change and stability over time, but, thus far, such approaches have been uncommon. Author/-s: Melissa Hines Publication: Handbook of Child Psychology and Developmental Science, 2015 Web link: http://onlinelibrary.wiley.com/doi/10.1002/9781118963418.childpsy320/abstract Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4 years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3 months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development. Author/-s: Vickie Pasterski; Carlo L. Acerini; David B. Dunger; Ken K. Ong; Ieuan A. Hughes; Ajay Thankamony; Melissa Hines Publication: Hormones and Behavior, 2015 Web link: http://www.sciencedirect.com/science/article/pii/S0018506X15000033 Psychomedical care in gender identity dysphoria during adolescence Introduction: In the clinical literature, the term gender dysphoria is used to define the perception of rejection that a person has to the fact of being male or female. In children and adolescents, gender identity dysphoria is a complex clinical entity. The result of entity is variable and uncertain, but in the end only a few will be transsexuals in adulthood. Objectives To review the current status of the etiology and prevalence, Spanish health care protocols, DSM-V, ICD-10 and international standards.

Psychomedical intervention in under 18 year-olds. Methodology A review of PubMed and UpToDate databases.

Presentation of a clinical case in adolescence woman > man. Results and conclusions There is evidence of a hormonal impact on the etiology of gender identity dysphoria and an underestimation of its prevalence.

Relevance to DSM-V, including the replacement of the term «gender identity disorder» by «dysphoria gender identity», and thus the partial removal of the previous disease connotation.

The seventh edition of the international standards World Professional Association for Transgender Health highlight the role of the therapist for advice on the way to the transition.

The Spanish 2012 guide stands out for its wealth of details and explanations, with a language targeted at different professionals.

Dysphoria gender identity must be studied by a multidisciplinary team, in which the psychotherapist must be expert in developmental psychopathology and evaluate emotional and behavioral problems. Author/-s: Isabel Sánchez Lorenzo; Juan José Mora Mesa; Olga Oviedo de Lúcas Publication: Revista de Psiquiatría y Salud Mental, 2015 Web link: http://www.sciencedirect.com/science/article/pii/S188898911500097X Brain responses to sexual images in 46,XY women with complete androgen insensitivity syndrome are female-typical Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images. We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls. Author/-s: Stephan Hamann; Jennifer Stevens; Janice Hassett Vick; Kristina Bryk; Charmian A.Quigley; Sheri A. Berenbaum; Kim Wallen Publication: Hormones and behaviour, 2014 Web link: http://www.sciencedirect.com/science/article/pii/S0018506X14001998 Exposure to prenatal life events stress is associated with masculinized play behavior in girls Previous research has shown that prenatal exposure to endocrine-disrupting chemicals can alter children's neurodevelopment, including sex-typed behavior, and that it can do so in different ways in males and females. Non-chemical exposures, including psychosocial stress, may disrupt the prenatal hormonal milieu as well. To date, only one published study has prospectively examined the relationship between exposure to prenatal stress and gender-specific play behavior during childhood, finding masculinized play behavior in girls who experienced high prenatal life events stress, but no associations in boys. Here we examine this question in a second prospective cohort from the Study for Future Families. Pregnant women completed questionnaires on stressful life events during pregnancy, and those who reported one or more events were considered "stressed". Families were recontacted several years later (mean age of index child: 4.9 years), and mothers completed a questionnaire including the validated Preschool Activities Inventory (PSAI), which measures sexually dimorphic play behavior. In sex-stratified analyses, after adjusting for child's age, parental attitudes toward gender-atypical play, age and sex of siblings, and other relevant covariates, girls (n=72) exposed to prenatal life events stress had higher scores on the PSAI masculine sub-scale (β=3.48; p=0.006) and showed a trend toward higher (more masculine) composite scores (β=2.63; p=0.08). By contrast, in males (n=74), there was a trend toward an association between prenatal stress and higher PSAI feminine sub-scale scores (β=2.23; p=0.10), but no association with masculine or composite scores. These data confirm previous findings in humans and animal models suggesting that prenatal stress is a non-chemical endocrine disruptor that may have androgenic effects on female fetuses and anti-androgenic effects on male fetuses. Author/-s: E. S. Barrett; J. B. Redmon; C. Wang; A. Sparks; S. H. Swan Publication: Neurotoxicology, 2014 Web link: http://europepmc.org/abstract/MED/24406375 Finger length ratios in Serbian transsexuals Abstract: Atypical prenatal hormone exposure could be a factor in the development of transsexualism. There is evidence that the 2nd and 4th digit ratio (2D : 4D) associates negatively with prenatal testosterone and positively with estrogens. The aim was to assess the difference in 2D : 4D between female to male transsexuals (FMT) and male to female transsexuals (MFT) and controls. We examined 42 MFT, 38 FMT, and 45 control males and 48 control females. Precise measurements were made by X-rays at the ventral surface of both hands from the basal crease of the digit to the tip using vernier calliper. Control male and female patients had larger 2D : 4D of the right hand when compared to the left hand. Control male’s left hand ratio was lower than in control female’s left hand. There was no difference in 2D : 4D between MFT and control males. MFT showed similar 2D : 4D of the right hand with control women indicating possible influencing factor in embryogenesis and consequently finger length changes. FMT showed the lowest 2D : 4D of the left hand when compared to the control males and females. Results of our study go in favour of the biological aetiology of transsexualism. Conclusion: Transsexualism in humans is biological in origin. Our findings support a biological etiology of MFT implicating decreased prenatal androgen exposure in MFT. 2D:4D could be potentially used as a marker for prenatal androgen exposure. Author/-s: Svetlana Vujović; Srdjan Popović; Ljiljana Mrvošević Marojević; Miomira Ivović; Milina Tančić-Gajić; Miloš Stojanović; Ljiljana V. Marina; Marija Barać; Branko Barać; Milena Kovačević; Dragana Duišin; Jasmina Barišić; Miroslav L. Djordjević; Dragan Micić Publication: The Scientific World Journal, 2014 Web link: http://www.hindawi.com/journals/tswj/aip/763563/ Identical Reared Apart Twins Concordant for Transsexuality A growing twin-based literature supports genetic influence on gender identity development. An international survey of adult transsexual twin pairs reported transition concordance values of 33.3 % (13 ∕ 39) for identical [monozygotic (MZ)] male pairs and 22.9 % (8 ∕ 35) for MZ female pairs. By contrast, transition concordance values for fraternal [dizygotic (DZ)] male and female twins were zero or approached zero (1 ∕ 36), consistent with genetic influence. Here, we report the first case of transsexualism in both reared apart brothers of a male-to-female MZ twin pair. One twin (AT) committed suicide at age 35 years; therefore, interviews were conducted in 2012–2013 with the surviving co-twin (LT) at age 50 years. Prior to AT’s death, DNA testing had confirmed the twins’ monozygosity, as did a twin-typing questionnaire administered to LT. […] LT learned that he had a twin at the age of 15 when his mother revealed this secret information inadvertently. When the twins were 15.5 years of age, LT’s mother arranged a reunion. Prior to meeting, by age 8 years both twins experienced gender discomfort, engaged in cross-dressing, and felt that they should have been born as the other gender. Also prior to meeting, both twins experienced unease with the anticipated and actual secondary sexual development of puberty. Furthermore, unbeknownst to his twin, at age 14 years LT was fully committed to undergoing sex reassignment surgery and so convinced his mother that she took him to see an urologist. Thus, both twins met the diagnostic criteria of the fifth edition of the Diagnostic and Statistical Manual (DSM-5) for gender dysphoria, in particular persistent cross-gender identification and a strong desire to change the sexual characteristics to those of the other gender. Genetic effects on transsexuality are strongly indicated by this unique case study. The nature and extent of family support also affect the behavioral adjustment of transsexual individuals, as evidenced by LT’s more favorable outcome and AT’s tragic outcome. Author/-s: Nancy Segal; Milton Diamond Publication: Letter to the Editor, Journal of Clinical and Experimental Medicine, 2014 Web link: http://hawaii.edu/PCSS/biblio/articles/2010to2014/2014-identical.html Increased Cross-Gender Identification Independent of Gender Role Behavior in Girls with Congenital Adrenal Hyperplasia: Results from a Standardized Assessment of 4- to 11-Year-Old Children While reports showing a link between prenatal androgen exposure and human gender role behavior are consistent and the effects are robust, associations to gender identity or cross-gender identification are less clear. The aim of the current study was to investigate potential cross-gender identification in girls exposed prenatally to high concentrations of androgens due to classical congenital adrenal hyperplasia (CAH). Assessment included two standardized measures and a short parent interview assessing frequency of behavioral features of cross-gender identification as conceptualized in Part A of the diagnostic criteria for gender identity disorder (GID) in the DSM-IV-TR. Next, because existing measures may have conflated gender role behavior with gender identity and because the distinction is potentially informative, we factor analyzed items from the measures which included both gender identity and gender role items to establish the independence of the two constructs. Participants were 43 girls and 38 boys with CAH and 41 unaffected female and 31 unaffected male relatives, aged 4- to 11-years. Girls with CAH had more cross-gender responses than female controls on all three measures of cross-gender identification as well as on a composite measure of gender identity independent of gender role behavior. Furthermore, parent report indicated that 5/39 (12.8%) of the girls with CAH exhibited cross-gender behavior in all five behavioral domains which comprise the cross-gender identification component of GID compared to 0/105 (0.0%) of the children in the other three groups combined. These data suggest that girls exposed to high concentrations of androgens prenatally are more likely to show cross-gender identification than girls without CAH or boys with and without CAH. Our findings suggest that prenatal androgen exposure could play a role in gender identity development in healthy children, and may be relevant to gender assignment in cases of prenatal hormone disruption, including, in particular, cases of severely virilized 46,XX CAH. Author/-s: Vickie Pasterski; Kenneth J. Zucker; Peter C. Hindmarsh; Ieuan A. Hughes; Carlo Acerin; Debra Spencer; Sharon Neufeld; Melissa Hines Publication: Awaiting publication by Springer, 2014 Web link: https://www.repository.cam.ac.uk/handle/1810/245845 Neural Activation During Mental Rotation in Complete Androgen Insensitivity Syndrome: the Influence of Sex Hormones and Sex Chromosomes Sex hormones, androgens in particular, are hypothesized to play a key role in the sexual differentiation of the human brain. However, possible direct effects of the sex chromosomes, that is, XX or XY, have not been well studied in humans. Individuals with complete androgen insensitivity syndrome (CAIS), who have a 46,XY karyotype but a female phenotype due to a complete androgen resistance, enable us to study the separate effects of gonadal hormones versus sex chromosomes on neural sex differences. Therefore, in the present study, we compared 46,XY men (n = 30) and 46,XX women (n = 29) to 46,XY individuals with CAIS (n = 21) on a mental rotation task using functional magnetic resonance imaging. Previously reported sex differences in neural activation during mental rotation were replicated in the control groups, with control men showing more activation in the inferior parietal lobe than control women. Individuals with CAIS showed a female-like neural activation pattern in the parietal lobe, indicating feminization of the brain in CAIS. Furthermore, this first neuroimaging study in individuals with CAIS provides evidence that sex differences in regional brain function during mental rotation are most likely not directly driven by genetic sex, but rather reflect gonadal hormone exposure. Author/-s: Judy van Hemmen; Dick J. Veltman; Elseline Hoekzema; Peggy T. Cohen-Kettenis; Arianne B. Dessens; Julie Bakker Publication: Cerebral Cortex, 2014 Web link: http://cercor.oxfordjournals.org/content/early/2014/11/28/cercor.bhu280.abstract Neurobiological bases of gender differences The study of gender differences in neuroscience is quite recently but demostrate the sexual brain dimorphism. The aim of this review is study the anatomic and functional gender brain differences. We examined the differences in the brain structures, morphologie, volume, gray/white matter ratio and laterality. We analized the hormonal influence in body asymmetry development and in the abilities acquisition. For all brain structures, male volumes were greater then female, but the gray/white matter ratio was consistenly higher across structures in women than men. The cingulate gyrus and insula exhibit strong asymmetries. The prenatal androgens stimule the development of right brain hemisphere and the right hemibody. The early organizational effects of sex steroides on the mammalian brain imply differences between men and women in some specific cognitive abilities. Author/-s: Teresa Guilera Lladós Publication: [to be completed], 2014 Web link: http://www.imedicinas.com/pfw_files/cma/gdo_upload/m610/Bases_neurobiologicas_de_las_diferencias_de_genero.doc Otoacoustic Emissions, Auditory Evoked Potentials and Self-Reported Gender in People Affected by Disorders of Sex Development (DSD) Both otoacoustic emissions (OAEs) and auditory evoked potentials (AEPs) are sexually dimorphic, and both are believed to be influenced by prenatal androgen exposure. OAEs and AEPs were collected from people affected by 1 of 3 categories of disorders of sex development (DSD) – (1) women with complete androgen insensitivity syndrome (CAIS); (2) women with congenital adrenal hyperplasia (CAH); and (3) individuals with 46,XY DSD including prenatal androgen exposure who developed a male gender despite initial rearing as females (men with DSD). Gender identity (GI) and role (GR) were measured both retrospectively and at the time of study participation, using standardized questionnaires. The main objective of this study was to determine if patterns of OAEs and AEPs correlate with gender in people affected by DSD and in controls. A second objective was to assess if OAE and AEP patterns differed according to degrees of prenatal androgen exposure across groups. Control males, men with DSD, and women with CAH produced fewer spontaneous OAEs (SOAEs) – the male-typical pattern – than control females and women with CAIS. Additionally, the number of SOAEs produced correlated with gender development across all groups tested. Although some sex differences in AEPs were observed between control males and females, AEP measures did not correlate with gender development, nor did they vary according to degrees of prenatal androgen exposure, among people with DSD. Thus, OAEs, but not AEPs, may prove useful as bioassays for assessing early brain exposure to androgens and predicting gender development in people with DSD. Author/-s: Amy B. Wisniewski; Blas Espinoza-Varas; Christopher E. Aston; Shelagh Edmundson; Craig A. Champlin; Edward G. Pasanen; Dennis McFadden Publication: Hormones and Behaviour, 2014 Web link: http://www.sciencedirect.com/science/article/pii/S0018506X14001391 Postnatal Testosterone Concentrations and Male Social Development Converging evidence from over 40years of behavioral research indicates that higher testicular androgens in prenatal life and at puberty contribute to the masculinization of human behavior. However, the behavioral significance of the transient activation of the hypothalamic–pituitary–gonadal (HPG) axis in early postnatal life remains largely unknown. Although early research on non-human primates indicated that suppression of the postnatal surge in testicular androgens had no measurable effects on the later expression of the male behavioral phenotype, recent research from our laboratory suggests that postnatal testosterone concentrations influence male infant preferences for larger social groups and temperament characteristics associated with the later development of aggression. In later assessment of gender-linked behavior in the second year of life, concentrations of testosterone at 3–4 months of age were unrelated to toy choices and activity levels during toy play. However, higher concentrations of testosterone predicted less vocalization in toddlers and higher parental ratings on an established screening measure for autism spectrum disorder. These findings suggest a role of the transient activation of the HPG axis in the development of typical and atypical male social relations and suggest that it may be useful in future research on the exaggerated rise in testosterone secretion in preterm infants or exposure to hormone disruptors in early postnatal life to include assessment of gender-relevant behavioral outcomes, including childhood disorders with sex-biased prevalence rates. Author/-s: Gerianne M. Alexander Publication: Froniters in Endocrinology, 2014 Web link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930918/ Sex Differentiation: Organizing Effects of Sex Hormones Men and women differ, not only in their anatomy but also in their behavior. Research using animal models has convincingly shown that sex differences in the brain and behavior are induced by sex hormones during a specific, hormone-sensitive period during early development. Thus, a male-typical brain is organized under the influence of testosterone, mostly acting during fetal development, whereas a female-typical brain is organized under the influence of estradiol, mostly acting after birth, during a specific prepubertal period. Sex differences in behavior reflect sex differences in the brain, mostly in the hypothalamus and the olfactory system, the latter being important in mate selection. There is also evidence, albeit clinical, for a role of testosterone in the sexual differentiation of the human brain, in particular in inducing male gender role behavior and heterosexual orientation. However, whether estradiol is involved in the development of a female brain in humans still needs to be elucidated. Author/-s: Julie Bakker Publication: Focus on Sexuality Research, 2014 Web link: http://link.springer.com/chapter/10.1007/978-1-4614-7441-8_1 The effect of 5a-reductase-2 deficiency on human fertility A most interesting and intriguing male disorder of sexual differentiation is due to 5α-reductase-2 isoenzyme deficiency. These males are born with ambiguous external genitalia due to a deficiency in their ability to catalyze the conversion of testosterone to dihydrotestosterone (DHT). DHT is a potent androgen responsible for differentiation of the urogenital sinus and genital tubercle into the external genitalia, urethra and prostate. Affected males are born with a clitoral-like phallus, bifid scrotum, hypospadias, blind shallow vaginal pouch from incomplete closure of the urogenital sinus and a rudimentary prostate. At puberty, the surge in mainly testosterone production prompts virilization, causing most to choose gender reassignment to male. Fertility is a challenge for affected men for several reasons. Uncorrected cryptorchidism is associated with low sperm production, and there is evidence of defective transformation of spermatogonia into spermatocytes. The underdeveloped prostate and consequent low semen volumes affect sperm transport. Additionally, semen may not liquefy due to a lack of prostate-specific antigen. In this review, we discuss the 5α-reductase-2 deficiency syndrome and its impact on human fertility. Author/-s: Hey-Joo Kang; Julianne Imperato-McGinley; Yuan-Shan Zhu; Zev Rosenwaks Publication: Fertility and sterility, 2014 Web link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031759/ White Matter Microstructure in Transsexuals and Controls Investigated by Diffusion Tensor Imaging Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects' sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development. Author/-s: Georg S. Kranz; Andreas Hahn; Ulrike Kaufmann; Martin Küblböck; Allan Hummer; Sebastian Ganger; Rene Seiger; Dietmar Winkler; Dick F. Swaab; Christian Windischberger, Siegfried Kasper; Rupert Lanzenberger Publication: The Journal of Neuroscience, 2014 Web link: http://www.jneurosci.org/content/34/46/15466.short This study was reported in some media articles: http://mobil.derstandard.at/2000010065276/Transgender-Neuronen-anders-vernetzt and http://www.sciencedaily.com/releases/2015/01/150107082133.htm . Are there parental socialization effects on the sex-typed behavior of individuals with congenital adrenal hyperplasia? Influences of prenatal androgen exposure on human sex-typical behavior have been established largely through studies of individuals with congenital adrenal hyperplasia (CAH). However, evidence that addresses the potential confounding influence of parental socialization is limited. Parental socialization and its relationship to sex-typical toy play and spatial ability were investigated in two samples involving 137 individuals with CAH and 107 healthy controls. Females with CAH showed more boy-typical toy play and better targeting performance than control females, but did not differ in mental rotations performance. Males with CAH showed worse mental rotations performance than control males, but did not differ in sex-typical toy play or targeting. Reported parental encouragement of girl-typical toy play correlated with girl-typical toy play in all four groups. Moreover, parents reported encouraging less girl-typical, and more boy-typical, toy play in females with CAH than in control females and this reported encouragement partially mediated the relationship between CAH status and sex-typical toy play. Other evidence suggests that the reported parental encouragement of sex-atypical toy play in girls with CAH may be a response to the girls' preferences for boys' toys. Nevertheless, this encouragement could further increase boy-typical behavior in girls with CAH. In contrast to the results for toy play, we found no differential parental socialization for spatial activities and little evidence linking parental socialization to spatial ability. Overall, evidence suggests that prenatal androgen exposure and parental socialization both contribute to sex-typical toy play. Author/-s: W. I. Wong; V. Pasterski; P. C. Hindmarsh; M. E. Geffner; M. Hines Publication: Archives of sexual behaviour, 2013 Web link: http://www.ncbi.nlm.nih.gov/pubmed/22810998 Behavioral Sexual Dimorphism in School-Age Children and Early Developmental Exposure to Dioxins and PCBs: A Follow-Up Study of the Duisburg Cohort Background: Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that have been characterized as endocrine disrupting chemicals (EDCs). Objectives: Within the Duisburg birth cohort study we studied associations of prenatal exposure to PCDD/Fs and PCBs with parent-reported sexually dimorphic behavior in children. Methods: We measured lipid-based and WHO 2005 -TEq-standardized PCDD/Fs and PCBs in maternal blood samples and in early breast milk using gas chromatography/high-resolution mass-spectrometry (GC/HRMS). At the age of 6–8 years parents (mostly mothers) reported sex-typical characteristics, preferred toys and play activities using the Preschool Activities Inventory (PSAI) which was used to derive feminine, masculine and difference (feminine – masculine) scores. We estimated exposure-outcome associations using multivariate linear regression. Between 91 and 109 children were included in this follow-up. Results: Mean blood levels of WHO 2005 TEq-standardized dioxins (Σ PCDD/Fs) were 14.5 ± 6.4 pg/g blood lipids, and of Σ PCBs 6.9 ± 3.8 pg/g blood lipids, with similar values for milk lipids. Regression analyses revealed some highly significant interactions between sex and exposure, e.g. for Σ PCBs in milk, pronounced positive (boys: β = 3.24; CI = 1.35, 5.14) or negative (girls: β = −3.59; CI = −1.10, −6.08) associations with reported femininity. Less pronounced and mostly insignificant but consistent associations were found for the masculinity score, positive for boys and negative for girls. Conclusions: Based on our results and the findings of previous studies, we conclude that there is sufficient evidence that EDCs modify behavioral sexual dimorphism in children, presumably by interacting with the hypothalamic-pituitary-gonadal (HPG) axis. Author/-s: Gerhard Winneke; Ulrich Ranft; Jürgen Wittsiepe; Monika Kasper-Sonnenberg; Peter Fürst; Ursula Krämer; Gabriele Seitner; Michael Wilhelm Publication: Environmental health perspectives, 2013 Web link: http://ehp.niehs.nih.gov/wp-content/uploads/121/11/ehp.1306533.pdf Digit ratios (2D:4D), postnatal testosterone and eye contact in toddlers Previous research has shown an association between eye contact and prenatal testosterone measured in amniocenteses samples. The purpose of this study was to test the association between eye contact and prenatal androgen action measured via second to fourth digit ratios (2D:4D ratios), and to explore the relationship between eye contact and postnatal testosterone levels. Participants included 72 children, between the ages of 18 and 24 months, and their parents. Salivary testosterone levels were obtained when children were 3-months old. At 18-months, 2D:4D ratios were measured and parent-child dyads participated in an 8-min play session that was recorded and later coded for duration and frequency of eye contact. Results indicated that larger 2D:4D ratios (indicative of lower androgen levels) significantly predicted longer duration and more frequency of eye contact, while postnatal testosterone levels were unrelated to eye contact. These novel findings suggest prenatal androgens may influence the emergence of social development. Author/-s: J. Saenz; Gerianne M. Alexander Publication: Biological psychology, 2013 Web link: http://www.ncbi.nlm.nih.gov/pubmed/23707563 From Gender Variance to Gender Dysphoria: Psychosexual development of gender atypical children and adolescents Summary: Children may show variability in their gender role behaviors, interests and preferences and/or their experienced gender identity (their experience to be male, female or a different gender). Within the male-female continuum of gender role expressions and gender identity three groups can be distinguished. First, the gender normative children: Their gender role and gender identity are congruent with their natal sex. Second, the gender variant children: These children show (mild) cross-gender behaviors, interests and preferences, and may experience a gender identity which is congruent with their natal sex to a lesser extent than is the case in gender normative children. And third, the gender dysphoric children: These children show extreme and enduring forms of cross-gender role expressions, experience a cross-gender identity and fulfill the criteria of a DSM-IV-TR diagnosis of Gender Identity Disorder (GID) (American Psychiatric Association 2000). In contrast to most of the gender variant children, gender dysphoric children may need clinical attention as a result of significant distress or a significant risk of distress, and/or impairment in important areas of functioning. Knowledge about the future development, the trajectories and possible associated factors of gender non-normative children (both gender variant and genderdysphoric) is however limited.

The studies described in this thesis aimed to enhance our understanding of the development of gender variant and gender dysphoric children and adolescents, and to identify factors associated with the persistence and desistence of gender dysphoria. In chapter 2 , we provided an overview of what is currently known about the trajectories and contributing factors to gender identity development, particularly during adolescence in the general population and in gender variant/gender dysphoric youth. Compared to what is known from gender identity development in gender variant or gender dysphoric children, studies of normative gender identity development during adolescence in the general population are lacking behind. With regard to the factors contributing to non-normative gender identity development, earlier studies mainly focused on the role of psychosocial factors. Factors such as elevated levels of psychopathology in the parents, increased anxiety of the child, and a lack of parental limit setting have been put forward as possible determinants. However, the evidence from these studies showed to be equivocal and it is unclear whether the factors that were associated with a non-normative gender identity development were the cause of this development or a consequence of the gender variance or gender dysphoria. More recently, research has focused on the role of biological factors on a non-normative gender identity development. Studies of individuals with a Disorder of Sex Development (DSD), congenital condi- tions in which the development of chromosomal, gonadal and/or anatomical sex is atypical (Hughes et al. 2006), point to the role of prenatal exposure to gonadal hormones and their effects on gender role behavior and possibly on gender identity development. From post mortem, neuropsychological, and brain imaging studies of individuals with gender dysphoria, differences between gender dysphoric individuals and members of their natal sex have been found. However, these differences were not found for all measures and the direction of the differences is not always consistent or not yet sufficient to form a basis for a broad theory on gender identity development. The current evidence makes clear that there is no simple relationship between psychological and social factors and gender identity development, and brain development and the development of gender identity. In addition to this, although several researchers have acknowledged that nature and nurture interact, they have not tried to integrate both aspects in their studies thus far. As for the future development of gender dysphoric children, our overview of the literature indicated that gender identity in childhood seems more malleable than later in adolescence or in adulthood. Furthermore, we described that adolescence is a crucial period for the consolidation of gender identity and persistence of gender dysphoria. We discussed that the onset of physical puberty in this period may steer this process, but that there are also indications that cognitive aspects of gender identity (e.g. confusion and ambivalence with ones gender identity) has its own influence. For those without a history of childhood gender dysphoria, adolescence may initiate gender dysphoria. Regardless of the various developmental trajectories of a non-normative gender identity development, adolescence can be denoted as a crucial developmental period for gender identity. In chapter 3 we reported on a study where we validated a 12-item dimensional scale that aims to measure gender dysphoria, in a sample of 1119 adolescents and adults (M age 24.6, range 12–75). The male (UGDS-M) and female (UGDS-F) versions of the Utrecht Gender Dysphoria Scale (UGDS) were assessed in a group of participants diagnosed with a GID (N=545), a group who was subthreshold for GID (N=103), participants with a DSD (N=60), and non-transgender heterosexual (N=219), gay/lesbian (N=150), and bisexual (N=42) controls. Both versions of the UGDS appeared to be reliable scales with a strong ability to discriminate between clinically referred gender dysphoric individuals and non-clinically referred controls and DSD participants. Sensitivity was 88.3 % (UGDS-M) and 98.5 % (UGDS-F), specificity was 99.5 % (UGDS-M) and 97.9 % (UGDS-F). Comparison of the mean total scores showed that there was significantly more gender dysphoria in participants diagnosed with a GID, compared to participants who were subthreshold for GID, for both versions. The two transgender groups showed significantly more gender dysphoria than the DSD and control participants. We concluded from our findings that these qualities make the instrument useful for clinical and research purposes. Chapter 4 reported on a 24 years longitudinal study where we examined whether childhood gender variance was associated with the report of a bi- or homosexual sexual orientation and gender discomfort in adulthood in the general population. In a sample of 406 boys and 473 girls we measured gender variance in childhood (M age 7.5, range 4–11) and sexual orientation and gender dysphoria in adulthood (M age 30.9, range 27–36). Our findings showed that the intensity and presence of childhood gender variance was higher in girls than in boys, and that gender variance was reported more frequently in younger children than in older children. Furthermore, we found that the presence of childhood gender variance was associated with the presence of a homosexual orientation in adulthood, but not with bisexuality. The chance of a homosexual orientation in sexual attraction, sexual fantasy, sexual behavior, and sexual identity were 8 to 15 times higher for both male and female participants with a history of gender variance as reported by the parents (10.2 % to12.2 %), compared to participants without a history of gender variance (1.2 % to 1.7 %). The presence of childhood gender variance was not significantly associated with gender discomfort/gender dysphoria in adulthood. We concluded in this study that childhood gender variance, at least as measured by the Child Behavior Checklist (CBCL), is not predictive for a gender dysphoric outcome in adulthood in the general population. Furthermore, the presence of childhood gender variance and a homosexual sexual orientation in adulthood are associated in the general population, but this association is much weaker than in clinically referred gender dysphoric children. Chapter 5 described the findings from a qualitative study where we tried to obtain a better understanding of the developmental trajectories of persistence and desistence of childhood gender dysphoria and the psychosexual outcome of gender dysphoric children. We interviewed 25 adolescents (M age 15.9, range 14–18), who were diagnosed with a Gender Identity Disorder (DSM-IV or DSM-IV-TR) in childhood (M age 9.4, range 6–12). Our findings on possible predictors in childhood for the different trajectories showed that the 14 persisters and 11 desisters reported quite similar childhood experiences, but subtle differences in their experience of gender and the labelling of their feelings were observed. As for underlying mechanisms and experiences that may have steered the persistence and desistence of gender dysphoria, we identified the period between the ages of 10 and 13 to be crucial. In the perceptions of the adolescents, three factors were related in this period to the intensification of gender dysphoria in persisters or remittance of gender dysphoric feelings in the desisters; (1) the changing social environment, where the social distance between boys and girls gradually increases, (2) the anticipation of, and actual body changes during puberty, and (3) the experience of falling in love, sexual attraction and sexual experiences. Interestingly, even in this relatively small sample of adolescents, we observed that the feelings of gender dysphoria did not completely remit in all desisters. Furthermore, our observation of high reports of sexual orientations and sexual attractions directed towards individuals of the same natal sex seemed to be in concordance with the earlier findings from the prospective quantitative literature on gender dysphoric children. Finally, the stories of the persisters and desisters on the effect of social role transitioning (in appearance and/or a name change or pronoun change) revealed that transitioning was experienced as a relief in persisters, but could result in a troublesome process of changing back to their original gender for desisters. Chapter 6 reported on a quantitative follow-up study that examined the factors associated with the persistence and desistence of childhood gender dysphoria, and adolescent feelings of gender dysphoria and sexual orientation. In a sample of 127 adolescents (79 boys, 48 girls), who were referred for gender dysphoria in childhood (age range 6–12) and followed up in adolescence (age range 15–19), we observed a persistence rate of 37 % (47 persisters out of the 127 adolescents). We examined childhood differences among persisters (N=47) and desisters (N=80) in demographics, developmental background, childhood psychological functioning, the quality of peer relations and childhood gender dysphoria, and adolescent reports of gender dysphoria, body image and sexual orientation. Our findings showed that persisters reported higher intensities of gender dysphoria, more body dissatisfaction and higher reports of a same natal-sex sexual orientation, compared to the desisters, and were in line with earlier findings from prospective follow-up studies in clinical populations.

As for the factors associated with the persistence of gender dysphoria, we found that a higher intensity of childhood gender dysphoria (through self- and parental report, and through cognitive and/or affective gender identity responses), an older age at referral, and transitioning (at least partially) to the preferred gender role were predictive of childhood gender dysphoria persistence. In addition to this, we found that the chance of persisting was higher in natal gender dysphoric girls than in boys, but that factors such as psychological functioning, the quality of peer relations, demographic (e.g. family structure, parents’ social economic class), and developmental background (e.g. birth weight, pregnancy duration) were not associated with the persistence of childhood gender dysphoria. Finally, our findings showed that the factors associated with the persistence of gender dysphoria were different for the two natal sexes. For natal boys, the age at referral, the gender role presentation, the self report of a cross-gender identification (“I am a boy” or “I am a girl”), and the parental report of the intensity of gender role behavior showed to be the major predictive factors for the persistence of gender dysphoria, whereas for girls, the self reported cross-gender identification and the intensity of gender dysphoria turned out to have a higher predictive value than the other evaluated factors. Chapter 7 presented a communication where we addressed the topic of social transitioning in gender dysphoric children in early childhood. We reported on our observation of increasing numbers in our clinical population of children who completely (change in clothing and hair style, first name, and use of pronouns) or partially (change in clothing and hair style, but did not have a name and pronoun change) transitioned between the period of the year 2000 and 2009. Before the year 2000, 2 prepubertal boys, out of 112 referred children to our clinic, were living completely in the female gender role. Between 2000 and 2004, 3.3 % (4 out of 121 children) had completely transitioned, and 19 % (23 out of 121 children) were partially transitioned when they were referred. In the period between 2005 and 2009 we observed that 8.9 % (16 out of 180 children) completely transitioned and 33.3 % (60 out of 180 children) partially transitioned at the time of referral. In discussing the increasing rates of socially transitioned gender dysphoric children we noted that follow-up studies show that the persistence rate of childhood gender dysphoria is about 15.8 %, and wondered what would happen to children who transitioned in childhood, but turned out to be desisters. We referred to two cases of natal girls, who transitioned early in childhood and for whom the gender dysphoria desisted. Their process of changing back to their original gender was reported to be a troublesome process (Chapter 5 and Steensma et al. 2011). We concluded that it is advisable to be very careful when taking steps regarding social transitioning during the early childhood years, as they might be difficult to reverse. In chapter 8 we described a cross-national investigation that examined the psychological functioning and the quality of peer relations between gender dysphoric youth from Toronto, Canada and Amsterdam, the Netherlands. In a sample of 544 children and 174 adolescents, referred to the specialized gender identity clinics in both countries, we assessed the Teacher’s Report Form to measure emotional and behavioral problems, the quality of peer relations and gender dysphoria. Our findings in both countries showed that the children were, on average, better functioning than the adolescents, and that the gender dysphoric boys showed to have poorer peer relations and more internalizing than externalizing problems compared to the gender dysphoric girls. As for the degree of behavioral problems in both countries, the quality of peer relations showed to be the strongest predictor. In discussing our findings we concluded that gender dysphoric children and adolescents showed the same pattern of emotional and behavioral problems in both countries, although there were significant differences in the prevalence of problems. Between the two countries, we found clear differences: Both the children and the adolescents from Canada had more emotional and behavioral problems and a poorer quality of peer relations than the children and adolescents from the Netherlands. In line with previous comparisons of gender dysphoric children from the two countries, we found that children and adolescents from the Netherlands presented with significantly more cross-gender behavior than those from Canada. The differences between the two countries seemed to be an effect of a poorer quality of peer relations in Canada, compared to the Netherlands. We hypothesized that this may be the result of a difference in social tolerance towards gender variant expressions, as cross-cultural studies indicate that the Netherlands is much more tolerant towards homosexuality, and most likely also towards gender variance, than most countries in the world (Veenhoven 2005). Author/-s: Thomas Dirk Steensma Publication: Dissertation, Vrije Universiteit Amsterdam, 2013 Web link: http://hdl.handle.net/1871/40250 Gender differences in neurodevelopment and epigenetics The concept that the brain differs in make-up between males and females is not new. For example, it is well established that anatomists in the nineteenth century found sex differences in human brain weight. The importance of sex differences in the organization of the brain cannot be overstated as they may directly affect cognitive functions, such as verbal skills and visuospatial tasks in a sex-dependent fashion. Moreover, the incidence of neurological and psychiatric diseases is also highly dependent on sex. These clinical observations reiterate the importance that gender must be taken into account as a relevant possible contributing factor in order to understand the pathogenesis of neurological and psychiatric disorders. Gender-dependent differentiation of the brain has been detected at every level of organization—morphological, neurochemical, and functional—and has been shown to be primarily controlled by sex differences in gonadal steroid hormone levels during perinatal development. In this review, we discuss how the gonadal steroid hormone testosterone and its metabolites affect downstream signaling cascades, including gonadal steroid receptor activation, and epigenetic events in order to differentiate the brain in a gender-dependent fashion. Author/-s: Wilson C. J. Chung; Anthony P. Auger Publication: European Journal of Physiology, 2013 Web link: http://link.springer.com/article/10.1007/s00424-013-1258-4 Postnatal testosterone levels and disorder relevant behavior in the second year of life The objective of the current study was to investigate the relationship between testosterone collected at 3-4 months of age and sex-linked disorder-relevant behaviors in the second year of life. Eighty-four children participated at 3-4 (when salivary testosterone levels were obtained and second to fourth digit ratios were measured) and 18-24 months of age (when behavioral ratings of aggression and verbal ability were coded from two 8-min play sessions). Parents also completed the Brief Infant-Toddler Social and Emotional Assessment, and the four subscales (Internalizing, Externalizing, Dysregulation, and Autism Spectrum Disorder) were used to indicate child specific problems. Greater postnatal testosterone levels in early infancy were predictive of more male-typical behaviors in the second year of life (i.e., more autism spectrum behaviors, less time vocalizing, and more Internalizing Problems). These results support the hypothesis that early infancy may be another critical period for the development of gender-linked behavior. Author/-s: J. Saenz; Gerianne M. Alexander Publication: Biological psychology, 2013 Web link: http://www.ncbi.nlm.nih.gov/pubmed/23727253 Sexual Differentiation of the Human Brain in Relation to Gender-Identity, Sexual Orientation, and Neuropsychiatric Disorders During the intrauterine period, a testosterone surge in boys masculinizes the fetal brain, whereas the absence of such a surge in girls results in a feminine brain. Since sexual differentiation of the genitals takes place much earlier in intrauterine life than sexual differentiation of the human brain, these two processes can be influenced independently of each other. Gender identity (the conviction of belonging to the male or female gender), sexual orientation (hetero-, homo-, or bisexuality), pedophilia, and the risks for neuropsychiatric disorders are programmed into our brain during early development. There is no proof that postnatal social environment has any crucial effect on gender identity or sexual orientation. We discuss the relationships between structural and functional sex differences of various brain areas and the way they change along with changes in the supply of sex hormones on the one hand and sex differences in behavior in health and disease on the other. Author/-s: Dick F. Swaab; Ai-Min Bao Publication: Neuroscience in the 21st century, 2013 Web link: http://link.springer.com/referenceworkentry/10.1007/978-1-4614-1997-6_115 The effects of prenatal sex steroid hormones on sexual differentiation of the brain Most of the anatomical, physiological and neurochemical gender-related differences in the brain occur prenatally. The sexual differences in the brain are affected by sex steroid hormones, which play important roles in the differentiation of neuroendocrine system and behavior. Testosterone, estrogen and dihydrotestosterone are the main steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The structural and behavioral differences in the female and male brains are observed in many animal species; however, these differences are variable between species. Animal and human (in vivo imaging and postmortem) studies on sex differences in the brain have shown many differences in the local distribution of the cortex, the gray-white matter ratio, corpus callosum, anterior commissure, hypothalamus, bed nucleus of the stria terminalis, limbic system and neurotransmitter systems. This review aims to evaluate the anatomical, physiological and neurochemical differences in the female and male brains and to assess the effect of prenatal exposure to sex steroid hormones on the developing brain. Author/-s: Serkan Karaismailoğlu; Ayşen Erdem Publication: Journal of the Turkish-German Gynecological Association, 2013 Web link: http://www.journalagent.com/z4/download_fulltext.asp?pdir=jtgga&plng=tur&un=JTGGA-86836 Early androgen effects on spatial and mechanical abilities: evidence from congenital adrenal hyperplasia. There is considerable controversy about the origins of sex differences in cognitive abilities, particularly the male superiority in spatial abilities. We studied effects of early androgens on spatial and mechanical abilities in adolescents and young adults with congenital adrenal hyperplasia (CAH). On tests of three-dimensional mental rotations, geography, and mechanical knowledge, females with CAH scored higher than their unaffected sisters, and males with CAH scored lower than their unaffected brothers. Exploratory regression analyses suggest that androgens affect spatial ability in females directly and through male-typed activity interests. Findings indicate that early androgens influence spatial and mechanical abilities, and that androgen effects on abilities may occur in part through effects on sex-typed activity interests. Author/-s: Sheri A. Berenbaum; K. L. Bryk; A. M. Beltz Publication: Behavioral neuroscience, 2012 Web link: http://www.ncbi.nlm.nih.gov/pubmed/22289044 Early androgens, activity levels and toy choices of children in the second year of life The hypothesis that stronger preferences for active play styles contribute to stronger preferences for male-typical toys was examined in 47 boys and 37 girls at 19-months of age using ambulatory monitoring technology (i.e., actigraphy) to measure activity levels during contact with male-typical, female-typical, and gender-neutral toys. Digit ratios and salivary testosterone levels were measured earlier in children at 3-4 months of age. There were no significant sex differences in digit ratios, salivary testosterone levels, or overall activity levels during toy play. In contrast, contact times showed large sex differences in infants' toy preferences. The within-sex comparisons showed that infant girls had significant preferences for female-typical toys over male-typical toys, whereas infant boys showed only a small preference for male-typical toys over female-typical toys. More male-typical digit ratios in early infancy predicted higher activity counts during toy play and less female-typical toy preferences in girls. However, in both sexes, activity levels were unrelated to toy preferences suggesting that factors other than activity level preferences contribute to the early emergence of gender-linked toy preferences. Author/-s: G. M. Alexander; J. Saenz Publication: Hormones and behaviour, 2012 Web link: http://www.unboundmedicine.com/medline/citation/22955184/Early_androgens_activity_levels_and_toy_choices_of_children_in_the_second_year_of_life_ Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans Background: Sex differences are present in many neuropsychiatric conditions that affect emotion and approach-avoidance behavior. One potential mechanism underlying such observations is testosterone in early development. Although much is known about the effects of testosterone in adolescence and adulthood, little is known in humans about how testosterone in fetal development influences later neural sensitivity to valenced facial cues and approach-avoidance behavioral tendencies. Methods: With functional magnetic resonance imaging we scanned 25 8 to 11-year-old children while viewing happy, fear, neutral, or scrambled faces. Fetal testosterone (FT) was measured via amniotic fluid sampled between 13 and 20 weeks gestation. Behavioral approach-avoidance tendencies were measured via parental report on the Sensitivity to Punishment and Sensitivity to Rewards questionnaire. Results: Increasing FT predicted enhanced selectivity for positive compared with negatively valenced facial cues in reward-related regions such as caudate, putamen, and nucleus accumbens but not the amygdala. Statistical mediation analyses showed that increasing FT predicts increased behavioral approach tendencies by biasing caudate, putamen, and nucleus accumbens but not amygdala to be more responsive to positive compared with negatively valenced cues. In contrast, FT was not predictive of behavioral avoidance tendencies, either through direct or neurally mediated paths. Conclusions: This work suggests that testosterone in humans acts as a fetal programming mechanism on the reward system and influences behavioral approach tendencies later in life. As a mechanism influencing atypical development, FT might be important across a range of neuropsychiatric conditions that asymmetrically affect the sexes, the reward system, emotion processing, and approach behavior. Author/-s: M. V. Lombardo; E. Ashwin; B. Auyeung; B. Chakrabarti; M. C. Lai; K. Taylor; G. Hackett; E. T. Bullmore; Sacha Baron-Cohen Publication: Biological psychiatry, 2012 Web link: http://www.ncbi.nlm.nih.gov/pubmed/22763187 Fetal Testosterone Influences Sexually Dimorphic Gray Matter in the Human Brain In nonhuman species, testosterone is known to have permanent organizing effects early in life that predict later expression of sex differences in brain and behavior. However, in humans, it is still unknown whether such mechanisms have organizing effects on neural sexual dimorphism. In human males, we show that variation in fetal testosterone (FT) predicts later local gray matter volume of specific brain regions in a direction that is congruent with sexual dimorphism observed in a large independent sample of age-matched males and females from the NIH Pediatric MRI Data Repository. Right temporoparietal junction/posterior superior temporal sulcus (RTPJ/pSTS), planum temporale/parietal operculum (PT/PO), and posterior lateral orbitofrontal cortex (plOFC) had local gray matter volume that was both sexually dimorphic and predicted in a congruent direction by FT. That is, gray matter volume in RTPJ/pSTS was greater for males compared to females and was positively predicted by FT. Conversely, gray matter volume in PT/PO and plOFC was greater in females compared to males and was negatively predicted by FT. Subregions of both amygdala and hypothalamus were also sexually dimorphic in the direction of Male > Female, but were not predicted by FT. However, FT positively predicted gray matter volume of a non-sexually dimorphic subregion of the amygdala. These results bridge a long-standing gap between human and nonhuman species by showing that FT acts as an organizing mechanism for the development of regional sexual dimorphism in the human brain. Author/-s: Michael V. Lombardo; Emma Ashwin; Bonnie Auyeung; Bhismadev Chakrabarti; Kevin Taylor; Gerald Hackett; Edward T. Bullmore; Simon Baron-Cohen Publication: The Journal of Neuroscience, 2012 Web link: http://www.jneurosci.org/content/32/2/674.abstract Intersex and Transsex: Atypical Gender Development and Social Construction […] In summary, the behaviors of intersexed and transgendered persons provide a wide range of evidence against many aspects of social science and social construction theory. Intersexed and transgendered persons, as well as typical persons, are each born with a certain background based upon evolutionary heritage, family genetics, uterine environment, and health factors that they will evidence in a socially permissive culture and limit in a restrictive one. The strongest gestational influences are from genetic and endocrinal organizing forces. Organizing factors are those genetic and hormonal influences established prenatally that influence postnatal behaviors set in motion by social or other environmental activation processes (such as puberty) or events (such as serious threats). Organizing factors influence or bias subsequent responses of the individual to environmental/social forces; they predispose the person to manifest behaviors and attitudes (biases) that have come to be recognized as appropriate. Sex-related activation effects occur postnatally; most noticeably at or after puberty. The lives of intersex and transgendered persons provide strong evidence for a realistic theory of sexual development: biased-interaction theory. Author-/s: Milton Diamond Publication: Women’s Studies Review, 2012 Web link: http://hawaii.edu/PCSS/biblio/articles/2010to2014/2012-intersex-and-transsex.html Relating Prenatal Testosterone Exposure to Postnatal Behavior in Typically Developing Children: Methods and Findings Testosterone levels during early development influence subsequent sex-typical behavior. These influences were initially identified in experimental research on nonhuman species. Additional research—primarily investigating individuals exposed to atypical hormone environments due to genetic disorders or maternal treatment with hormones during pregnancy—suggested that testosterone also influences the development of sex-typical behavior in humans. There is also interest in identifying relations between normal variability in the early hormone environment and normal variability in subsequent behavior. This article reviews studies that have assessed prenatal testosterone exposure in typically developing children using amniotic fluid sampling or maternal blood sampling. It concludes that both these approaches are promising, but both require larger samples than those used in most studies to date. Recommendations for future research also include using outcome measures that show sex differences, analyzing data within each sex, considering the time of day (as well as the time of gestation) when samples were taken, and reporting all the measures evaluated, not just those showing significant effects. Author/-s: Mihaela Constantinescu; Melissa Hines Publication: Child Development Perspectives, 2012 Web link: http://onlinelibrary.wiley.com/doi/10.1111/j.1750-8606.2012.00257.x/abstract Sex Steroids and the Organization of the Human Brain Studying the biological mechanisms underlying sexual differentiation in the human brain provides important insights into the etiology and trajectory of neurodevelopmental disorders in males and females (Baron-Cohen et al., 2011). Sex steroid hormones, the end products of the hypothalamus-pituitary-gonadal axis, exert powerful effects on the organization and sexual differentiation of brain structures. From animal studies, it has become clear that during early development, exposure of the brain to testosterone and estradiol leads to irreversible changes in the nervous system (McCarthy et al., 2012). Moreover, fetal exposure to sex steroids has a major impact on the sexual differentiation of the brain (McCarthy et al., 2012). For example, high levels of fetal testosterone (FT) result in brain masculinization in experimental animals, such as enlargements of the volume and soma size of the suprachiasmatic nucleus, bed nucleus of the stria terminalis, and ventromedial hypothalamus (Zuloaga et al., 2008). In humans, studies of the effects of FT often rely on indirect measures such as the ratio between the index finger (2D) and ring finger (4D) or on opposite-sex twin studies. Specifically, a smaller 2D:4D ratio correlates with higher FT exposure, and through the intrauterine presence of a male fetus, opposite-sex twin girls are exposed to higher FT levels than same-sex twin girls. Using the latter indirect measure of FT, earlier reports showed that total brain volume and cerebellum volume, typically found to be larger in males, were positively correlated with higher FT exposure (Peper et al., 2009). A recent paper by Lombardo et al. (2012) provided direct evidence for an association between FT levels and sexual differentiation of brain gray matter in humans. In this pioneering study of 28 developing boys, FT levels were determined from amniotic fluid. Amniocentesis was performed between 13 and 20 weeks of gestation, which is a critical period of brain masculinization. When these boys were 8–11 years old, a structural MRI was made. Using voxel-based morphometry, gray matter regions within the whole brain of these 28 boys were identified showing significant correlations with FT levels. The amygdala and hypothalamus were included as a priori regions of interest. Then, in a second normative sample of 217 (101 boys) children (NIH Pediatric MRI Data Repository), sexual dimorphisms in gray matter were determined. Finally, a conjunction analysis was performed to isolate brain regions whose direction of the FT correlation was congruent with the direction of sexual dimorphism. Lombardo et al. (2012) hypothesized that the size of brain areas that were normally larger in males than in females would correlate positively with FT, whereas the size of brain areas that are normally larger in females would correlate negatively with FT. Results showed that higher levels of FT were associated with larger right temporal/parietal junction and posterior superior temporal sulcus. As predicted, these brain areas were larger in males than in females in the normative sample. Conversely, FT level was negatively correlated with gray matter volumes within the planum temporale/ parietal operculum and within the posterior lateral orbitofrontal cortex. Again, in line with the hypothesis, these brain areas were larger in females than males in the normative sample. Having unique access to direct levels of FT, Lombardo and colleagues (2012) provide the first human evidence that FT contributes to the organization of gray matter structures in a sexually dimorphic way. The sexually dimorphic brain areas that Lombardo and colleagues (2012) found to be associated with FT could provide insight into sex differences found in cognitive and affective functioning, including language processing, mentalizing, social attention, and empathy. In summary, sex differences in these mental functions might result at least partially from FT effects on the underlying brain structures. FT levels did not correlate with volume in all sexual dimorphic gray matter areas in Lombardo et al. (2012), however. For example, the hypothalamus and subregions of the amygdala were normally larger in males, but these volumes were not correlated with FT levels. This is not wholly surprising, because numerous factors likely contribute to sex differences in brain morphology, such as estrogens, proteins encoded on sex chromosomes, and environmental factors (McCarthy et al., 2012). In contrast, FT levels did correlate with gray matter volume in a subregion of the amygdala (i.e., the ventromedial area of the amygdala) that is not sexually dimorphic. Interestingly, it has recently been proposed that some phenotypic endpoints that do not show sex differences nonetheless can be affected by different factors in males and females (McCarthy et al., 2012). Therefore, FT could affect the size of the ventromedial amygdala in males, but its size in females is affected by other factors. To test this hypothesis however, the inclusion of female (hormonal) data is required. Influences of sex steroid hormones on fetal brain development such as those identified by Lombardo et al. (2012) are thought to set the stage for additional effects of such hormones that occur during puberty and adolescence. Animal literature increasingly suggests that puberty represents a second critical period during which sex-steroid-related brain reorganization takes place. For example, in male rodents, testosterone treatment before and during adolescence, but not after adolescence, caused reorganization in parts of the amygdala and hypothalamus— brain areas involved in social behavior (Schulz et al., 2009). These data indicate that the adolescent brain remains sensitive to the organizational effects of steroid hormones. In humans, sex differences in subcortical and cortical gray matter become more prominent during puberty, but the contribution of sex hormones to this process seems to be sex- and regionspecific (Peper et al., 2011). Animal studies have also demonstrated that sex steroids affect myelination by acting on glial cells (Garcia-Segura and Melcangi, 2006). In humans, white matter sexual dimorphisms also become more prominent during puberty and adolescence: in boys, white matter microstructure increases more steeply than in girls (Bava et al., 2011), possibly under the influence of pubertal hormones. Recent human evidence indicates that the pubertal reorganization of white matter pathways is associated with increased levels of pubertal sex steroid hormones (Herting et al., 2012). Lombardo and colleagues (2012) point out that some of their participants (8–11 years) might have already entered puberty. If so, pubertal testosterone might have interacted with gray matter sex differences established during the prenatal period. The authors argue that by correcting their analyses for age, possible current testosterone effects on gray matter should have been controlled (as age and testosterone are highly correlated during puberty). However, after controlling for age, pubertal testosterone has been associated with individual differences in structural brain development (Peper et al., 2011). For example, a larger amygdala and hippocampus volume are related to increased levels of testosterone in both sexes regardless of age (Neufang et al., 2009). The importance of studying the effects of pubertal sex steroids on human brain structure is further underlined by the fact that there is a sexual differentiation in vulnerability to mental disorders before and around puberty (Zahn-Waxler et al., 2008). Sex differences in child and adolescent mental disorders can be roughly divided into two groups: (1) disorders with a marked male preponderance arising before puberty, such as conduct disorder, autism, and attention deficit-hyperactivity disorder;and (2) disorders with a marked female preponderance (2:1) arising during puberty, such as mood and anxiety-related disorders (Zahn- Waxler et al., 2008). Eating disorders show an even higher incidence in females and often arise in the course of puberty. Moreover, an earlier onset of pubertal development is associated with increases in eating and mood symptoms. It might be argued that during puberty, previously organized brain circuits are activated by changing gonadal hormoneenvironments, possibly setting the stage for sex differences in vulnerability to these mental disorders. Although sex steroids are not the single cause of these complex disorders, puberty might have a profound impact on the developmental trajectories of these neuropsychiatric illnesses (Zahn-Waxler et al., 2008). In conclusion, studying the influence of sex steroids on human brain structure not only gives important insights into the etiology of healthy brain maturation, but can also serve as a model for the development of neuropsychiatric illnesses with a skewed sex ratio. As Lombardo and colleagues (2012) emphasize, FT is an important developmental mechanism contributing to sexual differentiation of brain anatomy. Later surges of sex steroid hormones during puberty might play a vital role in further refining gray and white matter observed during this period. Author/-s: Jiska S. Peper; P. Cédric; M. P. Koolschijn Publication: The Journal of Neuroscience, 2012 Web link: http://www.jneurosci.org/content/32/20/6745.full.pdf Testosterone measured in infancy predicts subsequent sex-typed behavior in boys and in girls The testes are active during gestation, as well as during early infancy. Testosterone elevation during fetal development has been shown to play a role in human neurobehavioral sexual differentiation. The role of early postnatal gonadal activation in human psychosexual development is largely unknown, however. We measured testosterone in 48 full term infants (22 boys, 26 girls) by monthly urinary sampling from day 7 postnatal to age 6 months, and related the area under the curve (AUC) for testosterone during the first 6 months postnatal to subsequent sex-typed behavior, at the age of 14 months, using the Pre-School Activities Inventory (PSAI), and playroom observation of toy choices. In boys, testosterone AUC correlated significantly with PSAI scores (Spearman's rho = 0.54, p = 0.04). In addition, play with a train and with a baby doll showed the anticipated sex differences, and play with the train correlated significantly and positively with testosterone AUC in girls (Spearman's rho = 0.43, p = 0.05), while play with the doll correlated significantly and negatively with testosterone AUC in boys (Spearman's rho = − 0.48, p < 0.03). These results may support a role for testosterone during early infancy in human neurobehavioral sexual differentiation. Author/-s: Annamarja Lamminmäki; Melissa Hines; Tanja Kuiri-Hänninen; Leena Kilpeläinen; Leo Dunkel; Ulla Sankilampi Publication: Hormones and Behavior, 2012 Web link: http://www.sciencedirect.com/science/article/pii/S0018506X1200044X The relationship between second-to-fourth digit ratio and female gender identity Introduction: Gender identity and the second-to-fourth finger length ratio (2D : 4D) are discriminative between the sexes. However, the relationship between 2D : 4D and gender identity disorder (GID) is still controversial. Aim: The aim of this study is to investigate the relationship between 2D : 4D and score on the Gender Identity Scale (GIS) in female-to-male (FtM) GID subjects. Methods: Thirty-seven GID-FtM with testosterone replacement therapy from our clinic were included in this study. As controls, 20 male and 20 female volunteers participated from our institution (medical doctors and nurses). We photocopied left and right hands of the participants and measured the second and fourth finger lengths. Gender identity was measured with the GIS. Main outcome measures: 2D : 4D digit ratio and GIS in male, female, and GID-FtM subjects. Results: The 2D : 4D (mean ± standard deviation) in male, female, and GID-FtM were 0.945 ± 0.029, 0.999 ± 0.035, and 0.955 ± 0.029 in right hand and 0.941 ± 0.024, 0.979 ± 0.040, and 0.954 ± 0.036 in left hand, respectively. The 2D : 4D was significantly lower in male controls in both hands and GID-FtM in the right hand than in female controls (P < 0.05, analysis of variance). Multiple linear regression analysis revealed that "consistent gender identity" score in the higher domain in GIS and "persistent gender identity" score in the lower domain are statistically significant variables correlating with 2D : 4D in the right hands among biological females. Conclusions : The finger length ratio 2D : 4D in GID-FtM was significantly lower than in female controls in the right hand in this study. 2D : 4D showed a positive correlation with GIS score. Because 2D : 4D influences are assumed to be established in early life and to reflect testosterone exposure, our results suggest a relationship between GID-FtM and perinatal testosterone. Author/-s: S. Hisasue; S. Sasaki; T. Tsukamoto; S. Horie Publication: The Journal of Sexual Medicine, 2012 Web link: http://www.ncbi.nlm.nih.gov/pubmed/22738413 Biological and psychosocial correlates of gender-variant and gender-typical identities The aim of this thesis is examine biological and psychosocial factors that contribute to the development of gender-variant or gender-typical identities. Blanchard’s autogynephilia theory (Blanchard, 1989b) suggests that these factors are different in birth-assigned males with different sexual orientations. Previous research has found that genetics, prenatal hormone exposure, neuroanatomy, handedness, dermatoglyphics, fraternal birth order, and abuse are related to gender identity. While a number of investigators have studied these variables individually, this is the first known study to have examined the inter-relationships of these variables in one sample and to include participants with a wide range of gender identities. Data were collected from a convenience sample of 2 277 online-recruited participants with gender-variant and gender-typical identities using an online questionnaire. Participants were mainly white/Caucasian (92 %) adults living in the USA (54 %) and New Zealand (19 %). From the results, reported family concordance for gender-variance and a systematic review of case reports of twins with gender-variant identities indicated genetic determinants of gender identities. Finger-length ratio, systemising, and a systematic review of case reports of gender identity outcomes for adults with intersex and related conditions indicated prenatal hormone determinants of gender identities. Further evidence for biological factors came from elevated levels of non-right handedness among birth assigned females with gender-variant identities. Structural equation modelling showed that the positive relationship between abuse experience and degree of adult gender variance was partially mediated by recalled childhood gender-variance. This suggests abuse may be a cause as well as a result of gender-variance. Contrary to Blanchard’s theory, there were no differences in biological and psychosocial factors between birth-assigned male participants of different sexual orientations. This was the first research to find evidence that biological and psychosocial factors are the same for transsexuals as for persons with other gender-variant identities. Overall, these findings add support for a biological predisposition for gender-variant and gender-typical identities. Psychosocial determinants are likely to be complex and work in interaction with biological factors. Author/-s: Jaimie F. Veale Publication: Doctoral thesis, Massey University, Albany, New Zealand, 2011 Web link: http://www.jaimieveale.com/wp-content/uploads/2012/09/PhD-thesis.pdf Gender development and the human brain Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones. Author/-s: Melissa Hines Publication: Annual review of neuroscience, 2011 Web link: http://www.ncbi.nlm.nih.gov/pubmed/21438685 Gendered Occupational Interests: Prenatal Androgen Effects on Psychological Orientation to Things Versus People There is considerable interest in understanding women’s underrepresentation in science, technology, engineering, and mathematics careers. Career choices have been shown to be driven in part by interests, and gender differences in those interests have generally been considered to result from socialization. We explored the contribution of sex hormones to career-related interests, in particular studying whether prenatal androgens affect interests through psychological orientation to Things versus People. We examined this question in individuals with congenital adrenal hyperplasia (CAH), who have atypical exposure to androgens early in development, and their unaffected siblings (total N = 125 aged 9 to 26 years). Females with CAH had more interest in Things versus People than did unaffected females, and variations among females with CAH reflected variations in their degree of androgen exposure. Results provide strong support for hormonal influences on interest in occupations characterized by working with Things versus People. Author/-s: Adriene M. Beltz; Jane L. Swanson; Sheri A. Berenbaum Publication: Hormones and behavior, 2011 Web link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166361/ Prenatal endocrine influences on sexual orientation and on sexually differentiated childhood behaviour Both sexual orientation and sex-typical childhood behaviors, such as toy, playmate and activity preferences, show substantial sex differences, as well as substantial variability within each sex. In other species, behaviors that show sex differences are typically influenced by exposure to gonadal steroids, particularly testosterone and its metabolites, during early development (prenatally or neonatally). This article reviews the evidence regarding prenatal influences of gonadal steroids on human sexual orientation, as well as sex-typed childhood behaviors that predict subsequent sexual orientation. The evidence supports a role for prenatal testosterone exposure in the development of sex-typed interests in childhood, as well as in sexual orientation in later life, at least for some individuals. It appears, however, that other factors, in addition to hormones, play an important role in determining sexual orientation. These factors have not been well-characterized, but possibilities include direct genetic effects, and effects of maternal factors during pregnancy. Although a role for hormones during early development has been established, it also appears that there may be multiple pathways to a given sexual orientation outcome and some of these pathways may not involve hormones. Author/-s: Melissa Hines Publication: Frontiers in neuroendocrinology, 2011 Web link: http://www.ncbi.nlm.nih.gov/pubmed/21333673 Prenatal hormones and childhood sex segregation: playmate and play style preferences in girls with congenital adrenal hyperplasia. We investigated playmate and play style preference in children with congenital adrenal hyperplasia (CAH) (26 females, 31 males) and their unaffected siblings (26 females, 17 males) using the Playmate and Play Style Preferences Structured Interview (PPPSI). Both unaffected boys and girls preferred same-sex playmates and sex-typical play styles. In the conflict condition where children chose between a same-sex playmate engaged in an other-sex activity or an other-sex playmate engaged in a same-sex activity, boys (both CAH and unaffected brothers) almost exclusively chose playmates based on the preferred play style of the playmate as opposed to the preferred gender label of the playmate. By contrast, unaffected girls used play style and gender label about equally when choosing playmates. Girls with CAH showed a pattern similar to that of boys: their playmate selections were more masculine than unaffected girls, they preferred a boy-typical play style and, in the conflict condition, chose playmates engaged in a masculine activity. These findings suggest that prenatal androgen exposure contributes to sex differences in playmate selection observed in typically developing children and that, among boys and girls exposed to high levels of androgens prenatally, play style preferences drive sex segregation in play. Author/-s: V. Pasterski; M. E. Geffner, C. Brain; P. Hindmarsh; C. Brook; M. Hines Publication: Hormones and behaviour, 2011 Web link: http://www.ncbi.nlm.nih.gov/pubmed/21338606 Sexual differentiation of human behavior: effects of prenatal and pubertal organizational hormones A key question concerns the extent to which sexual differentiation of human behavior is influenced by sex hormones present during sensitive periods of development (organizational effects), as occurs in other mammalian species. The most important sensitive period has been considered to be prenatal, but there is increasing attention to puberty as another organizational period, with the possibility of decreasing sensitivity to sex hormones across the pubertal transition. In this paper, we review evidence that sex hormones present during the prenatal and pubertal periods produce permanent changes to behavior. There is good evidence that exposure to high levels of androgens during prenatal development results in masculinization of activity and occupational interests, sexual orientation, and some spatial abilities; prenatal androgens have a smaller effect on gender identity, and there is insufficient information about androgen effects on sex-linked behavior problems. There is little good evidence regarding long-lasting behavioral effects of pubertal hormones, but there is some suggestion that they influence gender identity and perhaps some sex-linked forms of psychopathology, and there are many opportunities to study this issue. Author/-s: Sheri A. Berenbaum; Adriene M. Beltz Publication: Frontiers in neuroendocrinology, 2011 Web link: http://www.ncbi.nlm.nih.gov/pubmed/21397624 Biological and psychosocial correlates of adult gender-variant identities: A review This article reviews research on biological and psychosocial factors relevant to the etiology of gender-variant identities. There is evidence for a genetic component of gender-variant identities through studies of twins and other within-family concordance and through studies of specific genes. Evidence that prenatal androgens play a role comes from studies that have examined finger length ratios (2D:4D), prevalence of polycystic ovary syndrome among female-to-male transsexuals, and individuals with intersex and related conditions who are more likely to have reassigned genders. There is also evidence that transsexuals have parts of their brain structure that is typical of the opposite birth-assigned gender. A greater likelihood of non-right-handedness suggests developmental instability may also contribute as a biological factor. There is a greater tendency for persons with gender-variant identities to report childhood abuse and a poor or absent relationship with parents. It is unclear if this is a cause or effect of a gender-variant identity. Parental encouragement of gender-variance is more common among individuals who later develop a gender-variant identity. We conclude that biological factors, especially prenatal androgen levels, play a role in the development of a gender-variant identity and it is likely that psychosocial variables play a role in interaction with these factors. Author/-s: Jaimie F. Veale; David E. Clarke; Terri C. Lomax Publication: Personality and Individual Differences, 2010 Web link: http://www.sciencedirect.com/science/article/pii/S0191886909004620 Digit ratio (2D:4D) is associated with traffic violations for male frequent car drivers Digit ratio (2D:4D) is a putative marker of prenatal hormone exposure. A lower digit ratio has been suggested as an index of higher testosterone relative to estrogen exposure during prenatal development. Digit ratio has been associated with a variety of psychological sex-dimorphic variables, including spatial orientation, aggression, or risk-taking behavior. The present study aimed to relate digit ratio to traffic violations for a male sample (N = 77) of frequent car drivers. Digit ratio was assessed via printout scans of the hand, and traffic offense behavior was assessed via self-reported penalty points as registered by the Central Register of Traffic Offenders in Germany. In addition, social desirability and sensation seeking were recorded. Results showed that digit ratio was inversely related to penalty point entries, suggesting more traffic violations for individuals with higher prenatal testosterone exposure. Sensation seeking was positively associated with traffic violations, but there was no relationship between sensation seeking and digit ratio, proposing additive effects of both variables. The results suggest that prenatal androgen exposure might be related to traffic violations for frequent car drivers. Author/-s: A. Schwerdtfeger; R. Heims; J. Heer Publication: Accident; analysis and prevention, 2010 Web link: http://www.ncbi.nlm.nih.gov/pubmed/19887167 Empathizing, systemizing and finger length ratio in a Swedish sample The Empathy- and Systemizing Quotients (EQ and SQ, respectively; Baron-Cohen, 2003) were determined in a Swedish sample consisting mainly of university undergraduates. Females had significantly higher EQ than males, who in turn scored higher on the SQ inventory. Gender explained 12-14% of the variation. Males were strikingly overrepresented in the group defined by a high SQ/low EQ profile or by a large SQ - EQ difference; females dominated among people with a low SQ/high EQ profile or by a large EQ - SQ difference. Students majoring in the natural sciences had higher SQs than psychology majors, but in both groups the gender difference in SQ and EQ was strong. For each participant a weighted composite score was generated by multivariate processing of the EQ and SQ data (Partial Least Square Discriminant Analysis). These scores were associated in a sex-linked fashion to a biometric measure reflecting prenatal testosterone exposure, i.e. the ratio between index (2D)- 