Gender Incongruence and Autistic Traits: Cerebral and Behavioral Underpinnings.

Gender dysphoria and autism spectrum disorder (ASD) co-occur at high rates. Yet, it is unknown whether gender dysphoria and ASD are associated with common or distinct neurobiological correlates or how they relate to experiences of gender-related body incongruence. Using the Social Responsiveness Scale, we assessed autistic traits in 99 transgender and 99 cisgender individuals and investigated their associations with gender-related body incongruence, measured via a visually based "Body Morph" test, and with cortical thickness in the brain. Autistic traits were significantly higher among transgender individuals, and those with higher autistic traits had higher body incongruence scoring. Among transgender individuals, higher autistic traits were linked with a thinner cortex bilaterally in the temporal pole and the superior and inferior temporal gyri. Autistic traits were only partly associated with cortical morphology patterns previously reported in transgender individuals; instead, they were primarily linked to temporal lobe areas mediating social cognition. While replicating the previous literature on the increased prevalence of autistic traits among transgender individuals, this study reports specific regions in the brains of transgender individuals where cortical thickness is associated with autistic traits.

The Epidemiology of Gender Dysphoria in Iran: The First Nationwide Study.

Gender dysphoria (GD) is defined as a persistent and distressful incongruence between one's gender identity and one's at-birth-assigned sex. Sex reassignment has been religiously accepted for transgender individuals in postrevolutionary Iran since 1987; however, very little is known about how many individuals seek and receive such treatment annually. This study provides the first nationwide effort to assess the prevalence of GD in Iran as a function of diagnosis. The medical records of all transgender individuals referred to the Iranian Legal Medicine Organization between March 2012 and March 2017 were reviewed. All individuals diagnosed with GD were contacted. A total of 839 medical records meeting study criteria were received and evaluated. The prevalence of transgender individuals was estimated to be 1.46 per 100,000 Iranians with a transwoman (TW)/ transman (TM) ratio of 1:2. The mean age of individuals with GD at the time of referral was 25.22 (SD = 6.25) years for TW and 25.51 (SD = 5.66) years for TM. The findings are twofold. First, gender dysphoria is less prevalent in Iran than has been reported in Western countries. Second, the sex ratio is skewed toward at-birth-assigned females, which differs from what has been reported in Western countries. These findings have been interpreted in light of Iran's legal system, which is based on Islamic penal codes. These findings are of utmost importance for both health providers and legislators, as it can illustrate a more accurate picture of the transgender population in Iran.

Psychiatric morbidity among adult transgender people in Iran.

Psychiatric morbidity among transgender and gender diverse people is thought to be to an important extent related to socio-cultural intolerance, but such morbidity has been understudied in non-western socio-political contexts. This study aims to report the psychiatric profiles of clients who are seeking gender-affirming treatment in a gender clinic in Iran. All transgender people who were consecutively referred to the Mashhad University of Medical Sciences in Mashhad, Iran, between February 2015 and December 2016 were investigated. Clients were evaluated during at least four sessions when sociodemographic and psychiatric characteristics were collected. Out of 209 clients, 205 were included (transmen (TM), N = 110; transwomen (TW) N = 95). A subset of these were assessed using Structured Clinical Interview based for DSM-5 (n = 154). The mean age of participants was 24.41 (SD = 6.316; range, 15-43). There was no significant difference between transmen and transwomen (p = 0.960); 48% (80 out of 154) of participants were found to have at least one current psychiatric condition currently, and 67% (138 out of 205) during their lifetime. Depressive and trauma- and stressor-related disorders were the most common conditions. Prevalence rates were similar in both genders. In both TM and TW groups, as many as 70% of the clients reported that they had experienced suicidal ideation. These findings are surprisingly similar to those of western studies despite the more extreme difficulties Iranian transgender people face in their lives in a non-western socio-political context.

The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group.

BACKGROUND: In contrast to cisgender persons, transgender persons identify with a different gender than the one assigned at birth. Although research on the underlying neurobiology of transgender persons has been accumulating over the years, neuroimaging studies in this relatively rare population are often based on very small samples resulting in discrepant findings. AIM: To examine the neurobiology of transgender persons in a large sample. METHODS: Using a mega-analytic approach, structural MRI data of 803 non-hormonally treated transgender men (TM, n = 214, female assigned at birth with male gender identity), transgender women (TW, n = 172, male assigned at birth with female gender identity), cisgender men (CM, n = 221, male assigned at birth with male gender identity) and cisgender women (CW, n = 196, female assigned at birth with female gender identity) were analyzed. OUTCOMES: Structural brain measures, including grey matter volume, cortical surface area, and cortical thickness. RESULTS: Transgender persons differed significantly from cisgender persons with respect to (sub)cortical brain volumes and surface area, but not cortical thickness. Contrasting the 4 groups (TM, TW, CM, and CW), we observed a variety of patterns that not only depended on the direction of gender identity (towards male or towards female) but also on the brain measure as well as the brain region examined. CLINICAL TRANSLATION: The outcomes of this large-scale study may provide a normative framework that may become useful in clinical studies. STRENGTHS AND LIMITATIONS: While this is the largest study of MRI data in transgender persons to date, the analyses conducted were governed (and restricted) by the type of data collected across all participating sites. CONCLUSION: Rather than being merely shifted towards either end of the male-female spectrum, transgender persons seem to present with their own unique brain phenotype. Mueller SC, Guillamon A, Zubiaurre-Elorza L, et al. The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group. J Sex Med 2021;18:1122-1129.

Cortical Gyrification in Transgender Individuals.

Gender incongruence (GI) is characterized by a feeling of estrangement from the own body in the context of self. GI is often described in people who identify as transgender. The underlying mechanisms are unknown. Data from MRI measurements and tests of own body perception triggered us to pose a model that GI in transgender persons (TGI) could be associated with a disconnection within the brain circuits mediating the perception of own body as self. This is a departure from a previous model of sex atypical cerebral dimorphism, introducing a concept that better accords with a core feature of TGI. The present MRI study of 54 hormone naive transmen (TrM), 38 transwomen (TrW), 44 cismen and 41 ciswomen show that cortical gyrification, a metric that reflects early maturation of cerebral cortex, is significantly lower in transgender compared with cisgender participants. This reduction is limited to the occipito-parietal cortex and the sensory motor cortex, regions encoding own body image and body ownership. Moreover, the cortical gyrification correlated inversely with own body-self incongruence in these regions. These novel data suggest that GI in TGI may originate in the neurodevelopment of body image encoding regions. The results add potentially to understanding neurobiological contributors to gender identity.

Cross-sex hormone treatment and own-body perception: behavioral and brain connectivity profiles.

Referrals for gender dysphoria (GD), characterized by a distressful incongruence between gender identity and at-birth assigned sex, are steadily increasing. The underlying neurobiology, and the mechanisms of the often-beneficial cross-sex hormone treatment are unknown. Here, we test hypothesis that own body perception networks (incorporated in the default mode network-DMN, and partly in the salience network-SN), are different in trans-compared with cis-gender persons. We also investigate whether these networks change with cross-sex hormone treatment. Forty transmen (TrM) and 25 transwomen (TrW) were scanned before and after cross-sex hormone institution. We used our own developed Body Morph test (BM), to assess the perception of own body as self. Fifteen cisgender persons were controls. Within and between-group differences in functional connectivity were calculated using independent components analysis within the DMN, SN, and motor network (a control network). Pretreatment, TrM and TrW scored lower "self" on the BM test than controls. Their functional connections were weaker in the anterior cingulate-, mesial prefrontal-cortex (mPFC), precuneus, the left angular gyrus, and superior parietal cortex of the DMN, and ACC in the SN "Self" identification and connectivity in the mPFC in both TrM and TrW increased from scan 1 to 2, and at scan 2 no group differences remained. The neurobiological underpinnings of GD seem subserved by cerebral structures composing major parts of the DMN.

Birth Order and Sibling Sex Ratio in Androphilic Males and Gynephilic Females Diagnosed With Gender Dysphoria From Iran.

BACKGROUND: This study investigated the effect of older brothers on sexual orientation in male adults diagnosed with gender dysphoria and the effect of older sisters on sexual orientation in female adults diagnosed with gender dysphoria from Iran. AIM: To assess for the presence of a fraternal birth order effect in transgender androphilic males and a sororal birth order effect in transgender gynephilic females. METHODS: The subjects were 92 transgender males and 107 transgender females (all of whom met the DSM-5 criteria for gender dysphoria), together with 72 male and 78 female clinical controls. All the transgender males were androphilic, all the transgender females were gynephilic (preferentially attracted to members of their own biological sex), and all of the clinical controls were heterosexual (none were transgender or had a diagnosis of gender dysphoria). OUTCOMES: In relation to the probands, we analyzed the sibship composition of our groups with regard to birth order and sibling sex ratio (brothers to sisters). RESULTS: The results for the transgender males confirmed the findings of 2 recent meta-analyses that older brothers increase the odds of androphilia in later-born males. The results for the transgender females did not clearly confirm one previous finding that older sisters increase the odds of gynephilia in later-born females-a finding obtained in a relatively large study that included gynephilic cisgender girls as well as girls diagnosed with gender dysphoria who will probably be predominantly gynephilic. CLINICAL IMPLICATIONS: The fraternal (later-born) birth order effect that we found for the transgender androphilic males, similar to that found in gay men, suggests a common underlying causal mechanism. STRENGTHS AND LIMITATIONS: Our study on Iranian patients diagnosed with gender dysphoria provides further generalizability for the study of birth order and sibling sex ratio that has, more often than not, been restricted to Western samples of adults diagnosed with gender dysphoria. It would be important to study these variables in Iranian gay men and lesbian women (without gender dysphoria) to further examine evidence for cross-cultural similarities when compared to Western samples. CONCLUSIONS: In contrast to the well-established fraternal birth order effect for males, the possible sororal birth order effect for females needs to be examined with additional samples. Khorashad BS, Zucker KJ, Talaei A. Birth Order and Sibling Sex Ratio in Androphilic Males and Gynephilic Females Diagnosed With Gender Dysphoria from Iran. J Sex Med 2020;17:1195-1202.

2D:4D Suggests a Role of Prenatal Testosterone in Gender Dysphoria.

Gender dysphoria (GD) reflects distress caused by incongruence between one's experienced gender identity and one's natal (assigned) gender. Previous studies suggest that high levels of prenatal testosterone (T) in natal females and low levels in natal males might contribute to GD. Here, we investigated if the 2D:4D digit ratio, a biomarker of prenatal T effects, is related to GD. We first report results from a large Iranian sample, comparing 2D:4D in 104 transwomen and 89 transmen against controls of the same natal sex. We found significantly lower (less masculine) 2D:4D in transwomen compared to control men. We then conducted random-effects meta-analyses of relevant studies including our own (k = 6, N = 925 for transwomen and k = 6, N = 757 for transmen). In line with the hypothesized prenatal T effects, transwomen showed significantly feminized 2D:4D (d ≈ 0.24). Conversely, transmen showed masculinized 2D:4D (d ≈ - 0.28); however, large unaccounted heterogeneity across studies emerged, which makes this effect less meaningful. These findings support the idea that high levels of prenatal T in natal females and low levels in natal males play a part in the etiology of GD. As we discuss, this adds to the evidence demonstrating the convergent validity of 2D:4D as a marker of prenatal T effects.

Recalled pre-school activities among adults with gender dysphoria who seek gender confirming treatment-An Iranian study.

Preschool play behaviors have been frequently shown to be associated with prenatal androgens. It has also been proposed that incongruent sex-typed play behaviors in childhood is associated with gender dysphoria in adulthood in both men and women. Most of these studies, however, have been conducted in western countries. In this study, we investigated the recalled childhood play behavior among a total number of 339 Iranian participants (n = 72 transwomen, n = 92 transmen, n = 75 cisgender men and n = 100 cisgender women) using Preschool Activity Inventory (PSAI). We found that PSAI mean scores of the four groups were significantly different (F(3,335 = 223.5, p < 0.001)). Both transmen and cisgender men scored significantly more masculine than transwomen and cisgender women but had no different with each other. Transwomen scored significantly more feminine than cisgender men and cisgender women. Our findings are in line with previous studies that suggest gender nonconforming play behaviors may be associated with gender dysphoria in adulthood. It also emphasizes the importance of this finding for in non-western clinical context and its implications.

Views of individuals with gender dysphoria and disorders of sex development on sexism: An Iranian study.

Background: Ambivalent sexist attitudes have been previously measured regarding several factors such as sex, race and religion. Aims: In this study, we evaluated the ambivalent sexism among Iranian individuals with gender dysphoria with or without disorders of sex development (DSD). Methods: Attitudes towards gender stereotypes were investigated using Ambivalent Sexism Inventory (ASI) among three groups of participants with varying psychosexual outcome. These groups were transpeople (N = 152, M = 25.44, SD = 6.52), people with DSD (N = 40, M = 21.2, SD = 2.24) and cisgender people (N = 195, M = 25.9, SD = 5.59). Results: Significant differences in both types of sexism, benevolent (F (2,383) = 134.217, p < .001) and hostile (F (2,383) = 93.765, p < .001), were found between transpeople, participants with DSD and controls. While scores of transpeople and people with DSD were not significantly different from each other (p = 0.191, Cohen's d = 0.38), both groups were significantly more sexist than controls on hostile sexism (p < 0.001, Cohen's d = 1.4 and 1.1). In benevolent sexism, there were significant differences between the scores of the trans, DSD and control groups, with individuals with DSD being most sexist followed by transgender people (p < 0.001) and controls showing the least degree of sexism (p < 0.001). Conclusion: Using the Gender Self-Socialization Model (GSSM), we propose that increased scores of ASI among individuals whose gender identity is incongruent with all or some of their physical features are attempts to attain gender typicality. This may lead to a higher degree of sexist beliefs than when all sex and gender characteristics are congruent.

Childhood Sex-Typed Behavior and Gender Change in Individuals with 46,XY and 46,XX Disorders of Sex Development: An Iranian Multicenter Study.

Disorders of sex development (DSD) are congenital conditions in which the typical genetic and hormonal profiles are affected and thereby the usual process of sexual differentiation. Most of these studies, however, have been conducted in Western countries. In the present study, preschool sex-typed activities of Iranian individuals with DSD and their age-matched non-affected male and female relatives were assessed using the Pre-School Activities Inventory (PSAI) modified for retrospective self-report. A total of 192 individuals participated in our study, including 33 46,XX individuals with congenital adrenal hyperplasia (CAH; M age = 10.36, SD = 5.52), 15 46,XY individuals with complete androgen insensitivity syndrome (CAIS; M age = 19.8, SD = 7.14), and 16 46,XY individuals with 5-alpha reductase deficiency type-2 (5α-RD-2; M age = 17.31, SD = 7.28), as well as one age-matched non-affected male and female relative for each patient. With regard to PSAI scores, male-identifying participants with 5α-RD-2 and male controls reported similar levels of male-typical childhood play. Female-identifying participants with 5α-RD-2 and CAH showed comparable scores: significantly less masculine and more feminine than male controls, but significantly more masculine and less feminine than females with CAIS and female controls. These findings support the role of androgens in the development of sex-typical childhood play behavior, with those being exposed to higher levels of fetal functional androgens expressing more masculine behavior at preschool ages.

Prenatal testosterone and theory of mind development: Findings from disorders of sex development.

Women on average perform better than men on the "Reading the Mind in the Eyes" test (RMET) which is a measure of Theory of Mind (ToM). The aim of this study was to assess whether these sex differences are influenced by differences in prenatal testosterone levels through a study on individuals with Disorders of Sex Development and matched controls. ToM performance was examined using the RMET in female-assigned-at-birth individuals with increased prenatal testosterone exposure (Congenital Adrenal Hyperplasia (CAH) and 5-alpha Reductase type-2 Deficiency (5α-RD-2)), female-assigned-at-birth individuals with testosterone insensitivity (Complete Androgen Insensitivity Syndrome (CAIS)), and their age-matched unaffected male and female relatives. A total number of 158 individuals participated in the study; 19 with 5α-RD-2, 17 with CAH, 18 women with CAIS, 52 matched unaffected men and 52 matched unaffected women. All subgroups were around 20 years of age. Women with CAH scored significantly lower on RMET than control women and CAIS individuals. CAIS individuals scored significantly higher than control men and participants with 5α-RD. Statistically, CAIS individuals' performance on RMET was similar to control women's, women with CAH did not differ significantly from control men and 5α-RD-2 individuals scored significantly lower than control men. These results, which are in line with previous theories, illustrate that performance on the RMET, as an index of ToM, may be influenced by variations in prenatal androgens levels.

Mental Health and Disorders of Sex Development/Intersex Conditions in Iranian Culture: Congenital Adrenal Hyperplasia, 5-α Reductase Deficiency-Type 2, and Complete Androgen Insensitivity Syndrome.

Sixty-one patients (22 patients with congenital adrenal hyperplasia [CAH] with a mean age of 14.86 years [range, 5-23], 20 patients with 5-α reductase deficiency type 2 [5α-RD-2] with a mean age of 19.5 years [range, 5-29], and 19 patients with complete androgen insensitivity syndrome [CAIS] with a mean age of 18.26 years [range, 5-28]) were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia, the Structured Clinical Interview for DSM-IV Axis I, Axis II, and the Global Assessment Functioning Scale. All participants were female-assigned at birth. Ten patients (16.4%) transitioned to the male gender. Overall, 68% of patients had one or more lifetime Axis I disorders, including 63.6% of the CAH participants, 90% of 5α-RD-2 participants, and 52.6% of the CAIS participants. The most commonly observed were affective disorders (27.9%), gender identity disorder (27.9%), and anxiety (16.4%). Our study demonstrates that mental health of Iranian patients with DSD is at risk. This might be due to the fact that patients with DSD conditions are mostly treated medically and their mental health is often superficially addressed in developing countries such as Iran, at least in the past. We argue that it is important to pay attention to the mental health issues of patients with DSD and focus on specific issues, which may vary cross-culturally.

Sexual orientation and medical history among Iranian people with Complete Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia.

OBJECTIVE: To report sexual orientation, relationship status and medical history of Iranian people with Differences of Sex Development (DSD) who were raised female. METHODS: Our participants consisted of nineteen 46,XY individuals with Complete Androgen Insensitivity Syndrome (CAIS) and eighteen 46,XX individuals with Congenital Adrenal Hyperplasia (CAH) who were raised as females and older than 13years. As well as their relationship status and detailed medical history, an expert psychiatrist assessed their sexual orientation by a semi-structured psychiatric interview with them and, where applicable, their parents. RESULTS: Five percent of CAH participants and 42% of CAIS participants were in a relationship, which was significantly different. All CAH individuals had been diagnosed at birth; 89% of CAIS had been diagnosed after puberty and due to primary amenorrhea and 11% were diagnosed in childhood due to inguinal hernia. Genital reconstructive surgery had been performed in 100% of CAH participants and 37% of CAIS. Regarding sexual contact experiences and sexual fantasies (androphilic, gynephilic or both), no significant differences were found. However, CAH females had significantly more gynephilic dreams (P=0.045). CONCLUSION: This study, notable as one of the rare from a non-western culture, described sexual, medical and socioeconomic status of 46,XX CAH and 46,XY CAIS individuals living in Iran. Although broadly in line with previous findings from Western cultures, Iranian CAH individuals had fewer romantic relationships, but in contrast to previous studies their sexual orientation was only different from CAIS in the contents of sexual dreams.

Psychosexual Outcome Among Iranian Individuals With 5α-Reductase Deficiency Type 2 and Its Relationship With Parental Sexism.

INTRODUCTION: Few studies exist on the psychosexual outcome of homogeneous groups of individuals with 5α-reductase deficiency type 2 (5α-RD-2) and the relation between gender changes and parental hostile and benevolent sexism, which are two components of ambivalent sexism that assume a stereotypical approach toward women in an overtly negative way or a chivalrous, seemingly positive way. AIM: To report on the psychosexual outcome of individuals with 5α-RD-2 and to investigate its relation to the level of parental sexism in a relatively large sample of Iranians with 5α-RD-2. METHODS: Twenty participants (mean age = 19.5 years, SD = 6.345) with a molecularly confirmed diagnosis of 5α-RD-2 who were assigned the female gender at birth and raised as female were included in the study. Participants and their parents were interviewed and their medical records were assessed. Parents also completed the Ambivalent Sexism Inventory (ASI), which includes hostile and benevolent sexism subscales. MAIN OUTCOME MEASURES: Psychosexual outcome and parental hostile and benevolent sexism measurements. RESULTS: Twelve of 20 participants (60%) were diagnosed with gender identity disorder not otherwise specified (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision). Ten of these transitioned to the male gender. The other 10 participants (50%), including the two diagnosed with gender identity disorder not otherwise specified, continued living in a female gender role. When comparing the ASI subscale scores between families of participants who changed their gender and those who did not, no significant difference was found for ASI total and hostile sexism scores, but there was a difference for benevolent sexism (P = .049): those whose daughters had changed their gender had higher benevolent sexism scores. CONCLUSION: The high prevalence of gender change and gender dysphoria reported in the literature was confirmed in this relatively large and homogeneous sample of Iranians with 5-α-RD-2 raised as female. Prenatal exposure to testosterone is hypothesized to play a role in the development of gender identity and sexual orientation, but parental attitudes also might be important. Although gender change in individuals with 5-α-RD-2 is often attributed to high levels of hostile sexism in some cultures, our findings show this to be associated with benevolent sexism.

The "Reading the Mind in the Eyes" Test: Investigation of Psychometric Properties and Test-Retest Reliability of the Persian Version.

The psychometric properties of the Persian "Reading the Mind in the Eyes" test were investigated, so were the predictions from the Empathizing-Systemizing theory of psychological sex differences. Adults aged 16-69 years old (N = 545, female = 51.7 %) completed the test online. The analysis of items showed them to be generally acceptable. Test-retest reliability, as measured by Intra-class correlation coefficient, was 0.735 with a 95 % CI of (0.514, 0.855). The percentage of agreement for each item in the test-retest was satisfactory and the mean difference between test-retest scores was -0.159 (SD = 3.42). However, the internal consistency of Persian version, calculated by Cronbach's alpha (0.371), was poor. Females scored significantly higher than males but academic degree and field of study had no significant effect.