[Frontal sinus anatomical scanographic study of transgender patients for feminization frontoorbitoplasty surgery]. / Étude anatomique scanographique du sinus frontal des patients transgenres en vue d'une chirurgie de frontoorbitoplastie de féminisation.

INTRODUCTION: Little is known about the anatomical elements that allow safe and predictable performance of fronto orbital surgery for facial feminization. The primary objective of this study was to analyze the characteristics (dimensions, pneumatization rate, and anterior wall thickness) of the frontal sinus in MtF transgender patients. The secondary objective was to establish reproducible criteria for CT measurements that could guide preoperative planning of frontal impaction in feminization frontoplasty (FF). MATERIALS: Fifty preoperative facial mass scans of FF surgery patients were included. The mean age of the operated patients was 34 years. The F line represented the ideal forehead tilt in the absence of a frontal hump. RESULTS: The height, width, depth, and thickness of the anterior sinus wall were 26.6mm (±5.7), 49.5mm (±11.3), 10.9mm (±3.3), and 3mm (±0.7), respectively. The mean sinus width to skull width ratio was 0.73 (±0.12). Six percent of patients had bilateral frontal sinus agenesis. An osteotomy of the anterior wall of the frontal sinus was performed in the 64% of patients with frontal sinus projection anterior to the F-line. The emergence of the supraorbital nerves from the frontal bone was through a bony notch in 73.8% of cases. CONCLUSIONS: Knowledge of the anatomy of the frontal sinus and preoperative study of the scans of the facial mass is essential for planning the FF. These characteristics guide the surgical technique of bone remodeling as well as the procedure for releasing the supraorbital nerves.

Neuroradiology in Transgender Care: Facial Feminization, Laryngeal Surgery, and Beyond.

Transgender individuals experience incongruence between their gender identity and the sex assigned to them at birth. This incongruence can cause many transgender individuals to experience distressing physical and mental discord, a diagnosis known as gender dysphoria. Craniofacial structures have distinct anthropometric characteristics that affect perceived masculinity and femininity. The face, neck, and voice are highly exposed anatomic areas that have recognizable gender-specific characteristics that may hinder a transgender individual's successful social integration and public acceptance. Reconstructive facial and laryngeal procedures are among the surgical options transgender persons may elect to undergo to better align their physical appearance with their gender identity. These include feminization surgeries such as facial feminization and reduction chondrolaryngoplasty, as well as masculinizing facial and laryngeal surgeries. Maxillofacial CT is frequently used in the preoperative evaluation of patients before facial feminization surgery (FFS). Several CT measurements guide surgeons to the optimal correction required in FFS to achieve appropriate aesthetic planes. Mapping important craniofacial landmarks to avoid untoward surgical complications is crucial. Transgender patients may encounter other neurologic complications that require neuroimaging evaluation. For example, gender-affirming hormone therapy (eg, estrogen and testosterone) may increase the risk of stroke or may influence growth of various hormone-sensitive tumors such as pituitary adenomas. Radiologists may interpret imaging examinations in transgender patients for routine care or for evaluation before and after facial and laryngeal surgeries and must be aware of the role of neuroimaging in the care of this population. An invited commentary by Callen is available online. The online slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2022.

Brain connectivity dynamics in cisgender and transmen people with gender incongruence before gender affirmative hormone treatment.

Large-scale brain network interactions have been described between trans- and cis-gender binary identities. However, a temporal perspective of the brain's spontaneous fluctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: (i) one state highly prevalent with sparse overall connections; (ii) a second with strong couplings mainly involving components of the salience, default, and executive control networks. Two states with global sparse connectivity but positive couplings (iii) within the sensorimotor network, and (iv) between salience network regions. Transmen had more dynamical fluidity than cismen, while cismen presented less meta-state fluidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fluidity and meta-state range dynamism was found in transmen. There exist gender differences in the temporal brain dynamism, characterized by distinct interrelations of the salience network as catalyst interacting with other networks. We offer a functional explanation from the neurodevelopmental cortical hypothesis of a gendered-self.

Implementation of transgender and gender diverse curriculum in medical imaging programs: A review of the literature.

INTRODUCTION: Sexual and gender minority patients experience significant inequities when accessing health care. Transgender and non-binary patients are at an even greater risk of experiencing health disparities due to their specialized health care needs. In the discipline of medical imaging, limited cultural competence, social stigma, and cis-heteronormative environments are barriers for these patients. There is an urgent need to improve medical imaging care for transgender and non-binary people; inclusion of sexual and gender minority content in medical imaging curriculum is one strategy to begin to address this need. METHOD: A review of the literature was undertaken to explore implementation of sexual and gender minority content in the curricula of medical imaging programs. RESULTS/DISCUSSION: Three main themes were identified: 1) educators' acknowledgement of the importance and value of adding sexual and gender minority content to healthcare curriculum; 2) educators' lack of a sense of preparedness, experience, and knowledge to adequately teach this content: and 3) lack of resources and institutional support to help develop curriculum. CONCLUSION: Including content in the curriculum related to the needs of transgender and non-binary patients will help ensure entry-to-practice Medical Radiation Technologists are better prepared to provide inclusive care.

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.

Effects of adult male rat feminization treatments on brain morphology and metabolomic profile.

Body feminization, as part of gender affirmation process of transgender women, decreases the volume of their cortical and subcortical brain structures. In this work, we implement a rat model of adult male feminization which reproduces the results in the human brain and allows for the longitudinal investigation of the underlying structural and metabolic determinants in the brain of adult male rats undergoing feminization treatments. Structural MRI and Diffusion Tensor Imaging (DTI) were used to non-invasively monitor in vivo cortical brain volume and white matter microstructure over 30 days in adult male rats receiving estradiol (E2), estradiol plus cyproterone acetate (CA), an androgen receptor blocker and antigonadotropic agent (E2 + CA), or vehicle (control). Ex vivo cerebral metabolic profiles were assessed by 1H High Resolution Magic Angle Spinning NMR (1H HRMAS) at the end of the treatments in samples from brain regions dissected after focused microwave fixation (5 kW). We found that; a) Groups receiving E2 and E2 + CA showed a generalized bilateral decrease in cortical volume; b) the E2 + CA and, to a lesser extent, the E2 groups maintained fractional anisotropy values over the experiment while these values decreased in the control group; c) E2 treatment produced increases in the relative concentration of brain metabolites, including glutamate and glutamine and d) the glutamine relative concentration and fractional anisotropy were negatively correlated with total cortical volume. These results reveal, for the first time to our knowledge, that the volumetric decreases observed in trans women under cross-sex hormone treatment can be reproduced in a rat model. Estrogens are more potent drivers of brain changes in male rats than anti-androgen treatment.

Neural Systems for Own-body Processing Align with Gender Identity Rather Than Birth-assigned Sex.

Gender identity is a core aspect of self-identity and is usually congruent with birth-assigned sex and own body sex-perception. The neuronal circuits underlying gender identity are unknown, but greater awareness of transgenderism has sparked interest in studying these circuits. We did this by comparing brain activation and connectivity in transgender individuals (for whom gender identity and birth-assigned sex are incongruent) with that in cisgender controls (for whom they are congruent) when performing a body self-identification task during functional magnetic resonance imaging. Thirty transgender and 30 cisgender participants viewed images of their own bodies and bodies morphed in sex toward or opposite to birth-assigned sex, rating each image to the degree they identified with it. While controls identified with images of themselves, transgender individuals identified with images morphed "opposite" to their birth-assigned sex. After covarying out the effect of self-similarity ratings, both groups activated similar self- and body-processing systems when viewing bodies that aligned with their gender identity rather than birth-assigned sex. Additionally, transgender participants had greater limbic involvement when viewing ambiguous, androgynous images of themselves morphed toward their gender identity. These results shed light on underlying self-processing networks specific to gender identity and uncover additional involvement of emotional processing in transgender individuals.

Masculinizing Genital Surgery: An Imaging Primer for the Radiologist.

OBJECTIVE. Masculinizing genital surgeries for transgender individuals are currently performed at only a select few centers; however, radiologists in any geographic region may be confronted with imaging studies of transgender patients. The imaging findings of internal and external genital anatomy of a transgender patient may differ substantially from the imaging findings of a cisgender patient. This article provides the surgical and anatomic basis to allow appropriate interpretation of preoperative and postoperative imaging findings. We also expand on the most common complications and associated imaging findings. CONCLUSION. As these procedures become more commonplace, radiologists will have a growing role in the care of transgender patients and will be faced with new anatomic variants and differential diagnoses. Familiarity with these anatomic variations and postoperative complications is crucial for the radiologist to provide an accurate and useful report.

Neuroimaging gender dysphoria: a novel psychobiological model.

Gender identity development is complex and involves several key processes. Transgender people experience incongruence between their biological and identified gender. This incongruence can cause significant impairment in overall functioning and lead to gender dysphoria (GD). The pathophysiology of GD is complex and is poorly understood. A PubMed search based on predetermined eligibility criteria was conducted to review neuropsychiatric articles focused on neurological, biological and neuroimaging aspects of gender development, transgender identity and GD. The information obtained from the literature was then used to formulize a GD model. Distinct gray matter volume and brain activation and connectivity differences were found in individuals with GD compared to controls, suggesting a neurobiological basis of GD; which leads to the concept of brain gender. Individuals with GD encounter a recurrent conflict between their brain gender and the societal feedback; which causes recurrent and ongoing cognitive dissonance, finally leading to GD and functional connectivity and activation changes in the transgender brain. GD has neurobiological basis, but it is closely associated with the individuals' interaction with the external world, their self-perception and the feedback received in return. We propose a novel model where the development of GD includes cognitive dissonance, involving anterior cingulate cortex and ventral striatum as the key brain structures. This model can be used to generate testable hypotheses using behavioral and neuroimaging techniques to understand the neuropsychobiology of GD.

Proandrogenic and Antiandrogenic Progestins in Transgender Youth: Differential Effects on Body Composition and Bone Metabolism.

Context: Progestins can be used to attenuate endogenous hormonal effects in late-pubertal transgender (trans) adolescents (Tanner stage B4/5 and G4/5). Currently, no data are available on the effects of progestins on the development of bone mass or body composition in trans youth. Objective: To study prospectively the evolution of body composition and bone mass in late-pubertal trans adolescents using the proandrogenic or antiandrogenic progestins lynestrenol (L) and cyproterone acetate (CA), respectively. Design and Outcome Measurements: Forty-four trans boys (Tanner B4/5) and 21 trans girls (Tanner G4/5) were treated with L or CA for 11.6 (4 to 40) and 10.6 (5 to 31) months, respectively. Anthropometry, grip strength, body composition, and bone mass, size, and density were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography before the start of progestin and before addition of cross-sex hormones. Results: Using L, lean mass [+3.2 kg (8.6%)] and grip strength [+3 kg (10.6%)] significantly increased, which coincided with a more masculine body shape in trans boys. Trans girls showed loss of lean mass [-2.2 kg (4.7%)], gain of fat mass [+1.5 kg (9.4%)], and decreased grip strength Z scores. CA limited normal bone expansion and impeded pubertal bone mass accrual, mostly at the lumbar spine [Z score: -0.765 to -1.145 (P = 0.002)]. L did not affect physiological bone development. Conclusion: Proandrogenic and antiandrogenic progestins induce body composition changes in line with the desired appearance within 1 year of treatment. Bone health, especially at the lumbar spine, is of concern in trans girls, as bone mass accrual is severely affected by androgen suppressive therapy.

Surgical and pharmacological reassignment: influence on transsexual cardiovascular risk profile.

BACKGROUND/AIM: To evaluate and stratify early cardiovascular risk of transsexuals who underwent pharmacological and/or surgical gender reassignment. METHODS: Fifty-six transsexuals were divided into two groups: group 1 - underwent gonadectomy (orchiectomy for transwomen and hystero-annessiectomy for transmen); group 2 - hormone replacement therapy alone. All participants underwent carotid artery intima-media thickness (C-IMT) and flow-mediated vasodilation (FMD) of brachial artery evaluations. RESULTS: FMD was lower in patients who had undergone gonadectomy compared with non-surgically treated patients (Group 1: 5.711 vs Group 2: 7.339, P < 0.0001). Mean C-IMT was higher in group 1 than group 2 (group 1: 0.733 vs group 2: 0.582). The duration of hormone therapy correlates positively with mean C-IMT (B = 0.001) and negatively with FMD (%) (B = - 0.007). CONCLUSIONS: Cardiovascular risk, which is expressed in terms of endothelial (FMD) and morphological (C-IMT) dysfunction, increases in subjects undergoing gonadectomy compared with those receiving cross-sex reassignment therapy alone.

Intrinsic network connectivity and own body perception in gender dysphoria.

Gender dysphoria (GD) is characterized by incongruence between one's identity and gender assigned at birth. The biological mechanisms of GD are unclear. We investigated brain network connectivity patterns involved in own body perception in the context of self in GD. Twenty-seven female-to-male (FtM) individuals with GD, 27 male controls, and 27 female controls underwent resting state fMRI. We compared functional connections within intrinsic connectivity networks involved in self-referential processes and own body perception -default mode network (DMN) and salience network - and visual networks, using independent components analyses. Behavioral correlates of network connectivity were also tested using self-perception ratings while viewing own body images morphed to their sex assigned at birth, and to the sex of their gender identity. FtM exhibited decreased connectivity of anterior and posterior cingulate and precuneus within the DMN compared with controls. In FtM, higher "self" ratings for bodies morphed towards the sex of their gender identity were associated with greater connectivity of the anterior cingulate within the DMN, during long viewing times. In controls, higher ratings for bodies morphed towards their gender assigned at birth were associated with right insula connectivity within the salience network, during short viewing times. Within visual networks FtM showed weaker connectivity in occipital and temporal regions. Results suggest disconnectivity within networks involved in own body perception in the context of self in GD. Moreover, perception of bodies in relation to self may be reflective rather than reflexive, as a function of mesial prefrontal processes. These may represent neurobiological correlates to the subjective disconnection between perception of body and self-identification.

A Structural Magnetic Resonance Imaging Study in Transgender Persons on Cross-Sex Hormone Therapy.

BACKGROUND: To date, research findings are inconsistent about whether the neuroanatomy in transgender persons resembles that of their natal sex or their gender identity. Moreover, few studies have examined the effects of long-term cross-sex hormonal treatment on neuroanatomy in this cohort. The purpose of the present study was to examine neuroanatomical differences in transgender persons after prolonged cross-sex hormone therapy. METHODS: Eighteen transgender men (female-to-male), 17 transgender women (male-to-female), 30 nontransgender men (natal men), and 27 nontransgender women (natal women) completed a high-resolution structural magnetic resonance imaging scan at 3 T. Eligibility criteria for transgender persons were gender-affirming surgery and at least 2 years of cross-sex hormone therapy. Exclusion criteria for nontransgender persons were presence of psychiatric or neurological disorders. RESULTS: The mean neuroanatomical volume for the amygdala, putamen, and corpus callosum differed between transgender women and natal women but not between transgender women and natal men. Differences between transgender men and natal men were found in several brain structures, including the medial temporal lobe structures and cerebellum. Differences between transgender men and natal women were found in the medial temporal lobe, nucleus accumbens, and 3rd ventricle. Sexual dimorphism between nontransgender men and women included larger cerebellar volumes and a smaller anterior corpus callosum in natal men than in natal women. The results remained stable after correcting for additional factors including age, total intracranial volume, anxiety, and depressive symptoms. CONCLUSIONS: Neuroanatomical differences were region specific between transgender persons and their natal sex as well as their gender identity, raising the possibility of a localized influence of sex hormones on neuroanatomy.

Anatomical and Functional Findings in Female-to-Male Transsexuals: Testing a New Hypothesis.

Gender dysphoria (GD) is characterized by incongruence between onés gender assigned at birth and the gender that one identifies with. The biological mechanisms of GD are unclear, especially in female-to-male transsexuals (FtM-TR). Here, we investigate whether distinct structural and functional patterns along cerebral midline networks processing own-body perception may constitute a biological correlate. METHOD: MRI of functional connectivity, cortical thickness, surface area, and gray matter volume was carried out in 28 female-to-male transsexuals (FtM-TR) and 68 cis-sexual controls (34 male). FtM-TR displayed thicker mid-frontal, precuneal-parietal, and lingual cortex than both male and female controls, whereas, in regions with reported anatomical sex differences among the controls, FtM-TR followed patterns of the gender assigned at their birth. FtM-TR also displayed weaker functional connections from the pregenual anterior cingulate to the insular cortex, and the temporo parietal junction compared with both control groups. Distinct structural and functional pattern in the own-body image network may represent biological markers for the dysphoric own-body perception in transgender individuals.

Subcortical gray matter changes in transgender subjects after long-term cross-sex hormone administration.

Sex-steroid hormones are primarily involved in sexual differentiation and development and are thought to underlie processes related to cognition and emotion. However, divergent results have been reported concerning the effects of hormone administration on brain structure including side effects like brain atrophy and dementia. Cross-sex hormone therapy in transgender subjects offers a unique model for studying the effects of sex hormones on the living human brain. In this study, 25 Female-to-Male (FtM) and 14 Male-to-Female (MtF) subjects underwent MRI examinations at baseline and after a period of at least 4-months of continuous cross-sex hormone administration. While MtFs received estradiol and anti-androgens, FtM subjects underwent high-dose testosterone treatment. The longitudinal processing stream of the FreeSurfer software suite was used for the automated assessment and delineation of brain volumes to assess the structural changes over the treatment period of cross-sex hormone administration. Most prominent results were found for MtFs receiving estradiol and anti-androgens in the form of significant decreases in the hippocampal region. Further analysis revealed that these decreases were reflected by increases in the ventricles. Additionally, changes in progesterone levels correlated with changes in gray matter structures in MtF subjects. In line with prior studies, our results indicate hormonal influences on subcortical structures related to memory and emotional processing. Additionally, this study adds valuable knowledge that progesterone may play an important role in this process.

A Review of the Status of Brain Structure Research in Transsexualism.

The present review focuses on the brain structure of male-to-female (MtF) and female-to-male (FtM) homosexual transsexuals before and after cross-sex hormone treatment as shown by in vivo neuroimaging techniques. Cortical thickness and diffusion tensor imaging studies suggest that the brain of MtFs presents complex mixtures of masculine, feminine, and demasculinized regions, while FtMs show feminine, masculine, and defeminized regions. Consequently, the specific brain phenotypes proposed for MtFs and FtMs differ from those of both heterosexual males and females. These phenotypes have theoretical implications for brain intersexuality, asymmetry, and body perception in transsexuals as well as for Blanchard's hypothesis on sexual orientation in homosexual MtFs. Falling within the aegis of the neurohormonal theory of sex differences, we hypothesize that cortical differences between homosexual MtFs and FtMs and male and female controls are due to differently timed cortical thinning in different regions for each group. Cross-sex hormone studies have reported marked effects of the treatment on MtF and FtM brains. Their results are used to discuss the early postmortem histological studies of the MtF brain.

Bone mass in young adulthood following gonadotropin-releasing hormone analog treatment and cross-sex hormone treatment in adolescents with gender dysphoria.

CONTEXT: Sex steroids are important for bone mass accrual. Adolescents with gender dysphoria (GD) treated with gonadotropin-releasing hormone analog (GnRHa) therapy are temporarily sex-steroid deprived until the addition of cross-sex hormones (CSH). The effect of this treatment on bone mineral density (BMD) in later life is not known. OBJECTIVE: This study aimed to assess BMD development during GnRHa therapy and at age 22 years in young adults with GD who started sex reassignment (SR) during adolescence. DESIGN AND SETTING: This was a longitudinal observational study at a tertiary referral center. PATIENTS: Young adults diagnosed with gender identity disorder of adolescence (DSM IV-TR) who started SR in puberty and had undergone gonadectomy between June 1998 and August 2012 were included. In 34 subjects BMD development until the age of 22 years was analyzed. INTERVENTION: GnRHa monotherapy (median duration in natal boys with GD [transwomen] and natal girls with GD [transmen] 1.3 and 1.5 y, respectively) followed by CSH (median duration in transwomen and transmen, 5.8 and 5.4 y, respectively) with discontinuation of GnRHa after gonadectomy. MAJOR OUTCOME MEASURES: How BMD develops during SR until the age of 22 years. RESULTS AND CONCLUSION: Between the start of GnRHa and age 22 years the lumbar areal BMD z score (for natal sex) in transwomen decreased significantly from -0.8 to -1.4 and in transmen there was a trend for decrease from 0.2 to -0.3. This suggests that the BMD was below their pretreatment potential and either attainment of peak bone mass has been delayed or peak bone mass itself is attenuated.

Breast cancer in male-to-female transsexuals: use of breast imaging for detection.

OBJECTIVE: The purposes of this article are to describe two cases of breast cancer in male-to-female transsexuals and to review eight cases previously reported in the literature. CONCLUSION: Breast cancer occurs in male-to-female transsexuals who receive high doses of exogenous estrogen and develop breast tissue histologically identical to that of a biologically female breast. This exposure to estrogen results in increased risk of breast cancer. The first patient described is a male-to-female transsexual with screening-detected ductal carcinoma in situ and a family history of breast cancer. The other patient is a male-to-female transsexual with invasive ductal carcinoma that was occult on diagnostic digital mammographic and ultrasound findings but visualized on digital breast tomosynthesis and breast MR images. The analysis of the eight previously reported cases showed that breast cancer in male-to-female transsexuals occurs at a younger age and is more frequently estrogen receptor negative than breast cancer in others born biologically male. Screening for breast cancer in male-to-female transsexuals should be undertaken for those with additional risk factors (e.g., family history, BRCA2 mutation, Klinefelter syndrome) and should be available to those who desire screening, preferably in a clinical trial.

Neovaginal perforation following sexual intercourse in a transsexual patient.

BACKGROUND: Neovaginal perforation can develop following sexual intercourse in patients that have undergone male to female gender reassignment surgery. In such cases urinary tract symptoms may mimic acute cystitis and acute pyelonephritis. CASE PRESENTATION: A 33-year old white transsexual patient presented to the emergency department with dysuria, hematuria, difficulty urinating, widespread groin pain, bilateral side pain, clear vaginal discharge, abdominal pain, and nausea 2-3 h after sexual intercourse. Abdominal tomography showed fluid around the vaginal cuff and air throughout the abdomen. Vaginography showed contrast leaking to the abdomen from the vaginal cuff. The patient was considered as vaginal perforation and admitted to clinic. CONCLUSION: Vaginal perforation should be considered in transsexual patients that develop urinary system symptoms following sexual intercourse. Such cases were treated medically without the need surgery.

Cerebral serotonin transporter asymmetry in females, males and male-to-female transsexuals measured by PET in vivo.

The serotonergic system modulates brain functions that are considered to underlie affective states, emotion and cognition. Several lines of evidence point towards a strong lateralization of these mental processes, which indicates similar asymmetries in associated neurotransmitter systems. Here, our aim was to investigate a potential asymmetry of the serotonin transporter distribution using positron emission tomography and the radioligand [(11)C]DASB in vivo. As brain asymmetries may differ between sexes, we further aimed to compare serotonin transporter asymmetry between females, males and male-to-female (MtF) transsexuals whose brains are considered to be partly feminized. Voxel-wise analysis of serotonin transporter binding in all groups showed both strong left and rightward asymmetries in several cortical and subcortical structures including temporal and frontal cortices, anterior cingulate, hippocampus, caudate and thalamus. Further, male controls showed a rightward asymmetry in the midcingulate cortex, which was absent in females and MtF transsexuals. The present data support the notion of a lateralized serotonergic system, which is in line with previous findings of asymmetric serotonin-1A receptor distributions, extracellular serotonin concentrations, serotonin turnover and uptake. The absence of serotonin transporter asymmetry in the midcingulate in MtF transsexuals may be attributed to an absence of brain masculinization in this region.