Mental Health Evaluation of Younger and Older Adolescents Referred to the Center of Expertise on Gender Dysphoria in Amsterdam, The Netherlands.

The present study aimed to investigate whether differences exist between younger and older presenting adolescents at the Center of Expertise on Gender Dysphoria regarding psychological functioning and autistic traits. A total of 1487 consecutively assessed adolescents between 2000 and 2018 were divided in younger presenters (age ≤ 13.9 years) and older presenters (age ≥ 14 years). Of younger presenters, 227 (41.1%) were assigned male at birth and 325 (58.9%) assigned female at birth. In older presenters, 279 (29.8%) were assigned male at birth and 656 (70.2%) assigned female at birth. Behavioral and emotional problems were assessed with the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). For autism traits, the Social Responsiveness Scale (SRS) was used. Compared to younger presenters, on both the CBCL and YSR older presenters had higher Total Problem (ß = 1.75, p = .005, CI 0.53-2.97, R2 = .04 and ß = 4.20, p < .001, CI 2.99-5.40, R2 = .07, respectively) and Internalizing Problem (ß = 4.43, p < .001, CI 3.13-5.74, R2 = .06 and ß = 6.69, p < .001, CI 5.31-8.07, R2 = .12, respectively) scores. Regarding autistic traits, a higher mean SRS total score was found in older presenting assigned males at birth (ß = 4.55, p = .036, CI 0.30-8.81, R2 = .34). In assigned females at birth, no statistically significant difference between older and younger presenters was found in mean SRS total score (ß = 1.19, p = .063, CI - 0.07 to 2.45, R2 = .39). Differences in mental health exist between younger and older presenting adolescents and call for an individualized approach in the clinical care of transgender adolescents.

Alterations in the inferior fronto-occipital fasciculus - a specific neural correlate of gender incongruence?

BACKGROUND: Increasing numbers of adolescents seek help for gender-identity questions. Consequently, requests for medical treatments, such as puberty suppression, are growing. However, studies investigating the neurobiological substrate of gender incongruence (when birth-assigned sex and gender identity do not align) are scarce, and knowledge about the effects of puberty suppression on the developing brain of transgender youth is limited. METHODS: Here we cross-sectionally investigated sex and gender differences in regional fractional anisotropy (FA) as measured by diffusion MR imaging, and the impact of puberty on alterations in the white-matter organization of 35 treatment-naive prepubertal children and 41 adolescents with gender incongruence, receiving puberty suppression. The transgender groups were compared with 79 age-matched, treatment-naive cisgender (when sex and gender align) peers. RESULTS: We found that transgender adolescents had lower FA in the bilateral inferior fronto-occipital fasciculus (IFOF), forceps major and corpus callosum than cisgender peers. In addition, average FA values of the right IFOF correlated negatively with adolescents' cumulative dosage of puberty suppressants received. Of note, prepubertal children also showed significant FA group differences in, again, the right IFOF and left cortico-spinal tract, but with the reverse pattern (transgender > cisgender) than was seen in adolescents. CONCLUSIONS: Importantly, our results of lower FA (indexing less longitudinal organization, fiber coherence, and myelination) in the IFOF of gender-incongruent adolescents replicate prior findings in transgender adults, suggesting a salient neural correlate of gender incongruence. Findings highlight the complexity with which (pubertal) sex hormones impact white-matter development and add important insight into the neurobiological substrate associated with gender incongruence.

Desired decision-making role and treatment satisfaction among trans people during medical transition: results from the ENIGI follow-up study.

BACKGROUND: Shared decision making (SDM) is particularly important in transition-related medical interventions (TRMIs) given the nature of treatment and history of gatekeeping in transgender health care. Yet few studies have investigated trans people's desired decision-making role within TRMI and factors that influence these desires. AIMS: The study investigated trans people's desired level of decision making during medical transition as well as possible sociodemographic predictors and correlations between decision-making desires and satisfaction with treatment. METHODS: Data were collected from a clinical sample from 3 trans health care centers, as part of the larger ENIGI study. The data consisted of 568 trans individuals (60.2% assigned male at birth) 20 to 82 years of age (mean age = 38.58 years) who took part in the study 4 to 6 years after initial clinical contact. Binary logistic regressions were conducted to determine whether independent variables predicted group membership in decision-making role subgroups while a Spearman rank-order correlation was conducted to determine the relationship between desired decision-making involvement and satisfaction with care. OUTCOMES: Main measures were desired decision-making role, satisfaction with treatment, age, education level, country of residence, treatment status, individual treatment progress score (ITPS), gender identity, and sex assigned at birth. RESULTS: The vast majority of participants wanted to make medical decisions themselves. Age, education level, country of residence, treatment status, gender identity, and sex assigned at birth showed no significant effects in desired level of decision making, while the ITPS neared significance. Satisfaction with treatment was overall very high. For participants assigned male at birth, desire for a more active role in decision making was negatively correlated with satisfaction of labia surgery. CLINICAL IMPLICATIONS: A desired decision-making role cannot be predicted based on the trans person's sociodemographic characteristics. More involvement from health professionals addressing medical information and education obligations may be needed when offering surgical construction of labia to individuals assigned male at birth. STRENGTHS AND LIMITATIONS: This study builds on the few existing analyses of desired levels of decision-making role among trans people during transition. It is the first to investigate the role of education level and treatment status/ITPS on the desire of decision-making role. Gender identity and influence of nonbinary identity were not investigated for treatment satisfaction as these items were presented based on sex assigned at birth. CONCLUSION: This study highlights that trans people in 3 European trans health care centers during medical transition desire a more active role in decision making. Satisfaction with treatment received was overall very high.

Children and adolescents in the Amsterdam Cohort of Gender Dysphoria: trends in diagnostic- and treatment trajectories during the first 20 years of the Dutch Protocol.

BACKGROUND: Twenty years ago, the Dutch Protocol-consisting of a gonadotropin-releasing hormone agonist (GnRHa) to halt puberty and subsequent gender-affirming hormones (GAHs)-was implemented to treat adolescents with gender dysphoria. AIM: To study trends in trajectories in children and adolescents who were referred for evaluation of gender dysphoria and/or treated following the Dutch Protocol. METHODS: The current study is based on a retrospective cohort of 1766 children and adolescents in the Amsterdam Cohort of Gender Dysphoria. OUTCOMES: Outcomes included trends in number of intakes, ratio of assigned sex at birth, age at intake, age at start of GnRHa and GAH, puberty stage at start of GnRHa, proportions of adolescents starting and stopping GnRHa, reasons for refraining from GnRHa, and proportions of people undergoing gender-affirming surgery. RESULTS: A steep increase in referrals was observed over the years. A change in the AMAB:AFAB ratio (assigned male at birth to assigned female at birth) was seen over time, tipping the balance toward AFAB. Age at intake and at start of GnRHa has increased over time. Of possibly eligible adolescents who had their first visit before age 10 years, nearly half started GnRHa vs around two-thirds who had their first visit at or after age 10 years. The proportion starting GnRHa rose only for those first visiting before age 10. Puberty stage at start of GnRHa fluctuated over time. Absence of gender dysphoria diagnosis was the main reason for not starting GnRHa. Very few stopped GnRHa (1.4%), mostly because of remission of gender dysphoria. Age at start of GAH has increased mainly in the most recent years. When a change in law was made in July 2014 no longer requiring gonadectomy to change legal sex, percentages of people undergoing gonadectomy decreased in AMAB and AFAB. CLINICAL IMPLICATIONS: A substantial number of adolescents did not start medical treatment. In the ones who did, risk for retransitioning was very low, providing ongoing support for medical interventions in comprehensively assessed gender diverse adolescents. STRENGTHS AND LIMITATIONS: Important topics on transgender health care for children and adolescents were studied in a large cohort over an unprecedented time span, limited by the retrospective design. CONCLUSION: Trajectories in diagnostic evaluation and medical treatment in children and adolescents referred for gender dysphoria are diverse. Initiating medical treatment and need for surgical procedures depends on not only personal characteristics but societal and legal factors as well.

Doing and undoing transgender health care: The ordering of 'gender dysphoria' in clinical practice.

A formal Gender Dysphoria classification- as outlined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders- is a prerequisite for the reimbursement of both gender-affirming medical care and transgender mental health care in the Netherlands. Gender Dysphoria and its conceptual precursors have always been moving targets: moving due to research, policy, care practices and activism both within and outside of medicine. This raises the question of what Gender Dysphoria is exactly. To elucidate this question, we turn to the people who use the concept in clinical practice to come to a diagnosis and treatment indication: mental health professionals working in gender-affirming medical care and transgender mental health care. Using a material semiotics approach, we reflect upon how Gender Dysphoria is done in clinical practice. Based on an analysis of seventeen practice-based interviews with clinicians as well as an examination of clinical guidelines and texts, we describe four modes in which Gender Dysphoria is ordered. These modes of ordering illustrate that Gender Dysphoria is not one, but multiple. We illustrate how in the mode of isolating, Gender Dysphoria is something which is carefully isolated from mental disorders, while in the modes doing the future and narrating, Gender Dysphoria is done as a continuous and predictable object of care. Such orderings of Gender Dysphoria potentially conflict with a fourth mode of ordering: the doing of diversity in transgender health care. The study's findings provide empirical insights into how transgender health care is currently done in The Netherlands and provide a foundation on which ethical debates on what good transgender health care should entail.

Sharing decisions amid uncertainties: a qualitative interview study of healthcare professionals' ethical challenges and norms regarding decision-making in gender-affirming medical care.

BACKGROUND: In gender-affirming medical care (GAMC), ethical challenges in decision-making are ubiquitous. These challenges are becoming more pressing due to exponentially increasing referrals, politico-legal contestation, and divergent normative views regarding decisional roles and models. Little is known, however, about what ethical challenges related to decision-making healthcare professionals (HCPs) themselves face in their daily work in GAMC and how these relate to, for example, the subjective nature of Gender Incongruence (GI), the multidisciplinary character of GAMC and the role HCPs play in assessing GI and eligibility for interventions. Given the relevance and urgency of these questions, we conducted a qualitative study among HCPs providing GAMC to transgender adults in the Netherlands. METHODS: In this qualitative research, we conducted 11 semi-structured interviews between May 2020 and February 2021 with HCPs (six mental health professionals, two HCPs in endocrinology, two in plastic surgery, and one in nursing) working in two distinct GAMC settings. We purposively sampled for professional background and years of experience in GAMC. We analyzed our interview data using thematic analysis. As some respondents were more inclined to speak about what should or ought to be done to arrive at good or right decision-making, we identified both ethical challenges and norms. Furthermore, in our analysis, we differentiated between respondents' explicit and implicit ethical challenges and norms and ascertained the specific context in which these challenges emerged. RESULTS: Respondents' ethical challenges and norms centered on (1) dividing and defining decisional roles and bounds, (2) negotiating decision-making in a (multidisciplinary) team, and (3) navigating various decision-making temporalities. These themes arose in the context of uncertainties regarding (1) GAMC's guidelines, evidence, and outcomes, as well as (2) the boundaries and assessment of GI. CONCLUSIONS: This interview study provides detailed empirical insight into both the explicit and implicit ethical challenges that HCPs experience and their ethical norms regarding decision-making. It also describes how uncertainties and (implicit) normativities concerning GAMC and GI pre-structure the moral environment in which these challenges and norms manifest. We provide normative reflections and recommendations on handling these ethical challenges in a way that is sensitive to the context in which they arise.

Suicidality in clinic-referred transgender adolescents.

Gender and sexually diverse adolescents have been reported to be at an elevated risk for suicidal thoughts and behaviors. For transgender adolescents, there has been variation in source of ascertainment and how suicidality was measured, including the time-frame (e.g., past 6 months, lifetime). In studies of clinic-referred samples of transgender adolescents, none utilized any type of comparison or control group. The present study examined suicidality in transgender adolescents (M age, 15.99 years) seen at specialty clinics in Toronto, Canada, Amsterdam, the Netherlands, and London, UK (total N = 2771). Suicidality was measured using two items from the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). The CBCL/YSR referred and non-referred standardization samples from both the U.S. and the Netherlands were used for comparative purposes. Multiple linear regression analyses showed that there was significant between-clinic variation in suicidality on both the CBCL and the YSR; in addition, suicidality was consistently higher among birth-assigned females and strongly associated with degree of general behavioral and emotional problems. Compared to the U.S. and Dutch CBCL/YSR standardization samples, the relative risk of suicidality was somewhat higher than referred adolescents but substantially higher than non-referred adolescents. The results were discussed in relation to both gender identity specific and more general risk factors for suicidality.

An examination of the influence of prenatal sex hormones on handedness: Literature review and amniotic fluid data.

Competing theories have posited roles for foetal androgen exposure in the development of human handedness. However, due to practical and ethical considerations, few studies have used hormonal measures to examine this possibility. The current paper reviews this literature and reveals a generally inconsistent pattern of results. We also present data from a longitudinal study of prenatal sex hormone exposure and subsequent handedness. More specifically, we examine correlations between testosterone and estradiol measured from second trimester amniotic fluid and hand preference (Dutch language version of the Edinburgh Handedness Inventory) and hand skill asymmetry (pegboard task) measured at 15 years of age. Prenatal sex hormone exposure was not associated with the direction of hand preference in either males or females. However, in females, high levels of prenatal testosterone were associated with weaker lateralisation of hand skill, and high levels of prenatal estradiol were associated with weaker hand preference. In addition, high levels of prenatal testosterone were associated with increased task duration (i.e., slow hand speed) for the right and left hands of males. The pattern of results observed here is not entirely consistent with any of the main theories linking sex hormones with handedness, suggesting that an association between these variables may be more complex than initially thought.

Long-Term Gender-Affirming Hormone Therapy and Cognitive Functioning in Older Transgender Women Compared With Cisgender Women and Men.

BACKGROUND: Long-term gender-affirming hormone therapy (GHT) in older transgender individuals could have beneficial effects on cognitive functioning. Cardiovascular risk factors and psychological factors are known determinants of cognition. Despite the rising number of older transgender individuals, only few studies have examined cognitive functioning in this population. AIM: We aimed to assess differences in cognitive functioning between transgender women, and non-transgender (cisgender) women and men, and investigated the contribution of cardiovascular risk factors and psychological factors on these differences. METHODS: In this study, 37 transgender women (age range 55 to 69) receiving GHT for at least ten years (range 10.2 to 41.6) were examined, and their cognitive functioning was compared to an age and education level matched cohort consisting of 222 cisgender women and men from the Longitudinal Aging Study Amsterdam. Linear regression analyses were performed. OUTCOMES: Cognitive functioning was assessed by neuropsychological tests including Mini-Mental State Examination (MMSE), Category Fluency animals, Letter Fluency D, 15-Word test (15WT) immediate and delayed recall. Additionally, cardiovascular risk factors and psychological factors such as cardiovascular disease, hypertension, antihypertensive use, statin use, diabetes mellitus, overweight, smoking, alcohol consumption, psychopharmaceutical use, anxiety and depression symptoms were collected. RESULTS: Transgender women had higher MMSE scores compared with cisgender women (+0.9, 95% CI 0.4 to 1.5), and cisgender men (+1.1, 95% CI 0.4 to 1.8). On all other tests transgender women performed similar to cisgender men. Transgender women performed at a lower level than cisgender women on 15WT immediate recall, -5.5, 95% CI -7.6 to -3.4, and 15WT delayed recall, -2.7, 95% CI -3.7 to -1.7, and equal to cisgender women on Fluency animals and Fluency D. Cardiovascular and psychological factors (i.e., cardiovascular disease and depression symptoms) partly explained differences on MMSE score between transgender women and cisgender-control groups. CLINICAL IMPLICATIONS: The results of this study do not indicate a need for tailored hormone treatment strategies for older transgender women, based on cognitive aspects after long-term GHT. STRENGTHS & LIMITATIONS: As one of the first studies, this study compared older transgender women to a large cohort of cisgender men and women regarding cognitive functioning and took into account numerous potential influencing factors. Limitations include difference in test procedures and the cross-sectional design of the study. CONCLUSION: Cognitive differences between transgender women and cisgender women and men were small, albeit significant. This may suggest that long-term GHT effects on cognitive functioning in older transgender women are minimal. van Heesewijk JO, Dreijerink KMA, Wiepjes CM, et al. Long-Term Gender-Affirming Hormone Therapy and Cognitive Functioning in Older Transgender Women Compared With Cisgender Women and Men. J Sex Med 2021;18:1434-1443.

Aftercare Needs Following Gender-Affirming Surgeries: Findings From the ENIGI Multicenter European Follow-Up Study.

BACKGROUND: While much emphasis has been put on the evaluation of gender-affirming surgery (GAS) approaches and their effectiveness, little is known about the health care needs after completion of these interventions. AIM: To assess post-GAS aftercare needs using a mixed-method approach and relate these to participant characteristics. METHODS: As part of the ENIGI follow-up study, data was collected 5 years after first contact for gender-affirming treatments in 3 large European clinics. For the current analyses, only participants that had received GAS were included. Data on sociodemographic and clinical characteristics was collected. Standard aftercare protocols were followed. The study focused on participants' aftercare experiences. Participants rated whether they (had) experienced (predefined) aftercare needs and further elaborated in 2 open-ended questions. Frequencies of aftercare needs were analyzed and associated with participant characteristics via binary logistic regression. Answers to the open-ended questions were categorized through thematic analysis. OUTCOMES: Aftercare needs transgender individuals (had) experienced after receiving GAS and the relation to sociodemographic and clinical characteristics. RESULTS: Of the 543 individuals that were invited for the ENIGI follow-up study, a total of 260 individuals were included (122 (trans) masculine, 119 (trans) feminine, 16 other, 3 missing). The most frequently mentioned aftercare need was (additional) assistance in surgical recovery (47%), followed by consultations with a mental health professional (36%) and physiotherapy for the pelvic floor (20%). The need for assistance in surgical recovery was associated with more psychological symptoms (OR=1.65), having undergone genital surgery (OR=2.55) and lower surgical satisfaction (OR=0.61). The need for consultation with a mental health professional was associated with more psychological symptoms and lower surgical satisfaction. The need for pelvic floor therapy was associated with more psychological symptoms as well as with having undergone genital surgery. Thematic analysis revealed 4 domains regarding aftercare optimization: provision of care, additional mental health care, improvement of organization of care and surgical technical care. CLINICAL IMPLICATIONS: Deeper understanding of post-GAS aftercare needs and associated individual characteristics informs health care providers which gaps are experienced and therefore should be addressed in aftercare. STRENGTHS & LIMITATIONS: We provided first evidence on aftercare needs of transgender individuals after receiving GAS and associated these with participant characteristics in a large multicenter clinical cohort. No standardized data on aftercare received was collected, therefore the expressed aftercare needs cannot be compared with received aftercare. CONCLUSION: These results underline a widely experienced desire for aftercare and specify the personalized needs it should entail. IJ de Brouwer, E Elaut, I Becker-Hebly et al. Aftercare Needs Following Gender-Affirming Surgeries: Findings From the ENIGI Multicenter European Follow-Up Study. J Sex Med 2021;18:1921-1932.

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.

Psychological Functioning in Non-binary Identifying Adolescents and Adults.

Gender diverse individuals who do not conform to society's binary gender expectations are more likely to experience difficulties in acceptance and in recognition of gender, compared to binary-identifying transgender people. This may accentuate the feeling that their gender identity is not socially recognized or validated. This study aimed to investigate psychological functioning among gender diverse adolescents and adults who identify beyond the binary gender spectrum. In both study populations, 589 clinically-referred gender diverse adolescents from the UK (n = 438 birth-assigned females and n = 151 birth-assigned males), and 632 clinically-referred gender diverse adults from the Netherlands (n = 278 birth-assigned females and n = 354birth-assigned males), we found that a higher degree of psychological problems was predicted by identifying more strongly with a non-binary identity. For adolescents, more psychological problems were related to having a non-binary gender identity and being assigned female at birth. In the adult population, experiencing psychological difficulties was also significantly related to having a stronger non-binary identity and having a younger age. Clinicians working with gender diverse people should be aware that applicants for physical interventions might have a broader range of gender identities than a binary transgender one, and that people with a non-binary gender identity may, for various reasons, be particularly vulnerable to psychological difficulties.

Decision-making approaches in transgender healthcare: conceptual analysis and ethical implications.

Over the past decades, great strides have been made to professionalize and increase access to transgender medicine. As the (biomedical) evidence base grows and conceptualizations regarding gender dysphoria/gender incongruence evolve, so too do ideas regarding what constitutes good treatment and decision-making in transgender healthcare. Against this background, differing care models arose, including the 'Standards of Care' and the so-called 'Informed Consent Model'. In these care models, ethical notions and principles such as 'decision-making' and 'autonomy' are often referred to, but left unsubstantiated. This not only transpires into the consultation room where stakeholders are confronted with many different ethical challenges in decision-making, but also hampers a more explicit discussion of what good decision-making in transgender medicine should be comprised of. The aim of this paper is to make explicit the conceptual and normative assumptions regarding decision-making and client autonomy underpinning the 'Standards of Care' and 'Informed Consent Model' currently used in transgender care. Furthermore, we illustrate how this elucidation aids in better understanding stakeholders' ethical challenges related to decision-making. Our ethical analysis lays bare how distinct normative ambiguities in both care models influence decision-making in practice and how foregrounding one normative model for decision-making is no moral panacea. We suggest that the first steps towards good decision-making in gender-affirming medical care are the acknowledgement of its inherent normative and moral dimensions and a shared, dialogical approach towards the decision-making process.

Sexual Desire Changes in Transgender Individuals Upon Initiation of Hormone Treatment: Results From the Longitudinal European Network for the Investigation of Gender Incongruence.

INTRODUCTION: Several steps in the transitioning process may affect sexual desire in transgender people. This is often underexposed by those providing gender-affirming care. AIM: To prospectively assess sexual desire during the first 3 years of hormonal therapy (HT) in transgender people. METHODS: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence. At baseline, different psychological questionnaires were administered. Sex steroids were measured at each follow-up visit. Data were analyzed cross-sectionally and prospectively. MAIN OUTCOME MEASURE: Prospective analysis of total, dyadic (with another person), and solitary (with oneself) sexual desire in 766 participants (401 transgender women [TW], 364 transgender men [TM]) was carried out using the Sexual Desire Inventory (SDI) questionnaire during a 3-year follow-up period, starting at the initiation of HT. Other factors associated with prospective changes were assessed. RESULTS: In TW, total, dyadic, and solitary SDI scores decreased during the first 3 months of HT. However, after 36 months, total and dyadic SDI scores were higher than baseline scores. Solitary scores after 36 months were comparable with baseline scores. In TM, total, dyadic, and solitary SDI scores increased over the first 3 months, remaining stable thereafter. However, total and dyadic SDI scores after 36 months were comparable with baseline scores, whereas solitary scores remained higher than baseline. Factors associated with a prospective increase in SDI scores included having undergone gonadectomy, no longer experiencing menstrual bleeding or higher gender dysphoria levels at baseline (in TM only). CLINICAL IMPLICATIONS: This study offers clear data on the time course of sexual desire after starting HT and thereby helps to inform people who want to start HT. Transgender people can be informed that changes in sexual desire after initiating HT are temporary. Over a longer period of time, the current research does not suggest induction of hypoactive sexual disorder in TW or long-term increased sexual desire in TM. STRENGTH & LIMITATIONS: Strengths include the prospective design of this large multicentric study, the well-defined cohort, controlling for HT, sex steroids, and other factors. Limitations include performing a data lock, the absence of an objective measure of sexual desire, and the timing of laboratory measurements. CONCLUSION: Gender-affirming HT only induces short-term changes in sexual desire in transgender people. Over a longer period of time, a net increase in dyadic sexual desire in TW receiving feminizing HT and sexual desire scores comparable with baseline in TM receiving virilizing HT, were observed. Defreyne J, Elaut E, Kreukels B, et al. Sexual Desire Changes in Transgender Individuals Upon Initiation of Hormone Treatment: Results From the Longitudinal European Network for the Investigation of Gender Incongruence Study. J Sex Med 2020;17:812-825.

Postnatal Effects of Sex Hormones on Click-Evoked Otoacoustic Emissions: A Study of Adolescents with Gender Dysphoria.

Click-evoked otoacoustic emissions (CEOAEs) are echo-like sounds, generated by the inner ear in response to click-stimuli. A sex difference in emission strength is observed in neonates and adults, with weaker CEOAE amplitudes in males. These differences are assumed to originate from testosterone influences during prenatal male sexual differentiation and to remain stable throughout life. However, recent studies suggested activational, postnatal effects of sex hormones on CEOAEs. Adolescents diagnosed with gender dysphoria (GD) may receive gonadotropin-releasing hormone analogs (GnRHa) in order to suppress endogenous sex hormones and, therefore, pubertal maturation, followed by cross-sex hormone (CSH) treatment. Using a cross-sectional design, we examined whether hormonal interventions in adolescents diagnosed with GD (62 trans boys, assigned female at birth, self-identifying as male; 43 trans girls, assigned male at birth, self-identifying as female), affected their CEOAEs compared to age- and sex-matched controls (44 boys, 37 girls). Sex-typical differences in CEOAE amplitude were observed among cisgender controls and treatment-naïve trans boys but not in other groups with GD. Treatment-naïve trans girls tended to have more female-typical CEOAEs, suggesting hypomasculinized early sexual differentiation, in support of a prominent hypothesis on the etiology of GD. In line with the predicted suppressive effects of androgens, trans boys receiving CSH treatment, i.e., testosterone plus GnRHa, showed significantly weaker right-ear CEOAEs compared with control girls. A similar trend was seen in trans boys treated with GnRHa only. Unexpectedly, trans girls showed CEOAE masculinization with addition of estradiol. Our findings show that CEOAEs may not be used as an unequivocal measure of prenatal androgen exposure as they can be modulated postnatally by sex hormones, in the form of hormonal treatment.

Mental Health of a Large Group of Adults With Disorders of Sex Development in Six European Countries.

OBJECTIVE: The aim of the study was to evaluate psychiatric symptoms among 1022 persons with various disorders of sex development (DSDs). METHODS: The study was a European multicenter cross-sectional clinical evaluation in six countries. The mean (SD) age of participants was 32.1 (13.4) years. The cohort consisted of 325 individuals with Turner syndrome, 219 individuals with Klinefelter syndrome (KS), female individuals with various XY-DSD conditions (107 with and 67 without androgenization), 87 male individuals with XY-DSD conditions, and 221 female individuals with congenital adrenal hyperplasia. The Hospital Anxiety and Depression Scale, the Short Autism Spectrum Quotient, the Adult Attention-Deficit/Hyperactivity Disorder Self-Report Scale, and self-reported mental health history were used to assess psychiatric symptoms. RESULTS: Across the six DSD diagnostic groups, clinical cutoff symptom scores were reached in 19.5% of participants for anxiety, in 7.1% for depression, in 4.1% for attention-deficit/hyperactivity disorder, and in 9.1% for autism. The mean depression and anxiety scores were higher compared with population norms in men with KS and men with XY-DSD. Compared with participants with other DSD conditions, men with KS reported significantly more mental health symptoms. Self-esteem, satisfaction with care, body dissatisfaction, and experiences of shame were associated with psychiatric symptoms in many DSD conditions. CONCLUSIONS: A substantial minority of adults with DSD, with KS in particular, experience psychiatric morbidity. Across DSD conditions, adults may share feelings of shame. Developing a positive self-esteem and body image may be challenging. Multidisciplinary DSD care that involves specialized mental health support can be of important value. TRIAL REGISTRATION: German Clinical Trials Register DRKS00006072.

Breast development and satisfaction in women with disorders/differences of sex development.

STUDY QUESTION: What are the levels of breast development and satisfaction in women with a Disorder/Difference of Sex Development (DSD)? SUMMARY ANSWER: Compared with normative data, women with DSD reached lower Tanner stages and reported less breast satisfaction. WHAT IS KNOWN ALREADY: Women with DSD may have chromosomal and hormonal variations that can impact typical breast development. While much emphasis is placed on genital development in this group, little is known about breast development, satisfaction and their association. STUDY DESIGN, SIZE, DURATION: Data collection was part of the cross-sectional European multicenter dsd-LIFE study. Fourteen recruiting sites included 1040 participants between February 2014 and September 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 695 female-identifying participants were included (Turner n = 332, 46,XY DSD n = 141 and congenital adrenal hyperplasia n = 222), with a median age of 28 years. Clinical (i.e. history of hormone and surgical treatments, Tanner breast examination) and patient-reported (i.e. breast satisfaction, relationship status, sexual satisfaction and experienced femininity) data was collected by independent trained research staff. The relationship between breast development, satisfaction and femininity was assessed. Control data on breast development and satisfaction in women without DSD was retrieved from the literature. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 695 participants, 61% had received estrogen replacement and 51% puberty induction therapy, whereas 2% had received breast augmentation surgery. Approximately 65% of participants had reached Tanner breast stage 5, which is substantially less than the general population (90%). Breast satisfaction was lower than normative data as well (P < 0.001, Cohen's d = 0.45). Breast size and breast satisfaction were associated with feelings of femininity. LIMITATIONS, REASONS FOR CAUTION: Limitations include the sample representativeness (e.g. regarding the clinical heterogeneity) and the limited in-depth knowledge on (prior) hormonal regimens. Furthermore, no (matched) control data was collected as part of this study. WIDER IMPLICATIONS OF THE FINDINGS: In order to support the psychosexual well-being of women with DSD, enhancing breast development by sufficient hormone replacement and possible augmentation surgery is advocated. The scope of DSD management should be beyond genital development only and consider breasts as well. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no. 305 373. There are no competing interests. TRIAL REGISTRATION NUMBER: German Clinical Trials Register: Registration identification number: DRKS00006072.

No correlation between serum testosterone levels and state-level anger intensity in transgender people: Results from the European Network for the Investigation of Gender Incongruence.

INTRODUCTION: Anger is a state of emotions ranging from irritation to intense rage. Aggression implies externalizing anger through destructive/punitive behaviour. The World Professional Association for Transgender Health (WPATH) Standards of Care, Edition 7 (SOC7) guidelines warn about aggression in transgender men (TM) on testosterone treatment. We aimed to assess whether anger intensity increases in TM and decreases in transgender women (TW) after initiation of gender affirming hormone therapy and to identify predictors for anger intensity in transgender people. METHODS: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Anger intensity was prospectively assessed in 898 participants (440 TM, 468 TW) by STAXI-2 (State-Trait Anger Expression Inventory-2) State Anger (S-Anger) during a three-year follow-up period, starting at the initiation of hormone treatment. Data were analysed cross-sectionally and prospectively. RESULTS: There was no change in STAXI-2 S-Anger scores. At three, twelve and thirty-six months of gender affirming hormone therapy, STAXI-2 S-Anger scores were not correlated to serum testosterone levels, although there was a correlation with various psychological measures after three and twelve months. TM experiencing menstrual spotting after three months had higher STAXI-2 S-Anger scores compared to those without (median 26.5 [18.0-29.8] versus 15.0 [15.0-17.0], P = 0.020). Changes in STAXI-2 S-Anger scores were not correlated to changes in serum testosterone levels after three, twelve and thirty-six months in TM or TW. CONCLUSIONS: State-level anger intensity is associated with psychological and/or psychiatric vulnerability, but not exogenous testosterone therapy or serum testosterone levels in transgender people.

Prevalence of Sexual Dysfunctions in Transgender Persons: Results from the ENIGI Follow-Up Study.

INTRODUCTION: Studies about sexual functioning in trans persons have mainly focused on sexual functioning after genital gender-affirming surgery, have had small sample sizes, and have not explored the broad range of possible sexual dysfunctions. Measuring sexual functioning in trans persons during transitioning is important to determine the kind of care trans persons may need in order to regain their sexual health. AIM: The first aim of the present study was to explore the prevalence of sexual function disturbances and dysfunctions (with distress) in trans women and trans men 4 to 6 years after initial clinical entry. The second aim was to compare the prevalence of sexual dysfunctions among the various treatment trajectories and between trans persons with or without further genital treatment intentions. METHODS: An online follow-up questionnaire was filled out by 518 trans persons (307 identifying predominantly feminine, 211 identifying predominantly masculine) as a part of the European Network for the Investigation of Gender Incongruence initiative. All participants had their initial clinical appointments in gender clinics in Ghent, Amsterdam, or Hamburg. MAIN OUTCOME MEASURE: The main outcome measures were the prevalence of sexual dysfunctions and medical treatment data, measured via self-report items. RESULTS: The most frequent sexual dysfunctions experienced by trans women and trans men were difficulties initiating and seeking sexual contact (26% and 32%, respectively) and difficulties achieving an orgasm (29% and 15%, respectively). Compared with trans women after hormone treatment and non-genital surgery, trans women after vaginoplasty less often experienced arousal difficulties, sexual aversion, and low sexual desire. Compared with trans men without medical treatment, trans men after a phalloplasty experienced sexual aversion and low sexual desire less often. No significant differences were found between participants with or without further genital treatment intentions. CLINICAL IMPLICATIONS: Clinicians should consider sexual counseling after medical treatments, paying particular attention to potential social and psychological barriers to the sexual health of their patients. STRENGTHS & LIMITATIONS: This study included all trans persons irrespective of treatment decisions, and focused on a broad range of potential sexual difficulties taking the distress criteria into account. Limitations include the cross-sectional design, the limited power for the comparison of treatment groups and the absence of validated questionnaires about sexual functioning for transgender persons. CONCLUSION: Sexual dysfunctions among trans men and women were very common among the various treatment groups and were unrelated to intentions to have further genital treatment. Although medical treatment may be helpful or even essential to developing good sexual health, a significant group of trans persons experienced sexual dysfunctions after genital surgery. Kerckhof ME, Kreukels BPC, Nieder TO, et al. Prevalence of Sexual Dysfunctions in Transgender Persons: Results from the ENIGI Follow-Up Study. J Sex Med 2019; 16:2018-2019.

Gender-Affirming Hormone Treatment Induces Facial Feminization in Transwomen and Masculinization in Transmen: Quantification by 3D Scanning and Patient-Reported Outcome Measures.

INTRODUCTION: Hormone treatment induces feminization of the body in transwomen and masculinization in transmen. However, the effect of hormone treatment on facial characteristics is still unknown. AIM: We aimed to study whether hormone treatment induces facial feminization and masculinization and how this potential change affects satisfaction and self-esteem. METHODS: In this single-center cohort study, we included 27 transwomen and 15 transmen who received standardized hormone treatment in the Center of Expertise on Gender Dysphoria, VU University Medical Center Amsterdam. Facial 3-dimensional images were obtained at baseline and at 3 and 12 months. At each image, 22 facial landmarks were placed. Furthermore, the FACE-Q Satisfaction with Facial Appearance Overall and the Rosenberg self-esteem scale were obtained at the same measurement points. MAIN OUTCOME MEASURES: The main outcome measures included the relative local shift of skin in millimeters in the 22 landmarks in the transverse (x-axis), coronal (y-axis), and sagittal (z-axis) anatomic axes, the color maps, and the outcomes of the questionnaires. RESULTS: After 12 months, cheek tissue in transwomen increased, with 0.50 mm (95% CI 0.04-0.96) in the x-axis and 1.08 mm (95% CI 0.31-1.85) in the z-axis. Tissue in the jaws decreased with -0.60 mm (95% CI -1.28-0.08) in the x-axis and -0.18 mm (95% CI -0.03-0.33) in the y-axis. Cheek tissue in transmen decreased with -0.45 mm (95% CI -1.00-0.11) in the x-axis and -0.84 mm (95% CI -1.92-0.25) in the z-axis. These changes already started after 3 months. An increase in satisfaction with the facial appearance was found in both transwomen and transmen. There were no changes in reported self-esteem. CLINICAL IMPLICATION: These results could lead to more realistic expectations of facial changes. Furthermore, our results suggest that the face continues to change for at least a year, which could suggest that performing facial feminization surgery after 1 year of hormone treatment might be too early. STRENGTH & LIMITATIONS: This study is the first that provides insight into the facial changes in transgender individuals receiving hormone treatment, and it introduces an objective method to examine (small) facial changes. Our study is limited by the poor reliability of the landmarks, the difficulty of facial fixation, and the lack of gender-specific questions in the questionnaires. CONCLUSIONS: Hormone treatment in transwomen induces an increase in cheek tissue and a decrease in jaw tissue. In transmen a tendency of decrease in cheek tissue and an increase in jaw tissue was found. These changes are in the direction of the desired gender. Tebbens M, Nota NM, Liberton NPTJ, et al. Gender-Affirming Hormone Treatment Induces Facial Feminization in Transwomen and Masculinization in Transmen: Quantification by 3D Scanning and Patient-Reported Outcome Measures. J Sex Med 2019;16:746-754.