Mixed Gonadal Dysgenesis: A Narrative Literature Review and Clinical Primer for the Urologist.

PURPOSE: Mixed gonadal dysgenesis is a difference of sex development that is often confused with other conditions. Individuals have a 45,X/46,XY karyotype. Gonads are characterized by a streak gonad and a dysgenetic testis at varying levels of descent. Persistent Müllerian structures are typical (eg, hemi-uterus). There is significant phenotypic heterogeneity of the internal and external genitalia that, together with different interpretations of the definition, have contributed to a poor understanding of the condition among pediatric urologists. Mixed gonadal dysgenesis is one manifestation of the 45,X/46,XY karyotype. 45,X/46,XY mosaicism can also be associated with typical female or male external genitalia. This review aims to clarify the mixed gonadal dysgenesis definition and to provide urologists with diagnostic and management considerations for affected individuals. MATERIALS AND METHODS: We searched 3 medical databases for articles related to mixed gonadal dysgenesis. 287 full-text abstracts and manuscripts were reviewed for content pertinent to: (1) Clarifying the definition of mixed gonadal dysgenesis, and (2) Describing the following related to the care of affected individuals: prenatal and neonatal evaluation and management, genital surgery, gonadal malignancy risk and management, fertility, gender dysphoria/incongruence, puberty and long-term outcomes, systemic comorbidities, and transitional care. RESULTS: 50 articles were included. Key points and implications for each of the above topics were summarized. CONCLUSIONS: Mixed gonadal dysgenesis exists on a wide phenotypic spectrum and management considerations reflect this heterogeneity. Care for individuals with mixed gonadal dysgenesis is complex, and decisions should be made in a multidisciplinary setting with psychological support.

Reckoning With Our Past and Righting Our Future: Report From the Behavior Therapy Task Force on Sexual Orientation and Gender Identity/Expression Change Efforts (SOGIECEs).

Sexual orientation and gender identity/expression change efforts (SOGIECEs) are discredited practices that are associated with serious negative effects and incompatible with modern standards for clinical practice. Despite evidence linking SOGIECEs with serious iatrogenic effects, and despite support for LGBTQ+-affirmative care alternatives, SOGIECE practices persist. In the 1970s and 1980s, Behavior Therapy published articles testing and/or endorsing SOGIECEs, thereby contributing to their overall development, acceptance, and use. The Behavior Therapy Task Force on SOGIECEs was assembled to conduct a rigorous review of the SOGIECE articles published in Behavior Therapy and to decide whether, and what, formal action(s) should be taken on these articles. This report provides a detailed review of the historic SOGIECE literature published in Behavior Therapy and outlines the Task Force's deliberative and democratic processes resulting in actions to: (1) add prominent advisory information to k = 24 SOGIECE papers in the form of digital "black box" disclaimers that caution readers that the SOGIECE practices tested or described in these papers are inconsistent with modern standards, (2) offset organizational financial benefits from the publication of these papers, and (3) promote LGBTQ+-affirmative practices. SOGIECEs are not the only concerning practices across the field's history, and the pages of today's scientific journals include practices that will be at odds with tomorrow's moral standards and ethical guidelines. This report calls for precautionary measures and editorial safeguards to minimize the future likelihood and impact of problematic published scholarship, including the need to fully include those with relevant lived experiences in all aspects of clinical science and peer review.

Body image and psychosocial outcomes in youth and young adults with differences of sex development: a multi-method study.

OBJECTIVE: Differences of sex development (DSD) can affect the physical health, appearance, and psychosocial functioning of affected individuals, but little is known about how subjective appearance perceptions (body image) impact psychosocial outcomes. This study evaluated body image and its associations with psychosocial outcomes including quality of life, resilience, and psychosocial adjustment. METHODS: This cross-sectional, multi-method study assessed body image and psychosocial outcomes including quality of life, adjustment, and resilience in 97 youth and young adults with DSD (mean age = 17 ± 3.7 years; 56% assigned female in infancy) using psychometrically sound instruments. A subsample (n = 40) completed qualitative interviews. RESULTS: Quantitative results indicated that overall, participants were satisfied with their physical appearance, although less so with their primary sex characteristics. Body image dissatisfaction was associated with poorer psychosocial adjustment, quality of life, and resilience. Qualitatively, youth and young adults reported a variety of perceptions, both positive and negative, related to their body image and the impact of living with a DSD condition. Themes identified included appearance management; effects of DSD on body image; diagnostic factors and features; attitudes about diagnosis; and treatment. CONCLUSIONS: Body image is significantly associated with psychosocial outcomes in youth and young adults with DSD, with qualitative findings highlighting both positive and negative body image experiences. Results have implications for clinical care including screening for appearance concerns, normalization of appearance variations, and intervention development to better support healthy body image and psychosocial functioning in youth and young adults with DSD.

Co-design and usability of an interactive web-based fertility decision aid for transgender youth and young adults.

OBJECTIVE: To develop a patient- and family-centered Aid For Fertility-Related Medical Decisions (AFFRMED) interactive website targeted for transgender and nonbinary (TNB) youth/young adults and their parents to facilitate shared decision-making about fertility preservation interventions through user-centered participatory design. METHOD: TNB youth/young adults interested in or currently receiving pubertal suppression or gender-affirming hormone treatment and parents of eligible TNB youth/young adults were recruited to participate in a series of iterative human-centered co-design sessions to develop an initial AFFRMED prototype. Subsequently, TNB youth/young adults and parents of TNB youth/young adults were recruited for usability testing interviews, involving measures of usability (i.e., After Scenario Questionnaire, Net Promotor Score, System Usability Scale). RESULTS: Twenty-seven participants completed 18 iterative co-design sessions and provided feedback on 10 versions of AFFRMED (16 TNB youth/young adults and 11 parents). Nine TNB youth/young adults and six parents completed individual usability testing interviews. Overall, participants rated AFFRMED highly on measures of acceptability, appropriateness, usability, and satisfaction. However, scores varied by treatment cohort, with TNB youth interested in or currently receiving pubertal suppression treatment reporting the lowest usability scores. CONCLUSIONS: We co-created a youth- and family-centered fertility decision aid prototype that provides education and decision support in an online, interactive format. Future directions include testing the efficacy of the decision aid in improving fertility and fertility preservation knowledge, decisional self-efficacy, and decision satisfaction.

Healthcare communication satisfaction and psychosocial outcomes in adolescents and young adults with differences of sex development.

OBJECTIVES: We examined: (1) healthcare communication satisfaction and psychosocial outcomes (resilience, QoL, and psychological adjustment) in adolescents and young adults (AYA) with differences of sex development (DSD), (2) differences in psychosocial outcomes between those who were highly satisfied and those who were less satisfied, and (3) group differences between adolescents (ages 12-17) and young adults (ages 18-26) regarding associations with healthcare communication and psychosocial outcomes. METHODS: AYA with DSD across four study sites reported on satisfaction with healthcare communication and psychosocial outcomes. Analyses included descriptive statistics (aim 1), independent samples t-tests (aim 2), and Pearson's correlations (aim 3). RESULTS: Participants reported high levels of satisfaction with healthcare communication. Higher healthcare communication satisfaction was associated with greater resilience (p = .01), better QoL (p = .02), and fewer internalizing problems (p = .04). For adolescents, higher healthcare communication satisfaction was associated with better psychosocial outcomes (p values ranging from.01-.04). No significant associations were found in the young adult group. CONCLUSIONS: Satisfaction with healthcare communication is related to positive psychosocial outcomes in adolescents with DSD. PRACTICE IMPLICATIONS: These data underscore the importance of optimizing communication with families, engaging AYA in early and ongoing discussions about their care, and including psychosocial providers in DSD care.

Reproductive Health in Trans and Gender Diverse Patients: Fertility related knowledge, attitudes, and decision-making among gender diverse youth - A narrative review.

In brief: Transgender and gender diverse (TGD) youth demonstrate low utilization of fertility preservation before medical and surgical gender-affirming interventions. However, a significant number of TGD youth have goals for parenthood and/or recognize that their attitude toward future family-building goals may change over time. In this narrative review, we conclude that TGD young people should have ongoing opportunities to discuss their family-building goals and options for fertility preservation. Validated decision tools can help facilitate these discussions. Abstract: The number of transgender and gender diverse (TGD) youth seeking care continues to increase, necessitating comprehensive counseling about potential long-term effects of gender-affirming medical interventions on fertility. The objective of this narrative review was to examine fertility-related knowledge, attitudes, and decision-making (including factors influencing decisions, decision regret, and decision tools) among TGD youth. We searched PubMed, PsycInfo, and Google Scholar for original, peer-reviewed research investigating TGD youth attitudes and knowledge of fertility and fertility preservation, perspectives on fertility counseling and fertility preservation decision-making, as well as fertility-related decision tools. We reviewed 106 studies; eight were included in this narrative review. Four studies assessed TGD youth knowledge and attitudes of fertility and fertility preservation, three examined perspectives on fertility counseling and fertility preservation decision-making, and three discussed development of decision tools. Key findings were that: (1) many TGD youth are aware of potential fertility-related impacts of gender-affirming treatments, but there are still unmet informational needs, (2) some TGD youth report an interest in future biological parenthood, and of those who are not currently interested in biological parenthood, many acknowledge their desires may change over time, (3) ongoing discussions about fertility and fertility preservation are critical, and (4) decision tools are in development. In conclusion, TGD youth and their caregivers should receive ongoing, comprehensive fertility counseling and decision tools may be helpful to facilitate these discussions and decisions in each youth's gender-affirming care journey.

Sexual Orientation/Gender Identity Discrimination and Chronic Pain in Children: A National Study.

INTRODUCTION: This study provides national estimates of parental perceived child sexual orientation or gender minority (SGM) discrimination and examines associations between SGM discrimination and chronic pain in children. METHODS: Cross-sectional analysis of the 2020 and 2021 National Survey of Children's Health (N=47,213). Caregivers of children ages 6-17 years old reported whether their child had ever been treated or judged unfairly (i.e., discrimination) because of their SGM identity. Chronic pain in children was defined as frequent or chronic difficulty with repeated or chronic physical pain during the past 12 months, as reported by caregivers. Weighted prevalence estimates for discrimination were calculated for the whole sample and sociodemographic subgroups. Associations between SGM discrimination and chronic pain were estimated using multivariable Poisson regression models adjusting for sociodemographic factors. Analyses were conducted 2022-2023. RESULTS: Within this nationally representative sample, parents reported 1.4% (95% CI 1.2%-1.6%) of children have experienced SGM-related discrimination. The prevalence was higher among adolescents, females at birth, and those living in suburban areas. Children who experienced discrimination had a higher prevalence of chronic pain (20.2%) compared to those who did not (7.0%, p<0.0001), with an adjusted prevalence rate ratio of 2.0 (95% CI 1.5-2.5, p<0.0001). CONCLUSIONS: Based on parent report, about 0.6 million children in the U.S. have experienced SGM-based discrimination; these children are twice as likely to have chronic pain. Findings highlight the importance of assessment and intervention for chronic pain in children who may experience marginalization and discrimination due to their sexual orientation and gender identity.

Elective nodal dissection for cN0 intermediate-grade parotid mucoepidermoid carcinoma: A NCDB study.

PURPOSE: To determine the occult nodal disease rate and whether elective regional lymph node dissection (RLND) confers any 10-year overall survival (OS) in cN0 intermediate-grade mucoepidermoid carcinoma (MEC) of the parotid gland. MATERIALS & METHODS: The National Cancer Database was reviewed from 2004 to 2016 on adults with cT1-4aN0M0 intermediate-grade parotid MEC undergoing resection with/without RLND. Comparisons between patients with and without RLND were made. Occult nodal rate and 10-year overall survival (OS) were determined. RESULTS: Out of 898 included patients with cN0 intermediate grade parotid MEC undergoing elective RLND, the occult nodal rate was 7.6%. This was significantly different from low-grade (3.9%) and high-grade (25.7%) cN0 disease. When stratified by pT-classification, marginal differences were identified between low-grade and intermediate-grade tumors, whereas high-grade tumors demonstrated increased occult nodal disease with low T-stage (pT1-pT2, 20.4% vs. 5.1%) and high T-stage (pT3-pT4a, 32.1% vs. 17.6%). Patients undergoing elective RLND were more often treated at an academic facility (53.8% vs. 41.2%), had higher pT3-pT4 tumors (19.2% vs. 10.4%), and more frequently underwent total/radical parotidectomy (46.0% vs. 29.9%) with adjuvant radiation therapy (53.8% vs. 41.0%) Cox-proportional hazard modeling did not identify RLND, regardless if stratified by nodal yield or pT-classification, nor nodal positivity as significant predictors of 10-year OS. CONCLUSIONS: The occult nodal disease in intermediate-grade parotid MEC is low and similar to low-grade. Elective RLND may have a limited impact on OS, though its effect on locoregional control remains unknown. LEVEL OF EVIDENCE: III.

The Airway Pocket: Novel Advancement in Endoscopic Submucosal Placement of Posterior Cartilage Graft.

Endoscopic technology has increased our options for treatment of airway stenosis in a minimally invasive manner. This novel technique advances endoscopic posterior graft placement by creation of an airway pocket, potentially reducing risk of graft migration and improving outcomes. Laryngoscope, 134:3402-3405, 2024.

Assessing Readiness for Transition From Pediatric to Adult Gender Affirming Care.

PURPOSE: Transitioning from pediatric to adult care is a critical juncture in the health of adolescents. Little is known about how best to optimize transition to adult care among transgender and nonbinary (TGNB) youth. While the Transition Readiness and Assessment Questionnaire (TRAQ) has been validated in other pediatric populations, it has not been studied in TGNB youth. Our aims were to pilot the use of the TRAQ for TGNB patients, describe transition readiness patterns, and identify factors associated with transition readiness. METHODS: The TRAQ was introduced into routine clinical care for patients and their caregivers in a large, urban pediatric gender program in the spring of 2021. We performed a retrospective chart review comparing TRAQ responses based on demographic and clinical data. RESULTS: We collected TRAQs from 153 adolescents (mean age: 19 years [standard deviation 2.36], range: 11-24). The TRAQ demonstrated good internal reliability with a Cronbach alpha of 0.926. Patients scored highest in the TRAQ subdomains of talking with providers and tracking health issues and lowest in the subdomains of managing medications and appointment keeping. Age and presenting to the appointment alone were associated with higher TRAQ scores. DISCUSSION: We found that the TRAQ is internally reliable in a sample of TGNB youth. Factors associated with higher TRAQ scores and patterns identified in TRAQ score subdomains provide an insight into the needs of TGNB youth preparing to transition to adult gender-affirming care. Future research should focus on tracking transition readiness longitudinally, developing and evaluating interventions to improve transition readiness, and assessing post-transition outcomes.

Supporting the Mental Health of Transgender and Gender-Diverse Youth.

Increasing numbers of youth are identifying as transgender or gender diverse (TGD), meaning their gender identity or expression do not conform to culturally defined expectations for their designated sex at birth. The mental health needs of TGD youth are diverse, and to effectively address these needs requires knowledgeable general pediatric providers, who often are families' first resource for education and support around gender diversity. To help general pediatric providers work more effectively with TGD youth, we describe the role of mental health providers working with TGD youth and how best to support TGD youth's access to gender-affirming mental health and medical interventions. [Pediatr Ann. 2023;52(12):e456-e461.].

Normoblastemia in COVID-19 patients is associated with more severe disease and adverse outcome.

OBJECTIVES: The clinical, pathological, and laboratory correlates of normoblastemia in COVID-19 patients have not been adequately explored. We sought to assess the frequency of normoblastemia in COVID-19, its association with other markers of disease, as well as other clinical outcomes. METHODS: All COVID-19 patients seen at our institution with at least one automated complete blood count (aCBC) evaluation from March to May 2020 were included in this retrospective cohort analysis. Results of aCBC and tests for markers of the acute phase response performed within 5 days before the first COVID-19 positive test and 14 days after the last positive test were reviewed. We also evaluated histologic features of the reticuloendothelial system of COVID-19 decedents. RESULTS: Among a total of 2501 COVID-19 patients, 715 (28.6%) were found to have normoblastemia. Patients with this abnormality had significantly higher (median, (1st quartile, 3rd quartile) WBC (15.7 (11.2, 23.1) u/L vs. 8.3 (6.2, 11.5) u/L), absolute neutrophil count (7.0 (5.1, 10.1) u/L vs. 5.1 (3.7, 7.3) u/L), immature granulocyte percentage (0.8 (0.5, 1.3)% vs. 0.5 (0.3, 0.8)%), ESR (76.0 (60.5, 100.0) mm/hr vs. 66.0 (45.0, 87.0) mm/hr), ferritin (1404.5 (645.0, 2871.0) ng/mL vs. 672.7 (313.4, 1348.0) ng/mL), INR (1.4 (1.2, 1.7) vs. 1.2 (1.1, 1.3)), D-dimer (8.2 (2.8, 20.0) ug/mL FEU vs. 1.5 (0.8, 3.7) µg/mL FEU), and IL-6 (216.6 (77.7, 315.0) pg/mL vs. 54.3 (23.2, 127.8) pg/mL) levels, and lower hemoglobin (12.5 (10.7, 14.2) g/dL vs. 13.2 (11.8, 14.6) g/dL) and absolute lymphocyte count (1.0 (0.7, 1.3) u/L vs. 1.1 (0.8, 1.5) u/L). The incidence of intubation and ventilation support (61.3% (65/106) vs. 10.5% (31/263)) and mortality rates (37.9%, 271/715 vs. 11.8%, 210/1786), were higher in normoblastemic patients. Multivariable logistic regression revealed normoblastemia to be an independent predictive biomarker of short-term mortality in COVID-19. CONCLUSION: Normoblastemia in COVID-19 is associated with markers of severe disease, extramedullary erythropoiesis, and adverse clinical outcome.

Pinna Edge Biopsy of 7 and 21 Day Old C57BL/6 Mice as a Method for Identification and Genotyping.

Identifying and genotyping mice prior to weaning can be useful for mouse colony management. Mice of an undesired genotype can be identified prior to weaning and removed from further study, resulting in a reduction of housing costs, and labor time. We hypothesized that a pinna edge biopsy (PEB) performed by removing a portion of its edge with scissors is a reliable method for identifying and genotyping mice on postnatal day (PND) 7 consistent with PND 21, weaned mice. The pinnae of 54 C57BL/NCrl6 mice were biopsied on PND 7, and another 54 were biopsied on PND 21. Nine pinna patterns were tested. The accuracy of pattern identification was assessed on PND 7, 14, 21, 30, and 63. The mean times were compared for performing the biopsy on PND 7 and PND 21 mice, and the average time taken to identify the patterns were determined. Weight, milk spot presence, pup rejection, morbidity, and mortality were examined at various time points. During the biopsy, bleeding of the pinna, urination, vocalization, and flinching were assessed. No significant differences were detected in DNA quality, relative DNA quantity, genotyping reliability, or body weight (P ≥ 0.05) between mice biopsied on PND 7 and PND 21. Flinching at the time of PEB was significantly higher in PND 21 mice as compared with PND 7 mice (P < 0.00001). Pinna pattern identification accuracy for mice biopsied on PND 7 and PND 21 were 96% and 98%, respectively. This study validates the use of PEB for simultaneous identification and genotyping of PND 7 mice.

Mental Health and Gender Affirmation of Black and Latine Transgender/Nonbinary Youth Compared to White Peers Prior to Hormone Initiation.

PURPOSE: To compare baseline mental health symptoms and gender affirmation between Black/Latine versus White transgender/nonbinary youth (BLTY vs. WTY) and examine relationships between gender affirmation and mental health symptoms, and whether associations differed by race/ethnicity subgroup. METHODS: Baseline data were analyzed from the gender-affirming hormone cohort of the Trans Youth Care United States Study-a 4-clinic site, observational study. Mental health symptoms assessed included depression, suicidality, and anxiety. Gender affirmation measures included the parental acceptance subscale from the perceived Parental Attitudes of Gender Expansiveness Scale-Youth Report; non-affirmation, internalized transphobia, and community connectedness subscales from the Gender Minority Stress and Resilience Measure-Adolescent; and self-reported living full time in affirmed gender. Fisher exact tests and independent sample t tests compared mental health symptoms and gender affirmation between subgroups. Logistic regression analyses evaluated associations between gender affirmation and mental health symptoms. Interaction analyses assessed differences in associations between subgroups. RESULTS: The sample (mean age 16 years, range 12-20 years) included 92 BLTY (35%) and 170 WTY (65%). Subgroups had comparable prevalence of depression and anxiety symptoms. WTY had higher prevalence of lifetime suicidality (73% vs. 59%; p = .02). There were no differences in gender affirmation. Among the whole sample, higher parental acceptance decreased odds of depression symptoms. Not living in affirmed gender increased odds of depression symptoms. Higher non-affirmation and internalized transphobia increased odds of depression and anxiety symptoms and suicidality. Associations did not vary by subgroup. DISCUSSION: BLTY and WTY had comparable mental health symptoms. For both subgroups, gender affirmation decreased odds of those symptoms.

Expanding upon the relationship between gender-affirming hormone therapy, neural connectivity, mental health, and body image dissatisfaction.

OBJECTIVE: Transgender/non-binary (TNB) youth are at increased risk for anxiety, depression, and suicidality compared to cisgender youth. Gender affirming hormone therapy (GAHT, i.e., testosterone or estrogen) is a standard of care option for TNB youth, and we have recently shown that GAHT (testosterone) in transgender youth assigned a female sex at birth is associated with reductions in internalizing symptomatology. The current analysis explores: 1) whether these benefits are observed in both TNB youth assigned female at birth (TNBAFAB) and TNB youth assigned male at birth (TNBAMAB) and 2) the extent to which body image dissatisfaction and alteration in neural circuitry relate to internalizing symptoms. METHOD: The current study is an expansion of a previous publication from our lab that explored the association between gender-affirming testosterone and internalizing symptomatology. While participants in our previous study consisted of 42 TNBAFAB youth, participants in the current study included adolescent TNBAFAB receiving GAHT (n = 21; GAHT+) and not receiving GAHT (n = 29; GAHT-) as well as adolescent GAHT+ TNBAMAB (n = 15) and GAHT- TNBAMAB (n = 17). Participants reported symptoms of trait and social anxiety, depression, suicidality in the past year, and body image dissatisfaction. Brain activation was measured during a face processing task designed to elicit amygdala activation during functional MRI. RESULTS: GAHT+ TNBAFAB had significantly lower rates of social anxiety, depression, and suicidality compared to GAHT- TNBAFAB. While there were no significant relationships between estrogen and depression and anxiety symptoms, longer duration of estrogen was related to less suicidality. Both testosterone and estrogen administration were related to significantly lower rates of body image dissatisfaction compared to GAHT- youth. No significant differences emerged for BOLD response in the left or right amygdala during the face processing task, however, there was a significant main effect of GAHT on functional connectivity between the right amygdala and the ventromedial prefrontal cortex, such that GAHT+ youth had stronger co-activation between the two regions during the task. Body image dissatisfaction, greater functional connectivity, their interaction effect, and age predicted depression symptomatology and body image dissatisfaction additionally predicted suicidality in the past year. CONCLUSION: The current study suggests that GAHT is associated with fewer short-term internalizing symptoms in TNBAFAB than in TNBAMAB, although internalizing symptoms among TNBAMAB may diminish with longer durations of estrogen treatment. Controlling for age and sex assigned at birth, our findings indicate that less body image dissatisfaction and greater functional connectivity between the amygdala and ventromedial prefrontal cortex were both predictors of fewer levels of internalizing symptoms following GAHT.

High Internalized Transphobia and Low Gender Identity Pride Are Associated With Depression Symptoms Among Transgender and Gender-Diverse Youth.

PURPOSE: Prior studies have identified a significant relationship between internalized transphobia and poor mental health among transgender and gender-diverse (TGD) adults; however, this relationship has not been extensively examined among youth. Further, little research has sought to explore protective factors, such as identity pride, and their influence on this relationship. We examined the association between internalized transphobia and depression and anxiety symptoms among TGD youth and explored the moderating role of gender identity pride on these associations. METHODS: Participants were 315 TGD youth ages 12-20 years (mean = 16; standard deviation = 1.89) seeking gender-affirming hormone treatment at one of four major pediatric hospitals across the United States. At the time of enrollment, participants were naïve to gender-affirming hormone treatment. Participants self-reported mental health, internalized transphobia, and identity pride. Multiple regression models were used with depression and anxiety symptoms as outcomes and age, designated sex at birth, and perceived parental support included as covariates. RESULTS: Greater internalized transphobia was associated with greater depressive symptoms, and gender identity pride moderated this relationship, such that greater gender identity pride was associated with fewer depressive symptoms. Greater internalized transphobia was significantly associated with greater anxiety symptoms; no moderation effect was observed for this relationship. DISCUSSION: Gender identity pride influenced mental health symptoms for youth experiencing internalized transphobia and represents a potential key protective factor. These results support efforts to further develop, test, and implement clinical inventions to bolster identity pride for TGD youth.

Gender Dysphoria: Optimizing Healthcare for Transgender and Gender Diverse Youth with a Multidisciplinary Approach.

Transgender and gender diverse (TGD) youth and their families are seeking medical and mental health care at increasing rates. As the number of multidisciplinary pediatric gender programs expands, we consider the history and evidence base for gender affirmative care and highlight existing models of care that can flexibly accommodate the diverse needs of TGD youth and their families. Comprehensive multidisciplinary care includes both medical and mental health providers who work collaboratively with TGD youth and their caregivers to assess gender-related support needs and facilitate access to developmentally appropriate medical and mental health interventions. In addition to direct health-care services, multidisciplinary care for TGD youth and their families extends into community training, education, community outreach, nonmedical programming, and advocacy for TGD youth.

Exogenous testosterone administration is associated with differential neural response to unfamiliar peer's and own caregiver's voice in transgender adolescents.

Changes in gonadal hormones during puberty are thought to potentiate adolescents' social re-orientation away from caregivers and towards peers. This study investigated the effect of testosterone on neural processing of emotional (vocal) stimuli by unfamiliar peers vs. parents, in transgender boys receiving exogenous testosterone as a gender-affirming hormone (GAH+) or not (GAH-). During fMRI, youth heard angry and happy vocal expressions spoken by their caregiver and an unfamiliar teenager. Youth also self-reported on closeness with friends and parents. Whole-brain analyses (controlling for age) revealed that GAH+ youth showed blunted neural response to caregivers' angry voices-and heightened response to unfamiliar teenage angry voices-in the anterior cingulate cortex. This pattern was reversed in GAH- youth, who also showed greater response to happy unfamiliar teenager vs. happy caregiver voices in this region. Blunted ACC response to angry caregiver voices-a pattern characteristic of GAH+ youth-was associated with greater relative closeness with friends over parents, which could index more "advanced" social re-orientation. Consistent with models of adolescent neurodevelopment, increases in testosterone during adolescence may shift the valuation of caregiver vs. peer emotional cues in a brain region associated with processing affective information.