"We Followed their Lead": Exploring Relational Change and Support among Caregivers of Transgender and Gender Diverse Youth.

Transgender and gender diverse youth and young adults (TGDY) experience higher mental health morbidity, including self-harm, suicide ideation, and suicide attempts, as compared to cisgender peers. Support from family members is associated with improved mental health outcomes for TGDY. However, little is known about the process that caregivers who consider themselves supportive undergo and how caregiver-youth relationships evolve through a TGDY's gender journey. Through a reflexive thematic analysis of 14 interviews conducted with caregivers of TGDY from April-July 2022, we sought to understand how caregivers who considered themselves supportive of TGDY navigated shifting relationships with themselves, their children, and their communities. Applying theories of Ambiguous Loss and Thriving Through Relationships, findings coalesced around several themes including reflecting on change, re-negotiating interpersonal relationships, and educating through relationships. The gender journeys of TGDY required caregivers to navigate relationships with self (feeling loss and wrestling with worry for their child), negotiate relationships with others (disclosing to extended family and social networks), and educate themselves and others through relationships (connecting through personal narratives from other families, parents supporting parents, learning to advocate for their child). The process of caregivers learning to support their children was facilitated through profound intrapersonal and interpersonal reflection, connection, and community. Understanding this process is important to inform educational interventions and programs that help caregivers learn to support and advocate effectively for TGDY.

Fertility preservation in transfeminine adolescents using TESE at the time of Histrelin Acetate subcutaneous implant placement: A Case Series.

BACKGROUND: Fertility preservation (FP) is an important aspect of the care of transgender patients in whom Gender Affirming Medical Treatment (GAT) may begin before puberty is completed. While there are overall few studies that can be used to guide conversations about long-term effects of GAT, there are concerns that GAT could negatively impact fertility. Prior studies have shown low utilization of FP in this population, with avoidance of delay in starting GAT cited as one of the most common reasons for foregoing FP. It is possible that strategies to mitigate delay in commencement of GAT can facilitate higher FP utilization, maintaining options for future family building. OBJECTIVE: To describe our institution's experience with Testicular Sperm Extraction (TESE) for FP and Histrelin Acetate (Supprelin) Subcutaneous Implantation for GAT commencement. STUDY DESIGN: A retrospective review of transfeminine adolescents at our institution from 2010 to 2022 who underwent TESE for FP at the time of Supprelin placement for GAT (FP/SP). Outcomes of interest included successful sperm retrieval, age at first visit to our institution's Transgender Multispecialty Service Health clinic (GeMS), age at time of FP/SP, testicular volume, and Tanner stage at time of FP/SP, and age when GnRH agonist (GnRHa) therapy was prescribed. Testosterone, LH, FSH, and Inhibin B values prior to combination FP/SP were also obtained. RESULTS: Ten patients from 2017 to 2022 underwent FP/SP after prescription of GnRHa based on Endocrine Society Guidelines. Successful sperm retrieval and storage was achieved in all patients. Median age at FP/SP was fourteen years 5.5 months (range 12y5m-16y8m). Median time from GnRHa prescription to FP/SP was two months (range 2-5 m). Mean testicular volume at time of FP/SP was 13.2 cc (SD 3.38 cc, range 8-17 cc), and median Tanner Stage was IV (range III-V). Average testosterone level was 301.60 (SD 173.04), LH 3.00 (SD 1.25), FSH 3.33 (SD 1.71), Inhibin B 208.50 (SD 87.44). CONCLUSIONS: Performing TESE for FP is feasible for transgender youth undergoing Histrelin implant placement, leading to short delays in starting GAT. Testicular volume and endocrine markers can provide preoperative insight into likelihood of successful sperm retrieval during TESE, are needed to identify which patients will have successful sperm retrieval to ensure optimal counseling and informed decision making for providers, patients and families.

Exploring the Impact of Legislation Aiming to Ban Gender-Affirming Care on Pediatric Endocrine Providers: A Mixed-Methods Analysis.

Context: Access to gender-affirming medical care is associated with better mental health outcomes in transgender and gender diverse youth. In 2021 and 2022, legislation aiming to ban gender-affirming medical care for youth was proposed in 24 states. Objective: This study aimed to (1) assess the impact of this legislation on pediatric providers based on legislative status of their state of practice and (2) identify the themes of concerns reported by them. Methods: A mixed-methods study was conducted via an anonymous survey distributed to pediatric endocrinology providers. Survey responses were stratified based on US state of practice, with attention to whether legislation aiming to ban gender-affirming care had been considered. Data were analyzed both quantitatively and qualitatively. Results: Of 223 respondents, 125 (56.0%) were currently providing gender-affirming medical care. A total of 103 (45.7%) respondents practiced in a state where legislation aiming to ban gender-affirming care had been proposed and/or passed between January 2021 to June 2022. Practicing in legislation-affected states was associated with negative experiences for providers including (1) institutional pressure that would limit the ability to provide care, (2) threats to personal safety, (3) concerns about legal action being taken against them, (4) concerns about their career, and (5) institutional concerns about engagement with media. Major qualitative themes emerging for providers in legislation-affected states included safety concerns and the impact of laws on medical practice. Conclusion: This study suggests that legislation aiming to ban health care for transgender youth may decrease access to qualified providers in affected states.

Gender Affirmation-Related Information-Seeking Behaviors in a Diverse Sample of Transgender and Gender-Diverse Young Adults: Survey Study.

BACKGROUND: Of the 1.6 million transgender and gender-diverse (TGD) people in the United States, approximately 700,000 are youth aged 13-24 years. Many factors make it difficult for TGD young people to identify resources for support and information related to gender identity and medical transition. These range from lack of knowledge to concerns about personal safety in the setting of increased antitransgender violence and legislative limitations on transgender rights. Web-based resources may be able to address some of the barriers to finding information and support, but youth may have difficulty finding relevant content or have concerns about the quality and content of information they find on the internet. OBJECTIVE: We aim to understand ways TGD young adults look for web-based information about gender and health. METHODS: In August 2022, 102 young adults completed a 1-time survey including closed- and open-ended responses. Individuals were recruited through the Prolific platform. Eligibility was restricted to people between the ages of 18-25 years who identified as transgender and were residents of the United States. The initial goal was to recruit 50 White individuals and 50 individuals who identified as Black, indigenous, or people of color. In total, 102 people were eventually enrolled. RESULTS: Young adults reported looking on the internet for information about a broad range of topics related to both medical- and social-gender affirmation. Most participants preferred to obtain information via personal stories. Participants expressed a strong preference for obtaining information from other trans people. CONCLUSIONS: There is a need for accessible, expert-informed information for TGD youth, particularly more information generated for the transgender community by members of the community.

How Should Clinicians Navigate Decision Making About Genital Reconstructive Surgeries Among Intersex and Transgender Populations?

Genital reconstructive surgeries (GRS) are available for a variety of indications and populations, including transgender and gender diverse (TGD) individuals and those with intersex traits/differences in sex development (I/dsd). Despite the common outcomes of GRS for TGD and I/dsd individuals, decision making about this surgical care differs between these populations and across the lifespan. Sociocultural perspectives on sexuality and gender dominate the ethics of GRS, and reform is needed within clinical ethics to center the autonomy of TGD and I/dsd individuals in informed consent processes. Such changes are necessary to ensure justice in health care for all sex and gender diverse individuals across the lifespan.

Neuropsychological and mental health concerns in a multicenter clinical sample of youth with turner syndrome.

Clinical practice guidelines for individuals with Turner syndrome (TS) recommend screening for neuropsychological concerns (NC) and mental health concerns (MHC). However, current provider screening and referral patterns for NC and MHC are not well characterized. Additionally, prevalence of and risk factors for NC and MHC vary across studies. This multicenter chart review study examined the prevalence, risk factors for, and management of NC and MHC in a cohort of 631 patients with TS from three pediatric academic medical centers. NC and/or MHC were documented for 48.2% of patients. Neuropsychological evaluation recommendations were documented for 33.9% of patients; 65.4% of the sample subsequently completed these evaluations. Mental health care recommendations were documented in 35.0% of records; subsequent documentation indicated that 69.7% of these patients received such services. Most notably, rates of documented MHC, NC, and related referrals differed significantly by site, suggesting the need for standardized screening and referral practices. TS diagnosis in early childhood was associated with an increased risk of NC. Spontaneous menarche was associated with increased risk of MHC. Younger age at growth hormone initiation was associated with both increased risk of isolated NC and co-occurring NC and MHC. Mosaic karyotype was associated with decreased risk of NC and MHC.

Prenatal diagnosis of sex chromosome aneuploidy-What do we tell the prospective parents?

Sex chromosome aneuploidy (SCA) can be detected on prenatal diagnostic testing and cell free DNA screening (cfDNA). High risk cfDNA results should be confirmed with diagnostic testing. This summary article serves as an update for prenatal providers and assimilates data from neurodevelopmental, epidemiologic, and registry studies on the most common SCA. This information can be helpful for counseling after prenatal diagnosis of sex chromosome aneuploidy. Incidence estimates may be influenced by ascertainment bias and this article is not a substitute for interdisciplinary consultation and counseling.

Integrating LGBTQIA + Community Member Perspectives into Medical Education.

ProblemLGBTQIA+ (lesbian, gay, bisexual, transgender, queer, intersex, asexual, and all sexual and gender minorities) people have unique health care needs related to their sexual orientation, gender identity and expression, and sex development. However, medical education has historically excluded LGBTQIA + health-related content in formal curricula. It is common for medical students to interact with diverse patient populations through clinical rotations; however, access to and knowledge about LGBTQIA + patients is inconsistently prioritized in medical schools. This is especially true for LGBTQIA + patients with intersecting historically marginalized identities, such as people of color and people with disabilities. Learning from and listening to medically underserved community members can help both medical students and educators better understand the unique health needs of these communities, and address implicit biases to improve health care and outcomes for their patients. Intervention: To address the lack of LGBTQIA + health-related content in medical education and improve access to and knowledge about LGBTQIA + patients, LGBTQIA + community members' perspectives and lived experiences were integrated into undergraduate medical education via four primary methods: Community Advisory Groups, community panel events, standardized patients, and community member interviews. Context: LGBTQIA + community members' perspectives and lived experiences were integrated into medical education at Harvard Medical School (HMS) as part of the HMS Sexual and Gender Minority Health Equity Initiative. Impact: LGBTQIA + community members' perspectives and lived experiences were successfully integrated into multiple aspects of medical education at HMS. During this process, we navigated challenges in the following areas that can inform similar efforts at other institutions: representation of diverse identities and experiences, meeting and scheduling logistics, structural barriers in institutional processes, and implementation of community member recommendations. Lessons Learned: Based on our experiences, we offer recommendations for integrating LGBTQIA + community members' perspectives into medical education. Engaging community members and integrating their perspectives into medical education will better enable medical educators at all institutions to teach students about the health care needs of LGBTQIA + communities, and better prepare medical students to provide affirming and effective care to their future patients, particularly those who are LGBTQIA+.

Harvard Medical School's Sexual and Gender Minority Health Equity Initiative: Curricular and Climate Innovations in Undergraduate Medical Education.

PROBLEM: Sexual and gender minority (SGM) populations face numerous health disparities. Medical school curricula lack adequate educational content preparing students for serving SGM patients, and medical students typically do not experience welcoming, inclusive educational environments conducive to learning about SGM health care. APPROACH: In 2018, Harvard Medical School (HMS) launched the 3-year Sexual and Gender Minority Health Equity Initiative to integrate SGM health content throughout the longitudinal core medical curriculum and cultivate an educational climate conducive for engaging students and faculty in SGM health education. The initiative employed innovative strategies to comprehensively review existing SGM health curricular content and climate; integrate content across courses and clerkships; lead with LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, intersex, asexual, and all sexual and gender minorities) community engagement; adopt an intersectional approach that centers racial equity; cultivate safe, affirming educational environments for LGBTQIA+ and non-LGBTQIA+ students and staff; ensure all graduating students are prepared to care for SGM patients; enhance faculty knowledge, skills, attitudes, and confidence teaching SGM health; evaluate effectiveness and impact of SGM health curricular innovations; prioritize sustainability of curricular innovations; and publicly share and disseminate SGM health curricular products and tools. OUTCOMES: Key outcomes of the initiative focused on 5 areas: development of 9 SGM health competencies, stakeholder engagement (HMS students and faculty, national SGM health experts, and LGBTQIA+ community members), student life and educational climate (increased LGBTQIA+ student matriculants, enhanced mentorship and support), curriculum development (authentic LGBTQIA+ standardized patient experiences, clerkship toolkit design), and faculty development (multimedia curriculum on content and process to teach SGM health). NEXT STEPS: In addition to refining curricular integration, evaluating interventions, and implementing comprehensive antiracist and gender-affirming educational policies, the next phase will involve dissemination by translating best practices into feasible approaches that any school can adopt to meet local needs with available resources.

Exploring Factors Associated with Decisions about Feminizing Genitoplasty in Differences of Sex Development.

STUDY OBJECTIVE: Infants with genital development considered atypical for assigned female sex may undergo feminizing genitoplasty (clitoroplasty and/or vaginoplasty) in early life. We sought to identify factors associated with parent/caregiver decisions regarding genitoplasty for their children with genital virilization. DESIGN: Longitudinal, observational study SETTING: Twelve pediatric centers in the United States with multidisciplinary differences/disorders of sex development clinics, 2015-2020 PARTICIPANTS: Children under 2 years old with genital appearance atypical for female sex of rearing and their parents/caregivers INTERVENTIONS/OUTCOME MEASURES: Data on the child's diagnosis and anatomic characteristics before surgery were extracted from the medical record. Parents/caregivers completed questionnaires on psychosocial distress, experience of uncertainty, cosmetic appearance of their child's genitalia, and demographic characteristics. Urologists rated cosmetic appearance. For 58 patients from the study cohort with genital virilization being raised as girls or gender-neutral, we compared these data across 3 groups based on the child's subsequent surgical intervention: (i) no surgery (n = 5), (ii) vaginoplasty without clitoroplasty (V-only) (n = 15), and (iii) vaginoplasty and clitoroplasty (V+C) (n = 38). RESULTS: Fathers' and urologists' ratings of genital appearance were more favorable in the no-surgery group than in the V-only and V+C groups. Clitorophallic length was greater in the V+C group compared with the V-only group, with substantial overlap between groups. Mothers' depressive and anxious symptoms were lower in the no-surgery group compared with the V-only and V+C groups. CONCLUSIONS: Surgical decisions were associated with fathers' and urologists' ratings of genital appearance, the child's anatomic characteristics, and mothers' depressive and anxious symptoms. Further research on surgical decision-making is needed to inform counseling practices.

Fertility Counseling Practices for Patients with Turner Syndrome in Pediatric Endocrine Clinics: Results of a Pediatric Endocrine Society Survey.

INTRODUCTION: Turner syndrome (TS) is associated with a high risk of primary ovarian insufficiency. Current guidelines recommend early fertility counseling for affected youth and their families. This study assessed clinical providers' (MD, NP, or PA) fertility counseling practices for girls with TS. METHODS: TS providers were invited to complete a survey via the Pediatric Endocrine Society listserv. Descriptive statistics summarized variables of interest. Correlations were used to identify associations between barriers/practice characteristics and fertility preservation (FP) referral. Thematic analysis was used to examine qualitative responses. RESULTS: 119 providers completed the survey. Seventy percent reported discussing fertility implications of TS routinely in pediatric care. Fifty-six percent reported often or always referring patients with spontaneous menarche to FP specialists, whereas only 19% reported often or always referring their patients without spontaneous menarche (p < 0.001). Barriers associated with FP referral frequency included unfamiliarity with FP options, belief that FP is not a possible goal for their patients, and absence of a local reproductive endocrinologist. Qualitatively, four referral barrier themes were identified: (1) questionable utility of referral, (2) lack of perceived interest among patients/families, (3) provider barriers (e.g., lack of knowledge), (4) logistical/structural barriers to accessing fertility-related care. DISCUSSION/CONCLUSION: Pediatric endocrinology providers report inconsistently discussing fertility implications of TS. The frequency of referral to an FP specialist and factors/barriers affecting the decision to refer remain variable. Future research should focus on expanding provider education, addressing barriers to high-quality fertility counseling and referral for patients with TS, and investigating FP outcomes in TS.

Care for Transgender Young People.

Clinicians of all disciplines, including pediatric endocrinologists, are likely to encounter transgender and gender-diverse (TGD) young people in their practice regardless of whether they specialize in gender-affirming medical care. Because of this, it is important to be aware of the ways in which medical professionals can affirm these individuals. Although gender-affirming therapy should always include affirmation including proper use of names and pronouns, the transition journey will look different for each patient. The gender-affirming care of TGD young people may include both medical and nonmedical interventions (e.g., social transition). Therapies utilized for medical gender transition such as gonadotropin-releasing hormone agonists and/or gender-affirming hormones have implications for growth, bone health, cardiovascular health, and fertility, although these impacts are not yet completely understood. This review provides an overview of the care of transgender young people as well as a summary of what is known about the outcomes of these therapies. Clinicians should advise TGD young people and their families of the known and unknown risks and work together with patients to decide upon a treatment and follow-up regimen that aligns with their individual gender affirmation and health goals.

A Body-Neutral and Gender-Neutral Modified Ferriman-Gallwey Diagram.

BACKGROUND: The modified Ferriman-Gallwey (mFG) diagram for scoring hirsutism uses images with traditionally Eurocentric feminine features. No reports have documented its utility in patients with other gender identities. CASE: A 16-year-old nonbinary masculine patient, assigned female sex at birth, was seen for hyperandrogenism and irregular menses. They declined an exam, citing body dysphoria, and declined self-documenting on the mFG diagram, expressing anxiety with gendered images. We subsequently developed a novel, gender-inclusive mFG diagram, which the patient was then comfortable using to document their hair pattern. SUMMARY AND CONCLUSION: This case documents how the binary gendered characteristics of the mFG diagram can impact the care of patients. As gender expression is highly individual, we created the first gender-inclusive version of the mFG diagram to enhance care for all patients.

The Health Care of Adults with Differences in Sex Development or Intersex Traits Is Changing: Time to Prepare Clinicians and Health Systems.

Historically, the majority of differences in sex development or intersex trait (dsd/I)-specific medical care has been provided by pediatric clinicians, leading to a dearth of adult clinicians qualified to care for this vulnerable population, and pediatricians reticent to transition patients to adult care. Recent changes in routine care of children and infants with dsd/I, including reconsidering the role of early genital surgeries, highlight the critical need to address the gaps in adult dsd/I health care. In this perspective, we describe three key educational and research approaches that can be implemented to build competency to care for adults with dsd/I and improve care across the lifespan.

Breakthrough Bleeding in Transgender and Gender Diverse Adolescents and Young Adults on Long-Term Testosterone.

STUDY OBJECTIVE: Amenorrhea is a goal of many transgender and gender diverse adolescent and young adult (TGD AYA) patients on testosterone gender-affirming hormone therapy (T-GAHT). Breakthrough bleeding can contribute to worsening gender dysphoria. Our objective was to evaluate breakthrough bleeding in TGD AYA on T-GAHT. DESIGN: Institutional review board-approved retrospective cohort. SETTING: Tertiary-care children's hospital. PARTICIPANTS: TGD AYA on T-GAHT >1 year. INTERVENTIONS: None; observational. MAIN OUTCOME MEASURES: Presence of, and risk factors for, breakthrough bleeding. RESULTS: Of the 232 patients who met inclusion criteria, one-fourth (n = 58) had 1 or more episodes of breakthrough bleeding, defined as bleeding after more than 1 year on T-GAHT. In comparing patients with breakthrough bleeding to those without, there were no significant differences between age of initiation, body mass index (BMI), race/ethnicity, testosterone type used, use of additional menstrual suppression, serum testosterone, or estradiol levels. Patients with breakthrough bleeding patients were on T-GAHT longer (37.3 ± 17.0 vs 28.5 ± 14.6 months, P < .001) and were more likely to have endometriosis (P = .049). Breakthrough bleeding began at a mean of 24.3 ± 17.2 months after T-GAHT initiation. Of those with breakthrough bleeding, 46 (79.3%) had no known cause, 10 (17.2%) bled only with missed T-GAHT doses, and 2 (3.4%) bled only when withdrawing from concomitant menstrual suppression. No breakthrough bleeding management method was found to be superior. CONCLUSION: Breakthrough bleeding is relatively common (25%) on T-GAHT despite early amenorrhea. Most cases do not have an identifiable cause. Our data did not show superiority of any 1 method for managing breakthrough bleeding on T-GAHT.

Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis.

WNT2B is a member of the Wnt family, a group of signal transduction proteins involved in embryologic development and stem cell renewal and maintenance. We recently reported homozygous nonsense variants in WNT2B in three individuals with severe, neonatal-onset diarrhea, and intestinal failure. Here we present a fourth case, from a separate family, with neonatal diarrhea associated with novel compound heterozygous WNT2B variants. One of the two variants was a frameshift variant (c.423del [p.Phe141fs]), while the other was a missense change (c.722 G > A [p.G241D]) that we predict through homology modeling to be deleterious, disrupting post-translational acylation. This patient presented as a neonate with severe diet-induced (osmotic) diarrhea and growth failure resulting in dependence on parenteral nutrition. Her gastrointestinal histology revealed abnormal cellular architecture particularly in the stomach and colon, including oxyntic atrophy, abnormal distribution of enteroendocrine cells, and a paucity of colonic crypt glands. In addition to her gastrointestinal findings, she had bilateral corneal clouding and atypical genital development later identified as a testicular 46,XX difference/disorder of sexual development. Upon review of the previously reported cases, two others also had anterior segment ocular anomalies though none had atypical genital development. This growing case series suggests that variants in WNT2B are associated with an oculo-intestinal (and possibly gonadal) syndrome, due to the protein's putative involvement in multiple developmental and stem cell maintenance pathways.

Monogenic Diabetes in a Child with Cystic Fibrosis: A Case Report and Review of the Literature.

Cystic fibrosis-related diabetes (CFRD) is associated with worsening pulmonary function, lower body mass index, increased infection frequency, and earlier mortality. While the incidence of CFRD is rising, its development in patients under the age of 10 years is uncommon. We present a 9-year-old girl with cystic fibrosis (CF) who presented with a 5-year history of nonprogressive hyperglycemia, demonstrated by abnormal oral glucose tolerance tests, glycated hemoglobin A1c (HbA1c) levels consistently >6.5%, and negative pancreatic autoantibodies. Subsequent genetic testing revealed a pathogenic heterozygous recessive mutation in the GCK gene at c.667G>A (p.Gly223Ser), consistent with a diagnosis of GCK-MODY. Significant dysglycemia in young children with CF should raise suspicion for alternative etiologies of diabetes and warrants further investigation. The clinical impact of underlying monogenic diabetes in patients with CF is unclear, and close follow-up is warranted. This case also offers unique insight on the impact of hyperglycemia in the absence of insulin deficiency on CF-specific outcomes.

Neurodevelopmental and Mental Health Screening for Patients with Turner Syndrome in Pediatric Endocrine Clinics: Results of a Pediatric Endocrine Society Survey.

INTRODUCTION: International Turner syndrome (TS) Clinical Practice Guidelines recommend screening for neurodevelopmental (ND) and mental health (MH) concerns in girls with TS; however, it remains unclear whether this is implemented in current practice. The objective of this mixed methods study was to assess screening practices for ND and MH in girls with TS from the perspective of pediatric endocrinologists. METHODS: Pediatric Endocrine Society members who provide care for girls with TS were invited to complete an electronic survey on screening practices. Descriptive statistics were used to summarize quantitative results concurrently with thematic analysis of free-text survey responses. RESULTS: A total of 124 surveys were completed (86% attending pediatric endocrinologists, 81% at academic institutions). Overall, 25% of providers reported their patients with TS received both ND and MH screenings. Only 9 (9%) respondents endorsed screening for ND concerns themselves, while more providers (26%) reported they screen for MH concerns. Multiple barriers to screening for ND and MH concerns within the clinical setting were endorsed. Nearly all providers (>93%) reported they would consider using a short, validated screening tool for ND and MH concerns if such tools were available. DISCUSSION: A minority of pediatric endocrinologists currently perform ND or MH screening for patients with TS, however, many would be interested in implementing a brief screening tool into their clinical practice. Given almost all girls with a TS diagnosis receive care from pediatric endocrinologists at least annually, this may be an effective method to increase the proportion of girls with TS who receive recommended screenings.