Clinical pharmacology in adolescent transgender medicine.

Adolescent transgender medicine is a growing clinical field. Gender-affirming medications for transgender youth may include gonadotropin-releasing hormone (GnRH) agonists, gender-affirming hormones or both. To evaluate the potential effects of GnRH agonists (puberty suppression) on pharmacokinetic processes for transgender youth, we searched PubMed from inception to May 2024 for publications on the effects of GnRH agonists on drug absorption, distribution, metabolism or excretion for transgender adolescents or effects on hormones (including gonadotropins, adrenal androgens, sex steroids) that are associated with changes in drug metabolism during puberty in the general adolescent population. No publications discussed the effects of GnRH agonist treatment on pharmacokinetic processes for adolescent transgender people. Sixteen publications observed marked decreases in gonadotropins and sex steroids for both adolescent transgender men and adolescent transgender women and slight effects on adrenal androgens. During GnRH agonist treatment, changes in body composition and body shape were greater for adolescent transgender people than for cisgender adolescent people. Further research is needed to better understand the effects of GnRH agonists on drug metabolism and other pharmacokinetic processes for transgender adolescents receiving GnRH agonists and other gender-affirming medications.

Family Support in Transgender and Gender-Diverse Young Adults Seeking Telehealth for Hormone Therapy.

Background: Family support (FS) is a key social determinant of health for transgender and gender-diverse (TGD) young adults. We examined the association between FS and health outcomes in young adults seeking gender-affirming hormone therapy (GAHT) from a US telehealth service. Methods: Cross-sectional data from TGD young adults ages 18-24 (n = 7,740) who provided demographic information and information on FS at intake were analyzed. Relationships between FS, geography, insurance status, rates of depression, and smoking status were examined. Results: Less than half of respondents reported having FS. Patients with FS reported lower rates of depression and higher incidence of previous gender-affirming medical care (e.g., hormone therapy, surgeries), had lower rates of being uninsured, and were more likely to reside in the Northeast or Western United States. Young adults assigned female at birth had higher rates of FS. Conclusion: FS may mitigate mental health disparities in TGD young adults including rates of depression. FS and insurance status are closely related in a geographically diverse population seeking telehealth services. The finding underscores the importance of FS as a social determinant of health and the unique characteristics of patients seeking telehealth services.

Comfort Providing Gender-Affirming Care and Preferences for Consultative Support Among Rural Pediatric Primary Care Providers.

Objective: To examine how specialist-to-pediatric primary care provider (PPCP) consultative support may impact PPCP comfort in providing gender-affirming care. Methods: PPCPs in West Virginia completed an electronic survey. T-tests compared comfort providing gender-affirming care and rank-sum tests compared the practicality of four consultative support modalities by time in practice and specialty. Results: Of 51 participants, 47.1% had been in practice for <10 years and 59.6% were trained in pediatrics. PPCPs with <10 years in practice and those trained in pediatrics were more comfortable providing gender-affirming care than those in practice >10 years and those trained in family medicine. PPCPs felt that telemedicine was more practical than tele-education, although they reported all consultative support modalities would increase comfort providing this care. Conclusions: Access to consultative support can increase PPCP comfort providing gender-affirming care, although certain modalities may be more effective for PPCPs with varying levels of experience and specialty training.

Evaluating an Electronic Consultation Platform to Support Pediatric Primary Care Providers in Caring for Transgender and Nonbinary Adolescents.

Background: An electronic consultation (e-consult) platform was implemented to support pediatric primary care providers (PCPs) in providing gender-affirming care to transgender and nonbinary (TNB) adolescents. Following implementation, a study was conducted to (1) explore how access to this e-consult platform impacts PCP confidence and referral patterns, (2) describe the content of questions, and (3) evaluate PCP's perspectives regarding platform usability. Methods: Following each submission, providers completed a 17-item survey. A total of 20 providers submitted 38 e-consults and 26 follow-up surveys between October 2021 and December 2022. Results: All PCPs reported a high overall value and increased confidence caring for TNB adolescents. Nearly one in five (19%) felt it allowed them to avoid submitting a specialty referral. Mean System Usability Scale score was 78.2 indicating good usability. Conclusion: This e-consult platform shows great promise in increasing PCP confidence providing gender-affirming care adolescents. More widespread utilization could help improve access to care and decrease specialty care referrals.

Telemedicine-Based Provision of Adolescent Gender-Affirming Medical Care to Promote Equitable Access.

Purpose: To explore transgender and nonbinary (TNB) young adults' (1) interest in receiving gender-affirming medications through telemedicine before age 18 years and (2) willingness to initiate this care with primary care providers (PCPs). Methods: Data were from a survey of TNB young adults who had not received gender-affirming medications before age 18 years. Chi-square and Wald tests identified demographic differences in telemedicine interest and willingness to initiate medications with their PCP as minors. Results: Among 280 respondents, 82.5% indicated interest in telemedicine and 42.0% were willing to initiate medications with their PCP. Black/African American respondents were more likely to indicate interest in telemedicine than White and multiracial respondents. Respondents from rural areas were more likely to indicate willingness to initiate medications with their PCP than those from urban areas. Conclusions: Telemedicine expansion and further support for PCPs may represent critical opportunities to promote equitable access to adolescent gender-affirming care.

Telemedicine Utilization Among Transgender and Gender-Diverse Adolescents Before and After the COVID-19 Pandemic.

Introduction: Little is known about how expansion of telemedicine services during the COVID-19 pandemic has affected access to gender-affirming care for transgender and gender-diverse (TGD) youth. The purpose of this study was to explore differences in demographic characteristics and visit completion rates at a multidisciplinary gender clinic before and after telemedicine implementation in March 2020 and among telemedicine users and nonusers. Methods: Data were from electronic health records of Seattle Children's Gender Clinic (SCGC) patients seen between April 2019 and February 2021. We assessed differences in demographic characteristics and care utilization (i.e., encounter type and status) between April 2019 and February 2020 (pre-telemedicine) and April 2020 and February 2021 (post-telemedicine). Results: Of the 1,051 unique patients seen at SCGC during this time period, majority groups were as follows: 62% identified as transmasculine/male, 68% were non-Hispanic White, and 76% resided within 50 miles of the clinic. Statistically significant differences were observed in patient pronouns and insurance type when comparing the pre- and post-telemedicine periods (p < 0.01). Half (52%) of post-telemedicine period encounters were conducted through telemedicine, and telemedicine encounters were significantly more likely to be completed (72% vs. 50%) and less likely to be canceled (21% vs. 46%) compared with in-person encounters. Conclusions: Telemedicine services facilitated continued access to gender-affirming care services for TGD youth during the COVID-19 pandemic. Although the introduction of telemedicine did not exacerbate demographic disparities in access to this care, further research and interventions are warranted to address the ongoing disparities in access to gender-affirming care for youth of color and rural youth.

Healthcare Experiences of Gender Diverse Youth Across Clinical Settings.

We explored gender diverse youth's experiences seeking and receiving gender-affirming care in various health system locations. Results provide evidence for system-, clinic-, and provider-level improvements to promote the development of affirming environments and to improve health outcomes for gender diverse youth.

Behavioral Health Diagnoses in Youth with Gender Dysphoria Compared with Controls: A PEDSnet Study.

OBJECTIVE: To assess the odds of a psychiatric or neurodevelopmental diagnosis among youth with a diagnosis of gender dysphoria compared with matched controls in a large electronic health record dataset from 6 pediatric health systems, PEDSnet. We hypothesized that youth with gender dysphoria would have higher odds of having psychiatric and neurodevelopmental diagnoses than controls. STUDY DESIGN: All youth with a diagnosis of gender dysphoria (n = 4173 age at last visit 16.2 ± 3.4) and at least 1 outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables to controls without gender dysphoria (n = 16 648, age at last visit 16.2 ± 4.8) using multivariable logistic regression. The odds of having psychiatric and neurodevelopmental diagnoses were examined using generalized estimating equations. RESULTS: Youth with gender dysphoria had higher odds of psychiatric (OR 4.0 [95% CI 3.8, 4.3] P < .0001) and neurodevelopmental diagnoses (1.9 [1.7, 2.0], P < .0001). Youth with gender dysphoria were more likely to have a diagnosis across all psychiatric disorder subcategories, with particularly high odds of mood disorder (7.3 [6.8, 7.9], P < .0001) and anxiety (5.5 [5.1, 5.9], P < .0001). Youth with gender dysphoria had a greater odds of autism spectrum disorder (2.6, [2.2, 3.0], P < .0001). CONCLUSIONS: Youth with gender dysphoria at large pediatric health systems have greater odds of psychiatric and several neurodevelopmental diagnoses compared with youth without gender dysphoria. Further studies are needed to evaluate changes in mental health over time with access to gender affirming care.

Nine Ways Parents Can Support Their Gender Diverse Children.

Parental support is associated with improved mental health outcomes for gender diverse youth (GDY). Parents often seek guidance from pediatric providers, but few studies explore what actions make GDY feel supported. Using a qualitative analysis of open-ended survey responses, we aimed to identify ways in which GDY want to be supported by their parents or caregivers. Nine key themes were identified, including using affirming language at home and other settings as desired by GDY, seeking education, and aiding in accessing affirming items and care. Findings from this study can help pediatric medical and mental health providers help parents to support their GDY.

Associations Between Gender Dysphoria, Eating Disorders, and Mental Health Diagnoses Among Adolescents.

PURPOSE: Transgender adolescents and adolescents with eating disorders (EDs) are known to have increased mental health comorbidity; however, little is understood about how gender dysphoria (GD), disordered eating and mental health disorders relate to each other. The purpose of this study was to examine associations between GD, ED, and mental health diagnoses among adolescents. METHODS: Data were extracted from the electronic health records of 57,353 patients aged 9-18 seen at a single pediatric health system between 2009 and 2022. Adjusted logistic regression models tested for associations between GD, ED, and mental health diagnoses. RESULTS: Youth with a GD diagnosis had significantly greater odds of also having an ED diagnosis compared to those without a GD diagnosis (adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI]: 2.98-4.64). Among those with an ED diagnosis, youth with a GD diagnosis had significantly lower odds of having an anorexia nervosa diagnosis (aOR = 0.34, 95% CI: 0.18-0.61) and significantly greater odds of having an unspecified or other specified ED diagnosis (aOR = 2.48, 95% CI: 1.56-3.93) compared to those without a GD diagnosis. Youth with both GD and ED diagnoses had significantly greater odds of also having a diagnosis of anxiety (aOR = 24.01, 95% CI: 14.85-38.83), depression (aOR = 48.41, 95% CI: 30.38-77.12), suicidality (aOR = 26.15, 95% CI: 16.65-41.05) and self-harm (aOR = 35.79, 95% CI: 22.48-56.98) as compared to those with neither a GD nor an ED diagnosis. DISCUSSION: Adolescents with co-occurring GD and ED diagnoses are at greater risk for anxiety, depression, suicidality, and self-harm as compared to youth with neither diagnosis. Further research is essential to understand the complex interplay of mental health concerns and EDs among gender diverse adolescents and to inform appropriate interventions.

Pediatric Gender Care in Primary Care Settings in West Virginia: Provider Knowledge, Attitudes, and Educational Experiences.

PURPOSE: Pediatric primary care providers (PPCPs) often care for gender diverse youth (GDY), particularly in rural areas, but little is known about their relevant knowledge, attitudes, or educational experiences regarding caring for this population. METHODS: This study surveyed PPCPs throughout the rural state of West Virginia using an online survey assessing 1) demographics, 2) knowledge, 3) attitudes, and 4) educational experiences. Knowledge and attitude scores were calculated and proportion-tests and t-tests were used to compare these scores by PPCP characteristics including age, time in practice, and training background. RESULTS: In total, 51 PPCPs from throughout the state completed the survey and 82% had cared for GDY in the prior year. Younger providers (

Demographic Differences in Gender Dysphoria Diagnosis and Access to Gender-Affirming Care Among Adolescents.

Purpose: The goal of this article was to identify demographic differences in receipt of gender dysphoria (GD) diagnosis and access to gender-affirming care (GAC) among adolescents whose gender identity and/or pronouns differed from their sex assigned at birth. Methods: Data were from 2444 patients who were 13-17 years old and had a documented gender identity and/or pronouns that differed from their sex assigned at birth in the electronic health record. Adjusted logistic regression models explored associations between demographic characteristics (sex assigned at birth, gender identity, race and ethnicity, language, insurance type, rural status) and presence of GD diagnosis and having accessed GAC. Results: The average predicted probability (Pr) of having received a GD diagnosis was 0.62 (95% confidence interval [CI] = 0.60-0.63) and of having accessed GAC was 0.48 (95% CI = 0.46-0.50). Various significant demographic differences emerged. Notably, Black/African American youth were the least likely to have received a GD diagnosis (Pr = 0.43, 95% CI = 0.33-0.54) and accessed GAC (Pr = 0.32, 95% CI = 0.22-0.43). Although there were no significant differences in GD diagnosis by insurance type, youth using Medicaid, other government insurance, or self-pay/charity care were less likely to have accessed GAC compared with youth using commercial/private insurance. Conclusion: Results indicate significant differences in both receipt of GD diagnosis and accessing GAC by various demographic characteristics, particularly among Black/African American youth. Identification of these differences provides an opportunity to further understand potential barriers and promote more equitable access to GAC among adolescents who desire this care.

Guardian Reasons for Accessing Their Transgender and Gender-Diverse Adolescent's Patient Portal Account.

PURPOSE: To understand if and why guardians access their adolescent child's electronic health record patient portal account. METHODS: Guardians of transgender and gender-diverse adolescents completed a survey regarding patient portal use. Descriptive statistics were used to describe items related to guardian access to adolescent portal accounts. RESULTS: Of 82 respondents, 37.8% indicated they had used their child's login to access the patient portal. Most indicated they accessed their adolescent's account because their child asked them to do so. Other common reasons included being worried they might miss important health information and not realizing there was a difference between patient and proxy accounts. DISCUSSION: Results of this study provide a more detailed understanding regarding guardian access to adolescent patient portals. Findings can be used to inform adolescent patient portal design and enrollment practices that protect adolescent confidentiality.

Desire for Gender-Affirming Medical Care Before Age 18 in Transgender and Nonbinary Young Adults.

Purpose: We aimed to understand transgender and nonbinary (TNB) young adults' desire to receive gender-affirming medical care (GAMC) before age 18 and identify barriers and facilitators to receiving this care in adolescence. Methods: A cross-sectional survey was administered to TNB young adults presenting for care between ages 18 and 20 in 2023. Descriptive statistics characterized the sample, χ2 tests with post hoc pairwise comparisons identified differences in desire for gender-affirming medications, outness, and parental consent by gender identity and sex assigned at birth, and t-tests evaluated differences in barriers and facilitators to receiving care by outness to parents. Results: A total of 230 TNB respondents had complete data. Nearly all (94.3%) indicated they desired GAMC before age 18. Half (55.7%) of the respondents reported being out about their gender identity to a parent before age 18. Outness, discussing desire for GAMC, and asking for consent to receive GAMC from a parent were significantly more common among participants who identified as men compared to those who identified as women and among those assigned female at birth compared to those assigned male at birth. No such differences emerged when comparing nonbinary individuals to those who identified as men or women. Lack of parental willingness to consent for GAMC was cited as the primary contributor of not having received care in adolescence. Conclusions: Many TNB young adults desire GAMC in adolescence; however, lack of parental support is a key barrier to receiving this care, suggesting a need for more readily available resources for parents to support TNB adolescents.

Caregiver perspectives on receiving gender-affirming care with their transgender and gender diverse adolescents via telemedicine.

Telemedicine may help improve access to gender-affirming care for transgender and gender diverse (TGD) adolescents. Parents or guardians (i.e., caregivers) of TGD adolescents play a critical role in supporting TGD adolescents in accessing this care. The purpose of this study was to explore caregivers' perspectives regarding their adolescent receiving pediatric gender-affirming care via telemedicine to help providers and health systems optimize this modality for future care delivery. Caregivers (n=18) of TGD adolescents ages 14-17 participated in semi-structured, individual interviews that were transcribed and analyzed qualitatively. Caregivers cited participating in visits from their home environment, decreased anxiety, COVID safety, ability to have more family members attend, no transportation demands, and effective delivery of care as advantages of telemedicine. Disadvantages included dysphoria or discomfort with self-image, impersonal provider-patient interactions, video teleconferencing fatigue, difficulty with portal navigation, connectivity issues, and lack of privacy. Caregivers largely deferred to their child's preference regarding the choice of visit modality, but many reported a preference for the first to be conducted in-person, and follow-up and less complex visits via telemedicine. Health systems should consider these perspectives as they adapt telemedicine infrastructure to better meet the needs of patients and their families.

Mental Health Diagnoses and Suicidality Among Transgender Youth in Hospital Settings.

Purpose: The purpose of this analysis is to: 1) describe the most common mental health diagnoses in the emergency department (ED) and inpatient hospital settings among transgender and gender diverse (TGD) youth vs. matched controls and 2) evaluate if a gender-affirming hormone therapy (GAHT) or gonadotropin-releasing hormone agonist (GnRHa) prescription decreased the risk of suicidality within these settings. Methods: Using the PEDSnet dataset (years 2009-2019), TGD youth aged 8-18 (n = 3414, with a median age at last visit of 16.2 [14.4, 17.7] years, were propensity-score matched to controls (n = 13,628, age 16.6 [14.2, 18.3] years). Relative risks of the most common mental health diagnoses within ED and inpatient settings were calculated for TGD youth compared with controls. Recurrent time-to-event analysis was used to examine whether GAHT or GnRHa attenuated the risk of suicidality among subsamples of TGD youth. Results: TGD youth had a higher relative risk (95% confidence interval [CI]) of mental health diagnoses and suicidality in the ED (5.46 [4.71-6.33]) and inpatient settings (6.61 [5.28-8.28]) than matched controls. TGD youth prescribed GAHT had a 43.6% lower risk of suicidality (hazard ratio [HR] = 0.564 [95% CI 0.36-0.89]) compared with those never prescribed GAHT during our study period or before GAHT initiation. TGD youth who were prescribed GnRHa therapy had a nonstatistically significant reduction in ED or inpatient suicidality diagnoses compared with those never prescribed GnRHa (HR = 0.79 [0.47-1.31]). Conclusion: Although risk of mental health diagnoses and suicidality in ED and inpatient settings was high among TGD youth, a GAHT prescription was associated with a significant reduction in suicidality risk.

Estimating Transgender and Gender-Diverse Youth Populations in Health Systems and Survey Data.

OBJECTIVES: To identify and examine demographic variation in estimates of gender-diverse youth (GDY) populations from the PEDSnet learning health system network and the Youth Risk Behavior Survey (YRBS). METHODS: The PEDSnet sample included 14- to 17-years-old patients who had ≥2 encounters at a member institution before March 2022, with at least 1 encounter in the previous 18 months. The YRBS sample included pooled data from 14- to 17-year-old in-school youth from the 2017, 2019, and 2021 survey years. Adjusted logistic regression models tested for associations between demographic characteristics and gender dysphoria (GD) diagnosis (PEDSnet) or self-reported transgender identity (YRBS). RESULTS: The PEDSnet sample included 392 348 patients and the YRBS sample included 270 177 youth. A total of 3453 (0.9%) patients in PEDSnet had a GD diagnosis and 5262 (1.9%) youth in YRBS self-identified as transgender. In PEDSnet, adjusted logistic regression indicated significantly lower likelihood of GD diagnosis among patients whose electronic medical record-reported sex was male and among patients who identified as Asian, Black/African American, and Hispanic/Latino/a/x/e. In contrast, in the YRBS sample, only youth whose sex was male had a lower likelihood of transgender identity. CONCLUSIONS: GDY are underrepresented in health system data, particularly those whose electronic medical record-reported sex is male, and Asian, Black/African American, and Hispanic/Latino/a/x/e youth. Collecting more accurate gender identity information in health systems and surveys may help better understand the health-related needs and experiences of GDY and support the development of targeted interventions to promote more equitable care provision.

Leuprolide Acetate for Puberty Suppression in Transgender and Gender Diverse Youth: A Comparison of Subcutaneous Eligard Versus Intramuscular Lupron.

PURPOSE: To compare the efficacy of intramuscular Lupron and subcutaneous Eligard, two formulations of leuprolide, for puberty suppression in transgender and gender diverse (TGD) youth. METHODS: A retrospective chart review of TGD youth receiving Lupron or Eligard 22.5 mg every 3 months was conducted to determine hormone levels obtained 1 hour after an injection (1hrPost) and patient-reported clinical puberty suppression. RESULTS: Forty eight patients were analyzed: 33% assigned female at birth of which 25% were premenarchal, mean age at first injection 13.7 years, and 50% received concurrent gender affirming hormones. Of these, 13% received Lupron, 52% Eligard, and 35% initially received Lupron then transitioned to Eligard due to drug shortages. There were 55 incidents of 1hrPost levels, 42 after Eligard and 13 after Lupron. Clinical puberty suppression occurred in all patients; however, biochemical suppression occurred in 90% of Eligard and 69% of Lupron (p = .06). DISCUSSION: Eligard and Lupron were both effective in suppressing clinical puberty progression in our population of TGD youth, of which 50% were receiving concurrent gender affirming hormones.

Adolescent Perspectives on the Use of Telemedicine for Confidential Health Care: An Exploratory Mixed-Methods Study.

PURPOSE: Telemedicine can improve access to adolescent health care, but adolescents may experience barriers to accessing this care confidentially. Gender-diverse youth (GDY) may especially benefit from telemedicine through increased access to geographically limited adolescent medicine subspecialty care but may have unique confidentiality needs. In an exploratory analysis, we examined adolescents' perceived acceptability, preferences, and self-efficacy related to using telemedicine for confidential care. METHODS: We surveyed 12- to 17-year-olds following a telemedicine visit with an adolescent medicine subspecialist. Open-ended questions assessing acceptability of telemedicine for confidential care and opportunities to enhance confidentiality were qualitatively analyzed. Likert-type questions assessing preference for future use of telemedicine for confidential care and self-efficacy to complete components of telemedicine visits confidentially were summarized and compared across cisgender versus GDY. RESULTS: Participants (n = 88) included 57 GDY and 28 cisgender females. Factors affecting the acceptability of telemedicine for confidential care related to patient location, telehealth technology, adolescent-clinician relationships, and quality or experience of care. Perceived opportunities to protect confidentiality included using headphones, secure messaging, and prompting from clinicians. Most participants (53/88) were likely or very likely to use telemedicine for future confidential care, but self-efficacy for completing components of telemedicine visits confidentially varied by component. DISCUSSION: Adolescents in our sample were interested in using telemedicine for confidential care, but cisgender and GDY recognized threats to confidentiality that may reduce acceptability of telemedicine for these services. Clinicians and health systems should carefully consider youth's preferences and unique confidentiality needs to ensure equitable access, uptake, and outcomes of telemedicine.