Laboratory Changes During Gender-Affirming Hormone Therapy in Transgender Adolescents.

OBJECTIVES: Guidelines for monitoring of medications frequently used in the gender-affirming care of transgender and gender-diverse (TGD) adolescents are based on studies in adults or other medical conditions. In this study, we aimed to investigate commonly screened laboratory measurements in TGD adolescents receiving gender-affirming hormone therapy (GAHT). METHODS: TGD adolescents were recruited from 4 study sites in the United States before beginning GAHT. Hemoglobin, hematocrit, hemoglobin A1c, alanine transaminase, aspartate aminotransferase, prolactin, and potassium were abstracted from the medical record at baseline and at 6, 12, and 24 months after starting GAHT. RESULTS: Two-hundred and ninety-three participants (68% designated female at birth) with no previous history of gonadotropin-releasing hormone analog use were included in the analysis. Hemoglobin and hematocrit decreased in adolescents prescribed estradiol (-1.4 mg/dL and -3.6%, respectively) and increased in adolescents prescribed testosterone (+1.0 mg/dL and +3.9%) by 6 months after GAHT initiation. Thirteen (6.5%) participants prescribed testosterone had hematocrit > 50% during GAHT. There were no differences in hemoglobin A1c, alanine transaminase, or aspartate aminotransferase. There was a small increase in prolactin after 6 months of estradiol therapy in transfeminine adolescents. Hyperkalemia in transfeminine adolescents taking spironolactone was infrequent and transient if present. CONCLUSIONS: Abnormal laboratory results are rare in TGD adolescents prescribed GAHT and, if present, occur within 6 months of GAHT initiation. Future guidelines may not require routine screening of these laboratory parameters beyond 6 months of GAHT in otherwise healthy TGD adolescents.

Acute HIV Diagnosis After Initiation of Pre-exposure Prophylaxis in a Young Adult Patient: A Case Report.

Oral pre-exposure prophylaxis (PrEP) in the prevention of human immunodeficiency virus (HIV) infection is highly effective, yet the majority of sexually active adolescents and young adults (AYAs) at highest risk for HIV infection, particularly AYA males who have sex with males, have not been prescribed this medication. Provider hesitancy in prescribing PrEP to at-risk AYA patients is often associated with concerns about patient nonadherence and its effect on inducing HIV medication resistance. This case report has two aims. First, to outline the clinical course for an AYA patient prescribed PrEP for 3 months and then found to have HIV with an M184V resistance mutation and subsequently started on HIV treatment. And second, to illustrate how the benefits of PrEP initiation outweigh its risks by presenting clinical data on resistance patterns to PrEP medications. The patient eventually achieved viral suppression within 5 months of starting HIV treatment which has been sustained up to 2 years. This case illustrates that M184V resistance mutations, although rarely associated with PrEP, are unlikely to impact options for HIV treatment. Providers should recommend and prescribe oral PrEP to AYA patients at risk for HIV infection without concern for nonadherence leading to HIV medication resistance.

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.

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.

Psychosocial Functioning in Transgender Youth after 2 Years of Hormones.

BACKGROUND: Limited prospective outcome data exist regarding transgender and nonbinary youth receiving gender-affirming hormones (GAH; testosterone or estradiol). METHODS: We characterized the longitudinal course of psychosocial functioning during the 2 years after GAH initiation in a prospective cohort of transgender and nonbinary youth in the United States. Participants were enrolled in a four-site prospective, observational study of physical and psychosocial outcomes. Participants completed the Transgender Congruence Scale, the Beck Depression Inventory-II, the Revised Children's Manifest Anxiety Scale (Second Edition), and the Positive Affect and Life Satisfaction measures from the NIH (National Institutes of Health) Toolbox Emotion Battery at baseline and at 6, 12, 18, and 24 months after GAH initiation. We used latent growth curve modeling to examine individual trajectories of appearance congruence, depression, anxiety, positive affect, and life satisfaction over a period of 2 years. We also examined how initial levels of and rates of change in appearance congruence correlated with those of each psychosocial outcome. RESULTS: A total of 315 transgender and nonbinary participants 12 to 20 years of age (mean [±SD], 16±1.9) were enrolled in the study. A total of 190 participants (60.3%) were transmasculine (i.e., persons designated female at birth who identify along the masculine spectrum), 185 (58.7%) were non-Latinx or non-Latine White, and 25 (7.9%) had received previous pubertal suppression treatment. During the study period, appearance congruence, positive affect, and life satisfaction increased, and depression and anxiety symptoms decreased. Increases in appearance congruence were associated with concurrent increases in positive affect and life satisfaction and decreases in depression and anxiety symptoms. The most common adverse event was suicidal ideation (in 11 participants [3.5%]); death by suicide occurred in 2 participants. CONCLUSIONS: In this 2-year study involving transgender and nonbinary youth, GAH improved appearance congruence and psychosocial functioning. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).

The effect of gender-affirming hormone treatment on serum creatinine in transgender and gender-diverse youth: implications for estimating GFR.

BACKGROUND: Equations for estimated glomerular filtration rate (eGFR) based on serum creatinine include terms for sex/gender. For transgender and gender-diverse (TGD) youth, gender-affirming hormone (GAH) treatment may affect serum creatinine and in turn eGFR. METHODS: TGD youth were recruited for this prospective, longitudinal, observational study prior to starting GAH treatment. Data collected as part of routine clinical care were abstracted from the medical record. RESULTS: For participants designated male at birth (DMAB, N = 92), serum creatinine decreased within 6 months of estradiol treatment (mean ± SD 0.83 ± 0.12 mg/dL to 0.76 ± 0.12 mg/dL, p < 0.001); for participants designated female at birth (DFAB, n = 194), serum creatinine increased within 6 months of testosterone treatment (0.68 ± 0.10 mg/dL to 0.79 ± 0.11 mg/dL, p < 0.001). Participants DFAB treated with testosterone had serum creatinine similar to that of participants DMAB at baseline, whereas even after estradiol treatment, serum creatinine in participants DMAB remained higher than that of participants DFAB at baseline. Compared to reference groups drawn from the National Health and Nutritional Examination Survey, serum creatinine after 12 months of GAH was more similar when compared by gender identity than by designated sex. CONCLUSION: GAH treatment leads to changes in serum creatinine within 6 months of treatment. Clinicians should consider a patient's hormonal exposure when estimating kidney function via eGFR and use other methods to estimate GFR if eGFR based on serum creatinine is concerning.

Histrelin Implants for Suppression of Puberty in Youth with Gender Dysphoria: A Comparison of 50 mcg/Day (Vantas) and 65 mcg/Day (SupprelinLA).

Purpose: Development of incongruent secondary sex characteristics in transgender youth can intensify or trigger the onset of gender dysphoria. Guidelines from professional organizations recommend gonadotropin-releasing hormone agonists, including histrelin implants (Vantas and SupprelinLA) to suppress endogenous puberty. Although Vantas does not have a pediatric indication, it is anecdotally being used in pediatric gender centers throughout the United States because of its substantially lower cost. This retrospective study aimed to determine if both implants were effective in suppressing the hypothalamic-pituitary-gonadal axis in early-to-mid pubertal youth with gender dysphoria. Methods: Youth with gender dysphoria receiving care at the Center for Transyouth Health and Development at Children's Hospital Los Angeles (CHLA) or participants from an ongoing observational trial with a histrelin implant placed for pubertal suppression at Tanner stage 2 or 3 were included. Sex steroid (testosterone or estradiol) and gonadotropin measurements at baseline (T0) and then 2 to 12 months following implant placement (T1) were abstracted from medical records. Results: Of the 66 eligible participants, 52% were designated female at birth. Most participants were white (60.6%). Twenty participants (30.3%) had a Vantas implant and 46 (69.7%) had a SupprelinLA implant. Mean age of insertion was 11.3 years. Gonadotropin and sex steroid levels were significantly decreased at T1 (2-12 months after insertion of implant), with no differences between implants. Conclusion: These results indicate that both implants are effective in suppressing puberty in early-to-mid pubertal youth with gender dysphoria. These data may inform decisions about insurance coverage of Supprelin and/or Vantas for youth with gender dysphoria.

Psychosocial Characteristics of Transgender Youth Seeking Gender-Affirming Medical Treatment: Baseline Findings From the Trans Youth Care Study.

PURPOSE: This study aimed to characterize two developmental cohorts of transgender and nonbinary youth enrolled in the Trans Youth Care Network Study and describe their gender identity-related milestones and baseline mental health and psychosocial functioning. METHODS: Trans Youth Care participants were recruited from four pediatric academic medical centers in the U.S. before initiating medical treatment for gender dysphoria either with gonadotropin-releasing hormone agonists (GnRHa) or gender-affirming hormones (GAH). GnRHa cohort data were collected from youth and a parent; GAH cohort data were collected from youth only. RESULTS: A total of 95 youth were enrolled in the GnRHa cohort. Mean age was 11.22 years (standard deviation = 1.46), and the majority were white (52.6%) and designated male at birth (51.6%). Elevated depression symptoms were endorsed by 28.6% of GnRHa cohort youth, and 22.1% endorsed clinically significant anxiety. Approximately one fourth (23.6%) endorsed lifetime suicidal ideation, with 7.9% reporting a past suicide attempt. A total of 316 youth were enrolled in the GAH cohort. The mean age was 16.0 years (standard deviation = 1.88), and the majority were white (62%) and designated female at birth (64.9%). Elevated depression symptoms were endorsed by 51.3% of the GAH cohort, and 57.3% endorsed clinically significant anxiety. Two-thirds (66.6%) endorsed lifetime suicidal ideation, with 24.6% reporting a past suicide attempt. Life satisfaction was lower among both cohorts compared with population-based norms. CONCLUSIONS: GnRHa cohort youth appear to be functioning better from a psychosocial standpoint than GAH cohort youth, pointing to possible benefits of accessing gender-affirming treatment earlier in life.

The Impact of Chest Binding in Transgender and Gender Diverse Youth and Young Adults.

PURPOSE: There is a sparsity of information on chest binding practices among transmasculine and gender diverse people regardless of age and even less information pertaining to adolescents and young adults (AYA). The purpose of this study was to understand binding trends in AYA and to recognize how chest binding impacts chest dysphoria and life satisfaction. METHODS: Data were collected from eligible participants via a national online survey. In this national, cross-sectional study, 684 surveys from AYA aged 13-24 years compared those who bind and those who do not bind. RESULTS: Most participants reported learning to bind online and were not connected to any type of gender care or community center. Participants in the binding cohort reported less "misgendering" than the nonbinding cohort, and there was a significant correlation between increased chest dysphoria and lower scores on life satisfaction. CONCLUSIONS: This study provides insight into how AYA obtain information about binding and how binding impacts their life. It also indicates that transmasculine and gender diverse AYA will continue to bind their chest to benefit from the protective factors experienced with chest binding. This study also highlights the importance of improved education for medical providers as well as parents/guardians regarding binding to support those who experience chest dysphoria or discomfort.

Low Bone Mineral Density in Early Pubertal Transgender/Gender Diverse Youth: Findings From the Trans Youth Care Study.

CONTEXT: Transgender youth may initiate GnRH agonists (GnRHa) to suppress puberty, a critical period for bone-mass accrual. Low bone mineral density (BMD) has been reported in late-pubertal transgender girls before gender-affirming therapy, but little is known about BMD in early-pubertal transgender youth. OBJECTIVE: To describe BMD in early-pubertal transgender youth. DESIGN: Cross-sectional analysis of the prospective, observational, longitudinal Trans Youth Care Study cohort. SETTING: Four multidisciplinary academic pediatric gender centers in the United States. PARTICIPANTS: Early-pubertal transgender youth initiating GnRHa. MAIN OUTCOME MEASURES: Areal and volumetric BMD Z-scores. RESULTS: Designated males at birth (DMAB) had below-average BMD Z-scores when compared with male reference standards, and designated females at birth (DFAB) had below-average BMD Z-scores when compared with female reference standards except at hip sites. At least 1 BMD Z-score was < -2 in 30% of DMAB and 13% of DFAB. Youth with low BMD scored lower on the Physical Activity Questionnaire for Older Children than youth with normal BMD, 2.32 ±â€…0.71 vs. 2.76 ±â€…0.61 (P = 0.01). There were no significant deficiencies in vitamin D, but dietary calcium intake was suboptimal in all youth. CONCLUSIONS: In early-pubertal transgender youth, BMD was lower than reference standards for sex designated at birth. This lower BMD may be explained, in part, by suboptimal calcium intake and decreased physical activity-potential targets for intervention. Our results suggest a potential need for assessment of BMD in prepubertal gender-diverse youth and continued monitoring of BMD throughout the pubertal period of gender-affirming therapy.

Physiological and Metabolic Characteristics of a Cohort of Transgender and Gender-Diverse Youth in the United States.

PURPOSE: The purpose of this study was to describe baseline physical and laboratory characteristics of participants in the largest prospective study of transgender and gender-diverse (TGD) youth in the United States. METHODS: Participants were recruited from four clinics which specialize in the care of TGD youth before starting either GnRH analogs for pubertal suppression or gender-affirming hormone treatment. Anthropometric and laboratory measurements were abstracted from the medical chart. Baseline characteristics including height, weight, body mass index, blood pressure, and laboratory measurements were compared with those of age-matched National Health and Nutritional Examination Survey comparison group. RESULTS: Seventy-eight TGD youth with a median age of 11 years (range 8-14 years) were recruited before pubertal suppression, of whom 41 (53%) were designated male at birth, and 296 participants with a median age of 16 years (range 12-20 years) were recruited before beginning gender-affirming hormones, of whom 99 (33%) were designated male at birth. The mean high-density lipoprotein cholesterol was lower in the study participants when compared with that of National Health and Nutritional Examination Survey participants (50.6 ± 12.3 mg/dL vs. 53.3 ± 13.3 mg/dL, p = .001). Otherwise, the study cohorts were similar in terms of body mass index, proportion of overweight and obesity, blood pressure, and baseline laboratory variables. CONCLUSIONS: Before starting gender-affirming treatment, TGD youth are physiologically similar to the general population of children and adolescents in the United States, with the exception of slightly lower high-density lipoprotein cholesterol. Evaluation of this cohort over time will define the physiological effects of pubertal blockade and gender-affirming hormone treatment.

Long-term Puberty Suppression for a Nonbinary Teenager.

Many transgender and gender-diverse people have a gender identity that does not conform to the binary categories of male or female; they have a nonbinary gender. Some nonbinary individuals are most comfortable with an androgynous gender expression. For those who have not yet fully progressed through puberty, puberty suppression with gonadotrophin-releasing hormone agonists can support an androgynous appearance. Although such treatment is shown to ameliorate the gender dysphoria and serious mental health issues commonly seen in transgender and gender-diverse young people, long-term use of puberty-suppressing medications carries physical health risks and raises various ethical dilemmas. In this Ethics Rounds, we analyze a case that raised issues about prolonged pubertal suppression for a patient with a nonbinary gender.

Creating the Trans Youth Research Network: A Collaborative Research Endeavor.

Purpose: This article outlines the process of establishing the Trans Youth Care Research Network, composed of four academic clinics providing care for transgender and gender-diverse (TGD) youth. The Network was formed to design and implement research studies to better understand physiologic and psychosocial outcomes of gender-affirming medical care among TGD youth. Methods: Formed in response to both the Institute of Medicine's report recommendation for an increase of data concerning sexual and gender minority populations and a transgender-specific NIH program announcement, The Center for Transyouth Health and Development at Children's Hospital Los Angeles, the Gender Management Service at Boston Children's Hospital, the Child and Adolescent Gender Center Clinic at Benioff Children's Hospital in San Francisco, and the Gender and Sex Development Program at Lurie Children's Hospital of Chicago established a collaborative research network that subsequently designed a longitudinal observational study of TGD youth undergoing medical interventions to address gender dysphoria. Results: Two cohorts, youth starting puberty blockers and youth starting gender-affirming hormones, are participating. Psychosocial measures that span multiple domains of mental and behavioral health are collected from youth and parents. Physiologic data are abstracted from patient's charts. Baseline and follow-up data of this large cohort will be disseminated through conferences, abstracts, posters, and articles. Conclusion: Since initiation of funding in 2015, a total of 497 participants have been enrolled in TYC across the four sites; gonadotropin releasing hormone analogs (GnRHa) cohort youth (n=93), GnRHa cohort parents (n=93), and gender affirming hormone cohort youth (n=311). As the network moves toward data dissemination, its lessons learned have helped strengthen the current study, as well as inform future endeavors in this field.

Impact of Early Medical Treatment for Transgender Youth: Protocol for the Longitudinal, Observational Trans Youth Care Study.

BACKGROUND: Transgender children and adolescents (ie, those who experience incongruence between assigned sex at birth and internal gender identity) are poorly understood and an understudied population in the United States. Since 2008, medical care for transgender youth has generally followed guidelines developed by professional consensus, given the paucity of empirical research, particularly in the US setting. OBJECTIVE: The objective of this research was to provide evidence-based data to inform clinical care for transgender youth. The study aims (1) to evaluate the impact of gonadotropin-releasing hormone agonists administered for puberty suppression on mental health, psychological well-being, and metabolic and physiologic parameters including bone health in a cohort of children and adolescents (Tanner stages 2-4) with gender dysphoria, comparing baseline and follow-up assessments, and (2) to determine the impact of gender-affirming hormones (eg, estradiol and testosterone) administered for phenotypic gender transition on mental health, psychological well-being, and metabolic and physiologic parameters in a cohort of adolescents with gender dysphoria, comparing baseline and follow-up assessments. METHODS: The study uses a longitudinal observational design to examine the outcomes of existing medical treatment protocols for gender dysphoria in two distinct cohorts: youth initiating puberty suppression and youth pursuing a phenotypic gender transition. Data on routine anthropometric and physiologic parameters are collected through chart abstraction, questionnaires, and research interviews in the 24-month study period. Audio computer-assisted self-interview and individual interview survey instruments are used to collect demographic, mental health, psychosocial, and behavioral data from parents and youth in the blocker cohort and only from youth in the gender-affirming hormone cohort at baseline and 6, 12, 18, and 24 months. RESULTS: Participant recruitment commenced in July 2016, and enrollment was completed in September 2018. A total of 90 participants were enrolled in the blocker cohort and 301 participants were enrolled in the gender-affirming hormone cohort. Findings based on baseline data are expected to be submitted for publication in 2019. CONCLUSIONS: This longitudinal, observational study is collecting critical data on the existing models of care for transgender youth that have been used in clinical settings for close to a decade, although with limited empirical research to support them. This research is a direct response to the Institute of Medicine report calling for such studies as well as the needs of clinicians and patients. Results from this study have the potential to significantly impact the medical and mental health services provided to transgender youth by making available rigorous scientific evidence on the impact and safety of early treatment based on the sexual development stage. Ultimately, we aim to understand if early medical intervention reduces the health disparities well known to disproportionately affect transgender individuals across their lifespan. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/14434.

The Impact of Cell Phone Support on Psychosocial Outcomes for Youth Living with HIV Nonadherent to Antiretroviral Therapy.

Mobile health interventions to promote adherence to antiretroviral therapy among adolescents and young adults living with HIV represent a promising strategy. This pilot study (N = 37) evaluated the psychosocial impacts of an efficacious adherence intervention, cell phone support (CPS). Participants receiving CPS reported significant decreases in perceived stress, depression, and illicit substance use, and increases in self-efficacy during at least one study assessment period, in comparison to participants receiving usual care. Future research using a larger sample should test for mediators of treatment efficacy to further characterize how cell phone interventions impact adherence.