Pubertal Suppression in Early Puberty Followed by Testosterone Mildly Increases Final Height in Transmasculine Youth.

Context: Treatment for transmasculine youth (TMY) can involve testosterone treatment and is sometimes preceded by gonadotropin-releasing hormone agonist (GnRHa) treatment for puberty blockade. GnRHas can increase final height in birth-assigned females with central precocious puberty. Maximizing final adult height (FAH) is an important outcome for many TMY. Objective: Our objective was to determine how GnRHa treatment before testosterone impacts FAH. Methods: Retrospective cohort study at 5 US transgender health clinics. Participants were 32 TMY treated with GnRHas in early to midpuberty before testosterone (GnRHa + T group) and 62 late/postpubertal TMY treated with testosterone only (T-only group). Results: The difference between FAH minus midparental target height (MPTH) was +2.3 ± 5.7 cm and -2.2 ± 5.6 cm in the GnRHa + T and T-only groups, respectively (P < .01). In the GnRHa + T group, FAH was 1.8 ± 3.4 cm greater than predicted adult height (PAH) (P < .05) and FAH vs initial height (IH) z-score was 0.5 ± 1.2 vs 0.16 ± 1.0 (P < .05). After adjusting for patient characteristics, each additional month of GnRHa monotherapy increased FAH by 0.59 cm (95% CI 0.31, 0.9 cm), stage 3 breast development at start of GnRHa was associated with 6.5 cm lower FAH compared with stage 2 (95% CI -10.43, -2.55), and FAH was 7.95 cm greater in the GnRHa + T group than in T-only group (95% CI -10.85, -5.06). Conclusion: Treatment with GnRHa in TMY in early puberty before testosterone increases FAH compared with MPTH, PAH, IH, and TMY who only received testosterone in late/postpuberty. TMY considering GnRHas should be counseled that GnRHas may mildly increase their FAH if started early.

Dermatologic needs of transgender and gender diverse youth: A retrospective cohort study.

Several dermatologic concerns are known to disproportionally affect transgender and gender-diverse (TGD) adults, but little is known about dermatologic conditions in TGD youth. This study assesses the prevalence of acne, androgenic alopecia, scarring from gender-affirming procedures, and eczema in pediatric TGD patients seen at Boston Children's Hospital between April 2021 and April 2022. The results demonstrate that, for TGD youth, the studied dermatologic concerns are common, referral rates to dermatology are low, and acne is significantly associated with testosterone use. Future studies should examine additional dermatologic concerns and barriers to accessing dermatologic care for this historically underserved population.

Gender-Affirming Surgery in Adolescents and Young Adults: A Review of Ethical and Surgical Considerations.

BACKGROUND: The number of transgender adolescents seeking gender-affirming surgery (GAS) in increasing. Surgical care of the adolescent transgender patient is associated with several unique technical, legal, and ethical factors. The authors present a review of the current literature on gender-affirming surgery for individuals under the age of legal majority and propose directions for future research. METHODS: A scoping review of recent literature was performed to assess evidence on gender-affirming surgery in individuals under the age of legal majority. Articles were included that examined either ethical or technical factors unique to pediatric GAS. Study characteristics and conclusions were analyzed in conjunction with expert opinion. RESULTS: Twelve articles were identified that met inclusion criteria. Ten of these articles discussed ethical challenges in adolescent GAS, seven discussed legal challenges, and five discussed technical challenges. Ethical discussions focused on the principles of beneficence, nonmaleficence, and autonomy. Legal discussions centered on informed consent and insurance coverage. Technical discussions focused on the effects of puberty blockade on natal tissue. CONCLUSIONS: Surgical care of the adolescent transgender patient involves important ethical, legal, and technical considerations that must be addressed by the clinical team. As the population of individuals seeking GAS after puberty blockade increases, future research is needed describing functional and psychosocial outcomes in these individuals.

The Evolution of Adolescent Gender-Affirming Care: An Historical Perspective.

While individuals have demonstrated gender diversity throughout history, the use of medication and/or surgery to bring a person's physical sex characteristics into alignment with their gender identity is relatively recent, with origins in the first half of the 20th century. Adolescent gender-affirming care, however, did not emerge until the late 20th century and has been built upon pioneering work from the Netherlands, first published in 1998. Since that time, evolving protocols for gender-diverse adolescents have been incorporated into clinical practice guidelines and standards of care published by the Endocrine Society and World Professional Association for Transgender Health, respectively, and have been endorsed by major medical and mental health professional societies around the world. In addition, in recent decades, evidence has continued to emerge supporting the concept that gender identity is not simply a psychosocial construct but likely reflects a complex interplay of biological, environmental, and cultural factors. Notably, however, while there has been increased acceptance of gender diversity in some parts of the world, transgender adolescents and those who provide them with gender-affirming medical care, particularly in the USA, have been caught in the crosshairs of a culture war, with the risk of preventing access to care that published studies have indicated may be lifesaving. Despite such challenges and barriers to care, currently available evidence supports the benefits of an interdisciplinary model of gender-affirming medical care for transgender/gender-diverse adolescents. Further long-term safety and efficacy studies are needed to optimize such care.

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.

Growth, growth potential, and influences on adult height in the transgender and gender-diverse population.

The sexually dimorphic trait of height is one aspect of the experience of transgender and gender-diverse (TGD) individuals that may influence their gender dysphoria and satisfaction with their transition. In this article, we have reviewed the current knowledge of the factors that contribute to one's final adult height and how it might be affected in TGD youth who have not experienced their gonadal puberty in the setting of receiving gonadotropin-releasing hormone analog (GnRHa) and gender-affirming hormonal treatment. Additional research is needed to characterize the influence of growth and final adult height on the lived experience of TGD youth and adults and how to best assess their growth, predict their final adult height, and how medical transition can be potentially modified to help them meet their goals.

Greater Than Expected Prevalence of Type 1 Diabetes Mellitus Found in an Urban Gender Program.

The prevalence of type 1 diabetes mellitus among transgender and gender diverse (TGD) youth is nearly five times higher than in the general pediatric population (9.9 per 1000 people vs. 1.93 per 1000 people). We hypothesize that minority stress experienced by TGD youth may lead to a higher prevalence of diabetes.

Pubertal Suppression for Transgender Youth and Risk of Suicidal Ideation.

BACKGROUND AND OBJECTIVES: Gonadotropin-releasing hormone analogues are commonly prescribed to suppress endogenous puberty for transgender adolescents. There are limited data regarding the mental health benefits of this treatment. Our objective for this study was to examine associations between access to pubertal suppression during adolescence and adult mental health outcomes. METHODS: Using a cross-sectional survey of 20 619 transgender adults aged 18 to 36 years, we examined self-reported history of pubertal suppression during adolescence. Using multivariable logistic regression, we examined associations between access to pubertal suppression and adult mental health outcomes, including multiple measures of suicidality. RESULTS: Of the sample, 16.9% reported that they ever wanted pubertal suppression as part of their gender-related care. Their mean age was 23.4 years, and 45.2% were assigned male sex at birth. Of them, 2.5% received pubertal suppression. After adjustment for demographic variables and level of family support for gender identity, those who received treatment with pubertal suppression, when compared with those who wanted pubertal suppression but did not receive it, had lower odds of lifetime suicidal ideation (adjusted odds ratio = 0.3; 95% confidence interval = 0.2-0.6). CONCLUSIONS: This is the first study in which associations between access to pubertal suppression and suicidality are examined. There is a significant inverse association between treatment with pubertal suppression during adolescence and lifetime suicidal ideation among transgender adults who ever wanted this treatment. These results align with past literature, suggesting that pubertal suppression for transgender adolescents who want this treatment is associated with favorable mental health outcomes.

Complex Medical Decision-Making for a Trans-Feminine Youth with a BRCA1 Mutation.

The risks of being a cisgender BRCA1/BRCA2 mutation carrier (BRCA1+/BRCA2+) are well documented, and recommendations to mitigate cancer risk in BRCA+ cisgender women are clear. However, there is a lack of guidance for BRCA+ transgender women. In this article, we discuss the case of a trans-feminine youth who presented at a gender clinic for medications for pubertal suppression and was identified as a BRCA1 mutation carrier. We explore principles of bioethics to consider when the potential risks of treatment are unclear. We discuss the unknown risks for a trans-feminine youth with a BRCA1 mutation and the potential benefits and risks of treatment options.

Induction and Maintenance of Amenorrhea in Transmasculine and Nonbinary Adolescents.

The treatment of persistent uterine bleeding in those patients who identify as transmasculine or nonbinary is often straightforward, but can be difficult in a subset of patients. This article reviews the physiology of the normal menstrual cycle and the hormonal influences on the endometrium, and then explores options for the treatment of persistent bleeding for people both already on testosterone and for those who are either not ready for or who do not desire testosterone.

Overrepresentation of Adopted Adolescents at a Hospital-Based Gender Dysphoria Clinic.

Purpose: We have noted a greater than expected prevalence of adopted children presenting to our multidisciplinary gender program for evaluation of gender dysphoria. Methods: A retrospective review of 184 patient charts was conducted to assess the prevalence of adopted children presenting to gender clinic. Results: Fifteen of 184 patients seen were living with adoptive families (8.2%). This is significantly higher than expected based on U.S. census data. Conclusion: Adopted children are referred to our gender program more than would be expected based on the percentage of adopted children in our state and the United States at large. This may be due to a true increased risk of gender dysphoria in adopted children, or could represent presentation bias. Gender programs should be prepared to provide assessments for adopted children. Further work is needed to understand the relationship between adopted status and gender development.

Generic and brand-name L-thyroxine are not bioequivalent for children with severe congenital hypothyroidism.

CONTEXT: In the United States, generic substitution of levothyroxine (L-T(4)) by pharmacists is permitted if the formulations are deemed to be bioequivalent by the Federal Drug Administration, but there is widespread concern that the pharmacokinetic standard used is too insensitive. OBJECTIVE: We aimed to evaluate the bioequivalence of a brand-name L-T(4) (Synthroid) and an AB-rated generic formulation (Sandoz, Princeton, NJ) in children with severe hypothyroidism. DESIGN: This was a prospective randomized crossover study in which patients received 8 weeks of one L-T(4) formulation followed by 8 weeks of the other. SETTING: The setting was an academic medical center. PATIENTS: Of 31 children with an initial serum TSH concentration >100 mU/L, 20 had congenital hypothyroidism (CH), and 11 had autoimmune thyroiditis. MAIN OUTCOME MEASURES: The primary endpoint was the serum TSH concentration. Secondary endpoints were the free T(4) and total T(3) concentrations. RESULTS: The serum TSH concentration was significantly lower after 8 weeks of Synthroid than after generic drug (P = .002), but thyroid hormone levels did not differ significantly. Subgroup analysis revealed that the difference in TSH was restricted to patients with CH (P = .0005). Patients with CH required a higher L-T(4) dose (P < .0004) and were younger (P = .003) but were not resistant to thyroid hormone; 15 of 16 CH patients had severe thyroid dysgenesis or agenesis on imaging. The response to generic vs brand-name preparation remained significant when adjusted for age. CONCLUSIONS: Synthroid and an AB-rated generic L-T(4) are not bioequivalent for patients with severe hypothyroidism due to CH, probably because of diminished thyroid reserve. It would therefore seem prudent not to substitute L-T(4) formulations in patients with severe CH, particularly in those <3 yr of age. Our results may have important implications for other severely hypothyroid patients in whom precise titration of L-T(4) is necessary.

Severe maternal hypothyroidism corrected prior to the third trimester is associated with normal cognitive outcome in the offspring.

BACKGROUND: Concern about potential harmful effects of early maternal hypothyroidism (MH) on fetal brain development has led to calls for universal screening early in, or even before, pregnancy. However, evidence in humans that adverse effects are irreversible if thyroid hormone replacement is initiated after the first trimester is limited. Severe MH due to thyrotropin (TSH) receptor blocking antibodies (Abs) is associated with profound cognitive delay in the offspring if MH is untreated or inadequately treated; here, we sought to determine the outcome if treatment is given in early pregnancy. METHODS: We identified three women who had TSH receptor blocking Ab-induced MH during pregnancy and were treated with L-thyroxine (L-T4), starting at 27 weeks, 5 weeks, and the first month of gestation. The corresponding pretreatment serum TSH levels in the two women in whom data were available were 68 and 65 mU/L, falling to 6 mU/L at 25 and 24 weeks of gestation, respectively. The third woman with MH required 0.5 mg of L-T4 to normalize her thyroid hormone levels by 4 months of gestation. Their infants were also treated with L-T4 after neonatal screening that identified congenital hypothyroidism (CH). Neuropsychological tests to assess intelligence, language, memory, and visual-motor performance were administered to these three infants at 5.4 years of age (range 5.1-6.1) and to three sibling controls at 6.8 years (range 9.1-3.0). RESULTS: Children born after MH had average or above average results on all parameters. Comparative scores of the neuropsychological tests in sibling pairs for full-scale intelligence quotient (IQ) and performance IQ were variable; some scores were higher and some were lower in CH children. CONCLUSIONS: Although the findings do not exclude a subtle impact of MH during early gestation on intellectual function, the normal cognitive outcome despite overt MH should provide data with which to counsel mothers who have overt hypothyroidism early in pregnancy. Aggressive thyroid hormone replacement as soon as possible is important, but early termination of the pregnancy because of fear that the baby will have significant cognitive delay is not warranted.