Biopsychosocial Assessments for Pubertal Suppression to Treat Adolescent Gender Dysphoria.

Transgender and gender diverse (TGD) adolescents are those whose gender identity is incongruent with societal expectations based on their sex assigned at birth.1 Some TGD adolescents may meet criteria for gender dysphoria, which requires at least 6 months of psychological distress related to gender incongruence.1 Such adolescents may seek pubertal suppression with a gonadotropin-releasing hormone agonist (GnRHa).1 GnRHa temporarily and reversibly suppress endogenous puberty, allowing adolescents to engage with care without puberty-related psychological distress.2 Most patients treated with GnRHa proceed to treatment with gender-affirming hormones (eg, estrogen or testosterone to induce puberty that aligns with their gender identity), whereas a small number choose to stop GnRHa treatment, allowing endogenous puberty to proceed.2 Longitudinal cohort and cross-sectional studies link GnRHa treatment to improved mental health outcomes, when provided in accordance with clinical guidelines.2.

The Importance of Non-Probability Samples in Minority Health Research: Lessons Learned from Studies of Transgender and Gender Diverse Mental Health.

Non-probability sampling methods utilize nonrandom research participant selection, which may generate study samples that are not representative of the general population. Non-probability sample studies are often regarded as inferior due to uncertainty about their generalizability and external validity. In reality, non-probability sampling offers advantages that make this method particularly valuable for minority health research. In this perspective article, we review the strengths and limitations of probability and non-probability samples, examining three landmark survey studies used to study transgender and gender diverse mental health. We conclude that both types of studies provide important and actionable data about mental health inequities experienced by minority populations.

Correction: Access to gender-affirming hormones during adolescence and mental health outcomes among transgender adults.

[This corrects the article DOI: 10.1371/journal.pone.0261039.].

Age of Realization and Disclosure of Gender Identity Among Transgender Adults.

PURPOSE: The "rapid-onset gender dysphoria" (ROGD) hypothesis theorized, based on a parent-report survey, a distinct and more transient form of gender dysphoria in which individuals purportedly come to understand themselves as transgender and/or gender diverse (TGD) suddenly during adolescence. This study evaluated components of ROGD by (1) estimating the prevalence among TGD adults of first realizing one's TGD identity after childhood (i.e., after the onset of puberty), and (2) assessing the median time between realizing one's gender identity and disclosing this to someone else. METHODS: We conducted a secondary analysis of the 2015 US Transgender Survey, a survey of 27,715 TGD adults in the United States. Participants were asked the age at which they first realized their gender identity was different than societal expectations based on their sex assigned at birth and grouped by "childhood realization" (ages ≤ 10 years) and "later realization" (ages > 10). They were also asked the age at which they first shared their gender identity with another person. RESULTS: Of 27,497 participants, 40.8% reported "later realization" of TGD identities. Within the "childhood realization" group, the median age of sharing one's gender identity with another person was 20. In this group, the median time between realization of one's gender identity and sharing this with another person was 14 years. DISCUSSION: A substantial proportion of TGD adults reported realizing their gender identity was different from societal expectations based on their sex assigned at birth during adolescence or later. Several years typically elapsed between participants' TGD identity realization and sharing this with another person. The results of this study do not support the ROGD hypothesis.

Sex Assigned at Birth Ratio Among Transgender and Gender Diverse Adolescents in the United States.

OBJECTIVE: Representatives of some pediatric gender clinics have reported an increase in transgender and gender diverse (TGD) adolescents presenting for care who were assigned female sex at birth (AFAB) relative to those assigned male sex at birth (AMAB). These data have been used to suggest that youth come to identify as TGD because of "social contagion," with the underlying assumption that AFAB youth are uniquely vulnerable to this hypothesized phenomenon. Reported changes in the AMAB:AFAB ratio have been cited in recent legislative debates regarding the criminalization of gender-affirming medical care. Our objective was to examine the AMAB:AFAB ratio among United States TGD adolescents in a larger and more representative sample than past clinic-recruited samples. METHODS: Using the 2017 and 2019 Youth Risk Behavior Survey across 16 states that collected gender identity data, we calculated the AMAB:AFAB ratio for each year. We also examined the rates of bullying victimization and suicidality among TGD youth compared with their cisgender peers. RESULTS: The analysis included 91 937 adolescents in 2017 and 105 437 adolescents in 2019. In 2017, 2161 (2.4%) participants identified as TGD, with an AMAB:AFAB ratio of 1.5:1. In 2019, 1640 (1.6%) participants identified as TGD, with an AMAB:AFAB ratio of 1.2:1. Rates of bullying victimization and suicidality were higher among TGD youth when compared with their cisgender peers. CONCLUSION: The sex assigned at birth ratio of TGD adolescents in the United States does not appear to favor AFAB adolescents and should not be used to argue against the provision of gender-affirming medical care for TGD adolescents.

Legislation restricting gender-affirming care for transgender youth: Politics eclipse healthcare.

In the past two years, in 25 US states, bills have been introduced to restrict access to gender-affirming medical care for minors. Some have already become law. We show how these bills, while purporting to "protect" trans youth, are really an assault on their ability, along with their parents' and physicians', to make healthcare choices and to receive medically necessary care. We discuss the evidence-based guidelines for the care of these patients, the positions taken by major medical societies against these bills, and the landscape of legal challenges that are being brought against these enacted laws.

Access to gender-affirming hormones during adolescence and mental health outcomes among transgender adults.

OBJECTIVE: To examine associations between recalled access to gender-affirming hormones (GAH) during adolescence and mental health outcomes among transgender adults in the U.S. METHODS: We conducted a secondary analysis of the 2015 U.S. Transgender Survey, a cross-sectional non-probability sample of 27,715 transgender adults in the U.S. Using multivariable logistic regression adjusting for potential confounders, we examined associations between access to GAH during early adolescence (age 14-15), late adolescence (age 16-17), or adulthood (age ≥18) and adult mental health outcomes, with participants who desired but never accessed GAH as the reference group. RESULTS: 21,598 participants (77.9%) reported ever desiring GAH. Of these, 8,860 (41.0%) never accessed GAH, 119 (0.6%) accessed GAH in early adolescence, 362 (1.7%) accessed GAH in late adolescence, and 12,257 (56.8%) accessed GAH in adulthood. After adjusting for potential confounders, accessing GAH during early adolescence (aOR = 0.4, 95% CI = 0.2-0.6, p < .0001), late adolescence (aOR = 0.5, 95% CI = 0.4-0.7, p < .0001), or adulthood (aOR = 0.8, 95% CI = 0.7-0.8, p < .0001) was associated with lower odds of past-year suicidal ideation when compared to desiring but never accessing GAH. In post hoc analyses, access to GAH during adolescence (ages 14-17) was associated with lower odds of past-year suicidal ideation (aOR = 0.7, 95% CI = 0.6-0.9, p = .0007) when compared to accessing GAH during adulthood. CONCLUSION: Access to GAH during adolescence and adulthood is associated with favorable mental health outcomes compared to desiring but not accessing GAH.

Chronic UV radiation-induced RORγt+ IL-22-producing lymphoid cells are associated with mutant KC clonal expansion.

Chronic ultraviolet (UV) radiation exposure is the greatest risk factor for cutaneous squamous cell carcinoma (cSCC) development, and compromised immunity accelerates this risk. Having previously identified that epidermal Langerhans cells (LC) facilitate the expansion of UV-induced mutant keratinocytes (KC), we sought to more fully elucidate the immune pathways critical to cutaneous carcinogenesis and to identify potential targets of intervention. Herein, we reveal that chronic UV induces and LC enhance a local immune shift toward RORγt+ interleukin (IL)-22/IL-17A-producing cells that occurs in the presence or absence of T cells while identifying a distinct RORγt+ Sca-1+ CD103+ ICOS+ CD2+/- CCR6+ intracellular CD3+ cutaneous innate lymphoid cell type-3 (ILC3) population (uvILC3) that is associated with UV-induced mutant KC growth. We further show that mutant KC clone size is markedly reduced in the absence of RORγt+ lymphocytes or IL-22, both observed in association with expanding KC clones, and find that topical application of a RORγ/γt inhibitor during chronic UV exposure reduces local expression of IL-22 and IL-17A while markedly limiting mutant p53 KC clonal expansion. We implicate upstream Toll-like receptor signaling in driving this immune response to chronic UV exposure, as MyD88/Trif double-deficient mice also show substantially reduced p53 island number and size. These data elucidate key immune components of chronic UV-induced cutaneous carcinogenesis that might represent targets for skin cancer prevention.

Timing of Social Transition for Transgender and Gender Diverse Youth, K-12 Harassment, and Adult Mental Health Outcomes.

PURPOSE: Many transgender and gender diverse (TGD) youth undergo a social transition in which they change their gender expression to align with their gender identity. Our objective was to examine associations between timing of social transition (during the prepubertal childhood period, adolescence, or adulthood) and adult mental health outcomes. METHODS: We conducted a secondary analysis of the 2015 U.S. Transgender Survey, a cross-sectional nonprobability survey of 27,715 TGD adults in the United States. Based on self-reports, participants were categorized as having undergone social transition during childhood (ages 3-9 years), adolescence (ages 10-17 years), or adulthood (ages ≥18 years). Using multivariable logistic regression, we examined associations between timing of social transition and adult mental health outcomes. RESULTS: After adjusting for demographic and potential confounding variables, childhood social transition was associated with lower odds of lifetime marijuana use (adjusted odds ratio .7, 95% confidence interval = .5-.8, p < .0001) when compared with adult social transition. Before adjusting for K-12 harassment based on gender identity, adolescent social transition was associated with adverse mental health outcomes, including greater odds of lifetime suicide attempts when compared with adult social transition (adjusted odds ratio 1.3, 95% confidence interval = 1.1-1.7, p = .004). These associations were no longer significant after further adjusting for K-12 harassment. CONCLUSIONS: Although past research has shown TGD youth who undergo social transition have favorable mental health outcomes in the short term, they may have worse mental health in adulthood if not protected from K-12 harassment based on gender identity. It is the responsibility of clinicians to emphasize the importance of adolescents having safe and affirming social environments.

Factors Leading to "Detransition" Among Transgender and Gender Diverse People in the United States: A Mixed-Methods Analysis.

Purpose: There is a paucity of data regarding transgender and gender diverse (TGD) people who "detransition," or go back to living as their sex assigned at birth. This study examined reasons for past detransition among TGD people in the United States. Methods: A secondary analysis was performed on data from the U.S. Transgender Survey, a cross-sectional nonprobability survey of 27,715 TGD adults in the United States. Participants were asked if they had ever detransitioned and to report driving factors, through multiple-choice options and free-text responses. A mixed-methods approach was used to analyze the data, creating qualitative codes for free-text responses and applying summative content analysis. Results: A total of 17,151 (61.9%) participants reported that they had ever pursued gender affirmation, broadly defined. Of these, 2242 (13.1%) reported a history of detransition. Of those who had detransitioned, 82.5% reported at least one external driving factor. Frequently endorsed external factors included pressure from family and societal stigma. History of detransition was associated with male sex assigned at birth, nonbinary gender identity, bisexual sexual orientation, and having a family unsupportive of one's gender identity. A total of 15.9% of respondents reported at least one internal driving factor, including fluctuations in or uncertainty regarding gender identity. Conclusion: Among TGD adults with a reported history of detransition, the vast majority reported that their detransition was driven by external pressures. Clinicians should be aware of these external pressures, how they may be modified, and the possibility that patients may once again seek gender affirmation in the future.

Geosocial Networking Application Use Among Sexual Minority Adolescents.

The following clinical scenario is a composite case that illustrates clinically important phenomena based on several patients.