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Controversy exists over puberty suppression (PS) in adolescents with gender dysphoria (GD). PS is preferentially achieved with GnRH analogues. By preventing the development of secondary sex characteristics, PS may improve psychological functioning, well-being, quality of life, emotional and behavioral (especially internalizing) problems and depressive symptoms, thus decreasing suicidality. PS can also extend the diagnostic period and give transgender adolescents time to explore their gender identity. GnRHa may also decrease the need for feminization/masculinization surgery. However, 2-year treatment with GnRHa may result in bone mass accrual retardation (decrease in BMD/BMAD z-scores), growth velocity deceleration (decrease in height SDS), increase in fat mass, temporary pause in oocyte/sperm maturation. The most common side effects of GnRHa are hot flashes, mood fluctuations, fatigue and headache. They are usually mild and rarely lead to GnRHa discontinuation. Based on current scientific evidence, PS could be recommended to adolescents who meet the diagnostic criteria of gender incongruence (by DSM-5 and/or ICD-11) and have long-lasting intense GD, which aggravates with puberty onset. Before initiating PS, possible mental issues should be addressed and informed consent (by the adolescent/ caregiver) should be given, after counseling on probable reproductive effects of GnRHa. GnRHa can only be started after the adolescent has entered Tanner stage 2. Nevertheless, published studies are inadequate in number, small in size, uncontrolled and relatively short-term, so that it is difficult to draw safe conclusions on efficacy and safety of GnRHa. Large long-term randomized controlled trials are needed to expand knowledge on this controversial issue and elucidate the benefit and risks of PS. [ABSTRACT FROM AUTHOR]

PurposeHistrelin implant (HI) is a gonadotropin-releasing hormone agonist (GnRHa) used in pediatrics to treat central precocious puberty (CPP) and for pubertal suppression in transgender/non-binary (TG/NB) youth with gender dysphoria. HI is designed for annual removal/replacement; however, effectiveness has been reported beyond 1 year. No previous study has assessed prolonged HI use in TG/NB youth. We hypothesize that HI is effective >12 months in TG/NB youth as described in children with CPP.MethodsThis retrospective, two-center study included 49 subjects with 50 HI retained ≥17 months, in TG/NB (42) and CPP (7). Pubertal suppression was assessed biochemically and/or clinically (testicular/breast exams). Escape from pubertal suppression and HI removal is also characterized.ResultsMost implants (42/50) maintained clinical/biochemical suppression for the duration of the study. The average use of a single HI was 37.5±13.6 months. Pubertal suppression escape occurred in eight subjects at average 30.4 months from placement: five had only biochemical; two clinical; and one both clinical and biochemical escape. After an average of 32.9 months, only 3/23 HI removed had adverse effects (HI broken, difficult removal).ConclusionExtended use of HI in our TG/NB and CPP subjects was efficacious, resulting in sustained biochemical and clinical pubertal suppression in most. Suppression escape occurred at 15-65 months. Complications at HI removal were infrequent. Keeping HI for extended time would improve cost and morbidity, while maintaining efficacy and safety for most patients.

Controversy exists over puberty suppression (PS) in adolescents with gender dysphoria (GD). PS is preferentially achieved with GnRH analogues. By preventing the development of secondary sex characteristics, PS may improve psychological functioning, well-being, quality of life, emotional and behavioral (especially internalizing) problems and depressive symptoms, thus decreasing suicidality. PS can also extend the diagnostic period and give transgender adolescents time to explore their gender identity. GnRHa may also decrease the need for feminization/masculinization surgery. However, 2-year treatment with GnRHa may result in bone mass accrual retardation (decrease in BMD/BMAD z-scores), growth velocity deceleration (decrease in height SDS), increase in fat mass, temporary pause in oocyte/sperm maturation. The most common side effects of GnRHa are hot flashes, mood fluctuations, fatigue and headache. They are usually mild and rarely lead to GnRHa discontinuation. Based on current scientific evidence, PS could be recommended to adolescents who meet the diagnostic criteria of gender incongruence (by DSM-5 and/or ICD-11) and have long-lasting intense GD, which aggravates with puberty onset. Before initiating PS, possible mental issues should be addressed and informed consent (by the adolescent/caregiver) should be given, after counseling on probable reproductive effects of GnRHa. GnRHa can only be started after the adolescent has entered Tanner stage 2. Nevertheless, published studies are inadequate in number, small in size, uncontrolled and relatively short-term, so that it is difficult to draw safe conclusions on efficacy and safety of GnRHa. Large long-term randomized controlled trials are needed to expand knowledge on this controversial issue and elucidate the benefit and risks of PS.

According to international transgender care guidelines, transgender adolescents should have medical decision-making competence (MDC) to start puberty suppression (PS) and halt endogenous pubertal development. However, MDC is a debated concept in adolescent transgender care and little is known about the transgender adolescents', their parents', and clinicians' perspectives on this. Increasing our understanding of these perspectives can improve transgender adolescent care. A qualitative interview study with adolescents attending two Dutch gender identity clinics (eight transgender adolescents who proceeded to gender-affirming hormones after PS, and six adolescents who discontinued PS) and 12 of their parents, and focus groups with ten clinicians was conducted. From thematic analysis, three themes emerged regarding transgender adolescents' MDC to start PS: (1) challenges when assessing MDC, (2) aspects that are considered when assessing MDC, and (3) MDC's relevance. The four criteria one needs to fulfill to have MDC—understanding, appreciating, reasoning, communicating a choice—were all, to a greater or lesser extent, mentioned by most participants, just as MDC being relative to a specific decision and context. Interestingly, most adolescents, parents and clinicians find understanding and appreciating PS and its consequences important for MDC. Nevertheless, most state that the adolescents did not fully understand and appreciate PS and its consequences, but were nonetheless able to decide about PS. Parents' support of their child was considered essential in the decision-making process. Clinicians find MDC difficult to assess and put into practice in a uniform way. Dissemination of knowledge about MDC to start PS would help to adequately support adolescents, parents and clinicians in the decision-making process. [ABSTRACT FROM AUTHOR]

Both in the United States and Europe, the number of minors who present at transgender healthcare services before the onset of puberty is rapidly expanding. Many of those who will have persistent gender dysphoria at the onset of puberty will pursue long-term puberty suppression before reaching the appropriate age to star t using gender-affirming hormones. Exposure to pubertal sex steroids is thus significantl y deferred in these individuals. Puberty is a critical period for bone development: increasing concentrations of estrogens and androgens (directly or after aromatization to estrogens) promote progressive bone growth and mineralization and induce sexually dimorphic skeletal changes. As a consequence, safety concerns regarding bone development and increased future fracture risk in transgender youth have been raised. We here review published data on bone development in transgender adolescents, focusing in par ticular on differences in age and pubertal stage at the start of puberty suppression, chosen strategy to block puberty progression, duration of puberty suppression, and the timing of re-evaluation after estradiol or testosterone administration. Results consistently indicate a negative impact of long-term puberty suppression on bone mineral density, especially at the lumbar spine, which is only partially restored after sex steroid administration. Trans girls are more vulnerable than trans boys for compromised bone health. Behavioral health measures that can promote bone mineralization, such as weight-bearing exercise and calcium and vitamin D supplementation, are strongly recommended in transgender youth, during the phase of puberty suppression and thereafter.

To compare the efficacy of intramuscular Lupron and subcutaneous Eligard, two formulations of leuprolide, for puberty suppression in transgender and gender diverse (TGD) youth. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Context: Growth is an important topic for many transgender boys. However, few studies have investigated the impact of puberty suppression (PS) and gender-affirming hormone treatment (GAHT) on growth and adult height. Objective: To evaluate the effect of PS and GAHT on growth and adult height. Design: Retrospective cohort study. Setting: Specialized gender identity clinic. Participants: A total of 146 transgender boys treated with GnRH analogues and testosterone who reached adult height. Main outcome measures: Growth, bone age (BA), adult height, and difference between adult height and predicted adult height (PAH) and midparental height. Results: In those with BA ≤14 years at start (n=61), a decrease in growth velocity and bone maturation during PS was followed by an increase during GAHT. Adult height was 172.0±6.9 cm; height SD score was similar to baseline (0.1; 95% CI, −0.2 to 0.4). Adult height was 3.9±6.0 cm above midparental height and 3.0±3.6 cm above PAH at start of PS. A younger BA at start PS was associated with an adult height significantly further above PAH. Conclusion: During PS, growth decelerated followed by an acceleration during GAHT. Although adult height SD score was similar to baseline, adult height was taller than predicted based on BA at baseline, especially in those who started treatment at a younger BA. It is reassuring that PS and GAHT do not have a negative impact on adult height in transgender boys and might even lead to a slightly taller adult height, especially in those who start at a younger age. [ABSTRACT FROM AUTHOR]

The Okayama University Gender Clinic provides comprehensive care with collaboration from multiple medical departments according to the Japanese Society of Psychiatry and Neurology’s Diagnostic and Therapeutic Guideline for Gender Identity Disorder (JSPN Guideline). 2947 patients (961 trans women [TW], 1986 trans men [TM]) have visited our outpatient office by the end of 2021. Only 175 (6%)were aged 15 and younger, the age group of junior high school students and younger. Looking back, this number began increasing sharply in 2019, when the total number of young cases was 46 or 27% of those seen in 2021. Most of those seen at age 9 or younger are TW. However, the sex ratio is reversed in the age group 10 and older, with a sharp increase in TMs seen. In early childhood, it is not noticeable when girls behave like boys, while it is noticeable when boys behave like girls. This may explain the higher number of TWs seen in this age group. Twenty percent (36/175)of the patients under 15 years of age had been diagnosed with autism spectrum disorder (ASD) at other hospitals, with a particularly high rate of 64% (7/11) of TW under 6 years of age. The reason for this may be that the ASD complication increases the likelihood that the patient will express atypical gender behavior without regard to the evaluation of others. Physical treatment for gender incongruence of childhood includes puberty suppression therapy at Tanner stage 2 or later. At the Okayama University Gender Clinic, 35 patients (27 TM, 8 TW) have been started on this therapy in accordance with JSPN Guideline. This treatment is reversible, and we believe that it should be positively considered for those who wish to receive it. [ABSTRACT FROM AUTHOR]

Background: Concerns exist regarding effects of puberty suppression on neurodevelopment. Intelligence is strongly correlated with educational achievement in the general population. This study aimed to examine the association between pre-treatment intelligence and educational achievement after gender-affirming treatment including puberty suppression in transgender adolescents to contribute to the emerging understanding of the effect that gender-affirming treatment including puberty suppression may have on cognitive development. Methods: IQ was measured in 72 adolescents (45 trans boys, 27 trans girls) at clinical entry (mean age 12.78 years), educational achievement was evaluated after gender-affirming treatment (mean age 20.40 years). Results: IQ pre-treatment and educational achievement post-treatment were positively associated (Nagelkerke R = 0.71). Discussion: The association between IQ pre-treatment and educational achievement post-treatment in transgender adolescents who received gender-affirming medical treatment including puberty suppression appears to be similar to the general population. This may reflect that gender-affirming medical treatment including puberty suppression does not negatively affect the association between IQ and educational achievement. [ABSTRACT FROM AUTHOR]

Purpose: Treatment of transgender adolescents with puberty suppression (PS) was developed to provide time for exploration before pursuing gender affirming medical treatment (GAMT) with irreversible effects. It may also result in a more satisfactory physical outcome for those who continue with GAMT. Despite being the current first choice treatment, little research has examined the function of PS from the perspectives of transgender adolescents, their parents, and clinicians. Insight into the perceived functions of PS will help to adequately support adolescents in their decision-making process and give them the care they need. Methods: Qualitative study using interviews with eight transgender adolescents who proceeded with GAMT after PS ("continuers"), six adolescents who discontinued PS ("discontinuers") and 12 parents, and focus groups with ten clinicians. Results: All informants considered inhibition of development of secondary sex characteristics an important function of PS. Most continuers saw PS as the first step of GAMT. Nevertheless, some were glad that the effects were reversible even if they didn't expect to change their minds. Some discontinuers did experience PS as an expanded diagnostic phase. One continuer used the time on PS to get used to living in the affirmed gender role, and several parents found the time helpful to adapt to their child's new gender role. PS provided clinicians more time for diagnostic assessment. Conclusions: Adolescents, parents and clinicians do not all report the same functions of PS. Although international guidelines emphasize providing time for exploration of gender identity as an important reason for PS, many adolescents nowadays seem to have clear ideas about their gender identity and treatment wishes, and experience PS as the first step of GAMT. For some discontinuers however, PS offered a valued period of exploration. Guidelines could be modified to provide more customized care, taking adolescents' and parents' ideas about the functions of PS into account. [ABSTRACT FROM AUTHOR]

Study Question: How do transfeminine adolescents and their parents experience fertility preservation via testicular sperm extraction (TESE)?, Summary Answer: Participants experienced the TESE process positively when provided with appropriate guidance to navigate the decisional dilemma between preserving future biological parenthood and the pressure to start puberty suppression early., What Is Known Already: Sperm banking through ejaculation is not feasible for all transfeminine adolescents due to genital dysphoria and early puberty; for this group, TESE is the only alternative. However, during early puberty, they must postpone or pause puberty suppression until spermatogenesis is fully developed., Study Design, Size, Duration: All consecutive TESE patients in our centre and their parents were invited to participate. Between December 2022 and May 2023, we included 6 adolescents and 10 parents. We used a qualitative approach based on semi-structured interviews to study the experience of the transfeminine adolescents and their parents., Participants/materials, Setting, Methods: Transfeminine adolescents diagnosed with gender dysphoria in early puberty (Tanner stage ≥2) who underwent TESE before the start of puberty suppression or gender-affirming hormones participated in this study. The interviews were recorded, manually transcribed and analysed using reflective thematic analysis focusing on understanding the participants' experiences of puberty and fertility preservation and the various factors and social processes influencing their decision to undergo TESE., Main Results and the Role of Chance: Transfeminine adolescents decide to undergo invasive fertility preservation because of a possible, future desire for parenthood. Parents stressed the importance of preventing future decisional regret. They both saw masturbation to obtain a semen sample as unreachable. Even though TESE is a surgical procedure with possible complications and pain afterwards, this alternative seemed less dysphoric to them.Adolescents had to postpone the start of puberty suppression, waiting for spermatogenesis to complete. Given the unpredictable development of puberty, they felt a lot of stress and anxiety during this period and were primarily concerned about the lowering of their voice. Because of this puberty-related stress, they were constantly balancing their motivations for fertility preservation against the early start of puberty suppression to prevent unwanted irreversible pubertal body changes. To support this decisional dilemma, adolescents and their parents need adequate communication with each other and their healthcare providers to reflect on their stress for pubertal change. Furthermore, close, continuous surveillance of their current mental state by their parents, together with their psychologist and pubertal development by their physicians, is needed. Despite the challenging decision and postponement of puberty suppression, they retrospectively experienced it positively without any regret., Limitations, Reasons for Caution: All adolescents successfully underwent TESE, with viable spermatozoa obtained and without complications. This may result in a more positive reflective experience regarding fertility preservation. Furthermore, the perspectives of adolescents with the intention of TESE but who already started with puberty suppression before the preservation were not included., Wider Implications of the Findings: This study helps healthcare providers improve their counselling and guidance of transfeminine adolescents who consider postponing puberty suppression for fertility preservation via TESE. The adolescents and their parents know more clearly what to expect during fertility preservation. Specific peer-support programs may facilitate the decision process for upcoming adolescents., Study Funding/competing Interest(s): No external funding was used for this study. None of the authors have any conflicts of interest., Trial Registration Number: Not applicable., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Context: Transgender adolescents can undergo puberty suppression (PS) and subsequent gender-affirming hormone therapy (GAHT) but little information is available on the expected rate of physical changes., Objective: To investigate the time course of body composition changes during PS and GAHT., Methods: In this study, retrospective data of 380 trans boys and 168 trans girls treated with PS prior to GAHT from a gender identity clinic were included. Total lean and fat mass Z-scores using birth-assigned sex as reference were determined using dual-energy X-ray absorptiometry., Results: In trans boys, lean mass Z-scores decreased (-0.32, 95% CI -0.41; -0.23) and fat mass Z-scores increased (0.31, 95% CI 0.21; 0.41) in the first year of PS and remained stable thereafter. Lean mass Z-scores increased (0.92, 95% CI 0.81; 1.04) and fat mass Z-scores decreased (-0.43, 95% CI -0.57; -0.29) only during the first year of testosterone,. In trans girls, both lean and fat mass Z-scores gradually changed over 3 years of PS (respectively -1.13, 95% CI -1.29; -0.98 and 1.06, 95% CI 0.90; 1.23). In the first year of GAHT, lean mass Z-scores decreased (-0.19, 95% CI -0.36; -0.03) while fat mass Z-scores remained unchanged after 3 years (-0.02, 95% CI -0.20; 0.16)., Conclusion: Compared with peers, trans girls experienced ongoing lean mass decrease and fat mass increase during 3 years of PS while in trans boys smaller changes were observed that stabilized after 1 year. A large increase in lean mass Z-scores occurred only during the first year of testosterone treatment. In trans girls, body composition changed only slightly during GAHT. This information can improve counseling about treatment effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To describe the case of a 17-year-old transgender boy who experienced breast development while on testosterone, having been suppressed with a gonadotropin-releasing hormone (GnRH) agonist prior to testosterone therapy Case report: A 17-year-old transgender boy presented with breast development after having been on a GnRH agonist and then testosterone since the age of 11 years, having never experienced breast development before, which was consistent with pubertal gynecomastia. A small decrease in the testosterone dose resulted in a significant reduction of gynecomastia. Despite the improvement, he went on to undergo chest surgery with the removal of the breast tissue. Discussion: Pubertal gynecomastia is a common phenomenon in the cisgender male population. However, it has not been previously described in transgender boys. The potential mechanisms for its occurrence were discussed. Conclusion: Transgender boys who undergo GnRH agonist treatment for puberty suppression and subsequently receive testosterone therapy for puberty induction may develop gynecomastia. Judicious adjustment of the testosterone therapy may lead to an improvement.

Within bioethics as well as in broader clinical practice, support for transgender and gender‐questioning adolescent access to pubertal suppression has often relied heavily on the desire to prevent risky, self‐destructive, and suicidal behavior. We argue that framing justifications for access to puberty suppression in this way can actually be harmful to both individual patients as well as to the broader trans population. This justification for access to care makes such access precarious, limits its scope, and introduces perverse incentives to the patient population that is being served. We go on to offer an alternative, positive defense of access to puberty‐blocking treatment for transgender youth grounded in the child's right to an open future. We argue that decisions related to pubertal suppression are both importantly weighty and potentially irreversible, and show why this justification is preferable to so‐called "informed consent" approaches. [ABSTRACT FROM AUTHOR]

In this essay, we consider the clinical and ethical implications of puberty blockers for pediatric gender dysphoria through the lens of "the child's right to an open future," which refers to rights that children do not have the capacity to exercise as minors, but that must be protected, so they can exercise them in the future as autonomous adults. We contrast the open future principle with the beliefs underpinning the gender affirming care model and discuss implications for consent. We evaluate claims that puberty blockers are reversible, discuss the scientific uncertainty about long-term benefits and harms, summarize international developments, and examine how suicide has been used to frame puberty suppression as a medically necessary, lifesaving treatment. In discussing these issues, we include relevant empirical evidence and raise questions for clinicians and researchers. We conclude that treatment pathways that delay decisions about medical transition until the child has had the chance to grow and mature into an autonomous adulthood would be most consistent with the open future principle., (© 2024. The Author(s).)

The evidence base for psychological benefits of GnRHA for adolescents with gender dysphoria (GD) was deemed "low quality" by the UK National Institute of Health and Care Excellence. Limitations identified include inattention to clinical importance of findings. This secondary analysis of UK clinical study data uses Reliable and Clinically Significant Change approaches to address this gap. The original uncontrolled study collected data within a specialist GD service. Participants were 44 12-15-year-olds with GD. Puberty was suppressed using "triptorelin"; participants were followed-up for 36 months. Secondary analysis used data from parent-report Child Behavior Checklists and Youth Self-Report forms. Reliable change results: 15-34% of participants reliably deteriorated depending on the subscale, time point and parent versus child report. Clinically significant change results: 27-58% were in the borderline (subclinical) or clinical range at baseline (depending on subscale and parent or child report). Rates of clinically significant change ranged from 0 to 35%, decreasing over time toward zero on both self-report and parent-report. The approach offers an established complementary method to analyze individual level change and to examine who might benefit or otherwise from treatment in a field where research designs have been challenged by lack of control groups and low sample sizes.

Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria Abstract: Objective: The suppression of physiological puberty using puberty-blocking pharmacological agents (PB) and prescribing cross-sex hormones (CSH) to minors with gender dysphoria (GD) is a current matter of discussion, and in some cases, PB and CSH are used in clinical practice for this particular population. Two systematic reviews (one on PB, one on CSH treatment) by the British National Institute for Clinical Excellence (NICE) from 2020 indicated no clear clinical benefit of such treatments regarding critical outcome variables. In particular, these two systematic NICE reviews on the use of PB and CSH in minors with GD detected no clear improvements of GD symptoms. Moreover, the overall scientific quality of the available evidence, as discussed within the above-mentioned two NICE reviews, was classified as "very low certainty" regarding modified GRADE criteria. Method: The present systematic review presents an updated literature search on this particular topic (use of PB and CSH in minors with GD) following NICE principles and PICO criteria for all relevant new original research studies published since the release of the two above-mentioned NICE reviews (updated literature search period was July 2020-August 2023). Results: The newly conducted literature search revealed no newly published original studies targeting NICE-defined critical and important outcomes and the related use of PB in minors with GD following PICO criteria. For CSH treatment, we found two new studies that met PICO criteria, but these particular two studies had low participant numbers, yielded no significant additional clear evidence for specific and clearly beneficial effects of CSH in minors with GD, and could be classified as "low certainty" tfollowing modified GRADE criteria. Conclusions: The currently available studies on the use of PB and CSH in minors with GD have significant conceptual and methodological flaws. The available evidence on the use of PB and CSH in minors with GD is very limited and based on only a few studies with small numbers, and these studies have problematic methodology and quality. There also is a lack of adequate and meaningful long-term studies. Current evidence doesn't suggest that GD symptoms and mental health significantly improve when PB or CSH are used in minors with GD. Psychotherapeutic interventions to address and reduce the experienced burden can become relevant in children and adolescents with GD. If the decision to use PB and/or CSH is made on an individual case-by-case basis and after a complete and thorough mental health assessment, potential treatment of possibly co-occurring mental health problems as well as after a thoroughly conducted and carefully executed individual risk-benefit evaluation, doing so as part of clinical studies or research projects, as currently done in England, can be of value in terms of generation of new research data. The electronic supplement (ESM) 1 is an adapted and abreviated English version of this work.

Background/aims: Transgender youths experience high rates of depression and suicidal ideation compared to cisgender peers. Previous studies indicate that endocrine and/or surgical interventions are associated with improvements to mental health in adult transgender individuals. We examined the associations of endocrine intervention (puberty suppression and/or cross sex hormone therapy) with depression and quality of life scores over time in transgender youths. Methods: At approximately 6-month intervals, participants completed depression and quality of life questionnaires while participating in endocrine intervention. Multiple linear regression and residualized change scores were used to compare outcomes. Results: Between 2013 and 2018, 50 participants (mean age 16.2 + 2.2 yr) who were naïve to endocrine intervention completed 3 waves of questionnaires. Mean depression scores and suicidal ideation decreased over time while mean quality of life scores improved over time. When controlling for psychiatric medications and engagement in counseling, regression analysis suggested improvement with endocrine intervention. This reached significance in male-to-female participants. Conclusion: Endocrine intervention may improve mental health in transgender youths in the US. This effect was observed in both male-to-female and female-to-male youths, but appears stronger in the former. [ABSTRACT FROM AUTHOR]

Individuals with gender dysphoria (as defined by Diagnostic and Statistical Manual of Mental Disorders or DSM-V) experience a marked incongruence between the sex assigned at birth and the experienced gender resulting in significant distress or impairment in social, occupational, or other important areas of functioning. For transgender and gender diverse minors, the Endocrine Society recommends a multidisciplinary approach to gender-affirming medical treatment that involves a physician and a mental health provider, also consistent with the World Professional Association for Transgender Health Standard of Care 8th Edition recommendations. This article will outline the role of medical providers in implementing safe and effective gender-affirming medical treatments in youth., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The past 15 years have seen the growth of puberty suppression as the prevailing approach to supporting gender non-conforming children and youth. Puberty suppression is considered to provide time for weighing up the pros and cons of medical transition. Research based on binary understandings of gender has demonstrated that a carefully selected group of gender non-conforming youth benefit from physical treatment and gender transition, but the research that details how psychologists can best support young people during this time is limited. This is the gap addressed by the current research. The purpose of the present study is to explore the meaning-making framework within which some clinical psychologists and gender non-conforming youth approach discussions of puberty suppression. Five semi-structured interviews were conducted with clinical psychologists working with gender non-conforming youth. The data were analysed using thematic analysis. The results indicate that there is pressure on gender non-conforming youth, often coming from families, friends and mass media, to buy into heteronormative and binary discourses regarding gender and what constitutes a good life. The results also indicate that the participants deploy affirmative and exploratory therapeutic strategies in their work, in order to enable gender non-conforming youth to make informed decisions regarding puberty suppression. Participants emphasized the importance of therapeutic approaches that explore non-binary gender discourses, alongside the use of puberty suppression and other medical interventions that enable clients to fit more with gender norms. The therapeutic balance between affirmation and exploration may shed light on how both research within the binary tradition and critics of binary assumptions are in danger of oversimplifying the process of gender identity development. This research highlights the importance of understanding the complex negotiation of gender discourses that are in tension with one another. [ABSTRACT FROM AUTHOR]

Introduction: Transgender and gender-diverse (TGD) youth are at greater risk for mental health and medical conditions than their cisgender peers; however, poor health outcomes and identity-based discrimination can be minimized in the context of optimal support. Approximately 1.7 million youth may be eligible for care covered by the Military Health System, which includes mental health and gender-affirming medications. The purpose of the current study is to identify sociodemographic characteristics, the psychosocial and behavioral risk profile, and health care utilization patterns of TGD dependent youth cared for in the U.S. military system to inform provider training and resource allocation.Materials and Methods: We performed a retrospective chart review by searching all medical records between July 1, 2014 and July 1, 2017 for diagnoses suggesting visits for TGD-services at a regional referral-based adolescent medicine clinic which cares for dependent children of active duty, activated selected reserve, and retired military service members between the ages of 9 and 24 years for a wide range of health care needs.Results: Fifty-three participants were included in this study. Sixty-four percent reported a transmasculine identity, 21% a transfeminine identity, and 15% a non-binary or undecided identity. The mean age at first gender-related visit was 14.5 years (SD 3.2). The mean number of primary care physicians and specialists seen by a given individual in a military treatment facility for any visit type since the implementation of the medical record system in 2005 was 12 (SD 6.8) and 10.2 (SD 7.8), respectively. Thirty-three percent of all patients assigned as female at birth were on testosterone therapy and 23% of all patients assigned as male at birth were on estrogen therapy at their most recent clinic visit. Twelve patients were undergoing pubertal suppression with an injectable or implantable gonadotropin-releasing hormone agonist. Seventy percent reported a history of suicidal ideation, 42% self-harm, 21% at least one suicide attempt, and 33% psychiatric hospitalization. Having strongly supportive parents was significantly associated with recognizing, disclosing and seeking treatment for gender nonconformity at an earlier age (ps ≤ 0.03) and marginally associated with less likelihood of current suicidal ideation (p = 0.06) compared to those with less supportive parents.Conclusions: This study elucidated the sociodemographic and behavioral risk profile of a sample of TGD youth in the MHS. Military and non-military health care providers across a broad spectrum of specialties should be knowledgeable about the unique psychosocial and medical needs, requisite sensitivity, and available referral options in the care of TGD youth. Assumptions about one's gender identity, sexual orientation, gender expression, or behaviors cannot be made based on birth-assigned sex. Further research is needed to investigate the health and wellbeing of TGD military-affiliated youth over time and to determine quality transgender-related services in support of this vulnerable and underserved population. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have assessed the effects of hormonal treatments such as gonadotropin-releasing hormone agonists (GnRHa) and gender-affirming hormones (GAH) on mental health outcomes in clinically referred gender-diverse young people from a younger age. Where this research has been conducted, findings have been mixed. This study investigated a cohort of young people before treatment, 1 year into GnRHa, and 1 year into GAH treatment to understand psychological and behavioral impacts over time. Methods: Thirty-eight young people (28 assigned female and 10 assigned male) referred to endocrinology, younger than 15 years at/beyond Tanner stage two, who received GnRHa followed by GAH treatment, were assessed in a retrospective analysis study. Young people completed the Youth Self Report (YSR), the Body Image Scale, and the Utrecht Gender Dysphoria Scale, while caregivers completed the Child Behavior Checklist (CBCL) and the Social Responsiveness Scale-2 at all time points. Results: Dissatisfaction with primary sexual characteristics ( p  = 0.02), gender dysphoria ( p  = 0.01), and social motivation ( p  = 0.04) improved significantly over time. Self-harm and suicidality also showed a general decrease. Caregivers reported a significant reduction in internalizing ( p  = 0.03) behaviors on the CBCL after GnRHa. Other subcategories of the YSR and CBCL were within normal ranges with no significant difference ( p  > 0.05). Conclusion: These findings demonstrate some improvements in psychological and behavioral outcomes in young people concurrently receiving psychosocial support and hormone treatment. Future research with larger and more diverse samples is warranted to further understand generalizability.

Puberty suppression is the reversible first step of endocrine medical treatment in transgender youth, and allows for two very important aspects of transgender management. Firstly, it buys the patient, family and their medical team time to fully evaluate the presence and persistence of gender dysphoria. Secondly, it successfully prevents the development of cis-gender unwanted secondary sexual characteristics. The latter, when present, almost certainly increase the burden of psychological co-morbidity for any transgender person. This management is modelled from treatment of gonadotropin-dependent precious puberty, with use of GnRH agonists at its core. With the increasing number of transgender youth treated, and the changing demographics of patients seeking medical care, providers are faced with the decision to start puberty blockade at younger ages than previous decades. This article will review the rationale behind puberty blockade for transgender children, the providers’ options for achieving this goal, the emerging literature for potential adverse effects on such an approach, as well as identify directions of potential future research. [ABSTRACT FROM AUTHOR]

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International guidelines recommend the use of Gonadotropin-Releasing Hormone (GnRH) agonists in adolescents with gender dysphoria (GD) to suppress puberty. Little is known about the way gender dysphoric adolescents themselves think about this early medical intervention. The purpose of the present study was (1) to explicate the considerations of gender dysphoric adolescents in the Netherlands concerning the use of puberty suppression; (2) to explore whether the considerations of gender dysphoric adolescents differ from those of professionals working in treatment teams, and if so in what sense. This was a qualitative study designed to identify considerations of gender dysphoric adolescents regarding early treatment. All 13 adolescents, except for one, were treated with puberty suppression; five adolescents were trans girls and eight were trans boys. Their ages ranged between 13 and 18 years, with an average age of 16 years and 11 months, and a median age of 17 years and 4 months. Subsequently, the considerations of the adolescents were compared with views of clinicians treating youth with GD. From the interviews with the gender dysphoric adolescents, three themes emerged: (1) the difficulty of determining what is an appropriate lower age limit for starting puberty suppression. Most adolescents found it difficult to define an appropriate age limit and saw it as a dilemma; (2) the lack of data on the long-term effects of puberty suppression. Most adolescents stated that the lack of long-term data did not and would not stop them from wanting puberty suppression; (3) the role of the social context, for which there were two subthemes: (a) increased media-attention, on television, and on the Internet; (b) an imposed stereotype. Some adolescents were positive about the role of the social context, but others raised doubts about it. Compared to clinicians, adolescents were often more cautious in their treatment views. It is important to give voice to gender dysphoric adolescents when discussing the use of puberty suppression in GD. Otherwise, professionals might act based on assumptions about adolescents' opinions instead of their actual considerations. We encourage gathering more qualitative research data from gender dysphoric adolescents in other countries. [ABSTRACT FROM AUTHOR]

Purpose Few transgender youth eligible for gender-affirming treatments actually receive them. Multidisciplinary gender clinics improve access and care coordination but are rare. Although experts support use of pubertal blockers and cross-sex hormones for youth who meet criteria, these are uncommonly offered. This study's aim was to understand barriers that transgender youth and their caregivers face in accessing gender-affirming health care. Methods Transgender youth (age 14–22 years) and caregivers of transgender youth were recruited from Seattle-based clinics, and readerships from a blog and support group listserv. Through individual interviews, focus groups, or an online survey, participants described their experiences accessing gender-affirming health care. We then used theoretical thematic analysis to analyze data. Results Sixty-five participants (15 youth, 50 caregivers) described barriers spanning six themes: (1) few accessible pediatric providers are trained in gender-affirming health care; (2) lack of consistently applied protocols; (3) inconsistent use of chosen name/pronoun; (4) uncoordinated care and gatekeeping; (5) limited/delayed access to pubertal blockers and cross-sex hormones; and (6) insurance exclusions. Conclusions This is the first study aimed at understanding perceived barriers to care among transgender youth and their caregivers. Themed barriers to care led to the following recommendations: (1) mandatory training on gender-affirming health care and cultural humility for providers/staff; (2) development of protocols for the care of young transgender patients, as well as roadmaps for families; (3) asking and recording of chosen name/pronoun; (4) increased number of multidisciplinary gender clinics; (5) providing cross-sex hormones at an age that permits peer-congruent development; and (6) designating a navigator for transgender patients in clinics. [ABSTRACT FROM AUTHOR]

Introduction Puberty suppression using gonadotropin-releasing hormone agonists (GnRHas) is recommended by current guidelines as the treatment of choice for gender dysphoric adolescents. Although GnRHas have long been used to treat precocious puberty, there are few data on the efficacy and safety in gender dysphoric adolescents. Therefore, the Endocrine Society guideline recommends frequent monitoring of gonadotropins, sex steroids, and renal and liver function. Aim To evaluate the efficacy and safety of GnRHa treatment to suppress puberty in gender dysphoric adolescents. Methods Forty-nine male-to-female and 67 female-to-male gender dysphoric adolescents treated with triptorelin were included in the analysis. Main Outcome Measures Physical examination, including assessment of Tanner stage, took place every 3 months and blood samples were drawn at 0, 3, and 6 months and then every 6 months. Body composition was evaluated using dual energy x-ray absorptiometry. Results GnRHa treatment caused a decrease in testicular volume in 43 of 49 male-to-female subjects. In one of four female-to-male subjects who presented at Tanner breast stage 2, breast development completely regressed. Gonadotropins and sex steroid levels were suppressed within 3 months. Treatment did not have to be adjusted because of insufficient suppression in any subject. No sustained abnormalities of liver enzymes or creatinine were encountered. Alkaline phosphatase decreased, probably related to a slower growth velocity, because height SD score decreased in boys and girls. Lean body mass percentage significantly decreased during the first year of treatment in girls and boys, whereas fat percentage significantly increased. Conclusion Triptorelin effectively suppresses puberty in gender dysphoric adolescents. These data suggest routine monitoring of gonadotropins, sex steroids, creatinine, and liver function is not necessary during treatment with triptorelin. Further studies should evaluate the extent to which changes in height SD score and body composition that occur during GnRHa treatment can be reversed during subsequent cross-sex hormone treatment. [ABSTRACT FROM AUTHOR]

Introduction: Puberty suppression by gonadotropin-releasing hormone analogs (GnRHa) is prescribed to relieve the distress associated with pubertal development in adolescents with gender dysphoria (GD) and thereby to provide space for further exploration. However, there are limited longitudinal studies on puberty suppression outcome in GD. Also, studies on the effects of psychological support on its own on GD adolescents' well-being have not been reported. Aim: This study aimed to assess GD adolescents' global functioning after psychological support and puberty suppression. Methods: Two hundred one GD adolescents were included in this study. In a longitudinal design we evaluated adolescents' global functioning every 6 months from the first visit. Main Outcome Measures. All adolescents completed the Utrecht Gender Dysphoria Scale (UGDS), a self-report measure of GD-related discomfort. We used the Children's Global Assessment Scale (CGAS) to assess the psychosocial functioning of adolescents. Results: At baseline, GD adolescents showed poor functioning with a CGAS mean score of 57.7 ± 12.3. GD adolescents' global functioning improved significantly after 6 months of psychological support (CGAS mean score: 60.7 ± 12.5; P < 0.001). Moreover, GD adolescents receiving also puberty suppression had significantly better psychosocial functioning after 12 months of GnRHa (67.4 ± 13.9) compared with when they had received only psychological support (60.9 ± 12.2, P = 0.001). Conclusion: Psychological support and puberty suppression were both associated with an improved global psychosocial functioning in GD adolescents. Both these interventions may be considered effective in the clinical management of psychosocial functioning difficulties in GD adolescents. [ABSTRACT FROM AUTHOR]

Purpose The Endocrine Society and the World Professional Association for Transgender Health published guidelines for the treatment of adolescents with gender dysphoria (GD). The guidelines recommend the use of gonadotropin-releasing hormone agonists in adolescence to suppress puberty. However, in actual practice, no consensus exists whether to use these early medical interventions. The aim of this study was to explicate the considerations of proponents and opponents of puberty suppression in GD to move forward the ethical debate. Methods Qualitative study (semi-structured interviews and open-ended questionnaires) to identify considerations of proponents and opponents of early treatment (pediatric endocrinologists, psychologists, psychiatrists, ethicists) of 17 treatment teams worldwide. Results Seven themes give rise to different, and even opposing, views on treatment: (1) the (non-)availability of an explanatory model for GD; (2) the nature of GD (normal variation, social construct or [mental] illness); (3) the role of physiological puberty in developing gender identity; (4) the role of comorbidity; (5) possible physical or psychological effects of (refraining from) early medical interventions; (6) child competence and decision making authority; and (7) the role of social context how GD is perceived. Strikingly, the guidelines are debated both for being too liberal and for being too limiting. Nevertheless, many treatment teams using the guidelines are exploring the possibility of lowering the current age limits. Conclusions As long as debate remains on these seven themes and only limited long-term data are available, there will be no consensus on treatment. Therefore, more systematic interdisciplinary and (worldwide) multicenter research is required. [ABSTRACT FROM AUTHOR]

Individuals with gender dysphoria experience distress associated with incongruence between their biologic sex and their identified gender. Gender dysphoric natal males receive treatment with antiandrogens and estrogens to become feminized (transsexual females), whereas natal females with gender dysphoria receive treatment with androgens to become masculinized (transsexual males). Because of the permanence associated with cross-sex hormone therapy ( CSHT), adolescents diagnosed with gender dysphoria receive gonadotropin-releasing hormone analogs to suppress puberty. High rates of depression and suicide are linked to social marginalization and barriers to care. Behavior, emotional problems, depressive symptoms, and global functioning improve in adolescents receiving puberty suppression therapy. Gender dysphoria, psychological symptoms, quality of life, and sexual function improve in adults who receive CSHT. Within the first 6 months of CSHT, changes in transsexual females include breast growth, decreased testicular volume, and decreased spontaneous erections, and changes in transsexual males include cessation of menses, breast atrophy, clitoral enlargement, and voice deepening. Both transsexual females and males experience changes in body fat redistribution, muscle mass, and hair growth. Desired effects from CSHT can take between 3 and 5 years; however, effects that occur during puberty, such as voice deepening and skeletal structure changes, cannot be reversed with CSHT. Decreased sexual desire is a greater concern in transsexual females than in transsexual males, with testosterone concentrations linked to sexual desire in both. Regarding CSHT safety, bone mineral density is preserved with adequate hormone supplementation, but long-term fracture risk has not been studied. The transition away from high-dose traditional regimens is tied to a lower risk of venous thromboembolism and cardiovascular disease, but data quality is poor. Breast cancer has been reported in both transsexual males and females, but preliminary data suggest that CSHT does not increase the risk. Cancer screenings for individuals of both natal and transitioned sexes should occur as recommended. More long-term studies are needed to ensure that CSHT regimens with the best outcomes can continue to be prescribed for the transsexual population. [ABSTRACT FROM AUTHOR]

Both in the United States and Europe, the number of minors who present at transgender healthcare services before the onset of puberty is rapidly expanding. Many of those who will have persistent gender dysphoria at the onset of puberty will pursue long-term puberty suppression before reaching the appropriate age to start using gender-affirming hormones. Exposure to pubertal sex steroids is thus significantly deferred in these individuals. Puberty is a critical period for bone development: increasing concentrations of estrogens and androgens (directly or after aromatization to estrogens) promote progressive bone growth and mineralization and induce sexually dimorphic skeletal changes. As a consequence, safety concerns regarding bone development and increased future fracture risk in transgender youth have been raised. We here review published data on bone development in transgender adolescents, focusing in particular on differences in age and pubertal stage at the start of puberty suppression, chosen strategy to block puberty progression, duration of puberty suppression, and the timing of re-evaluation after estradiol or testosterone administration. Results consistently indicate a negative impact of long-term puberty suppression on bone mineral density, especially at the lumbar spine, which is only partially restored after sex steroid administration. Trans girls are more vulnerable than trans boys for compromised bone health. Behavioral health measures that can promote bone mineralization, such as weight-bearing exercise and calcium and vitamin D supplementation, are strongly recommended in transgender youth, during the phase of puberty suppression and thereafter.

Referrals to the gender identity development service and gender identity clinics are increasing. Gender affirming medical interventions can adversely impact on fertility potential of the individual. Discussion about possible impact of various treatments such as GnRH agonists and cross over hormones (oestrogen or testosterone) and surgery of genitalia and reproductive organs should be discussed. Opportunity should be provided to discuss options for fertility preservation and assisted decision-making. It should be appreciated that transgender individuals have an increased incidence of mental health problems and barriers to care. Oocyte and sperm cryopreservation provide options for biological parenthood. [ABSTRACT FROM AUTHOR]

In the past few years, the introduction and rapid acceptance of puberty suppression has transformed the clinical treatment of children diagnosed with Gender Identity Disorder. This essay analyzes the narratives used by some advocates of this treatment, particularly the elements of saving children from the looming disaster of puberty and from future abject lives of violence and suicide as transgender adults. It briefly addresses the potential implications of this account for the well being of the children brought under clinical purview. [ABSTRACT FROM AUTHOR]

In this perspective, we argue that pubertal suppression with gonadotropin-releasing hormone analogues is a safe reversible intervention that should be made available to transgender and gender-diverse youth starting at early puberty. Recent data suggest puberty suppression is generally initiated among individuals once puberty has significantly progressed, thus reducing the effectiveness of the intervention. Delays and barriers to such care may systematically introduce permanent avoidable disadvantages for this vulnerable and marginalized group., Competing Interests: No competing financial interests exist., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

Some people, including minors, have a gender identity that does not correspond to the sex assigned at birth. They are known as trans* people, which is an umbrella term that encompasses transgender, transsexual, and other identities not conforming to the assigned gender. Healthcare units for trans* minors require multidisciplinary working, undertaken by personnel expert in gender identity, enabling, when requested, interventions for the minor and their social-familial environment, in an individualized and flexible way during the gender affirmation path. This service model also includes hormonal treatments tailored as much as possible to the individual's needs, beyond the dichotomic goals of a traditional binary model. This guide addresses the general aspects of professional care of trans* minors and presents the current evidence-based protocol of hormonal treatments for trans* and non-binary adolescents. In addition, it details key aspects related to expected body changes and their possible side effects, as well as prior counselling about fertility preservation., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: This study examined psychiatric comorbidity in adolescents with a gender identity disorder (GID). We focused on its relation to gender, type of GID diagnosis and eligibility for medical interventions (puberty suppression and cross-sex hormones). Methods: To ascertain DSM-IV diagnoses, the Diagnostic Interview Schedule for Children (DISC) was administered to parents of 105 gender dysphoric adolescents. Results: 67.6% had no concurrent psychiatric disorder. Anxiety disorders occurred in 21%, mood disorders in 12.4% and disruptive disorders in 11.4% of the adolescents. Compared with natal females ( n = 52), natal males ( n = 53) suffered more often from two or more comorbid diagnoses (22.6% vs. 7.7%, p = .03), mood disorders (20.8% vs. 3.8%, p = .008) and social anxiety disorder (15.1% vs. 3.8%, p = .049). Adolescents with GID considered to be 'delayed eligible' for medical treatment were older [15.6 years ( SD = 1.6) vs. 14.1 years ( SD = 2.2), p = .001], their intelligence was lower [91.6 ( SD = 12.4) vs. 99.1 ( SD = 12.8), p = .011] and a lower percentage was living with both parents (23% vs. 64%, p < .001). Although the two groups did not differ in the prevalence of psychiatric comorbidity, the respective odds ratios ('delayed eligible' adolescents vs. 'immediately eligible' adolescents) were >1.0 for all psychiatric diagnoses except specific phobia. Conclusions: Despite the suffering resulting from the incongruence between experienced and assigned gender at the start of puberty, the majority of gender dysphoric adolescents do not have co-occurring psychiatric problems. Delayed eligibility for medical interventions is associated with psychiatric comorbidity although other factors are of importance as well. [ABSTRACT FROM AUTHOR]