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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.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Betsi, Goulia, Sandhu and Xekouki.)

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).)

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: 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. 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.

Purpose: In recent years, an increasing number of specialized gender clinics have been prescribing gonadotropin-releasing hormone (GnRH) analogs to adolescents diagnosed with gender dysphoria (GD) to suppress puberty. This paper presents qualitative research on the hormone therapy (HT) experiences of older trans-people and their views on puberty suppression. The main aim of this research was to explore the psychological aspects of hormonal treatments for gender non-conforming adults, including the controversial use of puberty suppression treatments., Methods: Using a semi-structured interview format, ten adult trans-women were interviewed (mean age: 37.4) to explore their personal histories regarding GD onset and development, their HT experiences, and their views on the use of GnRH analogs to suppress puberty in trans-children and adolescents., Results: the interview transcripts were analyzed using the consensual qualitative research method from which several themes emerged: the onset of GD, childhood experiences, experiences with puberty and HT, views on the puberty suspension procedure, and the effects of this suspension on gender identity and sexuality., Conclusions: The interviews showed that overall, the participants valued the new treatment protocol due to the opportunity to prevent the severe body dysphoria and social phobia trans-people experience with puberty. It seems that the risk of social isolation and psychological suffering is increased by the general lack of acceptance and stigma toward trans-identities in the Italian society. However, during gender transitions, they highlight the need to focus more on internal and psychological aspects, rather than over-emphasize physical appearance. This study gives a voice to an under-represented group regarding the use of GnRH analogs to suppress puberty in trans-individuals, and collected firsthand insights on this controversial treatment and its recommendations in professional international guidelines.

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.

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., (© 2015 International Society for Sexual Medicine.)

Background: In recent years, puberty suppression by means of gonadotropin-releasing hormone analogs has become accepted in clinical management of adolescents who have gender dysphoria (GD). The current study is the first longer-term longitudinal evaluation of the effectiveness of this approach., Methods: A total of 55 young transgender adults (22 transwomen and 33 transmen) who had received puberty suppression during adolescence were assessed 3 times: before the start of puberty suppression (mean age, 13.6 years), when cross-sex hormones were introduced (mean age, 16.7 years), and at least 1 year after gender reassignment surgery (mean age, 20.7 years). Psychological functioning (GD, body image, global functioning, depression, anxiety, emotional and behavioral problems) and objective (social and educational/professional functioning) and subjective (quality of life, satisfaction with life and happiness) well-being were investigated., Results: After gender reassignment, in young adulthood, the GD was alleviated and psychological functioning had steadily improved. Well-being was similar to or better than same-age young adults from the general population. Improvements in psychological functioning were positively correlated with postsurgical subjective well-being., Conclusions: A clinical protocol of a multidisciplinary team with mental health professionals, physicians, and surgeons, including puberty suppression, followed by cross-sex hormones and gender reassignment surgery, provides gender dysphoric youth who seek gender reassignment from early puberty on, the opportunity to develop into well-functioning young adults., (Copyright © 2014 by the American Academy of Pediatrics.)

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]

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 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]

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]

Puberty suppression by means of gonadotropin releasing hormone (GnRH) analogs is considered a diagnostic aid in gender dysphoric adolescents. However, there are also concerns about potential risks, such as poor outcome or post-surgical regret, adverse effects on metabolic and endocrine status, impaired increment of bone mass, and interference with brain development. This case report is on a 22-year follow-up of a female-to-male transsexual, treated with GnRH analogs at 13 years of age and considered eligible for androgen treatment at age 17, and who had gender reassignment surgery at 20 and 22 years of age. At follow-up, he indicated no regrets about his treatment. He was functioning well psychologically, intellectually, and socially; however, he experienced some feelings of sadness about choices he had made in a long-lasting intimate relationship. There were no clinical signs of a negative impact on brain development. He was physically in good health, and metabolic and endocrine parameters were within reference ranges. Bone mineral density was within the normal range for both sexes. His final height was short as compared to Dutch males; however, his body proportions were within normal range. This first report on long-term effects of puberty suppression suggests that negative side effects are limited and that it can be a useful additional tool in the diagnosis and treatment of gender dysphoric adolescents. [ABSTRACT FROM AUTHOR]

This article focuses on therapeutic interventions with gender variant youth and, in particular, pubertal suppression. The aim is to address the question of which kinds of subjects are enabled, and which are made invisible, through discursive and clinical practices. The analysis demonstrates the conceptual value of drawing on discursive and queer theoretical approaches. The published work of selected clinicians is used as a way in to the complexities that various clinical understandings and approaches bring with them. A key focus is on problems inherent in the construction of gender variant youth as 'persisting' or 'desisting' in their cross-gender wishes. Psychologists working in this area have substantial challenges to face, such as the challenge of negotiating understandings about what is a 'successful' outcome and the complexity of reporting fluidity and uncertainty in the context of a scientific forum where 'results' are expected. This article addresses the challenge of engaging psychological, discursive and clinical practices in ways that enable empowered, viable, gender variant possibilities, rather than representing gender variant youth as incoherent subjects. [ABSTRACT FROM AUTHOR]