I have been working on researching the research on the use of "puberty blockers" in children for the purposes of transgendering them. My local children's hospital has a gender clinic but has refused my request to come learn about their treatment approach, a very unusual stance for a tertiary care teaching hospital. I asked my professional College library to do a literature search for me, to help ensure I wasn't missing any published articles, and they sent me a list of twenty-one items, which I have copied below for those of you who are also interested in the state of the science of this practice and may not have access to such resources. To be fair, these are only abstracts, but the general consensus appears supportive of the use of medications to block puberty and that these medications are reversible - despite no statement of evidence of reversibility in such an application (I have asked for another search specifically on that). Only one article expresses hesitancy to endorse the use of these medications in all youth gender dysphoric situations (#2; I am waiting for access to the full article). None challenges the presumption of the transgender narrative, which I find alarming.
1: Efficacy and Safety of Gonadotropin-Releasing Hormone Agonist Treatment to Suppress puberty in Gender Dysphoric Adolescents.Schagen, S. E., P. T. Cohen-Kettenis, H. A. Delemarre-van de Waal and S. E. Hannema.J Sex Med. 2016 Jul;13(7):1125-32.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.2: Gender dysphoria in children and adolescents: a review of recent research.Fuss, J., M. K. Auer and P. Briken.Curr Opin Psychiatry. 2015 Nov;28(6):430-4.PURPOSE OF REVIEW: With the advent of medical treatments such as puberty suppression and cross-sex hormones in gender dysphoric minors, there has been a debate around questions of gender identity and brain development. This review aimed to identify recent empirical studies that addressed this controversial topic. RECENT FINDINGS: Epidemiological data from several countries indicate that gender dysphoria in children and adolescents is far more common than initially anticipated. This is in line with the currently observed steady increase in referrals to gender clinics. Minors with gender dysphoria are a vulnerable population as they may face a high psychopathological burden. Recently published data on the long-term outcome of puberty suppression and subsequent hormonal and surgical treatment indicate that young people with gender dysphoria may benefit substantially with regard to psychosocial outcomes. Brain development studied by neuroimaging methods seems not to be disturbed by puberty suppression. SUMMARY: The first reports about long-term outcome in adolescents having undergone puberty suppression have shown promising results. However, in a substantial part of gender dysphoric minors, puberty suppression is not indicated so far because of psychiatric comorbidity and long-term follow-up data from these patients are still scarce. PMID: 26382161.Link to full text:3: Early Medical Treatment of Children and Adolescents With Gender Dysphoria: An Empirical Ethical Study.Vrouenraets, L. J., A. M. Fredriks, S. E. Hannema, P. T. Cohen-Kettenis and M. C. de Vries.J Adolesc Health. 2015 Oct;57(4):367-73.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. PMID: 26119518.Link to full text:4: Adolescents with gender dysphoria.Cohen-Kettenis, P. T. and D. Klink.Best Pract Res Clin Endocrinol Metab. 2015 Jun;29(3):485-95.Young people with gender dysphoria are increasingly seen by pediatric endocrinologists. Mental health child specialists assess the adolescent and give advice about psychological or medical treatment. Provided they fulfill eligibility and readiness criteria, adolescents may receive pubertal suspension, consisting of using gonadotrophin-releasing hormone analogs, later followed by cross-sex hormones (sex steroids of the experienced gender). If they fulfill additional criteria, they may have various types of gender affirming surgery. Current issues involve safety aspects. Although generally considered safe in the short-term, the long-term effects regarding bone health and cardiovascular risks are still unknown. Therefore, vigilance is warranted during and long after completion of the last gender affirming surgeries. The timing of the various treatment steps is also under debate: instead of fixed age limits, the cognitive and emotional maturation, along with the physical development, are now often considered as more relevant. PMID: 26051304.Link to full text:5: Puberty suppression and executive functioning: An fMRI-study in adolescents with gender dysphoria.Staphorsius, A. S., B. P. Kreukels, P. T. Cohen-Kettenis, D. J. Veltman, S. M. Burke, S. E. Schagen, F. M. Wouters, H. A. Delemarre-van de Waal and J. Bakker.Psychoneuroendocrinology. 2015 Jun;56:190-9.Adolescents with gender dysphoria (GD) may be treated with gonadotropin releasing hormone analogs (GnRHa) to suppress puberty and, thus, the development of (unwanted) secondary sex characteristics. Since adolescence marks an important period for the development of executive functioning (EF), we determined whether the performance on the Tower of London task (ToL), a commonly used EF task, was altered in adolescents with GD when treated with GnRHa. Furthermore, since GD has been proposed to result from an atypical sexual differentiation of the brain, we determined whether untreated adolescents with GD showed sex-atypical brain activations during ToL performance. We found no significant effect of GnRHa on ToL performance scores (reaction times and accuracy) when comparing GnRHa treated male-to-females (suppressed MFs, n=8) with untreated MFs (n=10) or when comparing GnRHa treated female-to-males (suppressed FMs, n=12) with untreated FMs (n=10). However, the suppressed MFs had significantly lower accuracy scores than the control groups and the untreated FMs. Region-of-interest (ROI) analyses showed significantly greater activation in control boys (n=21) than control girls (n=24) during high task load ToL items in the bilateral precuneus and a trend (p<0.1) for greater activation in the right DLPFC. In contrast, untreated adolescents with GD did not show significant sex differences in task load-related activation and had intermediate activation levels compared to the two control groups. GnRHa treated adolescents with GD showed sex differences in neural activation similar to their natal sex control groups. Furthermore, activation in the other ROIs (left DLPFC and bilateral RLPFC) was also significantly greater in GnRHa treated MFs compared to GnRHa treated FMs. These findings suggest that (1) GnRHa treatment had no effect on ToL performance in adolescents with GD, and (2) pubertal hormones may induce sex-atypical brain activations during EF in adolescents with GD. PMID: 25837854.Link to full text:6: Bone mass in young adulthood following gonadotropin-releasing hormone analog treatment and cross-sex hormone treatment in adolescents with gender dysphoria.Klink, D., M. Caris, A. Heijboer, M. van Trotsenburg and J. Rotteveel.J Clin Endocrinol Metab. 2015 Feb;100(2):E270-5.CONTEXT: Sex steroids are important for bone mass accrual. Adolescents with gender dysphoria (GD) treated with gonadotropin-releasing hormone analog (GnRHa) therapy are temporarily sex-steroid deprived until the addition of cross-sex hormones (CSH). The effect of this treatment on bone mineral density (BMD) in later life is not known. OBJECTIVE: This study aimed to assess BMD development during GnRHa therapy and at age 22 years in young adults with GD who started sex reassignment (SR) during adolescence. DESIGN AND SETTING: This was a longitudinal observational study at a tertiary referral center. PATIENTS: Young adults diagnosed with gender identity disorder of adolescence (DSM IV-TR) who started SR in puberty and had undergone gonadectomy between June 1998 and August 2012 were included. In 34 subjects BMD development until the age of 22 years was analyzed. INTERVENTION: GnRHa monotherapy (median duration in natal boys with GD [transwomen] and natal girls with GD [transmen] 1.3 and 1.5 y, respectively) followed by CSH (median duration in transwomen and transmen, 5.8 and 5.4 y, respectively) with discontinuation of GnRHa after gonadectomy. MAJOR OUTCOME MEASURES: How BMD develops during SR until the age of 22 years. RESULTS AND CONCLUSION: Between the start of GnRHa and age 22 years the lumbar areal BMD z score (for natal sex) in transwomen decreased significantly from -0.8 to -1.4 and in transmen there was a trend for decrease from 0.2 to -0.3. This suggests that the BMD was below their pretreatment potential and either attainment of peak bone mass has been delayed or peak bone mass itself is attenuated. PMID: 25427144.Link to full text:7: Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria.Costa, R., M. Dunsford, E. Skagerberg, V. Holt, P. Carmichael and M. Colizzi.J Sex Med. 2015 Nov;12(11):2206-14.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.8: Treatment for gender dysphoria in children: the new legal, ethical and clinical landscape.Smith, M. K. and B. Mathews.Med J Aust. 2015 Feb 2;202(2):102-4.Gender dysphoria is a condition in which a child's subjectively felt identity and gender are not congruent with her or his biological sex. Because of this, the child suffers clinically significant distress or impairment in social functioning. The Family Court of Australia has recently received an increasing number of applications seeking authorisation for the provision of hormones to treat gender dysphoria in children. Some medical procedures and interventions performed on children are of such a grave nature that court authorisation must be obtained to render them lawful. These procedures are referred to as special medical procedures. Hormonal therapy for the treatment of gender dysphoria in children is provided in two stages occurring years apart. Until recently, both stages of treatment were regarded by courts as special medical treatments, meaning court authorisation had to be provided for both stages. In a significant recent development, courts have drawn a distinction between the two stages of treatment, permitting parents to consent to the first stage. In addition, it has been held that a child who is determined by a court to be Gillick competent can consent to stage 2 treatment. The new legal developments concerning treatment for gender dysphoria are of ethical, clinical and practical importance to children and their families, and to medical practitioners treating children with gender dysphoria. Medical practitioners should benefit from an understanding of the recent developments in legal principles. This will ensure that they have up-to-date information about the circumstances under which treatment may be conducted with parental consent, and those in which they must seek court authorisation.9: Retrospective study of the management of childhood and adolescent gender identity disorder using medroxyprogesterone acetate.Lynch, M. M., M. M. Khandheria and W. J. Meyer, III.International Journal of Transgenderism. 2015;16(4):201-208.GnRH analogues are the standard therapy but expensive therapy for the suppression of pubertal changes in transsexual individuals. In the 1960s, medroxyprogesterone acetate was found to be efficacious in treating central precocious puberty by inhibiting the secretion of gonadotropins and/or interfering with gonadal steroid synthesis. To avoid the adverse effects and prohibitive cost of gonadotropin releasing hormone analogues, this study utilized medroxyprogesterone as an alternative treatment for puberty sex hormone suppression. The goal of this retrospective chart review is to determine the efficacy and safety of medroxyprogesterone. Sixteen subjects with Gender Identity Disorder less than 19 years were offered medroxyprogesterone to suppress puberty sex steroids. Seven male-to-female individuals were treated with the oral form of medroxyprogesterone. Six female-to-male individuals used depot medroxyprogesterone acetate; one used oral; and two refused. One decided to change back to being female. None of the patients discontinued therapy because of unwanted side-effects. In conclusion, medroxyprogesterone is an effective, safe, and affordable option for the suppression of pubertal hormones in teens desiring gender change. It is also an excellent option for those who have needle phobia. Response to treatment and compliance were favorable. (PsycINFO Database Record (c) 2016 APA, all rights reserved).10: Young adult psychological outcome after puberty suppression and gender reassignment.de Vries, A. L., J. K. McGuire, T. D. Steensma, E. C. Wagenaar, T. A. Doreleijers and P. T. Cohen-Kettenis.Pediatrics. 2014 Oct;134(4):696-704.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. PMID: 25201798.Link to full text:11: Approach to the patient: transgender youth: endocrine considerations.Rosenthal, S. M.J Clin Endocrinol Metab. 2014 Dec;99(12):4379-89.Compelling studies have demonstrated that "gender identity"--a person's inner sense of self as male, female, or occasionally a category other than male or female--is not simply a psychosocial construct, but likely reflects a complex interplay of biological, environmental, and cultural factors. An increasing number of preadolescents and adolescents, identifying as "transgender" (a transient or persistent identification with a gender different from their "natal gender"--ie, the gender that is assumed based on the physical sex characteristics present at birth), are seeking medical services to enable the development of physical characteristics consistent with their affirmed gender. Such services, including the use of agents to block endogenous puberty at Tanner stage 2 and subsequent use of cross-sex hormones, are based on longitudinal studies demonstrating that those individuals who were first identified as gender-dysphoric in early or middle childhood and who still meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. Furthermore, onset of puberty in transgender youth is often accompanied by increased "gender dysphoria"--clinically significant distress related to the incongruence between one's affirmed gender and one's "assigned (or natal) gender." Studies have shown that such distress may be ameliorated by a "gender-affirming" model of care. Although endocrinologists are familiar with concerns surrounding gender identity in patients with disorders of sex development, many providers are unfamiliar with the approach to the evaluation and management of transgender youth without a disorder of sex development. The goals of this article are to review studies that shed light on the biological underpinnings of gender identity, the epidemiology and natural history of transgenderism, current clinical practice guidelines for transgender youth, and limitations and challenges to optimal care. Prospective cohort studies focused on long-term safety and efficacy are needed to optimize medical and mental health care for transgender youth. PMID: 25140398.Link to full text:12: Gonadal suppressive and cross-sex hormone therapy for gender dysphoria in adolescents and adults.Smith, K. P., C. M. Madison and N. M. Milne.Pharmacotherapy. 2014 Dec;34(12):1282-97.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.13: Beyond the guidelines: challenges, controversies, and unanswered questions.Radix, A. and M. Silva.Pediatr Ann. 2014 Jun;43(6):e145-50.Transgender and gender-nonconforming youth have unique medical and psychosocial needs that frequently go unmet. For youth who wish to have their physical appearance congruent with their gender identity, treatment guidelines are available that advocate the use of gonadotropin-releasing hormone (GnRH) analogues (puberty blockers) and cross-sex hormone regimens. Although medical transition was once considered highly controversial, there is a mounting body of evidence that providing a supportive and affirming environment, as well as appropriate medical intervention, results in improved health outcomes. Primary care pediatricians may be unaware of current guidelines and consequently the need for treatment and/or timely referrals. Transgender youth often face other hurdles to initiation of therapy, including refusal of care and harassment in medical settings, denial of coverage by insurance plans, and the high cost of puberty blockers. Because transgender youth younger than 18 years depend on their families for medical decision making, they may be unable to access necessary medical treatment when parents do not support their transition plan. Medical transition impacts many aspects of the medical system, such as insurance coverage, billing, electronic health records, and preventive health care maintenance. These issues may become more apparent with the implementation of the Affordable Care Act (ACA) and increased use of electronic records and clinical decision support. The implementation of the ACA may also present new opportunities and protections for transgender individuals. Primary pediatricians are often the first providers families and youth reach out to for advice, and they can assist families with negotiating these complex medical, legal, social, and economic challenges and optimizing access to safe and appropriate health care services.14: Early Medical Intervention in Adolescents with Gender Dysphoria. [book section]Delemarre-van de Waal, H. A. (2014).In: Gender Dysphoria and Disorders of Sex Development Progress in Care and Knowledge: Springer, 2014. 193-203.15: Health care for gender variant or gender non-conforming children.Forcier, M. M. and E. Haddad.R I Med J (2013). 2013 Apr 01;96(4):17-21.Most children explore various aspects of gender and sexuality as children. Youth with consistent, persistent, and insistent gender non-conformity or gender dysphoria are important to identify in the pre- and early-pubertal years as early intervention and support may be lifesaving. Those whose gender non-conformity persists into puberty and adolescence are most likely to identify as transgender. Blocking pubertal development at Tanner stage 2 for pre-pubertal, gender non-conforming children is a relatively new but reversible and highly beneficial strategy to delay puberty, giving patients and families time to come up with a transition plan. Early identification, collaborative support from healthcare providers and mental health clinicians, and supportive interventions for both children and families grappling with gender variance may improve social and mental health outcomes for what has traditionally been considered a high-risk, vulnerable population.16: Guidelines for pubertal suspension and gender reassignment for transgender adolescents.Hembree, W. C.Child Adolesc Psychiatr Clin N Am. 2011 Oct;20(4):725-32.Pubertal suppression at Tanner stage 2 should be considered in adolescents with persistent gender identity disorder (GID). Issues related to achievement of adult height, timing of initiating sex steroid treatment, future fertility options, preventing uterine bleeding, and required modifications of genital surgery remain concerns. Concerns have been raised about altering neuropsychological development during cessation of puberty and reinitiation of puberty by the sex steroid opposite those determined by genetic sex. Collaborative assessment and treatment of dysphoric adolescents with persistent GID resolves these concerns and deepens our understanding of gender development. PMID: 22051008.Link to full text:17: Treatment of adolescents with gender dysphoria in the Netherlands.Cohen-Kettenis, P. T., T. D. Steensma and A. L. de Vries.Child Adolesc Psychiatr Clin N Am. 2011 Oct;20(4):689-700.In the Netherlands, gender dysphoric adolescents may be eligible for puberty suppression at age 12, subsequent cross-sex hormone treatment at age 16, and gender reassignment surgery at age 18. Initially, a thorough assessment is made of the gender dysphoria and vulnerabilities in functioning or circumstances. Psychological interventions and/or gender reassignment may be offered. Psychological interventions are offered if the adolescent needs to explore gender identity and treatment wishes, suffers from coexisting problems, or needs support and counseling during gender reassignment. Although more studies are necessary, this approach seems to contribute significantly to the well-being of gender dysphoric adolescents. PMID: 22051006.Link to full text:18: Puberty suppression in gender identity disorder: the Amsterdam experience.Kreukels, B. P. and P. T. Cohen-Kettenis.Nat Rev Endocrinol. 2011 May 17;7(8):466-72.The use of gonadotropin-releasing hormone analogs (GnRHa) to suppress puberty in adolescents with gender dysphoria is a fairly new intervention in the field of gender identity disorders or transsexualism. GnRHa are used to give adolescents time to make balanced decisions on any further treatment steps, and to obtain improved results in the physical appearance of those who opt to continue with sex reassignment. The effects of GnRHa are reversible. However, concerns have been raised about the risk of making the wrong treatment decisions, as gender identity could fluctuate during adolescence, adolescents in general might have poor decision-making abilities, and there are potential adverse effects on health and on psychological and psychosexual functioning. Proponents of puberty suppression emphasize the beneficial effects of GnRHa on the adolescents' mental health, quality of life and of having a physical appearance that makes it possible for the patients to live unobtrusively in their desired gender role. In this Review, we discuss the evidence pertaining to the debate on the effects of GnRHa treatment. From the studies that have been published thus far, it seems that the benefits outweigh the risks. However, more systematic research in this area is needed to determine the safety of this approach.19: Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study.de Vries, A. L., T. D. Steensma, T. A. Doreleijers and P. T. Cohen-Kettenis.J Sex Med. 2011 Aug;8(8):2276-83.INTRODUCTION: Puberty suppression by means of gonadotropin-releasing hormone analogues (GnRHa) is used for young transsexuals between 12 and 16 years of age. The purpose of this intervention is to relieve the suffering caused by the development of secondary sex characteristics and to provide time to make a balanced decision regarding actual gender reassignment. AIM: To compare psychological functioning and gender dysphoria before and after puberty suppression in gender dysphoric adolescents. METHODS: Of the first 70 eligible candidates who received puberty suppression between 2000 and 2008, psychological functioning and gender dysphoria were assessed twice: at T0, when attending the gender identity clinic, before the start of GnRHa; and at T1, shortly before the start of cross-sex hormone treatment. MAIN OUTCOME MEASURES: Behavioral and emotional problems (Child Behavior Checklist and the Youth-Self Report), depressive symptoms (Beck Depression Inventory), anxiety and anger (the Spielberger Trait Anxiety and Anger Scales), general functioning (the clinician's rated Children's Global Assessment Scale), gender dysphoria (the Utrecht Gender Dysphoria Scale), and body satisfaction (the Body Image Scale) were assessed. RESULTS: Behavioral and emotional problems and depressive symptoms decreased, while general functioning improved significantly during puberty suppression. Feelings of anxiety and anger did not change between T0 and T1. While changes over time were equal for both sexes, compared with natal males, natal females were older when they started puberty suppression and showed more problem behavior at both T0 and T1. Gender dysphoria and body satisfaction did not change between T0 and T1. No adolescent withdrew from puberty suppression, and all started cross-sex hormone treatment, the first step of actual gender reassignment. CONCLUSION: Puberty suppression may be considered a valuable contribution in the clinical management of gender dysphoria in adolescents.20: Endocrine treatment of transsexual persons: an Endocrine Society Clinical Practice Guideline: commentary from a European perspective.Meriggiola, M. C., E. A. Jannini, A. Lenzi, M. Maggi and C. Manieri.Eur J Endocrinol. 2010 May;162(5):831-3.The treatment of transsexual subjects is a challenging task for the endocrinologist who, in collaboration with the mental health professional and the surgeon, is called upon to confirm the diagnosis and adjust hormonal treatment aimed at suppressing endogenous sex hormones and to develop hormone characteristics of the desired gender. These guidelines are structured to provide evidence-based suggestions or, where evidence is lacking, expert recommendations on diagnostic procedures and hormonal treatment in adolescent and adult transsexuals, including long-term care and eligibility for surgery. The multidisciplinary approach to treatment, the additional diagnostic role of hormone administration and the need to maintain hormone levels within the physiological range are key suggestions stressed in the guidelines which are particularly important for an endocrinologist unfamiliar with this field. The need for psychological assessment before surgery is not common in many countries and should be stressed further in the guidelines. Some important issues such as time and method of hormone withdrawal before surgery together with when and which hormones should be administered after sex reassignment surgery has been completed also remain unclear. These guidelines represent a pivotal document for endocrinologists setting a standard for the care of transsexuals and providing directions for future research. PMID: 20150325.Link to full text:21: Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline.Hembree, W. C., P. Cohen-Kettenis, H. A. Delemarre-van de Waal, L. J. Gooren, W. J. Meyer, 3rd, N. P. Spack, V. Tangpricha and V. M. Montori.J Clin Endocrinol Metab. 2009 Sep;94(9):3132-54.OBJECTIVE: The aim was to formulate practice guidelines for endocrine treatment of transsexual persons. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence, which was low or very low. CONSENSUS PROCESS: Committees and members of The Endocrine Society, European Society of Endocrinology, European Society for Paediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, and World Professional Association for Transgender Health commented on preliminary drafts of these guidelines. CONCLUSIONS: Transsexual persons seeking to develop the physical characteristics of the desired gender require a safe, effective hormone regimen that will 1) suppress endogenous hormone secretion determined by the person's genetic/biologic sex and 2) maintain sex hormone levels within the normal range for the person's desired gender. A mental health professional (MHP) must recommend endocrine treatment and participate in ongoing care throughout the endocrine transition and decision for surgical sex reassignment. The endocrinologist must confirm the diagnostic criteria the MHP used to make these recommendations. Because a diagnosis of transsexualism in a prepubertal child cannot be made with certainty, we do not recommend endocrine treatment of prepubertal children. We recommend treating transsexual adolescents (Tanner stage 2) by suppressing puberty with GnRH analogues until age 16 years old, after which cross-sex hormones may be given. We suggest suppressing endogenous sex hormones, maintaining physiologic levels of gender-appropriate sex hormones and monitoring for known risks in adult transsexual persons. PMID: 19509099.Link to full text:
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