Walking through a frame ...

This morning I was walking along a neighbourhood street, beside a park.  Ahead of me on the sidewalk were two youngish women, one of whom was pushing a stroller.  As I walked by them, the youngster in the stroller called out "boy", and when there was no response from its mother, repeated "boy", and again, "boy."  When there had opened some distance between us, I could hear the women speaking in low volume to each other.  I imagined that they hadn't wanted to correct the child within my earshot, presumably not to embarrass me.  I wouldn't have been embarrassed, though.  

In the vernacular of trangenderism, I was misgendered, and if I were a transgendered person, I would have felt this as a bigoted, even vicious, attack on my identity.

I am not transgendered.  I am a woman.  I am a woman who has been "misgendered" since I was a child.  The first time, I was a kid, my family was camping, I went to use the bathroom, and when I stepped out, a woman was stepping in, and saw me, then angrily chastised me for using the wrong bathroom.  I felt ashamed, as though I had done something wrong, although I knew I was a girl and the correct bathroom for me to use was the women's bathroom.  When I got back to our campsite, I told my mother what had happened, and her attitude was the problem was not with me but with that woman.

My mother didn't care that I dressed in t-shirts and shorts, didn't care that I played baseball with the neighbourhood boys, didn't care that I wasn't interested in make-up and dolls and pink toys.  She let me be me.  Maybe I could have used a little coaching in the ways of the world, but my mother encouraged me not to play the girl game, because her experiences were that men were dangerous, and I think she believed the longer I could avoid that knowledge first-hand, the better.

This morning, I was not offended.  Instead, I thought of how the young child already had learned to categorize people, but, of note, was not categorizing, say, trees ("fir", "maple") as they went along.  Clearly, categorizing people was important, at least to its parents.

An interesting thing about categorizing people, or anything for that matter, is that it is a construct of  a thought process represented in language.  It is biologically obvious to categorize people by sex; we are born into one of two categories (unless we are intersex).  It is completely constructed and arbitrary to categorize us by gender.  Gender was originally applied to language; its application to people was a co-optation of the early transgenderists (eg John Money), when they realized they had to do some fancy footwork to obfuscate the theory that one could change sex.  One cannot change sex, but if one conflates sex with gender, and then changes gender, voila!, sex change.

Language is meant to be descriptive, but when it is used proscriptively,  it is restrictive.  As Ruth Barrett discusses in Female Erasure, language forms a frame, and it is either a frame you define for yourself, or a frame someone else defines for, and forces on, you.

The trangenderists have forced a frame on us about gender and sex.  Elizabeth Hungerford, in Female Erasure, brilliantly dissects this frame by showing how the transgenderists have taken the language women have developed to describe our experience of discrimination based on our sex and have distorted it to be about gender discrimination by cis against trans.  In either system, biologic women are the ones ultimately oppressed, but now not merely by men, but by men who claim to be women, and when men claim to be women, they remove biologic women from the discussion of sex discrimination and erase everything about our experiences as women.

Transgenderism is not a frame that fits women.  Transgenderism is a frame that reduces a woman to a concept, a feeling, that can be imagined and felt by anyone who claims it. 

Women cannot accept this frame. 

Women must hold to the frame we define for ourselves.

When a chair is political ...

It is reasonable for us, the public, to expect that our public educational institutions strive to remain free from political agendas. Indeed, our public educational institutions ought to teach how to recognize political agendas, as part of the process of teaching students how to think critically.

When a public institution accepts private funds, there is an immediate compromise on this expected intellectual independence. Even if the donor demands nothing more than their name on the lintel of a building, we are still imprinted with the message that what occurs inside that building is brought to us by the "good will" of the donor. That may seem harmless, and in this day and age of purported funding shortages, we are exhorted to be grateful for such philanthropy. However, it is impossible for our freedom of thought to be without compromise, to be free of coercion, when it is sponsored by a private individual. 

Often the political agenda is mild (personal aggrandizement). Often it is not, as in the situation of the creation of the "world's first chair in transgender studies." Its statement of purpose sounds great!

The Chair in Transgender Studies is devoted to fostering and supporting research into a broad range of topics concerned with improving the lives and circumstances of transgender and gender nonconforming people.

We exist because good research is the basis for solid reliable information about the real world. We need research to drive social change. We need research as the basis for good policies and better laws to improve the well-being of trans and gender nonconforming people.

Who could argue with such well-intentioned social justice? And yet ... it is exactly that, the rhetoric of social justice, carefully crafted to subtly intimidate by way of political correctness any questioning, which would be rebuked with accusations of prejudice, and when claims for inquiry are meted with censorship, we are back in the land of solipsism.

The agenda of this chair is not opaque. 

First, note the faculty in which it is placed: Social Sciences. Not the the Faculty of Medicine, not the Faculty of Science. It is not placed in a science-based faculty because there is no biologic science to the transgender paradigm.

Second, note the university: University of Victoria. Not McGill, not Harvard, not even the University of California Berkeley. And who is the first professor to hold this chair? Dr Aaron Devor, a self-proclaimed feminist butch lesbian sexologist who lives as a man.

And third, note the funding: the Tawani Foundation, created by Jennifer (James) Pritzker, of the Pritzker family, "one of America's richest families." 

One can say who else would fund and study transgender studies but those who are advocates? What's wrong with that? The problem is in the methods and the agenda. True science is furthered by searching for facts, for proposing hypotheses and then daring to set out to disprove them, to see them withstand the most stringent examination, rather than gathering narrative as evidence of proof. 

One more note: their statement of purpose includes the goal "to drive social change." This chair is simply a means of attempting to gain pseudo-academic credibility to advance the current narrative of transgenderism.

Reviewing the research of transgendering our youth ...

Here is the full text of the article.  I have highlighted some salient points, such as the comment about the prevalence of mental health issues among gender dysphoric youth and that it has not been evaluated how these are related (ie does gender dysphoria arise out of other mental health issues?) and that the prevalence of gender dysphoria varies across different countries, which I believe suggests that it is culturally-influenced, and thus more an expression of anxiety than of an underlying innate problematic gender.  Of alarming note is that the incidence of gender dysphoria is rising among young women:  we are at risk of losing our women!

Gender dysphoria in children and adolescents: a review of recent research 
Johannes Fussa , Matthias K. Auerb , and Peer Brikena 

Institute for Sex Research and Forensic Psychiatry, Center for Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg and b Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany Correspondence to Johannes Fuss, Institute for Sex Research and Forensic Psychiatry, Center for Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany. Tel: +49 40 7410 57688; e-mail: jo.fuss@uke.de Curr Opin Psychiatry 2015, 28:430–434 DOI:10.1097/YCO.0000000000000203 www.co-psychiatry.com Volume 28 Number 6 November 2015 REVIEW Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.  

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. Keywords adolescence, childhood, gender dysphoria, gender identity disorder, gender incongruence, gender variance, transsexual, transsexualism  

KEY POINTS

• Gender dysphoric minors have a high burden of psychiatric comorbidities. 

• Number of referrals to gender clinics of children and adolescents with gender dysphoria especially of natal females are ever increasing. 

• A recently published long-term study on puberty suppression and subsequent cross gender hormones in gender dysphoric minors highlights positive effects on psychosocial outcomes. 

• Brain development and function regarding executive functioning seems not to be disturbed by puberty suppression. 

• Hopefully, this review will encourage researchers and clinicians to perform further research, especially longterm follow-up studies, with gender dysphoric minors.

INTRODUCTION
When preparing for our ‘‘a year in review’’-lectures at the first biennial conference of the European Professional Association for Transgender Health (EPATH) in Ghent (Belgium) 2015, we (J.F. and M.K.A.) were puzzled about the increasing variety and number of studies in the field of gender dysphoria. Although some research topics are relevant for gender dysphoric people of all ages, there are also issues that vary profoundly across the lifespan. One of the most controversial and timely question in the field is the care for gender dysphoric minors. Recent research may help to tailor treatment to the needs and difficulties of gender dysphoric minors. In the present article, we thus review recent studies that investigated the aspects of gender dysphoria in children and adolescents. We will use the term gender dysphoria from the DSM-5 for the present review. The database PubMed was searched for empirical studies that were published between May 2014 and May 2015. To detect all relevant studies, we used the following search term: [(transgender OR transsexuality OR gender dysphoria OR gender incongruence OR gender identity disorder)] AND [‘2014/05/01’(Date Publication): ‘2015/05/ 01’(Date Publication)] and found 555 studies with a potential relevance for the present review. Out of these, we reviewed all studies that addressed the mental health of gender dysphoric minors.

EPIDEMIOLOGICAL DATA AND COMORBIDITY
The prevalence of gender dysphoria in general and particularly in child and adolescent samples varies considerably across different countries. To date, representative studies are extremely scarce. In 2014, Clark et al. [1& ] presented for the first time data from a nationally representative survey (Youth ’12 in New Zealand; n ¼ 8166) on the prevalence of transgenderism in adolescents. Transgender is an umbrella term for gender dysphoric people and those with an incongruence of natal gender and gender identity. From more than 8000 secondary school students, 1.2% indicated to identify as transgender, whereas 2.5% were not sure about their gender. From those who identified as transgender, roughly 40% were not exclusively opposite-sex attracted, which is comparable with adult samples [2]. Interestingly, identifying as transgender was also associated with a significantly higher burden of weekly school bullying (20%), current depressive symptoms (40%) and suicide attempts within the last 12 months (20%). However, it is still a causality dilemma if the mental health burden was a sequela of being stigmatized as transgender or mental disorder a risk factor that increased the likelihood of becoming transgender or both. There has been a move toward the first explanation (distress because of discrimination, stigmatization and prejudice) and away from psycho-pathologizing gender dysphoric people per se. Nevertheless, there is still a debate around this question because it very much affects the clinical decision-making of how to organize mental healthcare for gender dysphoric youth and adults in the first place. Two recent studies from the UK [3] and US [4] demonstrated in line with the study from New Zealand that the most prevalent associated problems of gender dysphoric adolescents were bullying, depression, suicide attempts and self-harm. All of these may well be understood as sequelae of encountering gender dysphoria. In adolescents with gender dysphoria in the UK, natal females presented significantly more often with self-harm and natal males with autism spectrum disorder. A relation between autism spectrum disorder and gender dysphoria was also scrutinized by VanderLaan et al. [5] who reported an elevation of obsessional interests in gender dysphoric children. It was suggested that kids with autism spectrum disorder ‘may hold more rigid views of what it is to be male or female’ [3] and thus be more at risk toward developing gender dysphoria if they do not feel fit within their binary categories of girls and boys. Another explanation was that cross-gender obsessional interests may rather be a symptom of gender dysphoria and only superficially autism-like [5] and that especially the fragility of identity experiences in gender dysphoric minors leads to a more rigid fixation on gender-based stereotypes. It was further speculated that prenatal exposure to high testosterone levels or high birth weight may be involved in the simultaneous development of gender dysphoria and autism spectrum disorder [6& ,7]. In contrast to these reports that predominantly described comorbid psychopathology without indicating if gender dysphoria preceded or resulted from it, Kaltiala-Heino et al. [6& ] published a retrospective analysis of all minors who were treated in their gender clinic in Tampere/Finland within a 2-year period. They concluded from their data that severe psychopathology was preceding the onset of gender dysphoria. Although natal girls were overrepresented and the prevalence of autism spectrum disorder is generally lower in natal girls, the comorbid prevalence for autism spectrum disorder was as high as 26% in their sample. They also found that bullying was a severe problem but reported that in two thirds of the cases it had already started before the onset of gender dysphoria and was not targeted on gender or sexual behavior. Most of their young patients needed additional care from a child and adolescent psychiatrist because of psychiatric problems (other than gender dysphoria), and the authors concluded that ‘comorbid disorders were thus severe and could seldom be considered secondary to gender dysphoria’. This report contradicted the findings in other countries where comorbid psychopathology was less prevalent and rather a result of difficulties associated with gender dysphoria [8]. To date, it is still unclear why different researchers in different countries find such different results concerning the mental health of gender dysphoric minors. Are there previous assumptions or assessment methods responsible for these differences? Is it that gender dysphoric minors in Finland (and other countries) are really on average more psychiatrically disordered than, for example, in the Netherlands? And if so, which social and biological factors drive this difference? A higher mental health burden for affective disorders in gender dysphoric adults, for example, has been described in Germany and Norway compared with the Netherlands and Belgium [9]. To answer the above-mentioned questions, we need more multicenter studies that include different countries in the next years. Thus, we will learn to what extent and in what form gender dysphoric children and adolescents need psychiatric care or psychotherapeutic interventions by mental health professionals (also approaches that are sometimes critically compared with reparative or conversion therapy in homosexual individuals need to have an evidence base if they are applied, especially as they are highly disputed and were banned in the United States recently [10]).

PUBERTY SUPPRESSION
Importantly, the adolescents from the above-mentioned studies were not treated with puberty suppression, yet Holt et al. [3] observed that ‘many of the difficulties increased with age’ (without puberty suppression). The studies were thus not able to differentiate whether the psychosocial burden was higher or lower after their wish for transitioning was fulfilled. Another crucial question is, in which adolescents gender dysphoria will persist (persisters) and in whom it will remit (desisters) and how this relates to long-term mental health. Follow-up studies indicate a decrease in gender dysphoria during puberty in 60 80% of adolescents [11]. Both those with persisting and with remitting gender dysphoria indicate that they considered the period between 10 and 13 years of age to be crucial for long-term gender identity [11]. In consequence, hormonal treatment in adolescents with persisting gender dysphoria may help to reduce mental health burden. After its first description in the 1990s [12], puberty suppression in gender dysphoric youth with gonadotropin-releasing hormone analogues (GnRHa) has become one form of treatment in many specialized centers around the world. The rationale is to give youth more time to explore their gender identity by inhibiting the onset of permanent bodily changes through puberty. The so-called ‘Dutch protocol’ [13] recommends to treat gender dysphoric minors after an extensive psychological evaluation (to exclude ‘desisters’) with puberty suppression at the age of 12 years and after the young people have reached the first stages of puberty (Tanner stage 2 3). Later, they become eligible for cross-sex hormones and sex-reassignment surgery at the age of 16 and 18, respectively. This protocol dramatically changed the treatment of gender dysphoric minors and has been a guideline for many clinicians. Of note, minor changes to this protocol have been suggested (e.g. young patients receive puberty suppression sometimes even earlier than at the age of 12 years if they reach Tanner stage 2–3 at earlier age and as GnRHa treatment is not recommended to expand 2 years in order to avoid a disturbed bone development, cross-sex hormones may be prescribed well before the age of 14 years [14]). To evaluate the ‘Dutch protocol’, de Vries et al. [15&&] published the first long-term results in 2014. They assessed the psychological functioning (gender dysphoria, body image, global functioning, depression, anxiety, emotional and behavioral problems), the objective (social and educational/professional functioning) and subjective (quality of life, satisfaction with life and happiness) well-being of 55 young transgender adolescents before the onset of puberty suppression (T0), when cross-sex hormones started (T1) and 1 year after sex-reassignment surgery (T2). They found that after surgery the psychological functioning and well-being had steadily improved and were similar or better than in same-age young adults from the general population. As expected, gender dysphoria and problems with the body image persisted through puberty suppression and remitted only after crosssex hormones and surgery. Body image difficulties are a core feature of gender dysphoria and are also present in young adult patients [16]. The majority of the 55 young adults indicated that they experienced the social transition as easy and none of them reported regret concerning the medical interventions. Moreover, intriguing is that none of the natal females had received a phalloplasty yet and nevertheless reported a good quality of life. This study impressively demonstrated that psychiatric problems in gender dysphoric youth improved through medical treatment with a combination of puberty suppression and cross-sex hormones and surgery in minors. However, the ‘Dutch protocol’ demands the ‘absence of psychiatric comorbidity’ [17] and thus minors who are psychologically unstable and suffer from psychiatric comorbidity are excluded from participation in such studies [13]. One reason to exclude those minors is that puberty suppression had been an experimental therapy approach without a sound evidence-base. This situation has, however, changed after publication of the de Vries study [15&&]. As Kaltiala-Heino et al. [6& ] demonstrated a substantial part of minors who present with gender dysphoria in Finland have a severe psychiatric comorbidity. It is, therefore, important to gain more insight into long-term follow-up of these minors. Also evidence to define factors that exclude minors from puberty suppression is needed (and also to identify ‘desisters’ beforehand). There seems to be a certain threshold of psychiatric comorbidity that is acceptable for clinicians to indicate puberty suppression. What defines this threshold and what defines psychological stability? Is only mild comorbid psychopathology reduced by medical treatments? And if not, is it ethical to exclude gender dysphoric minors from medical treatment just because they have a psychiatric comorbidity? These questions highlight that longitudinal studies in gender dysphoric minors addressing outcomes in relation to particular comorbidities (such as autism spectrum disorder) are needed urgently. Such a research may help to tone down the extremely emotional debate about treatment and diagnosis of children and adolescents with gender dysphoria. From clinical practice, we know that sometimes adult gender dysphoric patients have severe comorbid psychopathology (e.g. recurrent depression or borderline personality disorder) and nevertheless experience a dramatic improvement in mental health through transitioning and transition-related care. A recent long-term follow-up evaluation (> 10 years) points to the same conclusion [18]. However, some people do not experience a complete remission from psychopathology and need an ongoing psychotherapy or pharmacotherapy even after transitioning [18]. Especially the study by Kaltiala-Heino et al. [6& ] emphasizes that we need to be very clear about which kids we need to treat by which protocol because we have less time for decision-making with the looming onset of puberty and its irreversible bodily changes. We are not in a situation in which we can easily postpone a decision about transitioning into adulthood and refer to ethical statements inmedicine such as ‘in dubio abstine’ and ‘primum non nocere’ because either way by suppressing or not suppressing puberty we may harm. Some patients who because of psychiatric comorbidity were not eligible for treatment before the age of 18 years at the VU clinic in Amsterdam (where the ‘Dutch protocol’ was established) persisted in their wish for transition. For these children and adolescents, we need evidence whether medical interventions despite comorbid mental disorders are indicated or not.  

NEUROIMAGING AND PREDICTIVE MEASURES
A fear that was associated with puberty suppression in minors was that brain development during puberty might be disturbed by hormonal suppression. Especially the prefrontal cortex (PFC) undergoes profound plastic changes during puberty and early adolescence [19]. Therefore, Staphorsius et al. [20&&] studied executive functioning – which is highly dependent on the PFC and improves with age until adulthood – in gender dysphoric adolescents who were treated with puberty suppression. Using the Tower of London-fMRI paradigm, they found that puberty suppression had neither an effect on executive functioning in gender dysphoric boys nor in girls. However, they found that natal gender affected neural activation during the task in controls and puberty suppressed gender dysphoric adolescents. In contrast, unsuppressed adolescents with gender dysphoria exhibited no gender difference in neural activation. Thus, the authors concluded that ‘puberty suppression even seemed to make some aspects of brain functioning more in accordance with the natal gender’. This study was to our knowledge the first to investigate how puberty suppression affects brain development and to indicate that puberty suppression does not disturb brain development during puberty in gender dysphoric adolescents. From adult people with gender dysphoria, we know that cross-sex hormones have a profound effect on brain plasticity markers such as cortical thickness and brain-derived neurotrophic factor [21,22] and thus would expect long-term effects of puberty suppression and cross-sex hormones on brain plasticity in minors. There is also an ongoing debate about the diagnosis of gender identity disorder or gender incongruence in childhood. Some advocacy groups claim that the diagnosis pathologizes gender variant behavior of kids who do not have a stable gender identity yet but merely explore the gender boundaries. Using implicit and explicit measures, a recent study [23] investigated the gender cognition of gender dysphoric children. Of note, the population of the Olson study was highly selected: all children in this study were supported by their families to live according to their identified gender in the United States. Olson et al. [23] found on all measures that responses of gender dysphoric children were indistinguishable from controls, when matched by gender identity. They stressed that gender dysphoric ‘children are not confused, delayed, showing gender-atypical responding, pretending or oppositional – they instead show responses entirely typical and expected for children with their gender identity’. They even went further and suggested to test for the predictive value of the investigated measures in future research to possibly use them in clinical settings to identify those kids who remain stable in their gender identity in later life. In light of the Gender dysphoria in children and adolescents above-mentioned findings concerning puberty suppression, predictive measures may indeed be helpful in clinical decision making, especially for those kids with psychiatric comorbidity and add to other factors that were described earlier [24].  

CONCLUSION
In conclusion, more longitudinal research with gender dysphoric children and adolescents is needed to compare different strategies of care and to see longterm results especially in those minors with comorbid psychiatric disorders. The lack of evidence is even more pressing considering a recent study in which the dramatically increasing number of referrals to gender clinics was reported [25]. Particularly, the number of referred natal females is increasing [25]. To date, it is unclear what cultural and biological underpinnings are the driving forces behind this increase in gender dysphoria and how we should face it. 

Acknowledgements The authors would like to thank Hertha Richter-Appelt, Inga Becker and Timo Nieder for helpful comments. Financial support and sponsorship None. Conflicts of Interest There are no conflicts of interest.  

REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest
1. & Clark TC, Lucassen MF, Bullen P, et al. The health and well being of transgender high school students: results from the New Zealand adolescent health survey (Youth’12). J Adolesc Health 2014; 55:93–99. The first study with data from a nationally representative survey on the prevalence of transgenderism in adolescents.
2. Auer MK, Fuss J, Hohne N, et al. Transgender transitioning and change of selfreported sexual orientation. PLoS One 2014; 9:e110016.
3. Holt V, Skagerberg E, Dunsford M. Young people with features of gender dysphoria: demographics and associated difficulties. Clin Child Psychol Psychiatry 2014. [Epub ahead of print]
4. Reisner SL, Vetters R, Leclerc M, et al. Mental health of transgender youth in care at an adolescent urban community health center: a matched retrospective cohort study. J Adolesc Health 2014; 56:274–279.
5. VanderLaan DP, Postema L, Wood H, et al. Do children with gender dysphoria have intense/obsessional interests? J Sex Res 2015; 52:213–219.
6. & Kaltiala-Heino R, Sumia M, Tyolajarvi M, Lindberg N. Two years of gender identity service for minors: overrepresentation of natal girls with severe problems in adolescent development. Child Adolesc Psychiatry Ment Health 2015; 9:9. An important analysis that indicates a higher mental health burden in gender dysphoric minors compared with earlier studies from other countries.
7. VanderLaan DP, Leef JH, Wood H, et al. Autism spectrum disorder risk factors and autistic traits in gender dysphoric children. J Autism Dev Disord 2015; 45:1742–1750.
8. de Vries AL, Doreleijers TA, Steensma TD, Cohen-Kettenis PT. Psychiatric comorbidity in gender dysphoric adolescents. J Child Psychol Psychiatry 2011; 52:1195–1202.
9. Heylens G, Elaut E, Kreukels BP, et al. Psychiatric characteristics in transsexual individuals: multicentre study in four European countries. Br J Psychiatry 2014; 204:151–156.
10. Vilain EB, Bailey JM. What should you do if your son says he’s a girl? LA Times 2015.
11. Steensma TD, Biemond R, Boer Fd, Cohen-Kettenis PT. Desisting and persisting gender dysphoria after childhood: a qualitative follow-up study. J Child Psychol Psychiatry 2011; 16:499–516.
12. Cohen-Kettenis PT, van Goozen SH. Pubertal delay as an aid in diagnosis and treatment of a transsexual adolescent. Eur Child Adolesc Psychiatry 1998; 7:246–248.
13. Delemarre-van de Waal HA, Cohen-Kettenis PT. Clinical management of gender identity disorder in adolescents: a protocol on psychological and paediatric endocrinology aspects. Eur J Endocrinol 2006; 155:131–137.
14. Wu¨ sthof A Challenges in transgender youth healthcare in two European countries: multidisciplinary experiences and perspectives from the Amsterdam and the Hamburg consultation services for children and adolescents In EPATH 2015 Book of Abstracts: The First Conference of the European Professional Association of Transgender Health 12-14 March 2015 Ghent, Belgium
15. && de Vries AL, McGuire JK, Steensma TD, et al. Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics 2014; 134:696–704. The first long-term analysis of the mental health outcome after puberty suppression, hormonal and surgical treatment in gender dysphoric minors.
16. Becker I, Nieder TO, Cerwenka S, et al. Body image in young gender dysphoric adults: a European multi-center study. Arch Sex Behav 2015. [Epub ahead of print]
17. Cohen-Kettenis PT, Delemarre-van de Waal HA, Gooren LJ. The treatment of adolescent transsexuals: changing insights. J Sex Med 2008; 5:1892–1897.
18. Ruppin U, Pfafflin F. Long-term follow-up of adults with gender identity disorder. Arch Sex Behav 2015; 44:1321–1329.
19. Huttenlocher PR. Synaptic density in human frontal cortex: developmental changes and effects of aging. Brain Res 1979; 163:195–205.
20. && Staphorsius AS, Kreukels BP, Cohen-Kettenis PT, et al. Puberty suppression and executive functioning: an fMRI-study in adolescents with gender dysphoria. Psychoneuroendocrinology 2015; 56:190–199. The first study addressing the question if puberty suppression disturbs brain development in gender dysphoric minors using neuroimaging methods.
21. Fuss J, Hellweg R, Van Caenegem E, et al. Cross-sex hormone treatment in male-to-female transsexual persons reduces serum brain-derived neurotrophic factor (BDNF). Eur Neuropsychopharmacol 2015; 25:95–99.
22. Zubiaurre-Elorza L, Junque C, Gomez-Gil E, Guillamon A. Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals. J Sex Med 2014; 11:1248–1261.
23. Olson KR, Key AC, Eaton NR. Gender cognition in transgender children. Psychol Sci 2015; 26:467–474.
24. Steensma TD, McGuire JK, Kreukels BP, et al. Factors associated with desistence and persistence of childhood gender dysphoria: a quantitative follow-up study. J Am Acad Child Adolesc Psychiatry 2013; 52:582–590.
25. Aitken M, Steensma TD, Blanchard R, et al. Evidence for an altered sex ratio in clinic-referred adolescents with gender dysphoria. J Sex Med 2015; 12:756– 763. 

This Bears Repeating ...

If you read only one book to understand why transgenderism is a feminist issue, this is the one to read, and how to order it:

Still looking for the science ...

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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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