Care of Transgender/Gender Nonconforming Youth





Introduction


Concurrent with increasing public awareness of individuals whose gender identity is not aligned with their physical sex characteristics, there has been an increasing number of gender nonconforming/transgender youth seeking medical services to enable the development of physical characteristics consistent with their experienced gender. In eligible individuals, current clinical practice guidelines endorse use of agents to block endogenous puberty at Tanner stage 2 development with subsequent use of gender-affirming sex hormones, and are based on longitudinal studies demonstrating that youth first identified as gender dysphoric in childhood and who continue to meet mental health criteria for gender dysphoria (GD)/gender incongruence (GI) at early puberty are likely to be transgender as adults. Limited outcomes data support current practice and long-term studies are necessary to optimize care. This chapter reviews definitions relevant to gender nonconforming/transgender youth, epidemiology, developmental trajectories of gender, evidence supporting a role for biology in gender identity development, mental health comorbidities associated with GD, current treatment models, barriers to care, and priorities for research.


Definitions and epidemiology


According to the Merriam-Webster’s Medical Dictionary , sex and gender have distinct meanings. Sex refers to “either of two major forms of individuals that occur in many species and that are distinguished respectively as female or male, especially on the basis of their reproductive organs and structures.” In contrast, gender refers to the “behavioral, cultural, or psychological traits typically associated with one sex.” Gender itself is then subdivided into gender identity and gender role/behavior. Gender identity is a person’s internal sense of being male or female, whereas gender role is the expression of masculinity or femininity. There has been increasing recognition that gender identity exists on a spectrum and that some individuals identify as nonbinary. Sexual orientation is one’s sexual attraction toward partners of the opposite sex/gender (heterosexual), same sex/gender (homosexual), or both (bisexual). Gender identity does not predict sexual orientation. A person of any gender may have any sexual orientation.


“Gender Dysphoria,” listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM) V refers to clinically significant distress of at least 6 months, duration, related to the incongruence between one’s affirmed or experienced gender and one’s “assigned (or natal) gender” (gender incongruence). This term replaces gender identity disorder (GID), which was included in the earlier DSM IV. Replacing the term “disorder” with “dysphoria” underscores the concept that a transgender identity, in and of itself, is no longer considered pathological, and focuses clinical concern on the distress that an individual with GI may experience. A summary of terms used in this chapter is detailed in Box 19.1 .



Box 19.1

(From Hembree, W.C. et al. (2017). Endocrine treatment of gender-dysphoric/gender-incongruent persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrine Metab, 102 (11), 1–35; by permission of the Endocrine Society.)

Definitions of Terms Used in This Chapter





  • Biological sex, biological male or female: These terms refer to physical aspects of maleness and femaleness. As these may not be in line with each other (e.g., a person with XY chromosomes may have female-appearing genitalia), the terms biological sex and biological male or female are imprecise and should be avoided.



  • Cisgender: This means not transgender. An alternative way to describe individuals who are not transgender is “nontransgender people.”



  • Gender-affirming (hormone) treatment: See “gender reassignment”



  • Gender dysphoria: This is the distress and unease experienced if gender identity and designated gender are not completely congruent. In 2013 the American Psychiatric Association released the fifth edition of the DSM-5, which replaced “gender identity disorder” with “gender dysphoria” and changed the criteria for diagnosis.



  • Gender expression: This refers to external manifestations of gender, expressed through one’s name, pronouns, clothing, haircut, behavior, voice, or body characteristics. Typically, transgender people seek to make their gender expression align with their gender identity, rather than their designated gender.



  • Gender identity/experienced gender: This refers to one’s internal, deeply held sense of gender. For transgender people, their gender identity does not match their sex designated at birth. Most people have a gender identity of man or woman (or boy or girl). For some people, their gender identity does not fit neatly into one of those two choices. Unlike gender expression (see later), gender identity is not visible to others.



  • Gender identity disorder: This is the term used for GD/gender incongruence in previous versions of DSM (see “gender dysphoria”). The ICD-10 still uses the term for diagnosing child diagnoses, but the upcoming ICD-11 has proposed using “gender incongruence of childhood.”



  • Gender incongruence: This is an umbrella term used when the gender identity and/or gender expression differs from what is typically associated with the designated gender. Gender incongruence is also the proposed name of the gender identity–related diagnoses in ICD-11. Not all individuals with gender incongruence have gender dysphoria or seek treatment.



  • Gender variance: See “gender incongruence”



  • Gender reassignment: This refers to the treatment procedure for those who want to adapt their bodies to the experienced gender by means of hormones and/or surgery. This is also called gender-confirming or gender-affirming treatment .



  • Gender-reassignment surgery (gender-confirming/gender-affirming surgery): These terms refer only to the surgical part of gender confirming/gender-affirming treatment.



  • Gender role: This refers to behaviors, attitudes, and personality traits that a society (in a given culture and historical period) designates as masculine or feminine and/or that society associates with or considers typical of the social role of men or women.



  • Sex designated at birth: This refers to sex assigned at birth, usually based on genital anatomy.



  • Sex: This refers to attributes that characterize biological maleness or femaleness. The best known attributes include the sex-determining genes, the sex chromosomes, the H-Y antigen, the gonads, sex hormones, internal and external genitalia, and secondary sex characteristics.



  • Sexual orientation: This term describes an individual’s enduring physical and emotional attraction to another person. Gender identity and sexual orientation are not the same. Irrespective of their gender identity, transgender people may be attracted to women (gynephilic), attracted to men (androphilic), bisexual, asexual, or queer.



  • Transgender: This is an umbrella term for people whose gender identity and/or gender expression differs from what is typically associated with their sex designated at birth. Not all transgender individuals seek treatment.



  • Transgender male (also: trans man, female-to-male, transgender male): This refers to individuals assigned female at birth but who identify and live as men.



  • Transgender woman (also: trans woman, male-to female, transgender female): This refers to individuals assigned male at birth but who identify and live as women.



  • Transition: This refers to the process during which transgender persons change their physical, social, and/or legal characteristics consistent with the affirmed gender identity. Prepubertal children may choose to transition socially.



  • Transsexual: This is an older term that originated in the medical and psychologic communities to refer to individuals who have permanently transitioned through medical interventions or desired to do so.




A 2017 report from the Williams Institute of the University of California Los Angeles School of Law, informed by state level population-based surveys, indicated that 0.6% of US adults (25–64 years) and 0.7% of adolescents and young adults (13–24 years) identify as transgender. A population-based study of self-reported gender identity in 80,929 Minnesota high school students reported a prevalence of 2.7% gender nonconforming or transgender. Transgender prevalence estimates ranging from 0.5% to 1.3% of birth-assigned males and 0.4% to 1.2% of birth-assigned females have been reported in a recent international review, representing an estimate of 25 million transgender people worldwide. In recent years, there has been a striking inversion in the sex ratio of adolescents seeking services for GD, with a predominance of birth-assigned females.


Biological determinants of gender identity


Studies from several biomedical disciplines—genetics, endocrinology, and neurology—support the concept that there are biological underpinnings to gender identity development. Results of these studies support the concept that gender identity is not simply a psychosocial construct but likely reflects a complex interplay of biological, environmental, and cultural factors.


With respect to genetics and gender identity, a recent study reports heritability estimates for gender identity in the range of 30% to 60%. A study supporting a role for genetic factors in gender identity outcome in transgender individuals demonstrated a 39.1% concordance for GID (based on DSM-IV criteria) in 23 pairs of monozygotic twins, with no concordance for GID in 21 same-sex dizygotic female and male twin pairs or in seven opposite sex twin pairs. Although a number of investigators have sought to identify polymorphisms in specific candidate genes that may be more prevalent in transgender versus nontransgender controls, such studies have been inconsistent and lacking strong statistical significance.


With respect to hormonal influences on gender identity, it should be noted that most transgender individuals do not have a disorder/difference of sex development (DSD) or any obvious abnormality in sex steroid production or response. However, studies in individuals with a variety of DSDs have informed our understanding of the role that hormones (prenatal and early postnatal androgens, in particular) may play in gender identity development. For example, in studies of 46 XX individuals reared female, with virilizing congenital adrenal hyperplasia (CAH) caused by mutations in the CYP21A2 gene, there is a greater degree of a transgender identity outcome (female-to-male) than what would be expected in the general population. In a meta-analysis of 250 adults with this condition, raised female, although nearly 95% accepted a female gender identity, 5.2% reported either a male gender identity or GD. By comparison, the prevalence of a transgender identity in adults in recent population estimates in the United States is 0.5% to 0.7%. A separate study of adult 46 XX individuals with classical 21-hydroxylase deficiency demonstrated a relationship between severity of disease and gender identity outcome. Of 42 patients with the salt-wasting form, three (7.1%) either had GD or a male gender identity; no GD was seen in less severely affected individuals. A study in 46 XX youth with 21-hydroxylase deficiency (salt-wasting or simple virilizing) found that 12.8% demonstrated cross-gender identification. In a recent cross-sectional study from Europe, of 221 individuals with 46 XX CAH, 28 were noted to have experienced a “gender change”; in 25, this was reported to have occurred prepubertally; in one postpubertally; and in two the timing of “gender change” was unknown. The 25 individuals in this study described as having a prepubertal “gender change,” were, in fact, individuals who underwent feminizing genital surgery in the newborn period (before one’s gender identity is known); furthermore, the one individual reported in this study to have a gender change postpubertally was, in fact, a 46 XX individual with a male gender identity who had undergone masculinizing genital surgery (personal communication with Dr. Baudewijntje P.C. Kreukels, VU University Medical Center, Amsterdam). The report of this cross-sectional European study did not indicate the number of 46 XX CAH individuals reared female that actually developed either gender dysphonia or a male gender identity (personal communication with B.P.C. Kreukels). It is noteworthy that in 46 XX individuals with virilizing CAH from 21-hydroxylase deficiency, prenatal androgens are more likely to affect gender expression/behavior and sexual orientation than gender identity. A role for prenatal/early postnatal androgens in gender identity development is also supported by studies in a variety of other hormonal and nonhormonal DSDs.


With respect to brain and gender identity, numerous studies in transgender adults, carried out before treatment with gender-affirming sex hormones, indicate that some sexually dimorphic brain structures are more closely aligned with gender identity than with physical sex characteristics. A gray matter study in gender dysphoric youth has shown a similar trend. In addition, functional studies (e.g., analysis of hypothalamic blood flow in response to smelling odorous compounds and brain-imaging studies carried out during mental rotation tasks) demonstrate that patterns typically observed to be sexually dimorphic were more closely aligned with gender identity than with physical sex characteristics, even before treatment with gender-affirming sex hormones, in both transgender adolescents and adults.


Emergence and developmental trajectories of gender


To identify when a child is exhibiting gender nonconforming behavior, it is necessary to understand what gender behaviors are typical at various developmental stages and how these behaviors may change over time. It is also important to appreciate how some expressions of gender vary in different environments. Recent reports of higher estimated prevalence rates of GD among youth in Australasia, Western Europe, and North America may reflect a greater willingness of people to seek treatment, as a result increased access to multidisciplinary gender clinics, as well as societal changes in attitudes about gender diversity.


Infancy


Although sex differentiation begins during early fetal development, gender differences from birth throughout infancy are limited to gross movement and emotional expressivity. For example, boys produce fewer tongue movements and weaker suckling than girls during early life; however, infant boys spend more time awake and produce greater movement of their trunk and limbs. Finally, infant girls smile more than boys and are less likely to exhibit angry facial expressions. Additional differences in behavior between boys and girls either do not yet exist, or are unable to be detected with current technology at this very young time.


Early Childhood


An important milestone that starts to occur between 18 months and the second year of life is the emergence of gender identity. This occurs around the time language skills develop so that young children increasingly use gender labels (e.g., girl, boy, woman, man) as their speech evolves. Boys begin to exhibit preferences for gender-typed toys, such as trucks by 2 years of age, and by the third year of life children prefer same-sex peers and this preference intensifies over time. Interestingly, young children who understand and use gender labels are more likely to prefer gender-typed toys, in support of the self-socialization theory of gender development that posits children socialize themselves into gender categories.


Children referred for treatment of GD prefer cross-sex toys, activities, and playmates more than their gender conforming peers and siblings. These differences in early childhood are not surprising, as the majority of transgender teens and adults recall that the onset of their GD occurred before puberty. Unknown at this time, is whether children with GD use gender labels differently during early childhood or experience the emergence of gender identity differently from gender conforming peers, during the first 2 years of life. Also unknown at this time is whether or not preferences for same- or cross-sex toys, activities, and playmates are stable throughout childhood for either gender conforming or nonconforming children.


Adolescence


Fewer studies of gender development have been conducted in adolescents compared with younger children. The theory of gender intensification suggests that adolescents experience increased pressure to conform to societal expectations of masculinity and femininity, and this pressure acts to further strengthen their gender identity. Although some studies support this theory, others do not. Some adolescents who experienced GD as younger children no longer do so as adolescents (desisters), whereas others continue to experience GD, as they mature (persisters). Thus for some people, gender identity evolves during adolescence in ways not predicted from earlier childhood. As noted earlier, the stability of gender from early childhood through later life has not been well studied. However, some investigators have attempted to identify factors that predict GD “persisters” versus “desisters,” as detailed in the section on “Natural History of Gender Dysphoria,” later. One of the recommended areas of future research in youth with GD is to identify additional predictors of GD persistence.


Mental health comorbidities associated with gender dysphoria


Gender nonconforming people have historically presented with psychological symptoms, such as anxiety, depression, and suicidality and self-harm at rates much higher than the general population. Until recently, most studies of psychiatric comorbidities associated with GD were conducted in transgender adults who had limited family and peer support, as well as poor access to gender-affirming treatment and counseling. As research on mental health of gender nonconforming youth broadens to include those who are both supported during their social transition and who receive multidisciplinary care, comorbidities are fewer. Nonetheless, behavioral and emotional problems for gender nonconforming youth in the community who are, and are not, referred for treatment are increased. As these youth continue to be followed, evidence will build to address long-term safety and efficacy of multidisciplinary treatment on their health and wellbeing.


Internalizing Disorders and Gender Dysphoria


Data from nationally representative samples of students, and also clinic-based studies of youth seeking medical treatment for GD reveal marked increases in depression among transgender youth compared with their cisgender counterparts. Clinically significant anxiety is also common. In contrast, children with GD who socially transition with the support of their family exhibit levels of depression that are no different, and anxiety levels that are only mildly elevated, from age-matched population norms. Additional evidence that support of others is important to maintain good mental health for gender nonconforming youth are associations between poor peer relations (i.e., gets teased, not liked by others) and emotional problems. Thus internalizing disorders, such as depression and anxiety are not necessarily a comorbidity of GD per se. Rather, psychological distress is likely caused by social ostracism and maltreatment by others.


Suicidality and Nonlethal Self-Harm


Transgender youth are more likely to think about suicide, attempt suicide, and inflict nonlethal self-harm (i.e., cutting, burning, or hitting) than cisgender youth. Self-harm in youth with GD is most common among assigned females and those impacted by psychologic symptoms, such as anxiety and depression. A report from Ontario, Canada, found that transgender adolescents and young adults were more likely to have greater self-esteem and life satisfaction, as well as decreased depression, suicidal ideation, and suicide attempts if their parents were supportive of their gender identity, in comparison to those individuals whose parents were “somewhat to not at all supportive.” Further investigations of the impact of social support and of gender-affirming multidisciplinary care warrant greater resources and effort, as studies of transgender youth continue to expand in pediatric medicine.


Eating Disorders


In the largest survey study of transgender youth to date, a higher rate of eating disorders was observed compared with cisgender women. Furthermore, assigned females are at particular risk. A smaller study reported high rates of overweight and obesity among transgender youth. For these youth, having too little or too much body fat may be a way to hide undesired physical characteristics. Thus it is recommended to screen for eating disorders in gender nonconforming children and adolescents.


Traits of Autism Spectrum Disorder


There is growing evidence from parent and teacher ratings, as well as review of medical records, that traits of autism spectrum disorder (ASD) and GD cooccur in some youth and adults. Although ASD is more prevalent in boys than in girls, in gender conforming individuals, the association between ASD and GD is similar for both natal males and females. Although there are no clinical guidelines for the delivery of care to children and adolescents with cooccurring GD and ASD traits, initial consensus guidelines for assessment and care are available.


Natural history of gender dysphoria


Information about the natural history of GD is limited. This is in part because medical treatment has been inaccessible to many because of expense and/or stigmatization surrounding this condition. In addition, much of what is known about GD focuses on adults. Thus basic understanding about the natural history of GD in youth is only now being elucidated. Here we review what is currently understood about remission versus persistence of GD in children and adolescents, and also the impact of family support and medical treatment on mental health status of young people whose gender identity is incongruent with their natal sex.


Desistence Versus Persistence


Historically, the majority of children who presented for treatment of GD experienced remission (desisters) by late childhood or early adolescence. Studies of desisters, and also those who continue to experience GD into later adolescence and adulthood (persisters), are beginning to reveal factors that distinguish between these groups. Specifically, natal females, those with more intense GD in childhood and adolescence, and those who experience greater dissatisfaction with their primary and secondary sex characteristics are more likely to be persisters. Persisters are also more likely to be sexually attracted to members of their natal sex. In addition, when asked if they are a boy or a girl, children whose GD persists are more likely to report that they believe themselves to be the sex opposite their natal sex, whereas desisters are more likely to report that they wished they were the other sex. The possibility of remission of GD in later childhood or early adolescence, coupled with the ability to use the onset of puberty, as a diagnostic tool for persistence of GD, motivate recommendations for delaying pubertal suppression (see “Medical Treatment,” later) until after transyouth enter the first stages of puberty (Tanner stages 2–3).


Impact of Family Support and Treatment


Among prepubertal children with GD who have the support of their families and who have socially transitioned, depression is no different from population averages and anxiety is only mildly elevated. Later in development, puberty suppression is associated with improved psychosocial functioning in adolescents whose GD persists. Among older adolescents and young adults with GD who received puberty suppression, cross-sex hormone treatment, and in some cases gender reassignment surgery—psychological function was comparable with the general population. In all of these studies, mental health support was part of multidisciplinary care delivered by experienced healthcare teams. Thus many of the mental health comorbidities of GD discussed earlier are ameliorated when family support is coupled with access to multidisciplinary care for children and adolescents of various developmental stages.


Role of mental health in multidisciplinary care


The Standards of Care of the World Professional Association for Transgender Health (WPATH) (WPATH, 7th Version) and the Endocrine Society Clinical Practice Guideline for Gender-Dysphoric/Gender-Incongruent Persons promote several approaches for the psychological support of youth with GD and their families. It is recommended that youth receive mental healthcare before, during, and after their social and medical transition. Roles for mental healthcare providers include : the ability to assess GD/GI in children and adolescents and appropriately use the DSM and International Classification of Diseases for diagnosing these conditions ; provide counseling and supportive psychotherapy to youth and their families ; diagnose and treat other psychiatric conditions apart from GD ; refer for pubertal suppression, cross-sex hormone therapy; and gender reassignment surgery when appropriate, including assessment of comprehension of the risks and benefits of these treatments ; refer patients and families to peer support; and educate and advocate on behalf of patients and their families.


Both the WPATH and the Endocrine Society outline competency requirements for mental health professionals who provide services to children and adolescents with GD. These include training in child/adolescent gender development (including gender nonconforming identities and roles) and child/adolescent psychopathology, with a minimum of a Master’s degree in clinical psychology from an accredited program and relevant licensing, and supervised training and competency in psychotherapy or counseling, including treatment of GD, as well as continued education in these areas.


Social Transition


Some children benefit from a social (nonmedical) transition to help determine if their GD will remit or persist. Reversible changes that allow a child to live according to the gender they identify with at home and school (such as hair length, clothing, and name change) are associated with improved mental health among this group. Children who undergo social transition are less likely to experience remission of their GD, and it is unclear if this is because only those with stronger GD initiate social transition, or if social transition itself impacts the evolution of GD in youth. Because current understanding of the effects of childhood social transition on GD is limited, mental health professionals may work with families to determine if this option is best for their child. For example, social transition may be considered exploratory (as opposed to finite) and may be first attempted while families vacation or in the privacy of the home.


Medical treatment


Current Treatment Models


GD that either emerges or worsens with the onset of physical puberty is highly predictive of a transgender identity during adulthood. This observation is central to the rationale for medical intervention in eligible transgender adolescents. Medical care of transgender youth has been primarily informed by Clinical Practice Guidelines from the Endocrine Society and cosponsoring organizations and by Standards of Care from WPATH. These documents endorse the use of gonadotropin- releasing hormone (GnRH) agonists at Tanner Stage 2 of pubertal development (testicular volume > 4 mL for assigned males at birth or initial stages of breast budding for assigned females at birth) in adolescents who meet the criteria for GD (optimally determined by a qualified mental health gender specialist) that has either emerged or worsened with the onset of puberty. Additional criteria for initiation of pubertal suppression with GnRH agonists include the following: the adolescent has requested treatment and has provided informed assent and the parents or legal guardians have provided informed consent, and any coexisting medical or psychosocial concerns that could interfere with treatment have been addressed. GnRH agonists should not be used in prepubertal gender dysphoric children to block the initiation of puberty.


Considered fully reversible, GnRH agonists, by pausing puberty, provide additional time for gender identity exploration, without the pressure of continued pubertal progression, and prevent irreversible development of secondary sex characteristics associated with the puberty that is not aligned with the person’s affirmed gender identity. Such undesired physical changes include breast development, female body habitus, and potentially short stature in assigned females at birth, and Adam’s apple, lowered voice, male bone configuration, and potentially tall stature in assigned males at birth. A protocol for baseline and follow-up monitoring of physical examination, and laboratory testing during pubertal suppression with GnRH agonists is outlined in Box 19.2 . GnRH agonists, while the preferred option for pubertal suppression, are costly and often inaccessible. Alternatives for pubertal suppression include depot and oral progestins.


Jan 4, 2021 | Posted by in ENDOCRINOLOGY | Comments Off on Care of Transgender/Gender Nonconforming Youth
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