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 .

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.