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5α-RD-2 5α-reductase-2
17β-HSD-3 17β-hydroxysteroid dehydrogenase-3
AR Androgen receptor
BMD Bone mineral density
CAH Congenital Adrenal Hyperplasia
CAIS Complete androgen insensitivity syndrome
DSD Disorder of Sex Development
DSM Diagnostic and Statistical Manual of Mental Disorders
DXA Dual energy x-ray absorptiometry
ER Estrogen receptor
ES Endocrine Society
FSH Follicle stimulating hormone
FTM Female-to male
GID Gender Identity Disorder
GnRH Gonadotropin releasing hormone
HPG Hypothalamic-pituitary-gonadal
LH Luteinizing hormone
MTF Male-to female
PGR Progesterone receptor
SOC Standards of Care
WPATH World Professional Association for Transgender Health



Gender nonconforming/transgender youth, in increasing numbers, are seeking medical services to enable the development of physical characteristics consistent with their experienced gender. These services including use of agents to block endogenous puberty at Tanner stage 2 with 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 continue to meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. The goals of Part I of this chapter are to review terms and definitions applicable to gender nonconforming youth (and adults), endocrine, genetic and neuroanatomical studies that shed light on the biologic underpinnings of gender identity and to review the natural history of transgenderism, current clinical practice guidelines for transgender youth, and limitations and challenges to optimal care.

Terms and Definitions

“Gender identity” refers to a person’s inner sense of self as male or female (and is not always binary). In contrast, a person’s “sex” refers to the physical attributes that characterize biologic maleness or femaleness (eg, the genitalia). Most children, at birth, are assigned a “sex of rearing” (some mental health providers prefer the term “gender of rearing”) based on genital anatomy. With that assignment comes societal expectations of gender roles, behaviors, and expressions, which are sometimes referred to as a child’s “assigned (or natal) gender.” In contrast to “sex (or gender) of rearing,” “gender identity” can only be assumed, and not, in fact, known until an individual achieves a particular level of psychological development and self-awareness. “Cisgender” refers to an individual for whom gender identity and physical sex characteristics are in alignment.

“Gender nonconforming” is a term sometimes used when gender identity is not consistent with the gender assumed based on birth sex assignment. As defined by the American Psychiatric Association, “transgender” refers to a person who transiently or persistently identifies with a gender different from their “natal gender.” The World Professional Association for Transgender Health (WPATH) Standards of Care (SOC) describes “transgender” (adjective) as “a diverse group of individuals who cross or transcend culturally defined categories of gender” and “transsexual” (adjective) as “individuals who seek to change or have changed their ...

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