Approach to the patient: transgender youth: endocrine considerations

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.