In gender dysphoria associated with a disorder of sex development, the likelihood of later gender dysphoria is increased if prenatal production and utilization (via receptor sensitivity) of androgens are grossly atypical relative to what is usually seen in individuals with the same assigned gender. Examples include 46,XY individuals with a history of nor- bladder exst-rophy or penile agenesis) and who have been assigned to the female gender.
The likelihood of gender dysphoria is further enhanced by additional, prolonged, highly gender-atypical postnatal androgen exposure with somatic virilization as may occur in fe- male-raised and noncastrated 46,XY individuals with 5-alpha reductase-2 deficiency or 17-beta—hydroxysteroid dehydrogenase-3 deficiency or in female—raised 46,XX individuals with classical congenital adrenal hyperplasia with prolonged periods of non-adherence to glucocorticoid replacement therapy. However, the prenatal androgen milieu is more closely related to gendered behavior than to gender identity. Many individuals with dis- orders of sex development and markedly gender-atypical behavior do not develop gender dysphoria. Thus, gender-atypical behavior by itself should not be interpreted as an indi- cator of current or future gender dysphoria. There appears to be a higher rate of gender dysphoria and patient-initiated gender change from assigned female to male than from as- signed male to female in 46,XY individuals with a disorder of sex development.
Individuals with gender dysphoria have been reported across many countries and cul- tures. The equivalent of gender dysphoria has also been reported in individuals living in cultures with institutionalized gender categories other than male or female. It is unclear whether with these individuals the diagnostic criteria for gender dysphoria would be met.
Individuals with a somatic disorder of sex development show some correlation of final gender identity outcome with the degree of prenatal androgen production and utilization.
However, the correlation is not robust enough for the biological factor, where ascertain- able, to replace a detailed and comprehensive diagnostic interview evaluation for gender dysphoria.
Functional Consequences of Gender Dysphoria
Preoccupation with cross-gender wishes may develop at all ages after the first 2—3 years of childhood and often interfere with daily activities. In older children, failure to develop age-typical same-sex peer relationships and skills may lead to isolation from peer groups and to distress. Some children may refuse to attend school because of teasing and harass- ment or pressure to dress in attire associated with their assigned sex. Also in adolescents and adults, preoccupation with cross-gender wishes often interferes with daily activities.
Relationship difficulties, including sexual relationship problems, are common, and func- tioning at school or at work may be impaired. Gender dysphoria, along with atypical gender expression, is associated with high levels of stigmatization, discrimination, and victimization, leading to negative self—concept, increased rates of mental disorder comor- bidity, school dropout, and economic marginalization, including unemployment, with at- tendant social and mental health risks, especially in individuals from resource-poor family backgrounds. In addition, these individuals’ access to health services and mental health services may be impeded by structural barriers, such as institutional discomfort or inex- perience in working with this patient population.
Nonconformity to gender roles. Gender dysphoria should be distinguished from sim- ple nonconformity to stereotypical gender role behavior by the strong desire to be of an- other gender than the assigned one and by the extent and pervasiveness of gender-variant activities and interests. The diagnosis is not meant to merely describe nonconformity to stereotypical gender role behavior (e.g., "tomboyism” in girls, ”girly-boy” behavior in boys, occasional cross-dressing in adult men). Given the increased openness of atypical gender expressions by individuals across the entire range of the transgender spectrum, it is important that the clinical diagnosis be limited to those individuals whose distress and impairment meet the specified criteria.