Although histories of psychiatric treatments for substance abuse, adolescent adjustment disorders, serious suicidal thoughts, and depression are not uncommon in gender-dysphoric patients (Dixen et al. 1984), there is no evidence of increased frequency of comorbid diagnoses when nonclinical samples of transgendered males are assessed (Bentler and Prince 1970; Brown et al. 1996). However, those with GID who do present for treatment may have developed additional, secondary diagnoses (Breton and Cordier 1996; Modestin and Ebner 1995). Some of these disorders are defense mechanisms against the frustration, psychological pain, anxiety, and discrimination stemming from patients’ inability to live safely and comfortably in society in their desired gender roles.

For over a century (Lukianowicz 1959b), patients have presented with symptoms that have tended to seriously confound their gender identity conditions with other major psychiatric conditions. Although GID patients frequently report histories of anxiety and depressive disorders (Lothstein 1984), loneliness, social withdrawal, and dysfunctional intimate relationships, whether connected or not to their gender nonconformity, the question of the prevalence of comorbidity of gender dysphoria with other psychiatric diagnoses is inconclusive (Cole et al. 1997). Infrequently, psychosis may coexist with GID (Cole et al. 1997; Fisk 1973; Wise 1982). On the other hand, the symptom of genital self-mutilation may also be misdiagnosed as psychosis. Extreme opinions have been voiced regarding the treatment of gender-dysphoric conditions, and some have even labeled the surgical sex reassignment of transsexuals “a new type of psychosurgery” (Kavanaugh and Volkan 1978-1979). Others, on the basis of the results of testing performed in gender clinics (Bockting and Coleman 1992; P. Walker 1987), believe that all or most transsexual patients suffer from at least one accompanying Axis II condition. This has not been the experience of the author or of others who work outside of tertiary referral centers. When personality disorders are present, they are most likely to include borderline, schizoid, or histrionic features.

Recently, there have been reports of the co-occurrence of dissociative identity disorder and GID (Modestin and Ebner 1995). Devor (1994) described an FTM patient who experienced significant childhood abuse and later developed both of these conditions. Likewise, Brown (1999) reported a similar case in an MTF patient. Although the prevalence of the coincidence of these two disorders is not known, traditional interview questions exploring for dissociative disorders should be considered as part of the diagnostic process.

Further confounding the diagnosis of transsexualism are the following Axis III conditions sometimes associated with gender transposition: chromosomal abnormalities (e.g., Klinefelter’s syndrome [46,XXY]; a variety of mosaic patterns resulting in pseudohermaphroditism (Money et al. 1986; Rohatgi et al. 1987) in non-gender-dysphoric patients; endocrine abnormalities (e.g., 5-?-reductase deficiency with subsequent male pseudohermaphroditism) (Imperato-McGinley et al. 1979a, 1979b; Peterson et al. 1979); and abnormalities in gonadotropin levels (W. J. Meyer et al. 1986; Simpson and Saenger 1985). However, the etiological significance of these associated conditions is unclear. Patients with hormonal and genetic anomalies sometimes develop a gender identity and role (Money 1986, 1994a, 1994b; Money and Ehrhardt 1972) congruent with their assigned sex (Simpson and Saenger 1985), whereas patients with intersex disorders more often experience cross-gender identity development (Freund 1985). Intersexuality includes both the hormonal (i.e., ambiguous genitalia secondary to a prenatal sex hormone disorder) and the nonhormonal categories of genital ambiguity (i.e., chromosomally and gonadally male patients with penile agenesis, or cloacal exstrophy of the bladder and an uncorrectable split penis, or penile ablatio due to a circumcision accident) (Meyer-Bahlburg 1993, 1994).

Results of physical examinations and laboratory studies are normal for the vast majority of gender-dysphoric patients, with no known organic pathology connected to cross-gender symptoms (W. J. Meyer et al. 1986). No specialized tests exist that can assist with differential diagnosis. Genetic abnormalities are rare enough that obtaining karyotypes in the absence of other evidence of genetically based pathology is not indicated.