As listed in Table 5.1, before 1975, neither the International Classification of Diseases (ICD) by the World Health Organization (WHO) nor the Diagnostic and Statistical Manual of Mental Disorders (DSM) by the American Psychiatric Association (APA) included any terms, names, and codes that referred to the incongruence between a subject’s experienced and assigned gender. At that time the scientific literature, as explored by bibliographic engines developed by the US National Library of Medicine (PubMed and derivatives), depended on the clinical work conducted in the 1950s that led to Harry P. Benjamin’s description of the “transsexual phenomenon” in the USA [9]. At the time the literature had already coined terms such as “androgyne,” ”transvestism,” “transgender,” and “transsexual” and symptoms such as “desire to cross-dress” and “desire to change sex” had been identified and reported mostly in case reports and case series and scientific studies [10]. In the absence of a recognized classification of these conditions, nevertheless diagnostic psychological tests (i.e., the Bem Sex Role Inventory (BSRI) were developed (1971). The BSRI characterized personality as masculine, feminine, androgynous, or undifferentiated and was based on gender stereotypes, so what it was measuring was how well the person fit into a traditional sex role. At the same time, in terms of classification and etiology, transsexualism was considered mostly just as a symptom of another psychiatric disorder, especially schizophrenia or eventually a borderline personality disorder. As a consequence, there was neither interest nor a recognized definition and unique diagnosis and coding that allowed for the measurement of disease frequency. Therefore, before 1975 its epidemiology remained vague, and there could be numerous variants and levels of severity within the condition.

As far as clinical epidemiology, i.e., the study of determinants and effects of clinical decisions based on the transgender recognition or diagnosis by the subject and or by the medical community, medical journals reported male-to-female (MtF) and female-to-male (FtM) sex reassignment even before WWII but mostly as anecdotes. In 1965, the Hopkins Hospital became the first academic institution in the USA to perform sex reassignment surgeries. Before 1975 psychoanalytic literature held the belief that beneath the desire to change sex may lie a serious psychopathology – even of a psychotic nature – and that transsexual wishes may arise from oedipal conflict, preoedipal fixation, or schizophrenic processes [11]. Only in 1977 initially the Harry Benjamin International Gender Dysphoria Association (HBIGD), later (2007) renamed as the World Professional Association for Transgender Health (WPATH), join to provide standard of care (SOC) for transgender persons, which currently has produced its 7th edition (SOC7) [12].

In 1975 the ICD-9 of the WHO introduced specific psychiatric terms, conditions, and codes separate from other psychiatric diseases for sexual and gender identity disorders, particularly:

This classification created the opportunity for any gender identity disorder and for transsexualism in particular to calculate disease frequency, associations with subject’s characteristics and measures of impact.

In 1980 the DSM-III of APA confirmed the ICD-9 classification while specifying that the transsexualism diagnosis required:

Codes changed in ICD-10:

However, definitions remained relatively stable. Instead DSM-IV accommodated all strong and persistent cross-gender identification accompanied by persistent discomfort with one’s assigned sex previously listed separately as Gender Identity Disorder of Childhood, Gender Identity Disorder of Adolescence or Adulthood, and Transsexualism at both sexes and all ages in the unique DSM-IV code 532: Gender Identity Disorder.

As a result, between 1975 and 2013, the estimate of the overall frequency of “gender identity disorder” may have been consistent between classification systems (ICD vs DSM), whereas the frequency of transsexualism could only be measured based on ICD as DSM from 1994 to 2013 collapsed all subcategories within gender identity disorders. In addition, for all epidemiologic research conducted to date in this field, we should not underestimate the chance that exists for ascertainment bias (especially underreporting) for all the individuals who did not match the five DSM-IV diagnostic criteria for transsexualism but still could fit into the “gender identity disorder.” It is likely that the estimate of the frequency of such a group depended on historical period, societal pressures, sex assigned at birth, country, and especially attitudes and proficiency on the subject by the local medical communities. Differences in these nonbiological determinants may have caused biased estimates of the frequency of these conditions.

Also the future of epidemiologic estimates will depend, as for the past, primarily on case definition and attitudes toward case ascertainment. The long-lasting tendency to move gender identity questioning initially away from psychiatry and then away from the concept of “medical abnormality,” as advocated by some groups of subjects and professionals, may at the end determine the elimination of gender identity disorder, as it happened for definitions of homosexuality, which was no longer listed as a category of disorder in the seventh printing of the DSM-II, in 1974, and again from the DSM-III. In fact, in DSM-5 with the new term “gender dysphoria” and its definition as “A psychiatric condition separate from other psychiatric diseases with presence of clinically significant distress associated with the condition,” the clinical existence of a mental disorder in this field is restricted to the “significant distress” that may accompany gender identity issues. From the epidemiologic standpoint and to measure the frequency of this condition, it is then likely that accordingly the number of subjects meeting this definition will be reduced further, from previous, broader definitions which did not require such a “significant distress.” ICD-11 (expected to be released in 2017) and SOC7 of WPATH are consistent with this approach. In conclusion, the transsexual, transgender, and gender nonconforming people are likely to be considered more and more for their health needs rather than as carriers of a pathological condition. Consequently, in the future the epidemiologic measurement of the frequency of this health characteristic is likely to identify a human variation that has no specific abnormality meaning per se but is of clinical interest because it might be associated sometimes with pathological conditions or might require clinical intervention to satisfy a need of the subject.