The behavioural phenomenon of transsexualism (now gender identity disorder) is ancient. It has been recorded for centuries and in a broad range of cultures.⁽¹⁾ The historic behavioural picture is comparable to that seen clinically.

In the first half of the twentieth century medical reports of sex reassignment surgery were described in Europe, primarily in Switzerland.⁽²⁾ In the 1930s a wide-selling biography Man into Woman described a Dutch painter who underwent surgical sex reassignment.⁽³⁾ Contemporary interest in transsexualism surged in 1952 when George Jorgensen, an American, travelled to Denmark and underwent hormonal and surgical treatment to become Christine Jorgensen.⁽⁴⁾ The resultant international publicity yielded hundreds of people worldwide applying to the Danish doctors for similar treatment.⁽⁵⁾

By the mid-1960s there were surgeons scattered in several countries performing sex reassignment. Then in the United States at the Johns Hopkins Hospital and the University of Minnesota Hospitals and in the United Kingdom at Charing Cross Hospital, comprehensive sex reassignment programmes commenced. Extensive publicity was given to the Johns Hopkins programme as initially reported in the New York Times in 1966. It described the rationale for the programme and in the words of its director, ‘if the mind cannot be changed to fit the body, then perhaps we should consider changing the body to fit the mind’.⁽⁶⁾

In 1966 the first professional text on transsexualism was written by Harry Benjamin, widely acknowledged as the ‘father of transsexualism’.⁽⁷⁾ In 1969 the first multidisciplinary text was edited by the author and John Money.⁽⁶⁾ During the past 35 years the recognition of transsexualism, or gender identity disorder, as a treatable condition requiring psychiatric, endocrine, and surgical intervention has been accepted.

The prevalence of gender identity disorder in adults is estimated from a comprehensive appraisal in the Netherlands at 1 in 10 000 males and 1 in 30 000 females.⁽⁸⁾ At nearly all clinical centres the ratio of male-to-female patients ranges from 3:1 to 4:1, in favour of males. In some East European centres the ratio is 1:1 or reversed.⁽⁹⁾

Diagnostic criteria of gender identity disorder in adults in DSMIVTR⁽¹⁰⁾ include a stated desire to be the other sex, a desire to live and be treated as the other sex, or the conviction that he or she has the typical feelings and reactions of the other sex. There is a preoccupation for removal of primary and secondary sexual characteristics and for procedures to alter physically the sexual characteristics to simulate the other sex. The condition is not associated with physical intersex. ICD-10 diagnostic criteria are similar but there is no mention of intersex exclusion.⁽¹¹⁾

The search for the origins of transsexualism continues with an increasing bias towards those that are physiological. Some 20 years ago there was a false prophet in the guise of the HY antigen, on the Y chromosome believed to be influential in the development of the testes. A series of male transsexuals were found to be lacking this antigen and the tentative conclusion reached was that its absence resulted in a failure to masculinize the brain in the direction of a male identity.⁽¹²⁾ However, the author’s collaborative effort to replicate that study was not successful as all the male transsexuals studied appeared to have normal HY antigen.⁽¹³⁾

A more recent finding from the Netherlands implicates the brain region known as the bed nucleus of the stria terminalis. In a series of six male transsexuals studied at post-mortem over a 10-year period the size of the nucleus was comparable to that of typical females and not males.⁽¹⁴⁾ A criticism of this study is that the long-term oestrogen treatment for these males may have altered the size of the nucleus. In response the researchers argue that males treated with anti-male hormone drugs or oestrogen for prostate cancer do not have an alteration in the nucleus size from typical males. However, this treatment may not be comparable to that given to transsexuals. Another criticism is that the sex difference in size of the nucleus does not manifest until early adulthood whereas the symptoms of GID often manifest earlier.

Research with male transsexuals has revealed what might be indirect markers reflecting biological distinctions. In agreement with other researchers’ findings that male homosexuals have a greater likelihood of having older brothers,⁽¹⁵⁾ our homosexually oriented male transsexuals also have more older brothers.⁽¹⁶⁾ A theory behind this finding is that there is a progressive immunization with each pregnancy by the pregnant mother against the male foetus reflecting antigenicity of the Y chromosome. This would disrupt typical male development.

A higher ratio of aunts to uncles on the mother’s side has also been found in our male transsexuals⁽¹⁷⁾ a finding previously
reported by another researcher for male homosexuals.⁽¹⁸⁾ A theory here is that a semilethal factor has been operant in one generation (against uncles) that in the subsequent generation influences brain development resulting in an atypical behavioural pattern (homosexual or transsexual development). The finding is explainable with genomic imprinting where a gene can be dormant in one generation depending on which parent transmitted it.⁽¹⁷⁾

We also find that both male and female transsexuals are more often non-right-handed.⁽¹⁹⁾ Hand use preference begins in utero and may reflect hormonal levels or cerebral dysfunction.

For female transsexuals, a series of reports indicates a higher rate of polycystic ovarian disease.⁽²⁰⁾ Although such women secrete higher levels of androgen than typical females in adulthood, prenatal levels are unstudied. However, nearly all patients with polycystic ovarian disease are not transsexual and most female transsexuals do not have polycystic ovarian disease.

There have been no randomized controlled trials of treatment and clinical management has evolved from decades of experience.

Prior to recognition of transsexualism as a disorder deserving medical and psychiatric attention many patients self-mutilated or committed suicide⁽⁷⁾ Transsexual patients are helped by sympathetic assessment and intervention. However, transsexuals can be difficult patients to treat. It is a rare disorder in which patients make their own diagnosis, ‘I am transsexual’, and prescribe their own treatment, ‘I want sex-change hormones and surgery’. Patients can be demanding and impatient for the therapist’s acquiescence. They may be resentful for having to see a psychiatrist, holding the opinion that the desire for hormonal treatment and surgery should be sufficient, and psychiatric agreement should be unnecessary. Some patients will threaten self-mutilation or suicide if their demands and time schedules for demands are not met. Patients need to know that psychological stability is a key ingredient to successful negotiation of the cross-gender living trial period ‘Real Life Experience’ (see below) and recommendation for surgery, and that suicidal behaviour is a contraindication to going forward.