Gender identity disorder
Synonyms and keywords: Gender dysphoria

# Overview
Gender identity disorder or gender dysphoria is a condition characterized by the disparity between the gender one is born with and the gender one desires to live as. Gender dysphoria literally means 'being uncomfortable with one's assigned gender'. These individuals experience severe distress and impairment in overall functioning. Gender dysphoria can be broadly categorized into transsexualism, dual-role transvestism, and gender identity disorder of childhood. Since many cultures strongly disagree with cross-gender behavior, it often results in significant problems for affected individuals as well as their families. In many instances, discomfort is also due to the feeling that one's body is "wrong" or is meant to be different from the present state. This condition may arise at any age and intensify over time. Management is complex but early treatment is associated with lesser distress and better outcomes.

# Historical Perspective
- The concept of gender identity disorder is not recent but has been the center of objection in many cultures. Since ancient times as mentioned in mythology, people have existed who wish to lead a life of the opposite gender.
- A Greek tale mentions a woman raised as a man, who fell in love with another woman, and before the wedding, she was metamorphosed into a male. They both lived together thereafter. 
- Another evidence of gender diversity in history is from Hatshepsut, the Egyptian female pharaoh (1478-1458 BCE) who was portrayed as a bearded emperor. 
- A Roman king Elagabalus (218- 222 CE) was well-known for his beauty, his feminine dressing manner, and extensive use of cosmetics. As he wanted the people to remember him as a woman and wished to have female genitalia, he had approached a surgeon who could transform him. 
- The first sex reassignment surgery was by Harry Benjamin, who published a case of a woman trapped in the body of a man. It was later known as transsexualism. 
- Gender identity disorder and several other conditions such as fetishism, and homosexuality had no clear-cut classification margins and were overlapping until the 1950s.
- In 1957, John William Money proposed the concept of gender and focused on the conditions associated with sex development.

# Classification
- There are multiple classification systems for gender identity disorder.
- In 1980, the notion of this disorder was first mentioned in DSM-III. 
- DSM-III-R divided it into 3 broad types 'transsexualism','non-transsexualism', and 'not otherwise specified'. 
- DSM-IV combined the former two into gender identity disorder.
- ICD-10 categorized gender identity disorder into five main groups.
- DSM-5 has changed the terminology of gender identity disorder to gender dysphoria.

# Pathophysiology
- The exact pathogenesis of gender identity disorder is not fully understood.
- Gender identity disorder is hypothesized to be due to a combination of biological and cultural factors, the former having a predominant role.
- Multiple studies have demonstrated an admixture of hormonal, neuroanatomical, and genetic factors in the development of this disorder. However, a single candidate gene has not been isolated.
- It has been found that prenatal and postnatal neurohormonal factors also have a role.
- Brain-derived neurotrophic factor (BDNF) levels are significantly decreased in patients with gender identity disorder.

# Differential Diagnosis
- Body dysmorphic disorder
- Nonconformity to gender roles
- Other clinical presentations
- Castration
- Penectomy
- Schizophrenia
- Other psychotic disorders

# Epidemiology and Demographics

## Prevalence
The prevalence of gender dysphoria among adults is:
- 5-14 per 100,000 (0.005%-0.014%) in natal males
- 2-3 per 100,000 (0.002%-0.003%) in natal females
- In 2016, approximately 1.4 million individuals in the United States identified themselves as transgender.
- The prevalence of gender dysphoria is thought to be much higher than the actual numbers as most people don't want to participate in the studies due to social stigma.

## Age
- Patients of all age groups can develop gender identity disorder.
- It has been observed that most children with gender dysphoria do not continue to have this condition after puberty.

## Gender
- In adults, the prevalence of male-to-female transsexualism is higher than female-to-male transsexualism.
- The relationships of children with gender dysphoria have been found to be better with children of opposite-sex as compared to that of same-sex at the level of elementary school.
- Homosexual men have been found to have later than expected birth order.
- Feminine homosexual men usually have more than the expected number of brothers.

## Race
- Gender dysphoria is a multifactorial condition and the studies performed for determining racial predominance have presented variable results.
- Race and ethnicity play an important role in the management of gender dysphoria and the cross-cultural training of mental health professionals can result in better treatment outcomes. 

# Risk Factors
- The high degree of atypicality
- Habitual fetishistic transvestism
- High birth weight
- Genetic factors 
- Cigarette smoking 
- Autism spectrum disorder(ASD)

# Comorbidities
It is controversial if the conditions are coexistent with or develop as a result of gender dysphoria. Some of the comorbidities observed in various studies are:
- Borderline Personality Disorder
- Avoidant Personality Disorder
- Schizoid Personality Disorder
- Paranoid Personality Disorder
- Psychotic disorders
- Anxiety disorders

# Prognosis
The factors associated with poor prognosis are:
- Personality Disorder
- Psychiatric comorbidity
- Negative self-image
- Mental instability
- Sex reassignment at an older age

# Diagnostic criteria

## DSM-5 Diagnostic Criteria:
- According to DSM-5, gender dysphoria has been divided into:
- Gender dysphoria in children
- Gender dysphoria in adolescents and adults
- Other specified gender dysphoria
- Unspecified gender dysphoria

## Gender Dysphoria in Children

## Gender Dysphoria in Adolescents and Adults

## Other Specified Gender Dysphoria
- Symptoms of gender dysphoria cause clinically significant distress in social, occupational, and/or other domains of functioning but do not meet the full criteria for gender dysphoria.

## Unspecified Gender Dysphoria
- This category is used in the circumstances where the clinician chooses not to specify the reason that the full criteria for gender dysphoria are not met or have insufficient information to formulate a more specific diagnosis.

## ICD-10 Diagnostic Criteria
International Statistical Classification of Diseases and Related Health Problems has five categories for gender identity disorder: transsexualism, Dual-role Transvestism, Gender Identity Disorder of Childhood, Other Gender Identity Disorders, and Gender Identity Disorder, Unspecified.
Transsexualism has the following criteria:
- The desire to be accepted as or live as a member of the opposite gender, mostly accompanied by the wish to make one's body as congruent as possible with the preferred gender by the process of surgery and hormone treatment.
- The transsexual identity has been present continuously for a minimum of two years.
- The disorder is not secondary to a mental condition or a chromosomal abnormality.
Dual-role transvestism is characterized by:
- The individual wearing clothes of the opposite sex in order to experience temporary membership in the other sex.
- No sexual motivation has been found for the cross-dressing.
- No desire for permanent sex transformation.
Gender identity disorder of childhood has four criteria, which may be summed up as:
- The individual is persistently and severely distressed about being a girl/boy, and desires (or claims) to be a member of the opposite gender.
- The individual is preoccupied with the clothing, anatomy, and roles of the opposite gender, or rejects the clothing, anatomy, and roles of one's birth gender.
- Puberty has not been attained yet.
- The disorder must have been present for a minimum of 6 months.
The remaining two classifications have no specific criteria.
Many people assume that the classifications "transsexual" and "transvestite" can apply only to adults and therefore, the F64 section of the ICD-10 is often criticized, for example, the wish for sexual reassignment surgery (SRS) is perceived as a requirement for the diagnosis of "transsexualism".

# Treatment
- Management of gender dysphoria is often challenging and requires a multidisciplinary approach.
- Previously the management was primarily focused on sex reassignment surgery or psychotherapy but with the inundation of medical advances, a wide spectrum of treatment modalities are available now.
- Many factors have to be considered and treatment should be initiated in a step-wise manner emphasizing the detailed assessment, management of comorbid psychiatric conditions, facilitation of identity formation, management of sexual identity, and finally, the aftercare.
- For the treatment of gender dysphoria, there is a requirement of an expert team consisting of the diagnosing clinicians (including an endocrinologist), a mental health provider for adolescents, and a mental health professional for adults.

## Management of Children and Adolescents
- While treating children and adolescents, the center of focus should be ethical values of informed consent, harm avoidance or minimization, full disclosure, and life options maximization.
- There should be special consideration to patient autonomy and confidentiality, wherever the adolescent is competent to make the decisions. 
- Hormone treatment is generally not recommended for prepubertal gender dysphoric individuals. Treatment by gonadotropin-releasing hormone agonists(GnRH) is considered only if the adolescents have entered puberty at Tanner Stage 2.
- Gonadotropin-releasing hormone agonists suppress puberty in adolescents with gender dysphoria. 
- They pose threats in the form of adverse effects of the metabolic as well as endocrine nature. Their side effects are through the inability to increase the bone mass and significant interference with brain development. 
- However, the routine monitoring of gonadotropins, sex steroids, liver, and renal function in adolescents on gonadotropin-releasing hormone agonists is not necessary.
- There is limited evidence about the beginning of hormonal treatment before 13.5 to 14 years of age and therefore, is generally not recommended. 

## Management of Adults
- For adults with gender dysphoria, the treating clinicians should be well-trained in transgender-related diagnostic criteria, maintenance of mental health, optimum primary care, precise hormonal treatment, and timely surgery. 
- When endogenous sex steroid suppression requires high doses of extrinsic sex steroid hormones, the clinicians should consider surgically removing natal gonads to reduce the sex steroid related adverse effects. The side effects of sex steroids should be vigilantly monitored by the clinicians in these patients.
- Both transgender males and females should be monitored for gonadal cancer when surgical removal is incomplete.
- It has been observed that the adults who undergo sex reassignment surgery consider their sexual life as dissatisfactory. Adequate hormonal treatment, management of the underlying psychological issues, and having a partner resulted in a better subjective perception of sexual Quality of Life(QoL).
- Irrespective of the age of the patient, all the individuals with gender dysphoria live in a dilemma, worsened by societal disapproval. The treating team should utilize a holistic approach to cut down their misery.