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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

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 one desired to live with. 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 may 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 the mythology, people have existed who wish to lead a life of the opposite gender.[1]
  • A Greek tale mentions about 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. [2]
  • Another evidence of gender diversity in history is from Hatshepsut, the Egyptian female pharaoh (1478-1458 BCE) who was portrayed as a bearded emperor. [3]
  • 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. [4]
  • 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. [5]
  • Gender identity disorder and several other conditions like fetishism, homosexuality etc had no clear-cut classification margins and were overlapping till 1950s.
  • In 1957, John William Money proposed the concept of gender and focused on the conditions associated with sex development.[6]

Classification

  • There are multiple classification systems for gender identity disorder.
  • In 1980, the notion of this disorder was first mentioned in DSM-III. [7]
  • DSM-III-R divided it into 3 broad types- 'non-transsexualism', 'transsexualism' and 'not otherwise specified'. [8]
  • DSM- IV combined the former two into gender identity disorder.[9]
  • ICD-10 categorized gender identity disorder into five main groups.[10]
  • DSM-5 has changed the terminology of gender identity disorder to gender dysphoria.[11]

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 in relation with this condition.[12]
  • It has been found that prenatal and postnatal neurohormonal factors also have a role.
  • Brain derived neurotrophic factor (BDNF) levels have been found to be significantly decreased in patients with gender identity disorder.[13]

Differential Diagnosis

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[14]

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.[15]

Gender

  • In adults, the prevalence of male-to-female transsexualism is higher than female-to-male transsexualism.[16]
  • 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.[17]
  • Homosexual men have been found to have later than expected birth order.[18]
  • Feminine homosexual men usually have more than expected number of brothers.[18]

Race

  • Gender dysphoria is a multifactorial condition and the studies performed for determining the 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. [19]

Risk Factors

  • High degree of atypicality
  • Habitual fetishistic transvestism[14]
  • High birth weight[20]
  • Genetic factors [21]
  • Cigarette Smoking [22]
  • Autism Spectrum disorder(ASD)[20]

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-

Prognosis

The factors associated with poor prognosis are-

Diagnostic criteria

DSM-5 Diagnostic Criteria:

  • According to DSM-5, gender dysphoria has been divided into-
  1. Gender dysphoria in children
  2. Gender dysphoria in adolescents and adults
  3. Other specified gender dysphoria
  4. Unspecified gender dysphoria

Gender Dysphoria in Children[14]

“
  • A. A major incongruence between the assigned gender and the experienced/expressed gender for a minimum of 6 months' duration and should include at least six of the following (Criterion A1 must be included):
  • 1. The insistence that one belongs to the opposite gender or having a strong desire to be of the other gender (or any gender, different from the one assigned).
  • 2. In boys ( the assigned gender), a strong preference for cross-dressing or in girls (the assigned gender), a strong desire for wearing only typical masculine clothing and exhibiting resistance to the wearing of typical feminine clothing.
  • 3. A very strong preference for cross-gender roles in fantasy play.
  • 4. A strong preference for the toys, games, or activities used or engaged in by the opposite gender.
  • 5. Preference to play with the children of the other gender.
  • 6. In boys (the assigned gender), a strong rejection of typically masculine toys, games, and activities; or in girls (the assigned gender), a very strong rejection of feminine toys, games, and activities.
  • 7. A clear dislike of one’s sexual anatomy.
  • 8. A strong wish for the primary or secondary sex or both characteristics that match one’s experienced gender.

AND

  • B. The condition causes clinically significant distress or impairment in social, school, or other important domains of functioning.

Specify if;

With a disorder of sex development (like congenital adrenal hyperplasia or androgen insensitivity syndrome).

”

Gender Dysphoria in Adolescents and Adults[14]

“
  • A. A major incongruence between one’s assigned gender and experienced/expressed gender, of at least 6 months’ duration, involving at least two of the following:
  • 1. A marked incongruence between one’s experienced/expressed gender and primary or secondary or both sexual characteristics.
  • 2. A strong desire to be devoid of one’s primary and/or secondary sexual characteristics because of the incongruence with one’s experienced/expressed gender.
  • 3. A very strong desire for the primary and/or secondary sexual characteristics of the opposite gender.
  • 4. A desire to be of the other gender (or some alternative gender different from one’s assigned gender).
  • 5. A very strong desire to be treated as the other gender (or some alternative gender different from the assigned gender).
  • 6. A firm belief that one has the typical feelings and reactions of the other gender (or some alternative gender different from the assigned gender).

AND

  • B. The condition is associated with clinically significant distress or impairment in occupational, social, and/or other important areas of functioning.

Specify if:

  • Post transition: The individual has transitioned to full-time living in the desired gender and has undergone a minimum of one cross-sex medical procedure or treatment regimen like regular cross-sex hormone treatment or gender reassignment surgery confirming the desired gender (e.g., penectomy, vaginoplasty for a natal male; mastectomy or phalloplasty for a natal female).
 ”

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

Gender Identity Disorder
"Transsexualism"
ICD-10 F64
ICD-9 302.5
OMIM 600952
eMedicine med/3439 
MeSH F03.800.800.800 
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.[29]

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 period 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 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.
  • Earlier the management was primarily focussed on the sex reassignment surgery or the psychotherapy but with the inundation of medical advances, 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.[30]
  • For the treatment of Gender Dysphoria, there is a requirement of expert team consisting of the diagnosing clinicians (including an endocrinologist), a mental health provider for adolescents, and a mental health professional for adults.[31]

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.[32]
  • There should be special consideration to the patient autonomy and confidentiality, wherever the adolescent is competent to make the decisions. [33]
  • 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.[31]
  • Gonadotropin-releasing hormone agonists suppresses puberty in the adolescents with gender dysphoria. [34]
  • They pose threats in the form of adverse effects of the metabolic as well as endocrine nature. Their action is through the inability to increase the bone mass, and significant interference with brain development. [35]
  • However, the routine monitoring of gonadotropins, sex steroids, liver and renal function in adolescents on gonadotropin-releasing hormone agonists is not necessary.[34]
  • There is evidence regarding the beginning of hormonal treatment prior to 13.5 to 14 years of age and therefore, is generally not recommended. [31]

Management of Adults

  • For adults with gender dysphoria, the treating clinicians should be well-trained in transgender related diagnostic criteria, maintenance of mental health, providing optimum primary care, precise hormonal treatment, and timely surgery. [31]
  • 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.[31]
  • Both transgender males and females should be monitored for gonadal cancer when surgical removal is incomplete.[31]
  • 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 better subjective perception of sexual Quality of Life(QoL) in these individuals.[36]
  • Irrespective of the age of the patient, all the individuals with Gender Dysphoria suffer from the immense dilemma, which is worsened by societal disapproval. The treating team should utilize a holistic approach to cut down their misery.

References

  1. ↑ Dorlands Medical Dictionary
  2. ↑ Koh J (2012). "[The history of the concept of gender identity disorder]". Seishin Shinkeigaku Zasshi. 114 (6): 673–80. PMID 22844818.
  3. ↑ Poteat, Tonia; Rachlin, Katherine; Lare, Sean; Janssen, Aron; Devor, Aaron (2019). "History and Prevalence of Gender Dysphoria": 1–24. doi:10.1007/978-3-030-05683-4_1. ISSN 2523-3785.
  4. ↑ Poteat, Tonia; Rachlin, Katherine; Lare, Sean; Janssen, Aron; Devor, Aaron (2019). "History and Prevalence of Gender Dysphoria": 1–24. doi:10.1007/978-3-030-05683-4_1. ISSN 2523-3785.
  5. ↑ Koh J (2012). "[The history of the concept of gender identity disorder]". Seishin Shinkeigaku Zasshi. 114 (6): 673–80. PMID 22844818.
  6. ↑ Koh J (2012). "[The history of the concept of gender identity disorder]". Seishin Shinkeigaku Zasshi. 114 (6): 673–80. PMID 22844818.
  7. ↑ Koh J (2012). "[The history of the concept of gender identity disorder]". Seishin Shinkeigaku Zasshi. 114 (6): 673–80. PMID 22844818.
  8. ↑ Koh J (2012). "[The history of the concept of gender identity disorder]". Seishin Shinkeigaku Zasshi. 114 (6): 673–80. PMID 22844818.
  9. ↑ Koh J (2012). "[The history of the concept of gender identity disorder]". Seishin Shinkeigaku Zasshi. 114 (6): 673–80. PMID 22844818.
  10. ↑ Koh J (2012). "[The history of the concept of gender identity disorder]". Seishin Shinkeigaku Zasshi. 114 (6): 673–80. PMID 22844818.
  11. ↑ Koh J (2012). "[The history of the concept of gender identity disorder]". Seishin Shinkeigaku Zasshi. 114 (6): 673–80. PMID 22844818.
  12. ↑ Fisher, Alessandra D.; Ristori, Jiska; Morelli, Girolamo; Maggi, Mario (2018). "The molecular mechanisms of sexual orientation and gender identity". Molecular and Cellular Endocrinology. 467: 3–13. doi:10.1016/j.mce.2017.08.008. ISSN 0303-7207.
  13. ↑ Fontanari, Anna-Martha V.; Andreazza, Tahiana; Costa, Ângelo B.; Salvador, Jaqueline; Koff, Walter J.; Aguiar, Bianca; Ferrari, Pamela; Massuda, Raffael; Pedrini, Mariana; Silveira, Esalba; Belmonte-de-Abreu, Paulo S.; Gama, Clarissa S.; Kauer-Sant'Anna, Marcia; Kapczinski, Flavio; Lobato, Maria Ines R. (2013). "Serum concentrations of brain-derived neurotrophic factor in patients with gender identity disorder". Journal of Psychiatric Research. 47 (10): 1546–1548. doi:10.1016/j.jpsychires.2013.04.012. ISSN 0022-3956.
  14. ↑ 14.0 14.1 14.2 14.3 14.4 Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. 2013. ISBN 0890425558.
  15. ↑ Wallien, Madeleine S.C.; Cohen-Kettenis, Peggy T. (2008). "Psychosexual Outcome of Gender-Dysphoric Children". Journal of the American Academy of Child & Adolescent Psychiatry. 47 (12): 1413–1423. doi:10.1097/CHI.0b013e31818956b9. ISSN 0890-8567.
  16. ↑ Zucker, Kenneth J.; Lawrence, Anne A.; Kreukels, Baudewijntje P.C. (2016). "Gender Dysphoria in Adults". Annual Review of Clinical Psychology. 12 (1): 217–247. doi:10.1146/annurev-clinpsy-021815-093034. ISSN 1548-5943.
  17. ↑ Wallien, Madeleine S. C.; Veenstra, René; Kreukels, Baudewijntje P. C.; Cohen-Kettenis, Peggy T. (2009). "Peer Group Status of Gender Dysphoric Children: A Sociometric Study". Archives of Sexual Behavior. 39 (2): 553–560. doi:10.1007/s10508-009-9517-3. ISSN 0004-0002.
  18. ↑ 18.0 18.1 Blanchard, Ray; Zucker, Kenneth J.; Cohen-Kettenis, Petty T.; Gooren, Louis J. G.; Bailey, J. Michael (1996). "Birth order and sibling sex ratio in two samples of Dutch gender-dysphoric homosexual males". Archives of Sexual Behavior. 25 (5): 495–514. doi:10.1007/BF02437544. ISSN 0004-0002.
  19. ↑ Stanford, E. Percil; Bois, Barbara C. Du (1992). "Gender and Ethnicity Patterns": 99–117. doi:10.1016/B978-0-12-101277-9.50008-5.
  20. ↑ 20.0 20.1 VanderLaan, Doug P.; Leef, Jonathan H.; Wood, Hayley; Hughes, S. Kathleen; Zucker, Kenneth J. (2014). "Autism Spectrum Disorder Risk Factors and Autistic Traits in Gender Dysphoric Children". Journal of Autism and Developmental Disorders. 45 (6): 1742–1750. doi:10.1007/s10803-014-2331-3. ISSN 0162-3257.
  21. ↑ Heylens, Gunter; De Cuypere, Griet; Zucker, Kenneth J.; Schelfaut, Cleo; Elaut, Els; Vanden Bossche, Heidi; De Baere, Elfride; T'Sjoen, Guy (2012). "Gender Identity Disorder in Twins: A Review of the Case Report Literature". The Journal of Sexual Medicine. 9 (3): 751–757. doi:10.1111/j.1743-6109.2011.02567.x. ISSN 1743-6095.
  22. ↑ Hoffman, Leah; Delahanty, Janine; Johnson, Sarah E.; Zhao, Xiaoquan (2018). "Sexual and gender minority cigarette smoking disparities: An analysis of 2016 Behavioral Risk Factor Surveillance System data". Preventive Medicine. 113: 109–115. doi:10.1016/j.ypmed.2018.05.014. ISSN 0091-7435.
  23. ↑ Lothstein, Leslie M. (2010). "Psychological Testing With Transsexuals: A 30-Year Study". Journal of Personality Assessment. 48 (5): 500–507. doi:10.1207/s15327752jpa4805_9. ISSN 0022-3891.
  24. ↑ 24.0 24.1 24.2 Duišin, Dragana; Batinić, Borjanka; Barišić, Jasmina; Djordjevic, Miroslav L.; Vujović, Svetlana; Bizic, Marta (2014). "Personality Disorders in Persons with Gender Identity Disorder". The Scientific World Journal. 2014: 1–7. doi:10.1155/2014/809058. ISSN 2356-6140.
  25. ↑ 25.0 25.1 25.2 25.3 Hepp, U.; Kraemer, B.; Schnyder, U.; Miller, N.; Delsignore, A. (2005). "Psychiatric comorbidity in gender identity disorder". Journal of Psychosomatic Research. 58 (3): 259–261. doi:10.1016/j.jpsychores.2004.08.010. ISSN 0022-3999.
  26. ↑ 26.0 26.1 Bodlund, Owe; Kullgren, Gunnar (1996). "Transsexualism—General outcome and prognostic factors: A five-year follow-up study of nineteen transsexuals in the process of changing sex". Archives of Sexual Behavior. 25 (3): 303–316. doi:10.1007/BF02438167. ISSN 0004-0002.
  27. ↑ Terada, Seishi; Matsumoto, Yosuke; Sato, Toshiki; Okabe, Nobuyuki; Kishimoto, Yuki; Uchitomi, Yosuke (2012). "Factors predicting psychiatric co-morbidity in gender-dysphoric adults". Psychiatry Research. 200 (2–3): 469–474. doi:10.1016/j.psychres.2012.07.018. ISSN 0165-1781.
  28. ↑ Wålinder, Jan; Lundström, Bengt; Thuwe, Inga (2018). "Prognostic Factors in the Assessment of Male Transsexuals for Sex Reassignment". British Journal of Psychiatry. 132 (1): 16–20. doi:10.1192/S0007125000282895. ISSN 0007-1250.
  29. ↑ HBIGDA Standards Of Care For Gender Identity Disorders, Sixth Version
  30. ↑ Bockting, Walter; Coleman, Eli (1993). "A Comprehensive Approach to the Treatment of Gender Dysphoria". Journal of Psychology & Human Sexuality. 5 (4): 131–155. doi:10.1300/J056v05n04_08. ISSN 0890-7064.
  31. ↑ 31.0 31.1 31.2 31.3 31.4 31.5 Hembree, Wylie C; Cohen-Kettenis, Peggy T; Gooren, Louis; Hannema, Sabine E; Meyer, Walter J; Murad, M Hassan; Rosenthal, Stephen M; Safer, Joshua D; Tangpricha, Vin; T’Sjoen, Guy G (2017). "Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline". The Journal of Clinical Endocrinology & Metabolism. 102 (11): 3869–3903. doi:10.1210/jc.2017-01658. ISSN 0021-972X.
  32. ↑ Stein, Edward (2012). "Commentary on the Treatment of Gender Variant and Gender Dysphoric Children and Adolescents: Common Themes and Ethical Reflections". Journal of Homosexuality. 59 (3): 480–500. doi:10.1080/00918369.2012.653316. ISSN 0091-8369.
  33. ↑ Swann, Stephanie; Herbert, Sarah E. (2008). "Ethical Issues in the Mental Health Treatment of Gender Dysphoric Adolescents". Journal of Gay & Lesbian Social Services. 10 (3–4): 19–34. doi:10.1300/J041v10n03_02. ISSN 1053-8720.
  34. ↑ 34.0 34.1 Schagen, Sebastian E.E.; Cohen-Kettenis, Peggy T.; Delemarre-van de Waal, Henriette A.; Hannema, Sabine E. (2016). "Efficacy and Safety of Gonadotropin-Releasing Hormone Agonist Treatment to Suppress Puberty in Gender Dysphoric Adolescents". The Journal of Sexual Medicine. 13 (7): 1125–1132. doi:10.1016/j.jsxm.2016.05.004. ISSN 1743-6095.
  35. ↑ Cohen-Kettenis, Peggy T.; Schagen, Sebastiaan E. E.; Steensma, Thomas D.; de Vries, Annelou L. C.; Delemarre-van de Waal, Henriette A. (2011). "Puberty Suppression in a Gender-Dysphoric Adolescent: A 22-Year Follow-Up". Archives of Sexual Behavior. 40 (4): 843–847. doi:10.1007/s10508-011-9758-9. ISSN 0004-0002.
  36. ↑ Bartolucci, Constanza; Gómez‐Gil, Esther; Salamero, Manel; Esteva, Isabel; Guillamón, Antonio; Zubiaurre, Leire; Molero, Francisca; Montejo, Angel L. (2015). "Sexual Quality of Life in Gender‐Dysphoric Adults before Genital Sex Reassignment Surgery". The Journal of Sexual Medicine. 12 (1): 180–188. doi:10.1111/jsm.12758. ISSN 1743-6095.

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