The causes of gender incongruence/gender dysphoria are unknown. At first, hypotheses about causation addressed psychological factors and came mostly from a psychoanalytic perspective. Over the decades, however, available evidence has suggested a multifactorial aetiology, with biological and social factors rising in importance.[16]Swaab DF, Chung WC, Kruijver FP, et al. Sex differences in the human hypothalamus in the different stages of human life. Neurobiol Aging. 2003 May-Jun;24(suppl 1):S1-16.
http://www.ncbi.nlm.nih.gov/pubmed/12829102?tool=bestpractice.com
[17]American Psychiatric Association. Assessment and treatment of gender dysphoria and gender variant patients. 2018 [internet publication].
https://www.psychiatry.org/Psychiatrists/Search-Directories-Databases/Resource-Documents/2018/Assessment-and-Treatment-of-Gender-Dysphoria-and-G
There is known to be a slightly elevated rate of gender incongruence and dysphoria among people with Klinefelter's syndrome and congenital adrenal hyperplasia.[18]Diamond M, Watson LA. Androgen insensitivity syndrome and Kleinfelter's syndrome: sex and gender considerations. Child Adolesc Psychiatr Clin N Am. 2004 Jul;13(3):623-40.
http://www.ncbi.nlm.nih.gov/pubmed/15183377?tool=bestpractice.com
[19]Peterson RE, Imparato-McGinley J, Gautier T, et al. Male pseudohermaphroditism due to steroid 5 alpha reductase deficiency. Am J Med. 1977 Feb;62(2):170-91.
http://www.ncbi.nlm.nih.gov/pubmed/835597?tool=bestpractice.com
[20]Meyer-Bahlburg HF. Hormones and psychosexual differentiation: implications for the management of intersexuality, homosexuality and transsexuality. Clin Endocrinol Metab. 1982 Nov;11(3):681-701.
http://www.ncbi.nlm.nih.gov/pubmed/7139993?tool=bestpractice.com
[21]Dittmann RW, Kappes MH, Kappes ME, et al. Congenital adrenal hyperplasia II: gender-related behavior and attitudes in female salt-wasting and simple virilizing patients. Psychoneuroendocrinology. 1990;15(5-6):421-34.
http://www.ncbi.nlm.nih.gov/pubmed/2101964?tool=bestpractice.com
[22]Dittmann RW, Kappes MH, Kappes ME, et al. Gender related behavior and attitudes in female patients and sisters. Psychoneuroendocrinology. 1990;15(5-6):401-20.
http://www.ncbi.nlm.nih.gov/pubmed/2101963?tool=bestpractice.com
It is also known that birth-assigned males with gender incongruence and dysphoria are more likely than the general population to be left-handed.[23]Cohen-Kettenis PT, van Goozen SH, Doorn C, et al. Cognitive ability and cerebral lateralization in transsexuals. Psychoneuroendocrinology. 1998 Aug;23(6):631-41.
http://www.ncbi.nlm.nih.gov/pubmed/9802133?tool=bestpractice.com
A genetic association has been postulated as one possible cause of gender incongruence and gender dysphoria; a review of case report studies suggests higher rates in monozygotic twins versus dizygotic twins.[24]Heylens G, De Cuypere G, Zucker KJ, et al. Gender identity disorder in twins: a review of the case report literature. J Sex Med. 2012 Mar;9(3):751-7.
http://www.ncbi.nlm.nih.gov/pubmed/22146048?tool=bestpractice.com
There is some evidence to suggest that CYP17 is a gene associated with the development of gender incongruence and gender dysphoria in birth-assigned females.[25]Bentz EK, Hefler LA, Kaufmann U, et al. A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism. Fertil Steril. 2008 Jul;90(1):56-9.
https://www.fertstert.org/article/S0015-0282(07)01228-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/17765230?tool=bestpractice.com
Some observations suggest children and adults with gender incongruence and gender dysphoria show more features of autism spectrum disorder (ASD) than the general population.[12]Van Der Miesen AI, Hurley H, De Vries AL. Gender dysphoria and autism spectrum disorder: a narrative review. Int Rev Psychiatry. 2016;28(1):70-80.
http://www.tandfonline.com/doi/full/10.3109/09540261.2015.1111199
http://www.ncbi.nlm.nih.gov/pubmed/26753812?tool=bestpractice.com
[13]Glidden D, Bouman WP, Jones BA, et al. Gender dysphoria and autism spectrum disorder: a systematic review of the literature. Sex Med Rev. 2016 Jan;4(1):3-14.
http://www.ncbi.nlm.nih.gov/pubmed/27872002?tool=bestpractice.com
[26]Pasterski V, Gilligan L, Curtis R. Traits of autism spectrum disorders in adults with gender dysphoria. Arch Sex Behav. 2014 Feb;43(2):387-93.
http://www.ncbi.nlm.nih.gov/pubmed/23864402?tool=bestpractice.com
At one gender clinic prevalence of autistic traits consistent with a clinical diagnosis of ASD among individuals undertaking treatment was 5.5%, compared with reports of 0.5% to 2.0% ASD diagnoses in the general population.[26]Pasterski V, Gilligan L, Curtis R. Traits of autism spectrum disorders in adults with gender dysphoria. Arch Sex Behav. 2014 Feb;43(2):387-93.
http://www.ncbi.nlm.nih.gov/pubmed/23864402?tool=bestpractice.com
Transgender people with ASD sometimes have an atypical presentation of gender dysphoria/incongruence, which makes a correct diagnosis and determination of treatment options for gender dysphoria/incongruence more difficult.[12]Van Der Miesen AI, Hurley H, De Vries AL. Gender dysphoria and autism spectrum disorder: a narrative review. Int Rev Psychiatry. 2016;28(1):70-80.
http://www.tandfonline.com/doi/full/10.3109/09540261.2015.1111199
http://www.ncbi.nlm.nih.gov/pubmed/26753812?tool=bestpractice.com
[27]Richards C, Barrett J. Trans and Non-binary Gender Healthcare for Psychiatrists, Psychologists, and Other Health Professionals. Cambridge, UK: Cambridge University Press; 2020.