Evidence Supporting the Biologic Nature of Gender Identity

Aruna Saraswat, MD; Jamie D. Weinand, BA, BS; Joshua D. Safer, MD

Endocr Pract. 2015;21(2):199-204.

Conclusion

Current data suggest a biologic etiology for transgender identity. Studies of DSD patients and neuroanatomical studies provide the strongest evidence for the organic basis of transgender identity. Because the sample sizes of most studies on this subject were small, the conclusions must be interpreted with caution. Further research is required to assign specific biologic mechanisms for gender identity.

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Abbreviations
BDNF = brain-derived neurotrophic factor; BSTC = bed nucleus of the stria terminalis; CAH = congenital adrenal hyperplasia; DES = diethylstilbestrol; DSD = disorder of sex development; MTF = male-to-female; FTM = female-to-male

Table 1. Evidence for a Biologic Basis of Gender Identity
Studies showing rigid gender identity in patients with disorders (or differences) of sexual development (DSD)
• Congenital, nonhormonal conditions	Penile ablation/agenesis, cloacal exstrophy
Studies showing that gender identity may be associated with prenatal hormone exposure in some (perhaps otherwise predisposed) individuals
• Congenital adrenal hyperplasia
• Hormone deficiencies	5 alpha-reductase-2,
	17-beta-hydroxy-steroid dehydrogenase-3
Studies with gender identity associated with neuroanatomical differences
• Gray matter studies	BSTc
	Uncinate nucleus
	Putamen volumes
	Cortical thickness
	Hypothalamic response to odorous steroids
• White matter studies	Corpus callosum
	Microstructure differences
Studies with gender identity associated with genetic factors and exposures
• Steroid hormone genetics	Genes: CYP17, SRD5A2, ERb, androgen receptor
• Sex chromosome aneuploidy	Disomy-Y
• Twin case studies
• Neuroproteins	BDNF, NKB
• Prenatal exposures	Anticonvulsants, DES

Abbreviations: BDNF = brain-derived neurotrophic factor; BSTc = bed nucleus of stria terminalis; CYP17 = cytochrome P-450 17 alpha gene; DES = diethylstilbestrol; ERb = estrogen receptor beta gene; NKB = neurokinin B; SRD5A2 = steroid-5-alpha reductase, alpha polypeptide 2 gene.

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Evidence Supporting the Biologic Nature of Gender Identity

Conclusion

Tables

References

Authors and Disclosures

Authors and Disclosures

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