Genetic Link Between Gender Dysphoria and Sex Hormone Signaling

Foreman, Madeleine; Hare, Lauren May; York, Kate; Balakrishnan, Kara; Sánchez, Francisco J.; Harte, Fintan; Erasmus, Jaco; Vilain, Éric; Harley, Vincent R.

doi:10.1210/jc.2018-01105

Cited by 61 publications

(47 citation statements)

References 43 publications

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“…More recently, Foreman et al [116] conducted a study on a large sample of transwomen and control males, evaluating several candidate genes. The authors found a significant association between gender dysphoria and oestrogen receptor alpha (ERα), SRD5A2 and STS alleles, as well as ERα and SULT2A1 genotypes.…”

Section: The Shaping Effect Of Sex Hormones and Involved Genes On Bramentioning

confidence: 99%

Brain Sex Differences Related to Gender Identity Development: Genes or Hormones?

Ristori

Cocchetti

Romani

et al. 2020

IJMS

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The complex process of sexual differentiation is known to be influenced by biological and environmental determinants. The present review has the aim of summarizing the most relevant studies on the biological basis of sexual development, and in particular, it focuses on the impact of sex hormones and genetic background on the development of sexual differentiation and gender identity. The authors conducted a search of published studies on Medline (from January 1948 to December 2019). The evidence suggests that the sexual dimorphic brain could be the anatomical substrate of psychosexual development, on which gonadal hormones may have a shaping role during prenatal and pubertal periods. Additionally, according to several heritability studies, genetic components may have a role, but a promising candidate gene has not been identified. Even though growing evidence underlines the primary role of biological factors on psychosexual development, further studies are necessary to better explain their complex interactions.

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Section: The Shaping Effect Of Sex Hormones and Involved Genes On Bramentioning

confidence: 99%

Brain Sex Differences Related to Gender Identity Development: Genes or Hormones?

Ristori

Cocchetti

Romani

et al. 2020

IJMS

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“… 8 , 9 , 10 A genetic component may also be involved because siblings of transgender individuals are more likely to be transgender, compared with the general population. 11 , 12 Most genetic studies that analyze the genetic component of gender formation examine the implication of genetic polymorphisms related to the androgen receptor AR, 13 , 14 , 15 , 16 , 17 , 18 the aromatase CYP19A1, 13 , 14 , 15 , 16 , 17 , 18 the estrogen receptors ER (α and β), 13 , 14 , 15 , 16 , 17 , 18 , 19 as well as haplotypes and the interaction effects (epistasis) between polymorphisms. 20 …”

Section: Introductionmentioning

confidence: 99%

Analysis of Four Polymorphisms Located at the Promoter of the Estrogen Receptor Alpha ESR1 Gene in a Population With Gender Incongruence

et al. 2020

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Introduction Gender incongruence defines a state in which individuals feel discrepancy between the sex assigned at birth and their gender. Some of these people make a social transition from male to female (trans women) or from female to male (trans men). By contrast, the word cisgender describes a person whose gender identity is consistent with their sex assigned at birth. Aim To analyze the implication of the estrogen receptor α gene ( ESR1 ) in the genetic basis of gender incongruence. Main Outcome Measures Polymorphisms rs9478245, rs3138774, rs2234693, rs9340799. Method We carried out the analysis of 4 polymorphisms located at the promoter of the ESR1 gene (C1 = rs9478245, C2 = rs3138774, C3 = rs2234693, and C4 = rs9340799) in a population of 273 trans women, 226 trans men, and 537 cis gender controls. For SNP polymorphisms, the allele and genotype frequencies were analyzed by χ 2 test. The strength of the SNP associations with gender incongruence was measured by binary logistic regression. For the STR polymorphism, the mean number of repeats were analyzed by the Mann–Whitney U test. Measurement of linkage disequilibrium and haplotype frequencies were also performed. Results The C2 median repeats were shorter in the trans men population. Genotypes S/S and S/L for the C2 polymorphism were overrepresented in the trans men group ( P = .012 and P = .003 respectively). We also found overtransmission of the A/A genotype (C4) in the trans men population ( P = .017), while the A/G genotype (C4) was subrepresented ( P = .009]. The analyzed polymorphisms were in linkage disequilibrium. In the trans men population, the T(C1)-L(C2)-C(C3)-A(C4) haplotype was overrepresented ( P = .019) while the T(C1)-L(C2)-C(C3)-G(C4) was subrepresented ( P = .005). Conclusion The ESR1 is associated with gender incongruence in the trans men population. Fernández R, Delgado-Zayas E, Ramírez K, et al. Analysis of Four Polymorphisms Located at the Promoter of the Estrogen Receptor Alpha ESR1 Gene in a Population With Gender Incongruence. Sex Med 2020;8:490–500.

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“…Most recently, a large cohort association study involving 380 transgender females (TFs) and 344 control male subjects revealed an over-representation in TFs of several allele combinations including androgen receptor (AR) that were proposed to feminize male individuals thereby leading to TGism [10].…”

Section: Introductionmentioning

confidence: 99%

A Rare Case of 83-Year-Old Transgender Female: Can Thyroid Hormone Deficiency Be Involved in Transgenderism and Gender Dysphoria?

Frolov¹,

Polcaro²,

Lawson³

et al. 2020

ASM

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In the current report, we describe an 83-year-old biological male who selfidentified as a female by legally changing his first and middle names to female ones and whose death certificate states his sex as a female. The medical history of this individual indicated complete penectomy without further specification. Postmortem physical examination revealed an absence of penis with a large scrotum, transposed urethral orifice, and small testes. The histological analysis of the testes identified abnormal epithelium in the seminiferous tubules that lacked germ and Sertoli cells as well as the interstitium without Leydig cells present. The exome sequencing of the individual's DNA using the Next Generation Sequencing (NGS) Illumina platform revealed no genetic variants associated with either penile or urethral cancer that could have explained the complete penectomy, but pointed toward a potentially impaired production of T3 and T4 thyroid hormones which could account for the observed testicular malformation. Overall, the data obtained raise an important question as to whether the thyroid hormone axis could be an important part of the hormonal architecture supporting male sexual behavior.An 83-year-old TF cadaver was received through Saint Louis University (SLU) School of Medicine Gift of Body Program from an individual who had given his written informed consent. The body was embalmed through the right femoral artery with a mixture of water and a solution (2:1) containing 33.3% glycerin, 28.8% phenol, 4.6% formaldehyde, and 33.3% methanol. Anatomical DissectionThe cadaveric body was dissected according to [11].A. Frolov et al. Histological AnalysisTesticular tissue was procured from the embalmed body. Tissue fixation, paraffin embedding, sectioning, and staining with hematoxylin & eosin were performed by Research Microscopy and Histology Core, Department of Pathology, Saint Louis University (SLU) School of Medicine according to the standardized procedures. Images were captured on Olympus 41BX-EPI microscope equipped with the 10× UPlan FL N, 20× LUCPlan FL, and 40× UPlan FL N objectives. The data acquisition and image analysis were performed by using CellSens Standard software. Bone DensitometryBone density of the lumbar spine and left femoral neck of the embalmed body was measured in triplicates using certified Hologic QDR-4500 X-ray Bone Densitometer in the dual energy X-ray absorptiometry (DEXA) mode following the manufacturer's protocol. The respective average T-score values were used throughout the text. LimitationsThe deleterious (pathologic) genetic variants were identified by the exome sequencing of a single proband. The high scientific value of a single proband approach to unique human cases has been recently demonstrated [27].

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Genetic Link Between Gender Dysphoria and Sex Hormone Signaling

Cited by 61 publications

References 43 publications

Brain Sex Differences Related to Gender Identity Development: Genes or Hormones?

Brain Sex Differences Related to Gender Identity Development: Genes or Hormones?

Analysis of Four Polymorphisms Located at the Promoter of the Estrogen Receptor Alpha ESR1 Gene in a Population With Gender Incongruence

A Rare Case of 83-Year-Old Transgender Female: Can Thyroid Hormone Deficiency Be Involved in Transgenderism and Gender Dysphoria?

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