A sex difference in the human brain and its relation to transsexuality

Zhou, Jiang‐Ning; Hofman, Michel A.; Gooren, Louis; Swaab, Dick F.

doi:10.1038/378068a0

Cited by 677 publications

(382 citation statements)

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“…AVT and AVP treatment induces sex-specific reproductive behaviors in a range of vertebrate species, including the spawning reflex in fishes, amplexus in newts, and pair-bonding and parental care in voles (Carter et al, 1995;Egami, 1959;Macey et al, 1974;Moore, 1992). Perhaps the most striking comparison is between our results in fishes, which show a strict correlation between sexual behavior and AVT neurochemistry, and studies showing differences in forebrain peptidergic cell populations in human males who exhibit heterosexual vs homosexual (Swaab and Hofman, 1990) or transsexual (Zhou et al, 1995) behavior.…”

Section: Discussionsupporting

confidence: 62%

Life History, Neuroendocrinology, and Behavior in Fish

Grober

Bass

2002

Hormones, Brain and Behavior

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Section: Discussionsupporting

confidence: 62%

Life History, Neuroendocrinology, and Behavior in Fish

Grober

Bass

2002

Hormones, Brain and Behavior

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“…Postmortem studies have observed sex-atypical volumes and neuronal numbers in hypothalamic nuclei in the brains of individuals with GD (Garcia-Falgueras and Swaab, 2008;Kruijver et al, 2000;Zhou et al, 1995). Brain structure in individuals with GD has also been investigated in vivo.…”

Section: Introductionmentioning

confidence: 99%

Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain

Hoekzema

Schagen

Kreukels

et al. 2015

Psychoneuroendocrinology

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The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural gray matter (GM) volumes in 55 female-to-male and 38 male-to-female adolescents, 44 boys and 52 girls without GD and applied both univariate and multivariate analyses. In girls, more GM volume was observed in the left superior medial frontal cortex, while boys had more volume in the bilateral superior posterior hemispheres of the cerebellum and the hypothalamus. Regarding the GD groups, at whole-brain level they differed only from individuals sharing their gender identity but not from their natal sex. Accordingly, using multivariate pattern recognition analyses, the GD groups could more accurately be automatically discriminated from individuals sharing their gender identity than those sharing their natal sex based on spatially distributed GM patterns. However, region of interest analyses indicated less GM volume in the right cerebellum and more volume in the medial frontal cortex in female-to-males in comparison to girls without GD, while male-to-females had less volume in * Corresponding author. the bilateral cerebellum and hypothalamus than natal boys. Deviations from the natal sex within sexually dimorphic structures were also observed in the untreated subsamples. Our findings thus indicate that GM distribution and regional volumes in GD adolescents are largely in accordance with their respective natal sex. However, there are subtle deviations from the natal sex in sexually dimorphic structures, which can represent signs of a partial sex-atypical differentiation of the brain.

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“…Clear anatomical sex differences have also been described in the human bed nucleus of the stria terminalis (BST). The darkly staining posteromedial component of the BST (BST-dspm) and the central subdivision of the BST (BSTc) are both larger in men than in women (Allen and Gorski, 1990;Zhou et al, 1995;Kruijver et al, 2000). Differences in the size of the human BSTc have been related to the gender identity disorder transsexuality, in which subjects voice the strong feeling of being born in the wrong sex.…”

mentioning

confidence: 99%

Sexual Differentiation of the Bed Nucleus of the Stria Terminalis in Humans May Extend into Adulthood

2002

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Gonadal steroids have remarkable developmental effects on sex-dependent brain organization and behavior in animals. Presumably, fetal or neonatal gonadal steroids are also responsible for sexual differentiation of the human brain. A limbic structure of special interest in this regard is the sexually dimorphic central subdivision of the bed nucleus of the stria terminalis (BSTc), because its size has been related to the gender identity disorder transsexuality. To determine at what age the BSTc becomes sexually dimorphic, the BSTc volume in males and females was studied from midgestation into adulthood. Using vasoactive intestinal polypeptide and somatostatin immunocytochemical staining as markers, we found that the BSTc was larger and contains more neurons in men than in women. However, this difference became significant only in adulthood, showing that sexual differentiation of the human brain may extend into the adulthood. The unexpectedly late sexual differentiation of the BSTc is discussed in relation to sex differences in developmental, adolescent, and adult gonadal steroid levels.

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A sex difference in the human brain and its relation to transsexuality

Cited by 677 publications

References 25 publications

Life History, Neuroendocrinology, and Behavior in Fish

Life History, Neuroendocrinology, and Behavior in Fish

Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain

Sexual Differentiation of the Bed Nucleus of the Stria Terminalis in Humans May Extend into Adulthood

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