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2019-01-04

The Sexual Differentiation of the Human Brain: Role of Sex Hormones Versus Sex Chromosomes.

Curr Top Behav Neurosci. 2019 Jan 1. doi: 10.1007/7854_2018_70. [Epub ahead of print]

The Sexual Differentiation of the Human Brain: Role of Sex Hormones Versus Sex Chromosomes.

Bakker J1.

Author information
1Laboratory of Neuroendocrinology, GIGA Neurosciences, Liège University, Liège, Belgium. jbakker@uliege.be.

Abstract

Men and women differ, not only in their anatomy but also in their behavior. Research using animal models has convincingly shown that sex differences in the brain and behavior are induced by sex hormones during a specific, hormone-sensitive period during early development. Thus, male-typical psychosexual characteristics seem to develop under the influence of testosterone, mostly acting during early development. By contrast, female-typical psychosexual characteristics may actually be organized under the influence of estradiol during a specific prepubertal period. The sexual differentiation of the human brain also seems to proceed predominantly under the influence of sex hormones. Recent studies using magnetic resonance imaging have shown that several sexually differentiated aspects of brain structure and function are female-typical in women with complete androgen insensitivity syndrome (CAIS), who have a 46 XY karyotype but a female phenotype due to complete androgen resistance, suggesting that these sex differences most likely reflect androgen action, although feminizing effects of estrogens or female-typical socialization cannot be ruled out. By contrast, some male-typical neural characteristics were also observed in women with CAIS suggesting direct effects of sex chromosome genes in the sexual differentiation of the human brain. In conclusion, the sexual differentiation of the human brain is most likely a multifactorial process including both sex hormone and sex chromosome effects, acting in parallel or in combination.

男性と女性は、解剖学的構造だけではなく行動も異なる。動物モデルを用いた研究は、脳内の性差および行動が、初期の発達中の特定のホルモン感受性期間中に性ホルモンによって誘発されることと納得されることが示されている。このように、男性特有の精神的性的特徴はテストステロンの影響下で発達し、大部分は初期発達中に作用しているように思われる。それとは対照的に、女性特有の精神的性的特徴は、実際には特定の思春期前の期間中にエストラジオールの影響下で組織化されているかもしれません。人間の脳の性分化も性ホルモンの影響下で主に進行するようである。磁気共鳴画像法を用いた最近の研究は、46のXY核型を有するが完全なアンドロゲン耐性のために女性の表現型を有する完全型アンドロゲン不応症(CAIS)の女性において脳の構造および機能のいくつかの性分化側面が女性特有であることが示された。これらの性差はアンドロゲン作用を反映している可能性が最も高いが、エストロゲンの女性化効果または女性特有の社会化は排除できない。これとは対照的に、CAISの女性でも男性特有の神経特性がいくつか観察され、これはヒト脳の性分化における性染色体遺伝子の直接的な影響を示唆している。結論として、人間の脳の性分化は、性ホルモン効果と性染色体効果の両方を含む多因子プロセスであり、並行してまたは組み合わせて作用する可能性が最も高い。


KEYWORDS:
Androgens; Brain function; Brain structure; Complete androgen insensitivity syndrome; Estrogens; Magnetic resonance imaging; Sex differences; Sexual development

2018-09-02

Psychosocial and psychosexual aspects of disorders of sex development.

Best Pract Res Clin Endocrinol Metab. 2010 Apr;24(2):325-34. doi: 10.1016/j.beem.2009.11.005.

Psychosocial and psychosexual aspects of disorders of sex development.

Cohen-Kettenis PT

Author information
Department of Medical Psychology, VU University, PO Box 7057, 1007 MB Amsterdam, The Netherlands. pt.cohen-kettenis@vumc.nl

Abstract

Psychosocial aspects of the treatment of disorders of sex development (DSDs) concern gender assignment, information management and communication, timing of medical interventions, consequences of surgery, and sexuality. Although outcome is often satisfactory, a variety of medical and psychosocial factors may jeopardise the psychological development of children with DSDs. This sometimes results in the desire to change gender later in life. The clinical management of gender dysphoria in individuals with DSD may profit from methods and insights that have been developed for gender dysphoric individuals without DSD. In DSD care, clinical decisions are often made with long-lasting effects on quality of life and should be based on empirical evidence. Yet, such evidence (e.g., regarding gender assignment, information management and timing of surgery) is largely non-existent. DSD-specific protocols and educational materials need to be developed to standardise and evaluate interventions in order to facilitate decision making of professionals and individuals with DSD and enhance psychosocial care in this area.

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2018-08-22

Childhood Sex-Typed Behavior and Gender Change in Individuals with 46,XY and 46,XX Disorders of Sex Development: An Iranian Multicenter Study.

Arch Sex Behav. 2018 Aug 20. doi: 10.1007/s10508-018-1281-9. [Epub ahead of print]

Childhood Sex-Typed Behavior and Gender Change in Individuals with 46,XY and 46,XX Disorders of Sex Development: An Iranian Multicenter Study.

Khorashad BS1, Roshan GM2, Reid AG3, Aghili Z2, Moghadam MD4, Khazai B2, Hiradfar M5, Afkhamizadeh M6, Ghaemi N4, Talaei A2, Abbaszadegan MR7, Aarabi A7, Dastmalchi S8, Van de Grift TC9,10.

Author information イラン・オランダ


Abstract

Disorders of sex development (DSD) are congenital conditions in which the typical genetic and hormonal profiles are affected and thereby the usual process of sexual differentiation. Most of these studies, however, have been conducted in Western countries. In the present study, preschool sex-typed activities of Iranian individuals with DSD and their age-matched non-affected male and female relatives were assessed using the Pre-School Activities Inventory (PSAI) modified for retrospective self-report. A total of 192 individuals participated in our study, including 33 46,XX individuals with congenital adrenal hyperplasia (CAH; M age = 10.36, SD = 5.52), 15 46,XY individuals with complete androgen insensitivity syndrome (CAIS; M age = 19.8, SD = 7.14), and 16 46,XY individuals with 5-alpha reductase deficiency type-2 (5α-RD-2; M age = 17.31, SD = 7.28), as well as one age-matched non-affected male and female relative for each patient. With regard to PSAI scores, male-identifying participants with 5α-RD-2 and male controls reported similar levels of male-typical childhood play. Female-identifying participants with 5α-RD-2 and CAH showed comparable scores: significantly less masculine and more feminine than male controls, but significantly more masculine and less feminine than females with CAIS and female controls. These findings support the role of androgens in the development of sex-typical childhood play behavior, with those being exposed to higher levels of fetal functional androgens expressing more masculine behavior at preschool ages.


KEYWORDS:
Childhood play behavior; Disorders of sex development; Sex chromosome; Sex differences; Testosterone

2018-05-25

Prenatal androgen exposure and children's aggressive behavior and activity level.

Hormones and Behavior
Volume 96, November 2017, Pages 156-165

Prenatal androgen exposure and children’s aggressive behavior and activity level.

Horm Behav. 2017 Nov;96:156-165

Authors: Spencer D, Pasterski V, Neufeld S, Glover V, O'Connor TG, Hindmarsh PC, Hughes IA, Acerini CL, Hines M

Highlights

  • Prenatal androgen exposure linked to aggression but not activity in girls with CAH
  • Sex differences in aggression and activity found in healthy children
  • Amniotic fluid testosterone unrelated to aggression or activity in healthy sample
  • Amniotic fluid testosterone may not be an adequate measure for these outcomes


Abstract

Some human behaviors, including aggression and activity level, differ on average for males and females. Here we report findings from two studies investigating possible relations between prenatal androgen and children's aggression and activity level. For study 1, aggression and activity level scores for 43 girls and 38 boys, aged 4 to 11years, with congenital adrenal hyperplasia (CAH, a genetic condition causing increased adrenal androgen production beginning prenatally) were compared to those of similarly-aged, unaffected relatives (41 girls, 31 boys). Girls with CAH scored higher on aggression than unaffected girls, d=0.69, and unaffected boys scored higher on activity level than unaffected girls, d=0.50. No other group differences were significant. For study 2, the relationship of amniotic fluid testosterone to aggression and activity level was investigated in typically-developing children (48 girls, 44 boys), aged 3 to 5years. Boys scored higher than girls on aggression, d=0.41, and activity level, d=0.50. However, amniotic fluid testosterone was not a significant predictor of aggression or activity level for either sex. The results of the two studies provide some support for an influence of prenatal androgen exposure on children's aggressive behavior, but not activity level. The within-sex variation in amniotic fluid testosterone may not be sufficient to allow reliable assessment of relations to aggression or activity level.

2016-09-23

A Cross-Section Study of the Ontogeny of Gender Roles in Women with DSD.

A Cross-Section Study of the Ontogeny of Gender Roles in Women with DSD.

Curr Pediatr Rev. 2015;11(1):27-35

Authors: Wisniewski A, Aston CE

Abstract
A review of gender role (GR) differentiation from early childhood through adulthood was conducted on males and females in general, as well as on females affected by congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency or complete androgen insensitivity syndrome (CAIS). Additionally, retrospective and current, self-rated GR assessments were evaluated from women with CAH (n = 9) or CAIS (n = 12), and unaffected women and men ranging in age from 16 to 59 years. Overall, GR differentiation occurs in early childhood and persists through adulthood. With advanced age, this differentiation may evolve into androgyny or even become undifferentiated for the general population. While more studies of GR exist for girls and women with CAH compared to those affected by CAIS, some developmental patterns can be observed from the limited data that exist. First, girls and women with CAIS report a female GR that persists through adulthood. Second, girls and women with CAH are more likely to report less feminine/ more masculine play in childhood followed by interests in male-typical leisure activities and career choices in adulthood. However, our data indicate that women with CAH report more feminine/ less masculine patterns of GR with age. Self-reported GR for women with CAH was indistinguishable from that of women with CAIS at the time of study participation in adulthood. With the availability of effective medications for treating hormone deficiencies associated with CAH, affected women are expected to live a full lifespan. Thus, our understanding of psychosexual development into older age is warranted.