CAH-Mädchen und die Auswirkung pränataler Hormone auf das Verhalten

Mädchen mit Congenital Adrenal Hyperplasia haben aufgrund einer Überfunktion der Nebennierenrinde wesentlich mehr Testosteron als Mädchen, die davon nicht betroffen sind. Die Überfunktion wird nach der Geburt reguliert, so dass der Überschuss nur vor der Geburt, pränatal , vorliegt.

Ich schrieb dazu schon einmal:

Bei Congenital adrenal hyperplasia (CAH) ist die Hormonsynthese in den Nebennierenrinde gestört, die deswegen statt  Cortisol und Aldosteron vermehrt deren Vorstufen Pregnenolon und  Progesteron ausgeschüttet. Da die geringeren Mengen der eigentlich zu bildenden Stoffe in den passenden Gehirnregionen, zB dem Hypothalamus und die Hypophyse registriert wird, wird doch allgemein die Produktion der Nebennierenrinde hochgefahren, die dann auch vermehrt das Sexualhormon Testosteron ausschüttet. Dieser Effekt tritt bereits im Mutterleib ein und führt daher dazu, dass der Fötus einer erhöhten Testosteronkonzentration ausgesetzt ist. Dies sollte nach der Theorie der hormonellen Prägung der Geschlechter im Mutterleib dazu führen, dass die Mädchen sich insgesamt männlicher verhalten und eher bisexuell oder homosexuell sind.

Gerade da die Kinder nach der Geburt kein zusätzliches Testosteron mehr produzieren sind sie ansonsten unauffällige Mädchen, die demnach nach den sozialen Theorien die weiblichen Geschlechterrollen übernehmen sollten. Tatsächlich verhalten sie sich aber sehr männlich.

Ich habe mal ein paar Studien zusammen gesucht:

1. Melissa Hines et all, 2010:

Androgen and psychosexual development: Core gender identity, sexual orientation, and recalled childhood gender role behavior in women and men with congenital adrenal hyperplasia (CAH)

We assessed core gender identity, sexual orientation, and recalled childhood gender role behavior in 16 women and 9 men with congenital adrenal hyperplasia (CAH) and in 15 unaffected female and 10 unaffected male relatives, all between the ages of 18 and 44 years. Women with CAH recalled significantly more male-typical play behavior as children than did unaffected women, whereas men with and without CAH did not differ. Women with CAH also reported significantly less satisfaction with the female sex of assignment and less heterosexual interest than did unaffected women. Again, men with CAH did not differ significantly from unaffected men in these respects. Our results for women with CAH are consistent with numerous prior reports indicating that girls with CAH show increased male-typical play behavior. They also support the hypotheses that these women show reduced heterosexual interest and reduced satisfaction with the female sex of assignment. Our results for males are consistent with most prior reports that boys with CAH do not show a general alteration in childhood play behavior. In addition, they provide initial evidence that core gender identity and sexual orientation are unaffected in men with CAH.
Finally, among women with CAH, we found that recalled male-typical play in childhood correlated with reduced satisfaction with the female gender and reduced heterosexual interest in adulthood. Although prospective studies are needed, these results suggest that those girls with CAH who show the greatest alterations in childhood play behavior may be the most likely to develop a bisexual or homosexual orientation as adults and to be dissatisfied with the female sex of assignment.

Hines hat sich um die Forschung auf dem Gebiet sehr verdient gemacht. ihre Forschung zeigt, dass Mädchen, die davon betroffen sind weniger zufrieden mit ihrer Rolle als Frau sind und auch eher homosexuell werden. Studien dieser Art haben leider aufgrund der Seltenheit der Krankheit den Nachteil, dass sie üblicherweise eine kleine Teilnehmerzahl haben. Umso erstaunlicher ist es, dass in diesem Bereich überhaupt Homosexualität überprüft werden kann, die bei der Bevölkerung bei Frauen ein Anteil von ca. ein Prozent hat. Die Mädchen sind unzufriedener mit ihrer Rolle, sie zeigen eher typische Spielverhalten wie bei Jungs, umso mehr sie dieses Verhalten haben umso mehr sind sie auch später unzufrieden und umso eher haben Sie weniger Interesse an heterosexuellen Sex.

Resnick et all 1986
Early hormonal influences on cognitive functioning in congenital adrenal hyperplasia.

Administered a cognitive test battery that emphasized spatial ability, verbal fluency, and perceptual speed and accuracy to 17 females (aged 12.7–23.2 yrs) and 8 males (aged 13–29.9 yrs) with congenital adrenal hyperplasia (CAH) and 13 normal female relatives (aged 11.4–31.1 yrs) and 14 unaffected male relatives (aged 12.5–28.8 yrs). In addition, 13 fathers and 15 mothers of CAH patients participated. Ss also completed the Progressive Matrices, a vocabulary test, and an early life activities questionnaire (ELAQ). Findings indicate that CAH females, as compared with normal females, showed significantly enhanced performance on hidden pattern, card rotation, and mental rotation tests of spatial ability. On the ELAQ, CAH females, relative to normal females, showed significantly lower frequencies of participation in activities involving verbal expression and a trend toward greater participation in spatial manipulation activities. However, differences between CAH females and normal females in early childhood activities did not account for observed differences in spatial ability, given the absence of a significant correlation between the spatial manipulation activity scale and spatial ability. There was an absence of reliable differences between male CAH patients and controls across spatial tasks. Results are consistent with an effect of pre- and perinatal androgenizing hormones on the development of spatial ability. (58 ref) (PsycINFO Database Record (c) 2016 APA, all rights reserved)

Also eine Studie, in der man Eigenschaften verglichen hat. Die CA H Mädchen schnitten besser ab bei Sachen die dem räumlichen Denken, mentaler Rotation und allgemein Fähigkeiten, ihres räumliche Denken betreffen. Bei sprachlichen Tests hingegen schnitten sie schlechter ab. Gleichzeitig bestand kein Zusammenhang mit besonderen Aktivitäten in der Kindheit, so dass diese insoweit als Grundlage für die Fähigkeiten ausscheiden. Eine Vielzahl von Studien weist nach, dass bei räumlichen Denken ein Geschlechterunterschied besteht und dieses mit insbesondere pränatalen Testosteron in Verbindung steht und zudem dieses wiederum insbesondere auch für Naturwissenschaften etc. eher gebraucht wird. Zudem zeigen Studien, dass Testosteron häufig mit verminderten Sprachfähigkeiten einhergeht.  Hier soll allerdings auch frühes postnatales Testosteron eine Rolle spielen.

Louise Friesen et all, 2009

Gender Role Behavior, Sexuality, and Psychosocial Adaptation in Women with Congenital Adrenal Hyperplasia due to CYP21A2 Deficiency

Context: Gender-atypical behavior has been described in young girls as well as in women with congenital adrenal hyperplasia (CAH) due to a CYP21A2deficiency.

Objective: The aim of the study was to assess health-related, psychosexual, and psychosocial parameters and correlate the results to CYP21A2 genotype.

Design and Participants: Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire and a validated quality of life instrument [psychological general well-being (PGWB) formula] to identify psychosexual and psychosocial parameters. The patients were divided into four CYP21A2 genotype groups.

Results: The women with CAH held more male-dominant occupations (30%) compared to controls (13%) (P = 0.04), especially those in the null genotype group (55%) (P = 0.006). They also reported a greater interest in rough sports (74%) compared to controls (50%) (P = 0.007). Eight women with CAH (14%) reported a prime interest in motor vehicles, compared to none of the controls (P= 0.002). Non-heterosexual orientation was reported by 19% of women with CAH (P = 0.005), 50% in the null genotype group (P = 0.0001), 30% in I2splice (NS), and 5% in I172N (NS). PGWB total score did not differ between patients and controls.

Conclusion: We identified increased gender-atypical behavior in women with CAH that could be correlated to the CYP21A2 genotype. This speaks in favor of dose-dependent effects of prenatal androgens on the development of higher brain functions. The impact of the disease on upbringing and interpersonal relationships did not correlate with disease severity, indicating that other factors, such as coping strategies, are important for psychosocial adaptation. This illustrates the need for psychological support to parents and patients.

Gender-atypical behavior in Swedish women with congenital adrenal hyperplasia is correlated to their CYP21A2 genotype.

auch hier wurden wieder deutliche Unterschiede festgestellt. Im Vergleich zur Kontrollgruppe arbeiteten 30 % mehr der Frauen in einer männlich dominierten Beschäftigung, einer speziellen gehen sogar 55 % nach.

74 % berichteten, dass Sie ein großes Interesse an „härteren Sportarten“hatten, während dies lediglich bei 50 % der Kontrollgruppe der Fall war. 8 Frauen hatten ein Interesse an Kraftfahrzeugen, dagegen waren es in der Kontrollgruppe keine Frau. Zudem hatten 19 % der Frauen mit CA H eine nicht heterosexuelle Orientierung und aus der Gruppe mit dem bestimmten Genen sogar 30 %. Auch hier werden insoweit gewaltige Unterschiede deutlich.

Sheri Berenbaum, 1998

Effects of Early Androgens on Sex-Typed Activities and Interests in Adolescents with Congenital Adrenal Hyperplasia

The goal of this study was to examine the relation of early androgen exposure to sex-typed activities and interests in adolescence. Participants aged 9–19 years included 24 girls and 18 boys with congenital adrenal hyperplasia (CAH) and 16 unaffected sisters and 24 unaffected brothers who served as controls. Using standardized questionnaires, adolescents reported on their participation in sex-typed activities and interest in sex-typed occupations, and parents reported on the adolescents‘ activities. As hypothesized, girls with CAH showed sex-atypical preferences: increased interest in male-typical activities and careers and reduced interest in female-typical activities and careers compared to the unexposed control girls. These results extend findings of sex-atypical play in young girls with CAH and suggest that the sex-atypical activities and interests of females with CAH reflect direct effects of androgens on the developing brain rather than social responses to virilized genitalia. These results also suggest that population sex differences in activities and interests arise in part from sex differences in early androgens.

Auch in dieser Stunde Studie wurde deutlich, dass CH Frauen für Frauen ansonsten untypischere Präferenzen haben. Sie zeigen ein größeres Interesse an sie untypischen Tätigkeiten und Karrieren und ein reduziertes Interesse in für Frauen typische Aktivitäten und Karrieren. Zudem spielen sie anders.

Ralf Dittmann et all, 1990

Congenital adrenal hyperplasia I: Gender-related behavior and attitudes in female patients and sisters

Thirty-five female patients with congenital adrenal hyperplasia (CAH) were compared to a group of 16 healthy sisters in regard to gender-related behavioral patterns, present attitudes, and plans for the future. A semi-structured interview with the subjects, ages 11 to 41 yr, and their mothers concentrated on four to five age stages. Results of retrospective data from single items as well as from several related composite scales (“interests and behavior,” “appearance,” “overall scores”) revealed significant group differences: Both in mother-assessment and self-assessment, CAH patients showed a “more masculine” orientation than their sisters, but this was far from consistent across all age stages, especially for single items. Unexpectedly, the gender-behavior differences between CAH patients and sisters did not hold for certain items and scales of “social behavior” (e.g., assertiveness, dominance, acceptance in peer groups) and, in contrast to some of the existing literature, also not for “high-energy expenditure.” With regard to expectations for the future, CAH patients had less of a “wish to have their own children” and a higher preference for “having a career versus staying at home.”

Age, socioeconomic status, intelligence, and presence or absence of a sister as possibly intervening psychosocial/demographic factors could not explain the group differences in behavior. Degree of genital masculinization (Prader stages) or “onset and quality” of therapy as measures of pre- and postnatal androgenization, respectively, could also not account for the degree of the “more masculine” orientation in the CAH group. Nevertheless, the overall results are compatible with earlier findings on the masculinizing effects of prenatal androgens on behavior in humans and point to a time period after sexual differentiation of the genitalia and before birth as the most likely one for the effects of prenatal hormones on behavioral masculinization in humans.

Auch hier wieder eine Studie, die männlicheres Verhalten zeigt, diesem im direkten Vergleich mit Schwestern. Der Vergleich mit der Schwester dient natürlich insoweit zu, dass man bestimmte soziokulturelle Faktoren, etwa eine Beeinflussung aus dem Haushalt oder der näheren Umgebung untersucht. Hier zeigt sich, dass der Effekt auch unter diesen Gesichtspunkten zu beobachten ist. Die CA H Frauen hatten einen geringeren Wunsch nach eigenen Kindern und eine höhere Präferenz dafür, eine Karriere zu haben  statt zu Hause zu bleiben.

Jan Helleday et all, 1993

Personality characteristics and platelet MAO activity in women with congenital adrenal hyperplasia (CAH)

Personality traits and platelet monoamine oxidase (MAO) activity were studied in 22 women, 17–34 years old, with prenatal virilization due to congenital adrenal hyperplasia (CAH) (21-hydroxylase deficiency) and 22 healthy controls. The CAH group differed significantly on two of the eight scales of the Karolinska Scales of Personality (KSP), which have earlier shown significant gender differences. Both differences were in the masculine direction, with a high, male level, score for Detachment and a lower score for Indirect Aggression. The Detachment scale reflects distance in social relations, and has earlier been shown to be strongly gender differentiating. There was no significant difference in platelet MAO activity between the CAH group and the controls. Although an influence of psychosocial factors cannot be excluded, the results suggest a possible association between prenatal androgen exposure and the high Detachment score for the CAH group. Gender differences in empathy, affiliation motivation, intimacy and maternal behavior may be relevant parallels.

hier wurde also Persönlichkeitstests durchgeführt, die insbesondere auch ansonsten dazu führen, dass Geschlechterunterschiede festgestellt werden. Die CAH Mädchen weichen hier in die männliche Richtung ab, insbesondere im Bereich Distanziertheit.  zudem neigten sie weniger zu indirekter Aggression, die ansonsten bei Frauen einen höheren Wert hatten

Melissa Hines, 1994

Androgen and the Development of Human Sex‐typical Behavior: Rough‐and‐Tumble Play and Sex of Preferred Playmates in Children with Congenital Adrenal Hyperplasia (CAH)

We hypothesized that girls with congenital adrenal hyperplasia (CAH), who experience higher than normal levels of androgens prenatally, would show masculinization of behaviors that show sex differences. Therefore, we examined rough‐and‐tumble play and sex of preferred playmates in 3–8‐year‐old children with CAH and in unaffected 3–8‐year‐old male and female relatives. The hypothesized sex differences in rough‐and‐tumble play were seen, with unaffected boys showing more rough‐and‐tumble play than unaffected girls. However, CAH girls were similar to unaffected girls. Additionally, CAH boys showed reduced rough‐and‐tumble play. In contrast, sex of preferred playmates showed the hypothesized pattern of results. There were sex differences, with unaffected boys preferring boys and unaffected girls preferring girls. In addition, the preferences of girls with CAH were masculinized compared to those of unaffected girls. Results are discussed in terms of possible influences of social, hormonal, and illness factors.

Auch hier waren also die Spielpräferenzen der CAH Mädchen denen der Männer eher angeglichen und sie haben auch mit anderen Jungs gespielt.

RebeccaKnickmeyer, SimonBaron-Cohen et all, 2006

Androgens and autistic traits: A study of individuals with congenital adrenal hyperplasia

Testosterone promotes male-typical neural and behavioral development in non-human mammals. There is growing evidence that testosterone exerts similar influences on human development, although the range of behaviors affected is not completely known. This study examined the hypothesis that autistic traits are increased following prenatal exposure to abnormally high levels of testosterone caused by congenital adrenal hyperplasia (CAH). Sixty individuals with CAH (34 female, 26 male) and 49 unaffected relatives (24 female, 25 male) completed the Autism Spectrum Quotient (AQ). Females with CAH scored significantly higher than unaffected females on total AQ score, largely due to enhanced scores on subscales measuring social skills and imagination. These results suggest that prenatal exposure to high levels of testosterone influences some autistic traits and that hormonal factors may be involved in vulnerability to autism.

Simon Baron-Cohen ist ja einer der engagiertesten Vertreter der Theorie, dass Autismus eine Form von einem extrem männlichen Gehirn ist. Demnach ist es konsequent zu untersuchen, wie Mädchen mit CA H in diesem Bereich abschneiden. Wie erwartet liegen sie auf der Autismus Skala höher

Zucker et all, 1996

Psychosexual Development of Women with Congenital Adrenal Hyperplasia

Women with congenital adrenal hyperplasia (CAH) (N= 31) and their unaffected sisters or female cousins (N= 15) participated in a study of psychosexual development. All participants were ≥18 years of age (mean age, 25 years; range, 18–40). Comparisons were also made between the CAH women with the salt-wasting (SW) form of the disorder and those with simple virilization (SV). A psychosexual assessment protocol examined six variables: (1) sex assignment at birth (probands only); (2) recalled sex-typed behavior during childhood; (3) gender identity and gender role identification in adulthood; (4) relationship status; (5) sexual orientation in fantasy; and (6) sexual orientation in behavior. Salt-wasting status and sex assignment at birth were also ascertained for the CAH women who either refused to participate in the study (N= 10) or could not be traced (N= 13). Compared to the controls, the women with CAH recalled more cross-gender role behavior and less comfort with their sense of “femininity” during childhood. The two groups did not differ in degree of gender dysphoria in adulthood, although the probands showed more cross-gender role identification. Three of the nonparticipant probands were living, as adults, in the male social role (2 reared from birth as boys and 1 who changed from the female to the male social role during adolescence). The CAH women and the controls did not differ in relationship status (married/cohabiting vs. single). The CAH women had lower rates of exclusive heterosexual fantasy and fewer sexual experiences with men than the controls; however, the CAH women did not have more sexual experiences with women than the controls. Comparisons between the SW and SV revealed several differences: the SW were less likely to be assigned to the female sex at birth, recalled more cross-gender role behavior during childhood, were less likely to be married or cohabiting, and had lower rates of sexual experiences with men. The results were discussed in relation to the effects of prenatal androgens on psychosexual differentiation.

auch hier das Bild, das sich auch schon in den anderen Studien gezeigt hat. Die CAH Mädchen zeigten mehr Verhalten der männlichen Geschlechterrolle und waren weniger einverstanden mit der Bewertung von Weiblichkeit in ihrer Kindheit. Zudem waren CAH Frauen häufiger homosexuell und hatten demzufolge auch mehr sexuelle Erfahrung mit Frauen. Sie waren seltener verheiratet und lebten selten mit einem Partner zusammen und hatten weniger sexuelle Erfahrung mit Männern

Hines et all, 2003

Spatial abilities following prenatal androgen abnormality: targeting and mental rotations performance in individuals with congenital adrenal hyperplasia

In most mammals, behaviors that show sex differences are influenced by androgen during early life. In the current study, the hypothesis that androgen influences the development of human spatial abilities was investigated. Participants included 40 females and 29 males with congenital adrenal hyperplasia (CAH), a genetic disorder that causes overproduction of adrenal androgens beginning prenatally, and 29 unaffected female and 30 unaffected male relatives of individuals with CAH. Participants ranged in age from 12–45 years. Measures of spatial abilities included two mental rotations tasks and two targeting tasks, all of which showed large sex differences favoring males in the unaffected relative controls. Females with CAH (exposed to higher than normal levels of androgen prenatally) performed better than unaffected females on the targeting tasks, and resembled unaffected males and males with CAH in this respect. However, females with CAH did not perform better than unaffected females on the measures of mental rotations abilities. Males with CAH showed unaltered performance on the targeting tasks, and impaired performance on the mental rotations tasks. Results are discussed in terms of differences in experiential and hormonal contributions to different spatial abilities, as well as in terms of possible differences in critical periods for hormonal influences on targeting versus mental rotations abilities. Specifically, we speculate that, although androgen may influence targeting abilities prenatally, if hormones influence the development of mental rotations ability, they do so at some other time, perhaps during the first six months of postnatal life.

auch hier wird wieder der Unterschiede festgestellt, die CAH Mädchen hatten eher Leistungen, die denen der Männern entsprachen.

Servin et all, 2016

Prenatal androgens and gender-typed behavior: A study of girls with mild and severe forms of congenital adrenal hyperplasia.

Gender-typed behaviors and interests were investigated in 26 girls, aged 2-10 years, affected with congenital adrenal hyperplasia (CAH) and in 26 unaffected girls matched for age. Girls with CAH were more interested in masculine toys and less interested in feminine toys and were more likely to report having male playmates and to wish for masculine careers. Parents of girls with CAH rated their daughters‘ behaviors as more boylike than did parents of unaffected girls. A relation was found between disease severity and behavior indicating that more severely affected CAH girls were more interested in masculine toys and careers. No parental influence could be demonstrated on play behavior, nor did the comparison of parents‘ ratings of wished for behavior versus perceived behavior in their daughters indicate an effect of parental expectations. The results are interpreted as supporting a biological contribution to differences in play behavior between girls with and without CAH

und auch hier immer wieder das gleiche Bild. Mädchen mit CAH interessieren sich eher für Spielzeug, mit dem sonst Jungs spielen und sind weniger interessiert an Spielzeug, mit den sonst Mädchen spielen. Sie spielen lieber mit Jungs und sie stellen sich Karrieren vor, die sich sonst eher Jungs vorstellen. Die Eltern bewerten auch das Verhalten ihrer Töchter mit CAH eher als typisch für Jungs, gleichzeitig wurde kein elterliche Einfluss festgestellt und auch keine Übereinstimmung damit, was die Eltern gerne als Verhalten bei dem Kind gehabt hätten.

Nordenström et all, 2002

Sex-Typed Toy Play Behavior Correlates with the Degree of Prenatal Androgen Exposure Assessed by CYP21 Genotype in Girls with Congenital Adrenal Hyperplasia 

Previous studies have shown that girls with congenital adrenal hyperplasia (CAH), a syndrome resulting in overproduction of adrenal androgens from early fetal life, are behaviorally masculinized. We studied play with toys in a structured play situation and correlated the results with disease severity, assessed by CYP21 genotyping, and age at diagnosis. Girls with CAH played more with masculine toys than controls when playing alone. In addition, we could demonstrate a dose-response relationship between disease severity (i.e. degree of fetal androgen exposure) and degree of masculinization of behavior. The presence of a parent did not influence the CAH girls to play in a more masculine fashion. Four CAH girls with late diagnosis are also described. Three of the four girls played exclusively with one of the masculine toys, a constructional toy. Our results support the view that prenatal androgen exposure has a direct organizational effect on the human brain to determine certain aspects of sex-typed behavior.

in dieser Studie wurde das Ergebnis, dass die Kinder dann lieber mit männlichen Spielzeug spielen bestätigt und es wurde zudem festgestellt, dass auch eine Übereinstimmung mit der Menge an pränatalen Androgenen besteht.

Meyer-Bahlburg et al, 2008

Sexual Orientation in Women with Classical or Non-classical Congenital Adrenal Hyperplasia as a Function of Degree of Prenatal Androgen Excess

46,XX individuals with classical congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme, 21-hydroxylase, show variable degrees of masculinization of body and behavior due to excess adrenal androgen production. Increased bisexuality and homosexuality have also been reported. This article provides a review of existing reports of the latter and presents a new study aimed at replicating the previous findings with detailed assessments of sexual orientation on relatively large samples, and at extending the investigation to the mildest form, non-classical (NC) CAH. Also, this is the first study to relate sexual orientation to the specific molecular genotypes of CAH. In the present study, 40 salt-wasters (SW), 21 SV (simple-virilizing), 82 NC, and 24 non-CAH control women (sisters and female cousins of CAH women) were blindly administered the Sexual Behavior Assessment Schedule (SEBAS-A, 1983 ed.; H. F. L. Meyer-Bahlburg & A. A. Ehrhardt, Privately printed). Most women were heterosexual, but the rates of bisexual and homosexual orientation were increased above controls not only in women with classical CAH, but also in NC women, and correlated with the degree of prenatal androgenization. Classifying women by molecular genotypes did not further increase the correlation. Diverse aspects of sexual orientation were highly intercorrelated, and principal components analysis yielded one general factor. Bisexual/homosexual orientation was (modestly) correlated with global measures of masculinization of non-sexual behavior and predicted independently by the degree of both prenatal androgenization and masculinization of childhood behavior. We conclude that the findings support a sexual-differentiation perspective involving prenatal androgens on the development of sexual orientation.

und in dieser Studie geht es um den Nachweis, dass auch die sexuelle Orientierung mit der Dosis an Androgenen korreliert.