Studiensammlung 4: (Prenatale) Hormone und Geschlechterunterschiede im Gehirn und Verhalten

Und weil wir heute eh schon eine Studie hier zu Gehirnunterschieden haben hier ein paar weitere Studien:

1.

Fetal Testosterone Influences Sexually Dimorphic Gray Matter in the Human Brain

In nonhuman species, testosterone is known to have permanent organizing effects early in life that predict later expression of sex differences in brain and behavior. However, in humans, it is still unknown whether such mechanisms have organizing effects on neural sexual dimorphism. In human males, we show that variation in fetal testosterone (FT) predicts later local gray matter volume of specific brain regions in a direction that is congruent with sexual dimorphism observed in a large independent sample of age-matched males and females from the NIH Pediatric MRI Data Repository. Right temporoparietal junction/posterior superior temporal sulcus (RTPJ/pSTS), planum temporale/parietal operculum (PT/PO), and posterior lateral orbitofrontal cortex (plOFC) had local gray matter volume that was both sexually dimorphic and predicted in a congruent direction by FT. That is, gray matter volume in RTPJ/pSTS was greater for males compared to females and was positively predicted by FT. Conversely, gray matter volume in PT/PO and plOFC was greater in females compared to males and was negatively predicted by FT. Subregions of both amygdala and hypothalamus were also sexually dimorphic in the direction of Male > Female, but were not predicted by FT. However, FT positively predicted gray matter volume of a non-sexually dimorphic subregion of the amygdala. These results bridge a long-standing gap between human and nonhuman species by showing that FT acts as an organizing mechanism for the development of regional sexual dimorphism in the human brain.

Ergänzung:

(FT was measured from amniotic fluid samples collected between 13 and 20 weeks of gestation (mean FT, 0.79 nmol/L; SD, 0.34 nmol/L; range, 0.25–1.70 nmol/L).

2.

The Impact of Sex, Puberty, and Hormones on White Matter Microstructure in Adolescents

Background: During adolescence, numerous factors influence the organization of the brain. It is unclear what influence sex and puberty have on white matter microstructure, as well as the role that rapidly increasing sex steroids play. Methods: White matter microstructure was examined in 77 adolescents (ages 10–16) using diffusion tensor imaging. Multiple regression analyses were performed to examine the relationships between fractional anisotropy (FA) and mean diffusivity (MD) and sex, puberty, and their interaction, controlling for age. Follow-up analyses determined if sex steroids predicted microstructural characteristics in sexually dimorphic and pubertal-related white matter regions, as well as in whole brain. Results: Boys had higher FA in white matter carrying corticospinal, long-range association, and cortico-subcortical fibers, and lower MD in frontal and temporal white matter compared with girls. Pubertal development was related to higher FA in the insula, while a significant sex-by-puberty interaction was seen in superior frontal white matter. In boys, testosterone predicted white matter integrity in sexually dimorphic regions as well as whole brain FA, whereas estradiol showed a negative relationship with FA in girls. Conclusions: Sex differences and puberty uniquely relate to white matter microstructure in adolescents, which can partially be explained by sex steroids.

Ergänzung:

Hormonal Assessment
Four milliliters of blood was collected via venipuncture between the hours of 7:00 to 10:00 AM at the Oregon Clinical and Translational Research Institute in the same week as the imaging session.

3.

Regional sex differences in grey matter volume are associated with sex hormones in the young adult human brain

Previous studies suggest organizing effects of sex hormones on brain structure during early life and puberty, yet little is known about the adult period. The aim of the present study was to elucidate the role of 17β-estradiol, progesterone, and testosterone on cortical sex differences in grey matter volume (GM) of the adult human brain. To assess sexual dimorphism, voxel-based morphometry (VBM) was applied on structural magnetic resonance images of 34 healthy, young adult humans (17 women, 17 men, 26.6 ± 5 years) using analyses of covariance. Subsequently, circulating levels of sex hormones were associated with regional GM using linear regression analyses. After adjustment for sex and total GM, significant associations of regional GM and 17β-estradiol were observed in the left inferior frontal gyrus (β = 0.39, p = 0.02). Regional GM was inversely associated with testosterone in the left inferior frontal gyrus (β = −0.16, p = 0.04), and with progesterone in the right temporal pole (β = −0.39, p = 0.008). Our findings indicate that even in young adulthood, sex hormones exert organizing effects on regional GM. This might help to shed further light on the underlying mechanisms of both functional diversities and congruence between female and male brains.

4.

Pubertal hormones organize the adolescent brain and behavior

Maturation of the reproductive system during puberty results in elevated levels of gonadal steroid hormones. These hormones sculpt neural circuits during adolescence, a time of dramatic rewiring of the nervous system. Here, we review the evidence that steroid-dependent organization of the adolescent brain programs a variety of adult behaviors in animals and humans. Converging lines of evidence indicate that adolescence may be a sensitive period for steroid-dependent brain organization and that variation in the timing of interactions between the hormones of puberty and the adolescent brain leads to individual differences in adult behavior and risk of sex-biased psychopathologies.

5.

Prenatal hormones and childhood sex-segregation: Playmate and play style preferences in girls with congenital adrenal hyperplasia

We investigated playmate and play style preference in children with congenital adrenal hyperplasia (CAH) (26 females, 31 males) and their unaffected siblings (26 females, 17 males) using the Playmate and Play Style Preferences Structured Interview (PPPSI). Both unaffected boys and girls preferred same-sex playmates and sex-typical play styles. In the conflict condition where children chose between a same-sex playmate engaged in an other-sex activity or an other-sex playmate engaged in a same-sex activity, boys (both CAH and unaffected brothers) almost exclusively chose playmates based on the preferred play style of the playmate as opposed to the preferred gender label of the playmate. By contrast, unaffected girls used play style and gender label about equally when choosing playmates. Girls with CAH showed a pattern similar to that of boys: their playmate selections were more masculine than unaffected girls, they preferred a boy-typical play style and, in the conflict condition, chose playmates engaged in a masculine activity. These findings suggest that prenatal androgen exposure contributes to sex differences in playmate selection observed in typically-developing children, and that, among boys and girls exposed to high levels of androgens prenatally, play style preferences drive sex segregation in play.

6.

Prenatal Hormones and Postnatal Socialization by Parents as Determinants of Male-Typical Toy Play in Girls With Congenital Adrenal Hyperplasia

Toy choices of 3- to 10-year-old children with congenital adrenal hyperplasia (CAH) and of their unaffected siblings were assessed. Also assessed was parental encouragement of sex-typed toy play. Girls with CAH displayed more male-typical toy choices than did their unaffected sisters, whereas boys with and without CAH did not differ. Mothers and fathers encouraged sex-typical toy play in children with and without CAH. However, girls with CAH received more positive feedback for play with girls’ toys than did unaffected girls. Data show that increased male-typical toy play by girls with CAH cannot be explained by parental encouragement of male-typical toy play. Although parents encourage sex-appropriate behavior, their encouragement appears to be insufficient to override the interest of girls with CAH in cross-sexed toy

7.

Increased aggression and activity level in 3- to 11-year-old girls with congenital adrenal hyperplasia

Experimental research in a wide range of mammals has documented powerful influences of androgen during early development on brain systems and behaviors that show sex differences. Clinical research in humans suggests similar influences of early androgen concentrations on some behaviors, including childhood play behavior and adult sexual orientation. However, findings have been inconsistent for some other behaviors that show sex differences, including aggression and activity level in children. This inconsistency may reflect small sample sizes and assessment limitations. In the present study, we assessed aggression and activity level in 3- to 11-year-old children with CAH (38 girls, 29 boys) and in their unaffected siblings (25 girls, 21 boys) using a questionnaire that mothers completed to indicate current aggressive behavior and activity level in their children.

Data supported the hypotheses that:

  • 1. unaffected boys are more aggressive and active than unaffected girls;
  • 2. girls with CAH are more aggressive and active than their unaffected sisters; and
  • 3. boys with and without CAH are similar to one another in aggression and activity level.

These data suggest that early androgens have a masculinizing effect on both aggressive behavior and activity level in girls.

8.

Prenatal androgen exposure alters girls’ responses to information indicating gender-appropriate behaviour

Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as selfsocialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to selfsocialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development.

9.

How early hormones shape gender development

Highlights
Prenatal androgens influence sex-related characteristics to varying degrees.
• Androgens facilitate male-typed activities through interest in things versus people.
• Androgens are associated with some aspects of brain structure and activation.
• Current work is focused on interplay of hormones and social environment.
• Relevant to questions regarding sex-related psychopathology, prenatal programming.
 
Many important psychological characteristics show sex differences, and are influenced by sex hormones at different developmental periods. We focus on the role of sex hormones in early development, particularly the differential effects of prenatal androgens on aspects of gender development. Increasing evidence confirms that prenatal androgens have facilitative effects on male-typed activity interests and engagement (including child toy preferences and adult careers), and spatial abilities, but relatively minimal effects on gender identity. Recent emphasis has been directed to the psychological mechanisms underlying these effects (including sex differences in propulsive movement, and androgen effects on interest in people vs things), and neural substrates of androgen effects (including regional brain volumes, and neural responses to mental rotation, sexually arousing stimuli, emotion, and reward). Ongoing and planned work is focused on understanding the ways in which hormones act jointly with the social environment across time to produce varying trajectories of gender development, and clarifying mechanisms by which androgens affect behaviors. Such work will be facilitated by applying lessons from other species, and by expanding methodology. Understanding hormonal influences on gender development enhances knowledge of psychological development generally, and has important implications for basic and applied questions, including sex differences in psychopathology, women’s underrepresentation in science and math, and clinical care of individuals with variations in gender expression.

10.

The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development

Highlights

• Adolescence is a sensitive period for the effects of hormones on brain and behavior.
• Testicular hormones masculinize and defeminize social and reproductive behaviors.
• Ovarian hormones have both feminizing and defeminizing effects on female behavior.
• Gonadal steroid hormones drive many brain structural changes during adolescence.
• Adolescence may be part of a protracted postnatal steroid-sensitive period.

Abstract
Adolescence is a developmental period characterized by dramatic changes in cognition, risk-taking and social behavior. Although gonadal steroid hormones are well-known mediators of these behaviors in adulthood, the role gonadal steroid hormones play in shaping the adolescent brain and behavioral development has only come to light in recent years. Here we discuss the sex-specific impact of gonadal steroid hormones on the developing adolescent brain. Indeed, the effects of gonadal steroid hormones during adolescence on brain structure and behavioral outcomes differs markedly between the sexes. Research findings suggest that adolescence, like the perinatal period, is a sensitive period for the sex-specific effects of gonadal steroid hormones on brain and behavioral development. Furthermore, evidence from studies on male sexual behavior suggests that adolescence is part of a protracted postnatal sensitive period that begins perinatally and ends following adolescence. As such, the perinatal and peripubertal periods of brain and behavioral organization likely do not represent two discrete sensitive periods, but instead are the consequence of normative developmental timing of gonadal hormone secretions in males and females.

11.

Effects of chromosomal sex and hormonal influences on shaping sex differences in brain and behavior: Lessons from cases of disorders of sex development

Sex differences in brain development and postnatal behavior are determined largely by genetic sex and in utero gonadal hormone secretions. In humans however, determining the weight that each of these factors contributes remains a challenge because social influences should also be considered. Cases of disorders of sex development (DSD) provide unique insight into how mutations in genes responsible for gonadal formation can perturb the subsequent developmental hormonal milieu and elicit changes in normal human brain maturation. Specific forms of DSDs such as complete androgen insensitivity syndrome (CAIS), congenital adrenal hyperplasia (CAH), and 5α-reductase deficiency syndrome have variable effects between males and females, and the developmental outcomes of such conditions are largely dependent on sex chromosome composition. Medical and psychological works focused on CAH, CAIS, and 5α-reductase deficiency have helped form the foundation for understanding the roles of genetic and hormonal factors necessary for guiding human brain development. Here we highlight how the three aforementioned DSDs contribute to brain and behavioral phenotypes that can uniquely affect 46,XY and 46,XX individuals in dramatically different fashions

Aus der Studie:

CAH ein Schaubild

CAH, CAIS und 5-alpha reductace Deficiency: ein Schaubild

Weiteres aus der Studie:

Research focused on cases of DSD have helped the scientific community better understand the interplay between gonadal hormones and sex chromosome complement with regard to generating some of the sex differences observed in humans. These works have shed light on the likelihood that testosterone exposure, as opposed to sex chromosomes, is a larger contributing factor for guiding one’s sexual orientation and to a lesser extent gender identity. We see that 46,XX CAH individuals that have been exposed to in utero testosterone experience a greater degree of dissatisfaction in gender assignment in addition to above-average levels of homosexual and bisexual fantasies, a proxy for sexual preference. As previously mentioned, other variables are present in CAH cases such as life-long medical interventions and psychosocial confounds. These variables may constitute an environmental factor that, when coupled with biological predispositions, generates variations in sexual orientation and gender identity. That sexual orientation is determined solely by in utero hormonal milieu is unlikely. We see that the vast majority of CAH women, despite having been exposed to above-average levels of testosterone, identify as heterosexual as measured by both partners and sexual fantasies. The science of sexual orientation is still weakly understood at the mechanistic level; however, considerable amounts of research have proposed many possibilities for the causes of same-sex attraction (LeVay, 2012; Bailey et al., 2016).

The strongest evidence that adds support for the influence of testosterone in structuring gender identity comes from the work focused on 46,XY CAIS, in which nearly all individuals researched indicate feelings typical of female gender. In addition to self-reports and clinical evaluations, recent fMRI studies have also demonstrated that CAIS women not only feel female but also neurologically respond more similarly to 46,XX women than to 46,XY men when observing sexual images. However, new studies are continually emerging suggesting that gender identity and sexual orientation in individuals with CAIS are not as clear as once thought, and the rates of nonheterosexual and gender dysphoria may be much higher than currently stated. In addition to CAH and CAIS, 5α-reductase deficiencies have also demonstrated the strong role of testosterone’s ability to organize the human brain hormonally and influence adult gender identity and behavior. If early in utero exposure had no influence in guiding brain gender, we would expect considerable difficulty with the female-to-male transition observed in pubertal years in those with 5α-reductase deficiency. What we observe, however, is that an overwhelming majority of individuals with this condition comfortably transitioned into the new gender role at puberty, a worldwide observation occurring throughout many different types of social environments. Despite the convincing findings for the role of testosterone in generating these observations, the influence of social and other environmental variables are also factors that require consideration.

Cognitive Conclusions
Studying cases of DSDs has also provided insight into some of the biological parameters that generate sex differences in cognitive abilities such as visuospatial awareness and targeting ability. From studies with 46,XX CAH individuals it has been well established that in utero androgen exposure seems to enhance the ability to mentally rotate objects as well as improving hand–eye coordination during targeting tasks. This trait appears to be dependent on sex chromosome complement in addition to hormone exposure, insofar as 46,XY males with CAH actually perform worse than their matched controls, which is unexpected given the fact that CAH males would have equal or elevated levels of circulating testosterone. This raises the notion, as mentioned above, that proper timing and dosage are also likely to be important for enhancing such abilities and that simply having above-average levels of testosterone during development would not generate a “super-male.” CAIS provides another insight into this matter, demonstrating that the ability to respond to testosterone on an XY background is critical to establishing baseline spatial performance abilities. fMRI studies demonstrate that 46,XY CAIS had less inferior parietal lobe neuroactivation when performing spatial rotation tasks, a feature that resembles 46,XX females more than control genetic males. These fMRI studies on CAIS individuals once again minimize social influences and allow for a more unbiased assessment of the requirement for testosterone over genetic composition for shaping these cognitive performance sex differences.
Structural Conclusions
From the MRI studies that have been conducted in patients with CAH, it is clear that DSDs affect more than gonadal development. As highlighted, the central nervous system is highly sensitive to various hormones, and imbalances of these can greatly affect downstream behavior as well as overall brain structure. Variations in amygdala volume seem to be present in some individuals with CAH; however the effect is different depending on sex chromosome composition. Specifically, 46,XY males with CAH show unilateral reductions in the left amygdala, whereas 46,XX females with CAH show bilateral reductions in overall volume. Alterations in amygdala volume seem to be consistent with long-term glucocorticoid replacement therapies because findings for non-CAH patients on such hormone regiments also show amygdala abnormalities. The documentations of white matter irregularities seem to be unaffected by chromosomal sex and to cause similar variations in both males and females with CAH. The explanations for these results are not agreed upon, and more research will be needed before causations can be associated with the unusual white matter findings. Although limited, these discoveries have opened a new area for potential investigation focusing on the role of glucocorticoid influences in the developing brain in addition to the more frequently studied gonadal hormonal contributions. Unfortunately, no extensive structural studies have been conducted in patients with CAIS or 5α-reductase deficiencies. These findings would be invaluable in determining the direct effect of testosterone on the structures that in MRI studies have shown alterations in CAH. Future work focusing on outcomes in individuals with DSD will continue to aid in deciphering the contributions of chromosomal sex and hormones to shaping the sexually dimorphic human brain.

12.

Feminists wrestle with testosterone: Hormones, socialization and cultural interactionism as predictors of women’s gendered selves 

Sociology of gender has developed beyond a personality-centered idea of ‘‘sex-roles’’ to an approach that stresses interaction and social structure. At the same time, there has been a concurrent development in the psychological sex-differences and medical literatures toward including the biological bases of sex-typed behavior and gender identities. In this paper, while we conceptualize gender as a social structure, we focus only on the individual level of analysis: testing the relative strength of (maternal circulating) prenatal hormones, childhood socialization, and the power of expectations attached to adult social roles (cultural interactionist) as explanations for women’s self-reported feminine and masculine selves. Our findings are complex, and support some importance of each theory. Prenatal hormones, childhood socialization, and cultural interactionism were all influential factors for gendered selves. While cultural expectations predicted only feminine selves, prenatal hormones were more robust predictors of masculine sense of self. While personality may be a relatively stable characteristic influenced by the body and childhood socialization, our results reinforce the importance of studying how the social world responds to and reinforces gendered personality.

12.

Genetic association suggests that SMOC1 mediates between prenatal sex hormones and digit ratio

Abstract

Men and women differ statistically in the relative lengths of their index and ring fingers; and the ratio of these lengths has been used as a biomarker for prenatal
testosterone. The ratio has been correlated with a wide range of traits and conditions including prostate cancer, obesity, autism, ADHD, and sexual orientation. In a genome-wide association study of 979 healthy adults, we find that digit ratio is strongly associated with variation upstream of SMOC1 (rs4902759: P = 1.41 9 10-8) and a meta-analysis of this and an independent study shows a probability of P = 1.5 9 10-11. The protein encoded by SMOC1 has recently been shown to play a critical role in limb development; its expression in prostate tissue is dependent on sex hormones, and it has been implicated in the sexually dimorphic development of the gonads. We put forward the hypothesis that SMOC1 provides a link between prenatal hormone exposure and digit ratio.

Anmerkung: Finde ich interessant: Wenn das Protein, welches Einfluss auf die Entwicklung der Gliedmaßen hat, wiederum abhängig von Testosteron ist, dann würde das durchaus erklären, warum die Digit Ratio ein Indikator  für pränatales Testosteron ist, es könnte je nach Zusammenspiel auch zeigen, warum es ein teilweise unzuverlässiger Anzeiger ist, eben weil die Mechanismen unterschiedlich sind.

13.

Exposure to prenatal life events stress is associated with masculinized play behavior in girls

Previous research has shown that prenatal exposure to endocrine-disrupting chemicals can alter children’s neurodevelopment, including sex-typed behavior, and that it can do so in different ways in males and females. Non-chemical exposures, including psychosocial stress, may disrupt the prenatal hormonal milieu as well. To date, only one published study has prospectively examined the relationship between exposure to prenatal stress and gender-specific play behavior during childhood, finding masculinized play behavior in girls who experienced high prenatal life events stress, but no associations in boys. Here we examine this question in a second prospective cohort from the Study for Future Families. Pregnant women completed questionnaires on stressful life events during pregnancy, and those who reported one or more events were considered “stressed”. Families were recontacted several years later (mean age of index child: 4.9 years), and mothers completed a questionnaire including the validated Preschool Activities Inventory (PSAI), which measures sexually dimorphic play behavior. In sex-stratified analyses, after adjusting for child’s age, parental attitudes towards gender-atypical play, age and sex of siblings, and other relevant covariates, girls (n=72) exposed to prenatal life events stress had higher scores on the PSAI masculine sub-scale (β=3.48, p=0.006) and showed a trend towards higher (more masculine) composite scores (β=2.63, p=0.08). By contrast, in males (n=74), there was a trend towards an association between prenatal stress and higher PSAI feminine sub-scale scores (β=2.23, p=0.10), but no association with masculine or composite scores. These data confirm previous findings in humans and animal models suggesting that prenatal stress is a non-chemical endocrine disruptor that may have androgenic effects on female fetuses and anti-androgenic effects on male fetuses.

Anmerkung: Die Werte sind allerdings anscheinend sehr gering

14.

Relations between prenatal testosterone levels and cognitive abilities at 4 years.

Relations between prenatal testosterone (T) levels and cognitive abilities at age 4 were examined for 28 girls and 30 boys. Prenatal T levels were measured in 2nd trimester amniotic fluid samples obtained by amniocentesis and were examined in relation to scores on tests of cognitive abilities. For girls, prenatal T levels showed a curvilinear (inverted U-shaped) relation to language comprehension and classification abilities. Linear relations also were observed in that prenatal T levels were inversely related to girls‘ scores on tasks assessing counting and number facts. Similarly, girls with high average block building scores had lower prenatal T and cognitive abilities were not observed. The observation of relations in girls and not boys is discussed, and the findings are examined in relation to theories of hormone-behavior relations.

15.

Relations between prenatal testosterone and cerebral lateralization in children.

Several theorists have proposed that the sex steroid testosterone acts on the fetal brain during a critical period of development to influence cerebral lateralization (N. Geschwind & A. M. Galaburda, 1987; M. Hines & C. Shipley, see PA, Vol 71:8996; S. F. Witelson, see PA, Vol 79:26441. In the present study. relations were examined between prenatal testosterone levels in 2nd trimester amniotic fluid and lateralization of speech, affect, and handedness at age 10. Girls with higher prenatal testosterone levels were more strongly right-handed and had stronger left-hemisphere speech representation. Boys with higher prenatal testosterone levels had stronger right-hemisphere specialization for the recognition of emotion. This pattern of results is most consistent with Witelson’s (1991) claim that prenatal testosterone leads to greater lateralization of function.

Werte von Testosteron bei Mann und Frau über verschiedene Lebensphasen

Das Testosteron in biologischen Theorien zu Geschlecht und Geschlechterunterschieden eine wichtige Rolle spielt sollte den meisten Lesern dieses Blogs inzwischen deutlich geworden sein. Es lohnt sich daher einmal die unterschiedlichen Testosteronstände – pränatal und postnatal – näher zu betrachten. Hier also eine Grafik dazu:

 

Testosteron Maenner Frauen
Testosteron Maenner Frauen

Hier sieht man gut, wie unterschiedlich die Werte für Männer und Frauen sind und das bereits vor der Geburt und mit einiger Bewegung. Auch kurz nach der Geburt steigt der Testosteronspiegel bei männlichen Babies noch einmal deutlich an.  Das passt natürlich gut zu den Theorien, wie Geschlechterunterschiede durch pränatales Testosteron entstehen. Gut zu erklären wäre damit auch, wie in der Pubertät mit dem ansteigenden Testosteronspiegel das Interesse an Sex entsteht.

Zudem hatte Roslin auch noch einmal auf Zahlen hingewiesen:

Childhood

Testosterone levels are relatively low during infancy, averaging less than 30 nanograms/deciliter, or ng/dL, in male babies and below 10 ng/dL in female infants, according to the University of Michigan Health System. By 10 to 13 years of age, boys should have between 1 and 619 ng/dL of testosterone in their blood, while girls will run somewhere between 2 and 33 ng/dL.

Adolescence

Testosterone is a major trigger for puberty in boys, and normal blood levels in adolescent males surge as high as 970 ng/dL by the age of 17. A 17-year-old female, on the other hand, usually has only 8 to 53 ng/dL in her blood.

Adulthood

According to MayoClinic.com, testosterone levels in men peak during the teen and early adult years, then decrease about 1 percent a year after age 30. Men in their 20s or 30s generally score testosterone levels of 270 to 1,080 ng/dL, but women in that age bracket run between 10 and 70 ng/dL.

Senior Years

Testosterone drops down to 350 to 890 ng/dL in men between the ages of 40 to 59 years, and then stays between 350 and 720 ng/dL after the age of 60. Adult women run between 10 and 70 ng/dL before menopause, but see a big drop to 7 to 40 ng/dL with the onset of menopause.

Man sieht also auch noch mal in den Zahlen und üblichen Schwankungen, dass der Testosteronspiegel von Männern und Frauen sehr unterschiedlich sind.

Zu den Auswirkungen:

Geschlechterunterschiede : Typen und Mechanismen

Ein interessanter Artikel fasst einiges aus dem Gebiet der Geschlechterunterschiede kurz zusammen:

Interessant als kurzen Überblick finde ich die Einteilung der Geschlechterunterschiede:

  • Type I – sexual dimorphism Endpoint consists of two forms, one more prevalent in males and the other more prevalent in females. Endpoint may be present in one sex and absent in the other. Copulatory behavior, bird song, nurturing, postpartum aggression, courtship displays
  • Type II – sex differences Endpoint exists on a continuum and average is different between males and females. Pain thresholds, food preferences and intake, odor detection, fear, anxiety, learning, memory, stress responding, sensory processing
  • Type III – sex convergence & divergence Endpoint is the same in males and females but neural underpinnings are different. Alternatively, a sex difference may appear only in response to a challenge such as injury or stress. Parental behavior, problem solving strategies, response to stress

Also einmal verschiedene Ausprägungen bei den Geschlechtern, dann verschiedene Ausprägungen im Schnitt der Geschlechter, wobei es prinzipiell alle Zwischenstufen in jedem Geschlecht gibt, also verschiedene Häufungen und relativ gleiches Verhalten mit verschiedenen Mechanismen, die in bestimmten Fällen auch zu einer anderen Reaktion führen.

Und zu den Anfängen der Forschung:

The study of sex differences in the brain can trace its origins back to the mid 1800’s, when Arnold Berthold removed the testes from roosters and noted that they became less aggressive and lost interest in hens. He concluded that “The testis acts on the blood, and the blood acts on the whole organism”. The modern era of behavioral endocrinology began with the pioneering work of Frank A. Beach in the 1940s but is more clearly demarcated by the iconic report of Phoenix, Goy, Gerall and Young in 1959, which articulated the Organizational/activational hypothesis of hormone action (see (Becker et al., 2002). This theory states that gonadally derived steroid hormones early in development organize the substrate controlling adult sexual behavior, creating permanent sex differences in neural circuits, and that this organized substrate is then activated by the sex-specific hormonal milieu of adulthood. The same principles were applied to sexual differentiation of bird song some 15 years later and included the discovery of highly dimorphic song control nuclei (Arnold et al., 1996; Wade and Arnold, 2004). These observations spawned a cottage industry of research into the hormonal and neural control of reproductive physiology and behavior that has revealed numerous sex differences at every level of organization in the brain (Pfaff et al., 2002). Yet the field has remained a subdiscipline within neuroscience–interesting, but not mainstream.

Es ist denke ich wichtig sich bewußt zu machen, dass die Regelung von Geschlechterunterschieden über Hormone  im Tierreich sehr weit verbreitet ist. Vögel und Säugetiere sind evolutionstechnisch gesehen weit von einander entfernt. Sie trennen jedenfalls 100 Millionen Jahre. Es ist also ein sehr altes System, das auch bei den Säugetieren, insbesondere der Maus, gut erforscht ist. Es ist schwieriger zu erklären, dass es beim Menschen nicht genutzt wird, gerade weil dieser am Körper deutliche Zeichen eines unterschiedlichen Selektionsdrucks zeigt als das es dort nicht mehr vorhanden ist.

Und zu dem Mechanismus an sich:

A central part of explaining sex differences is to identify the factors that makes a trait different in males and females. A good first experiment is to ask if the sex difference is caused by gonadal hormones, as hormones induce the large majority of sex differences. You can either ask, is my adult sex difference determined by steroid hormones in adulthood (Figure 1)? Or, is my adult sex difference the consequence of developmental exposure to steroids (Figure 2)? The emphasis on development stems from the overwhelming evidence supporting an early sensitive period, usually perinatal, for the organizational or enduring effects of hormones. Puberty should be considered as well, as it has recently been recognized as an additional sensitive period for enduring effects of hormones (Sisk and Zehr, 2005). Regardless of the timing of the sensitive period, the approach you take depends on a number of considerations, including the species you are studying and the question you are asking. Moreover, in humans one is constrained by the inability to manipulate hormones except in adulthood, or to assess intracerebral steroid concentrations. Thus, one has to rely instead on serum or saliva assays, indirect markers of developmental steroid exposure (Breedlove, 2010), or so-called “experiments of nature” (Hines, 2010) in which individuals are developmentally exposed to exaggerated amounts of steroid (i.e. congenital adrenal hyperplasia) or are insensitive to or produce inadequate amounts of steroid (i.e. androgen insensitivity, silencing mutations in genes for ER or aromatase). Nonetheless, in any study a comprehensive analysis would include assessment of both developmental and adult hormonal effects, but this is often neither practical nor necessary.

Soweit für Leser dieses Blogs nichts ungewöhnliches. Die Hormone bewirken entweder noch im Mutterleib (pränatal) oder um die Geburt herum (perinatal) eine „Vorformatierung“ des Gehirns. Die Schwierigkeiten beim Menschen sind ebenfalls klar: Menschenexperimente kann man nur sehr eingeschränkt durchführen, es bleiben insofern gerade die Sonderfälle, bei denen „die Natur“ die Experimente bereitstellt.

The importance of early life programming pervades all of neuroscience but is perhaps best exemplified in the profound impact of hormones on the developing brain to “organize” or “program” the brain as male or female across the life span. Many sex differences are developmentally organized and then activated, or revealed, by the action of adult steroids, but this is not always the case. Moreover, one can never assume that there is a timepoint when there are no sex differences. Even primary cell cultures of neural cells from an early age show sex differences (Carruth et al., 2002; Nunez and McCarthy, 2008). In addition, sex differences in adulthood are frequently traced to developmental origins.

Auch hier muss man sich eben bewusst sein, dass wir nicht einfach nach Blaupausen gebaut werden, sondern langsam wachsen. Geschlechterunterschiede müssen nicht bereits am Anfang voll ausgestaltet sein, sie können auch später entstehen oder weiterentwickelt werden. Wichtige Zeitpunkte sind eben die pränatale Phase und später die Pubertät.

Unlike drugs for which doses in neonates can be scaled down from adults as a function of bodyweight, steroids are impacted by circulating binding globulins that are present in newborns but not adults. Moreover, some steroids are both a primary ligand of receptors and metabolic precursor to other biologically active steroids. In rats and mice, testosterone exerts masculinizing effects on the brain and spinal cord, but testosterone is also converted to estradiol by aromatization and this steroid exerts distinct masculinizing effects. Some endpoints are responsive only to estrogens, others only to androgens while still others seem to require both. You can distinguish these possibilities by using non-aromatizable androgens, direct administration of estrogens, inhibitors of aromatization or selective steroid receptor antagonists. Mutant mice that lack specific functional steroid receptors can also help distinguish the receptors that mediate the steroid effects, although a complication is that receptor knock-outs often do not allow one to discriminate between neonatal and adult effects of the hormone. Because of the potent masculinizing effects of estrogens, rodents have evolved a protective mechanism against the high circulating levels of this steroid in the pregnant dam in the form of alpha-fetoprotein, a steroid binding globulin that sequesters estrogens in the circulation of the fetus and prohibits (perhaps selectively) its entry into the brain. As a result, when studying the masculinizing effects of estradiol on the neonatal rodent brain, doses need to be as much as ten times higher than that given to the adult. In primates, the dominant masculinizing hormones are androgens. Dosage is less of an issue in this case since alpha-fetoprotein does not bind androgens and therefore does not block masculinization. Details on the administration of exogenous hormones and quantification of endogenous hormones and phases of the female reproductive cycle can be found in (Becker et al., 2005).

Auch dies wird leider häufig übersehen. Es ist nicht einfach nur Testosteron oder andere Hormone direkt, sondern eben auch der dazugehörige Apparat, der zu unterschiedlichen Wirkungen führen kann. Wenn die Rezeptoren beispielsweise das Hormon nicht erkennen oder schwächer erkennen oder es aus bestimmten Gründen nicht an der richtigen Stelle umgewandelt wird, dann kann dies zu entsprechenden Veränderungen bzw. vom Schnitt abweichenden Verhalten führen.

Serious consideration of the potential for genetic contributions to sex differences in the brain is relatively new to the scene. The previous hegemony of hormones was the result of a combination of factors, not the least of which were technical difficulties of separating hormonal and genetic influences. A limited tool set is now available, limited in that it is mostly restricted to mice, but information gained provides a spring board for investigation of other animal models and humans. The Four-Core-Genotypes model consists of genetically modified mice in which the testis-determining gene, Sry, which initiates testicular development from the bipotential gonad, has been moved from the Y chromosome to an autosome (Figure 4). This produces XX mice that develop testes as well as XY mice that lack Sry and therefore develop ovaries. Comparison of these genotype/gonad phenotype reversed animals to those in which genotype and gonads are matched distinguishes between sex differences directly driven by X or Y genes, versus those driven by hormonal products of the gonads. To date this model system has confirmed the supremacy of hormones for most of the first type of sex differences, sex dimorphisms directly relevant to reproduction, but has revealed a genetic basis to several of the second type of sex difference, those related to social behavior, habit formation and nociception (Arnold and Chen, 2009). Similar conclusions were found in a parallel approach in which SF-1 knockout mice develop without gonads; in this model neural sex differences directly associated with reproduction were largely, but not completely, absent in agonadal XX vs. XY mice, but others persisted (Budefeld et al., 2008). Mice lacking functional steroid receptors or synthetic enzymes further expand the arsenal of models for separating hormonal from genetic effects.

An Mäusen lässt sich natürlich besser forschen als an Menschen. Aber die  Ergebnisse bei den Mäusen zeigen, wie ein solches System bei Säugetieren funktionieren kann. Natürlich lässt sich das nicht direkt übertragen und beim Menschen könnten beispielsweise bestimmte Verhaltensunterschiede eher genetisch oder eher hormonell sein, unabhängig von der Maus.

Jungen kommen immer früher in die Pubertät

Ein Spiegelartikel über die früher einsetzende Pubertät von Jungen:

Die amerikanischen Jungs kommen heute zwischen sechs Monaten und zwei Jahren früher in die Pubertät als noch vor ein paar Jahrzehnten. Das hat eine Studie des US-Instituts Pediatric Research in Office Settings (PROS) ergeben. Bisher war eine immer frühere körperliche Entwicklung nur für Mädchen durch Studien belegt und akzeptiert. Für Jungs fehlten große Untersuchungen, unter anderem, weil der Pubertätseintritt bei ihnen schwerer zu erfassen ist. Während bei Mädchen etwa die erste Periode einfach dokumentiert werden kann, fehlt bei Jungs ein derartig eindeutiger Faktor.

Beide Geschlechter kommen immer früher in die Pubertät, was letztendlich auch bedeutet, dass immer jüngere Kinder sexueller werden und sexuelle Interessen haben. Das wiederum mag dazu beitragen, dass jüngere Kinder auch früher sexualisierte Kleidung tragen und sich entsprechend verhalten und auf das andere Geschlecht reagieren. Beides hat natürlich auch gesellschaftliche Folgen, weil eben damit auch die Zeiten des ersten Sex nach vorne verlagert werden und in gewisser Weise die Kindheit verkürzt wird.

Interessanterweise gibt es wohl gewisse Unterschiede zwischen den Völkern:

Laut der Analyse erreichen afroamerikanische Jungs als erstes dieses Entwicklungsstadium, bei ihnen zeigten sich mit durchschnittlich 9,14 Jahren die ersten Anzeichen der körperlichen Veränderung. Bei den weißen Jungs setzten die Veränderungen mit durchschnittlich 10,14 Jahren ein. Nachzügler waren die lateinamerikanischen Jungs, die durchschnittlich mit 10,4 Jahren die ersten Anzeichen für eine Pubertät entwickelten.

Schwarze kommen im Schnitt also ein ganzes Jahr früher in die Anfänge der Pubertät. 9 Jahre finde ich dabei ein erstaunlich frühes Alter, mit dem ich nicht gerechnet hätte.

Die Gründe sind wohl noch unklar:

och haben Forscher nur vage Vermutungen, die hauptsächlich auf Mädchen zutreffen: So hatten Studien zum Beispiel gezeigt, dass Übergewicht mit einem frühen Einsatz der Pubertät zusammenhängt. Auch scheinen psychische Faktoren eine Rolle zu spielen. Mädchen, die ohne Vater aufwachsen, scheinen früher in die Pubertät zu kommen.

Ebenfalls diskutiert wird der Einfluss von Chemikalien auf die Entwicklung, die Sexualhormone beeinflussen. Da es sich dabei allerdings vor allem um das weibliche Sexualhormon Östrogen handelt, lässt sich die Theorie nicht einfach auf Jungs übertragen – Östrogen könnte bei ihnen genau gegengesetzt wirken und die Entwicklung eher verzögern. Ebenfalls unklar ist, wie die beobachteten ethnischen Unterschiede zustande kommen. Auch das sollen weitere Studien klären.

Was die genauen Ursachen sind, ist sicherlich interessant. Mal sehen, was weitere Studien zum Vorschein bringen.

Die Wirkung von Testosteronpräparaten

Zu der direkten Wirkung zusätzlich eingenommenen Testosterons hatte ich schon zwei Fälle zitiert:

Es sind natürlich immer Einzelgeschichten, aber ich halte sie dennoch für interessant und repräsentativ, da die Wirkung auch ansonsten in der Medizin beschrieben wird.

Hier noch Auszüge aus einer weiteren Schilderung:

It’s been really interesting to notice how things have changed over the last few weeks, since I started using a gel that delivers testosterone through the skin. I had a bit of a heads up regarding what to expect from some of the transgender men who have shared their stories with me, but there’s a big difference between their experiences and mine. After all, testosterone has been the primary sex hormone in my life and I don’t share their experience of switching from a primarily estrogen/progesterone-based system to a primarily testosterone-based system. For me, it’s been more like coming back to myself, rather than coming into myself (a phrase I’ve heard some trans* guys use when describing testosterone).

The biggest effect that I noticed almost right away was that I started feeling more energetic.I’m waking up more alert, I have more focus, I don’t get tired as easily, and I’m sleeping better. It’s as if the dial had been slowly getting turned down and now it’s back where it belongs. Life seems brighter and I feel a lot happier. I’m a lot more optimistic in the face of challenges and my “can do” attitude has returned. (Good timing, too. September has been an especially busy month.)

At the same time, I’m also a bit more irritable. Little things trigger anger more easily and it’s taking more work to contain and manage it. Most of the people in my life haven’t really noticed it, but my partner certainly has seen me get irritated or cranky more easily. That’s often the case- she saw the effects of my dysregulated blood sugar much sooner than anyone else, too. I’m also more easily distracted when I’m doing something that I’d prefer to skip. I have less patience for the tasks I need to do that I wish I didn’t have to do. And being interrupted when I’m working on something feels much more annoying than it did before.

Both my renewed energy and my increased irritability have been fascinating to observe, in as much as I can from the inside. I remember being a teenager not being able to sit still because I wanted to jump up and do stuff. I also recall how easily I’d freak out about things that seemed hugely important at the time and really were nothing to worry about. Part of what I’ve been sitting with around this is a deeper understanding of how much biology shapes how we interpret the world and how we choose to act in response.

Along those lines, I’ve also noticed that my urge to look at people I find attractive has has increased. Walking down the street or sitting on the train, I have more of an impulse to check folks out. I’m glad that I have more practice at managing my sexual energy than when I was younger.

Ich finde hier gerade die Gegenüberstellung zur Pubertät ganz interessant. Der höhere Testosteronspiegel hat auch hier bedeutende Konsequenzen und man muss lernen mit dieser Umstellung umzugehen. Auch diese Wirkung der Sexualhormone wird in einem Gleichheitsfeminismus radikal ausgeblendet, obwohl sie inzwischen gut erforscht ist.

 

Auswirkung postnataler Hormone auf das Gehirn

Eine Studie zu den Auswirkungen postnataler Hormone auf das Gehirn:

Objective: Sex hormones are not only involved in the formation of reproductive organs, but also induce sexually-dimorphic brain development and organization. Cross-sex hormone administration to transsexuals provides a unique possibility to study the effects of sex steroids on brain morphology in young adulthood.

Methods: Magnetic resonance brain images were made prior to, and during, cross-sex hormone treatment to study the influence of anti-androgen + estrogen treatment on brain morphology in eight young adult male-to-female transsexual human subjects and of androgen treatment in six female-to-male transsexuals.

Results: Compared with controls, anti-androgen + estrogen treatment decreased brain volumes of male-to-female subjects towards female proportions, while androgen treatment in female-to-male subjects increased total brain and hypothalamus volumes towards male proportions.

Conclusions: The findings suggest that, throughout life, gonadal hormones remain essential for maintaining aspects of sex-specific differences in the human brain.

Quelle: Changing your sex changes your brain: influences of testosterone and estrogen on adult human brain structure

Aus der Studie:

It is well established in mammals that differences in male and female brain structures can be reversed by sex hormones, even in adulthood (1). However, it is not known whether alterations in sex hormone levels can change structures of the human brain in adulthood. In human adults, the volumes of the brain and hypothalamus of males tend to be larger than those of females (2). The preoptic nucleus of the hypothalamus is even twice as large in males as in females (3). Moreover, in some studies, when comparing the fractions of gray and white matter in the brain, adult females as compared with males were found to have a higher fraction of gray matter, whereas adult males as compared with females had a higher fraction of white matter (4, 5).

Also bei Männern mehr graue Masse, bei Frauen mehr weiße Masse und bei Transsexuellen jeweils Veränderungen hin zu dem anderen Geschlecht hin

The changes in total brain and hypothalamus volumes following cross-sex hormone treatment in the transsexuals were mirrored by changes in their third and lateral ventricle volumes, i.e. treatment with estrogens and anti-androgens in MFs increased third and lateral ventricle volumes, whereas treatment with androgens decreased the third and lateral ventricle volumes in FMs. This suggests that the total brain volume changes are at least in part due to changes in medial brain structures surrounding these ventricles (including, but not limited to, the hypothalamus, which lies in close proximity to the third ventricle). Considering that the effects were not specific for gray (neurons, glia) or white (myelinated axonal fibers) matter suggests that both alterations in nerve cells as well as in axonal fibers may be implicated in the anatomical brain changes following cross-sex hormone treatment in humans. It is not surprising that the influences of sex hormones on the brain were not limited to the hypothalamus, but were also expressed as changes in total brain size. Estrogen and androgen receptor mRNA containing neurons are not limited to the hypothalamus, but are distributed throughout the adult human brain (18).

Es scheint also, als hätte postnatales Testosteron eine andere Auswirkung auf die Gehirnstruktur als pränatales. Gewisse Strukturen scheinen angleichbar zu sein, andere nicht.