Prenatal androgen influences on the brain: A review, critique, and illustration of research on congenital adrenal hyperplasia.

Sex hormones, especially androgens, contribute to sex and gender differences in the brain and behavior. Organizational effects are particularly important because they are thought to be permanent, reflecting hormone exposure during sensitive periods of development. In human beings, they are often studied with natural experiments in which sex hormones are dissociated from other biopsychosocial aspects of development, such as genes and experiences. Indeed, the greatest evidence for organizational effects on sex differences in human behavior comes from studies of females with congenital adrenal hyperplasia (CAH), who have heightened prenatal androgen exposure, female-typical rearing, and masculinized toy play, activity and career interests, spatial skills, and some personal characteristics. Interestingly, however, neuroimaging studies of females with CAH have revealed few neural mechanisms underlying these hormone-behavior links, with the exception of emotion processing; studies have instead shown reduced gray matter volumes and reduced white matter integrity most consistent with other disease-related processes. The goals of this narrative review are to: (a) describe methods for studying prenatal androgen influences, while offering a brief overview of behavioral outcomes; (b) provide a critical methodological review of neuroimaging research on females with CAH; (c) present an illustrative analysis that overcomes methodological limitations of previous work, focusing on person-specific neural reward networks (and their associations with sensation seeking) in women with CAH and their unaffected sisters in order to inform future research questions and approaches that are most likely to reveal organizational hormone effects on brain structure and function.

Family environmental antecedents of pubertal timing in girls and boys: A review and open questions.

Across nonhuman species, pubertal timing is affected by the social environment, with consequences for reproductive success and behavior. In human beings, variations in pubertal timing have not been systematically examined in relation to social environmental antecedents, although their psychological consequences are well documented. This paper focuses on links in human beings between pubertal timing and the childhood social environment, with several sections: A review of studies relating pubertal timing to the family context, a key aspect of the social environment; challenges in studying the issue; and opportunities for future work that takes advantage of and creates links with evidence in other species. The review shows that pubertal timing in girls is accelerated by adversity in aspects of the early family social context, with effects small in size; data in boys are not sufficient to enable conclusions. Inferences from existing studies are limited by variations in conceptualizations and measurement of relevant aspects of puberty and of the family social environment, and by methodological issues (e.g., reliance on existing data, use of retrospective reports, nonrandom missing data). Open questions remain about the nature, mechanisms, and specificity of the links between early family social environment and pubertal timing (e.g., form of associations, consideration of absence of positive experiences, role of timing of exposure). Animal studies provide a useful guide for addressing these questions, by delineating potential hormonal mechanisms that underlie links among social context, pubertal timing, and behavior, and encouraging attention to aspects of the social environment outside the family, especially peers.

Family Experiences and Parent Personality as Antecedents of Pubertal Timing in Girls and Boys.

Pubertal timing may be influenced by typical variations in early family environmental events, but questions remain concerning the roles of specific parenting factors, developmental age of exposure to events, moderation by child temperament, and comparability of effects for girls and boys. This study focused on these questions utilizing longitudinal data from 733 same-sex twins (45% girls) in the U.S.; family context was measured at ages 1-3, 4-5, and 6-7 years and pubertal status was assessed annually via self-report at ages 9-15, enabling estimates of pubertal timing. Home environment at ages 4-5 years predicted pubertal timing better than home environment at other ages for both girls and boys, but parent personality was more predictive than home experiences (e.g., divorce, parental harshness, family conflict). Thus, effects of family environment must be considered within the context of parent characteristics, encouraging caution in implicating early environmental experiences as direct influences on early pubertal timing.

Does puberty affect the development of behavior problems as a mediator, moderator, or unique predictor?

Pubertal timing matters for psychological development. Early maturation in girls is linked to risk for depression and externalizing problems in adolescence and possibly adulthood, and early and late maturation in boys are linked to depression. It is unclear whether pubertal timing uniquely predicts problems; it might instead mediate the continuity of behavior problems from childhood to adolescence or create psychological risk specifically in youth with existing problems, thus moderating the link. We investigated these issues in 534 girls and 550 boys, measuring pubertal timing by a logistic model fit to annual self-report measures of development and, in girls, age at menarche. Prepuberty internalizing and externalizing behavior problems were reported by parents. Adolescent behavior problems were reported by parents and youth. As expected, behavior problems were moderately stable. Pubertal timing was not predicted by childhood problems, so it did not mediate the continuity of behavior problems from childhood to adolescence. Pubertal timing did not moderate links between early and later problems for girls. For boys, early maturation accentuated the link between childhood problems and adolescent substance use. Overall, the replicated links between puberty and behavior problems appear to reflect the unique effects of puberty and child behavior problems on the development of adolescent behavior problems.

Evidence needed to understand gender identity: Commentary on Turban & Ehrensaft (2018).

Turban and Ehrensaft (2018) have provided a thoughtful review of transgender identity in children and adolescents, emphasizing the benefits of the affirmative approach in maintaining positive psychological health in transgender individuals. The review reveals significant gaps in our understanding of gender identity regarding its nature, development, plasticity, causes, and links with other aspects of gender, and of the long-term benefits and costs of childhood social transitions. A full understanding of transgender identity requires studying cisgender identity too, and recognition that gender identity is continuous, develops across time and is not synonymous with gender expression or variations in gender-typed characteristics. Considerable evidence is needed before we can be confident that we are providing optimal treatment for children who are gender variant.

Gendered Peer Involvement in Girls with Congenital Adrenal Hyperplasia: Effects of Prenatal Androgens, Gendered Activities, and Gender Cognitions.

A key question in understanding gender development concerns the origins of sex segregation. Children's tendencies to interact with same-sex others have been hypothesized to result from gender identity and cognitions, behavioral compatibility, and personal characteristics. We examined whether prenatal androgen exposure was related to time spent with boys and girls, and how that gendered peer involvement was related to sex-typed activities and gender identity and cognitions. We studied 54 girls with congenital adrenal hyperplasia (CAH) aged 10-13 years varying in degree of prenatal androgen exposure: 40 girls with classical CAH (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical CAH (NC-CAH) exposed to low, female-typical, prenatal androgens. Home interviews and questionnaires provided assessments of gendered activity interests and participation, gender identity, and gender cognitions. Daily phone calls over 7 days assessed time spent in gendered activities and with peers. Girls with both C-CAH and NC-CAH interacted more with girls than with boys, with no significant group differences. The groups did not differ significantly in gender identity or gender cognitions, but girls with C-CAH spent more time in male-typed activities and less time in female-typed activities than did girls with NC-CAH. Time spent with girls reflected direct effects of gender identity/cognitions and gender-typed activities, and an indirect effect of prenatal androgens (CAH type) through gender-typed activities. Our results extend findings that prenatal androgens differentially affect gendered characteristics and that gendered peer interactions reflect combined effects of behavioral compatibility and feelings and cognitions about gender. The study also shows the value of natural experiments for testing hypotheses about gender development.

From Genes to Behavior Through Sex Hormones and Socialization: The Example of Gender Development.

Irving Gottesman is known primarily for his work in psychopathology, but he also had a long-standing interest in understanding psychological development generally (typical and atypical). Through his mentorship, he also influenced work in gender development. Characteristics related to sex and gender are ideally suited to study the interplay of genes and environment across development. We discuss how gender development is influenced by gonadal hormones present during early life, but not in a simple way. We describe some of the challenges and opportunities to extend our understanding of the complexity of gender development. Throughout, we consider the kinds of questions Gottesman would likely have asked and emphasize his influence on our work.

Linking Prenatal Androgens to Gender-Related Attitudes, Identity, and Activities: Evidence From Girls With Congenital Adrenal Hyperplasia.

Key questions for developmentalists concern the origins of gender attitudes and their implications for behavior. We examined whether prenatal androgen exposure was related to gender attitudes, and whether and how the links between attitudes and gendered activity interest and participation were mediated by gender identity and moderated by hormones. Gender attitudes (i.e., gender-role attitudes and attitudes about being a girl), gender identity, and gender-typed activities were reported by 54 girls aged 10-13 years varying in degree of prenatal androgen exposure, including 40 girls with classical congenital adrenal hyperplasia (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical (NC) CAH exposed to low, female-typical, prenatal androgens. Both girls with C-CAH and NC-CAH reported positive attitudes about being a girl and egalitarian gender attitudes, consistent with their female-typical gender identity. In contrast, girls with C-CAH had more male-typed activity interest and participation than girls with NC-CAH. Gender attitudes were linked to activities in both groups, with gender identity mediating the links. Specifically, gender-role attitudes and positive attitudes about being a girl were associated with feminine gender identity, which in turn was associated with decreased male-typed activity interests and participation, and increased female-typed activity interests. Our results are consistent with schema theories, with attitudes more closely associated with gender identity than with prenatal androgens.

Genetic influences on pubertal development and links to behavior problems.

Genetic influences on adolescent psychological development are likely to be mediated and moderated by pubertal hormones. Combining genetic analyses with advanced models of pubertal development, we extended work on the measurement and psychological significance of puberty. We examined how genetic and environmental influences on puberty vary by the way that development is described (logistic versus linear models versus traditional methods) and the different aspects of puberty (adrenarche vs. gonadarche), and how genes and environment contribute to the covariation between different descriptions and aspects of puberty, and between pubertal development and behavior problems (substance use, age at sexual initiation). We also considered how puberty moderated the heritability of psychological outcomes (internalizing and externalizing problems), and sex differences. Participants from the Colorado Longitudinal Twin Study (403 girls, 395 boys) reported their pubertal development annually from ages 9 through 15; they and their parents reported their behavior in mid-to-late adolescence. There was a large genetic contribution to pubertal timing for both sexes no matter how it was measured, but findings for pubertal tempo varied by method. Genetic covariation accounted for most of the phenotypic correlations among different indicators of pubertal timing, and between pubertal timing and psychological outcome. We consider the implications of our results for understanding how pubertal hormones mediate or moderate genetic and environmental influences on psychological development.

Oral contraceptives and cognition: A role for ethinyl estradiol.

This article is part of a Special Issue "Estradiol and cognition". Estrogens have been seen to play a role in human cognitive abilities, but questions remain about the cognitive impact of ethinyl estradiol, which is contained in many oral contraceptives (OCs). Inconsistencies in past studies likely reflect small samples and heterogeneous groups of OC users. The aims of the present work were to examine OC effects on sex-typed spatial and verbal abilities by (a) comparing mental rotations and expressional fluency in normally-cycling (NC) women and men to OC users considered as a heterogeneous group and then to homogeneous groups of OC users created by classifying pills according to their active constituents, and (b) determining the relation between synthetic hormone doses in OCs and mental rotations and expressional fluency. Participants were 136 men, 93 NC women, and 148 OC users, including homogeneous monophasic (n = 55) and triphasic (n = 43) OC groups, aged 18 to 30 years. Significant effects of OC use were seen in homogeneous group comparisons but not when OC users were considered as a heterogeneous group. On mental rotations, men outperformed women, and monophasic OC users outperformed NC women. The latter difference may be attributable to estradiol, as ethinyl estradiol was inversely related to spatial ability among OC users and was lower in monophasic than in triphasic users. On expressional fluency, NC women and monophasic OC users outperformed men, and monophasic users outperformed triphasic users. Thus, results show the importance of ethinyl estradiol and of considering pill constituents when studying the cognitive effects of OCs.

Brain responses to sexual images in 46,XY women with complete androgen insensitivity syndrome are female-typical.

Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images. We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls.

Using behavioural network mapping to investigate dyadic play in girls with congenital adrenal hyperplasia.

Examining mechanisms underlying sex differences in children's play styles, we studied girls with congenital adrenal hyperplasia (CAH) who provide a test of the relative effects of prenatal androgens versus rearing, and of behavioural similarity versus gender identity and cognitions. In this exploratory study, 40 focal children (girls and boys with and without CAH), aged 3-8 years, played for 14 min with a same-sex peer in a task designed to elicit rough-and-tumble play. Time-indexed ratings of positive affect and vigour of activity were evaluated via network mapping for sex-related differences in both levels and play dynamics (temporal relations among behaviours). Results suggest influences of both gender identity-aligned social cognitions and prenatal androgens: there was greater dyadic synchrony between positive affect for girls (regardless of CAH status) than boys, but girls with CAH displayed positive affect levels and directed vigorous peer play dynamics similar to boys.

Pubertal timing in adolescence and adulthood: Relations among contemporaneous and retrospective measures.

Pubertal development has short- and long-term effects on psychological adjustment. Many studies of long-term effects rely on retrospective measurement of pubertal timing, but such measures often reflect different aspects of puberty than those assessed in adolescence, raising questions about the utility and interpretation of retrospective reports. The present study leveraged longitudinal data collected in adolescence and established adulthood to determine: (1) the correspondence between pubertal timing indexed from logistic growth curves of self-reported physical development assessed contemporaneously across adolescence and pubertal timing indexed relative to peers assessed retrospectively in adulthood; (2) the associations between the two pubertal timing measures and psychological adjustment; and (3) potential recall biases. Participants were 748 individuals (50.1% female; 91.6% White) from two longitudinal studies who reported on their pubertal development annually from Grades 3-9, psychological adjustment (age at sexual initiation, substance use, depression) in late adolescence, and retrospective pubertal timing in established adulthood (Mage = 32.76; SD = 4.43). Results indicate moderate-to-high convergence between retrospective and contemporaneous indices. Most participants, especially women, had the same pubertal timing classification (i.e., early, on time, or late), but early-maturing adolescents often recalled on-time development as adults. Retrospective and contemporaneous indices were associated with psychological adjustment in similar ways, with some attenuation in the retrospective measure, especially for men. There was little evidence of recall bias due to age at retrospective assessment or time since puberty. Findings generally support the use of retrospective pubertal timing measures, with the recognition that some relations with adjustment may be weakened. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cognitive effects of variations in pubertal timing: is puberty a period of brain organization for human sex-typed cognition?

There is considerable interest in the organizational effects of pubertal sex hormones on human sex-related characteristics. Recent evidence from rodents suggests that there is a decreasing window of sensitivity to sex hormones throughout adolescence. If adolescence also represents a period of brain organization in human beings, then the timing of exposure to sex-typical hormones at puberty should have long-term effects on sex-typed characteristics: individuals with early timing should be more sex-typed than individuals with late timing. We tested this hypothesis in 320 young adults by relating their pubertal timing (retrospective comparison to peers) to cognitive abilities that show sex differences. Results provide partial support for the hypothesis. For men, pubertal timing was inversely related to scores on a test of three-dimensional mental rotations. Effects do not appear to be due to duration of hormone exposure (time since puberty), but other potential influences need further study.

Predictors and consequences of gender typicality: the mediating role of communality.

Considerable work has shown the benefits for psychological health of being gender typed (i.e., perceiving oneself in ways that are consistent with one's sex). Nevertheless, little is known about the reasons for the link. In two studies of young adults (total N = 673), we studied (1) the ways in which gender typing is predicted from gender-related interests and personal qualities, and (2) links between gender typing and adjustment (self-esteem and negative emotionality). In the first study, gender typicality was positively predicted by a variety of gender-related characteristics and by communal traits, a female-typed characteristic; gender typicality was also positively associated with adjustment. To clarify the role of communality in predicting gender typicality and its link with adjustment, we conducted a follow-up study examining both gender typicality and "university typicality." Gender typicality was again predicted by gender-related characteristics and communality, and associated with adjustment. Further, university typicality was also predicted by communality and associated with adjustment. Mediation analyses showed that feelings of communality were partly responsible for the links between gender/university typicality and adjustment. Thus, the psychological benefits suggested to accrue from gender typicality may not be specific to gender, but rather may reflect the benefits of normativity in general. These findings were discussed in relation to the broader literature on the relation between identity and adjustment.

Sexual differentiation of human behavior: effects of prenatal and pubertal organizational hormones.

A key question concerns the extent to which sexual differentiation of human behavior is influenced by sex hormones present during sensitive periods of development (organizational effects), as occurs in other mammalian species. The most important sensitive period has been considered to be prenatal, but there is increasing attention to puberty as another organizational period, with the possibility of decreasing sensitivity to sex hormones across the pubertal transition. In this paper, we review evidence that sex hormones present during the prenatal and pubertal periods produce permanent changes to behavior. There is good evidence that exposure to high levels of androgens during prenatal development results in masculinization of activity and occupational interests, sexual orientation, and some spatial abilities; prenatal androgens have a smaller effect on gender identity, and there is insufficient information about androgen effects on sex-linked behavior problems. There is little good evidence regarding long-lasting behavioral effects of pubertal hormones, but there is some suggestion that they influence gender identity and perhaps some sex-linked forms of psychopathology, and there are many opportunities to study this issue.

Vision contributes to sex differences in spatial cognition and activity interests.

Sex differences in a variety of psychological characteristics are well-documented, with substantial research focused on factors that affect their magnitude and causes. Particular attention has focused on mental rotation, a measure of spatial cognition, and on activity interests. We studied whether sex differences in visual perception-luminance contrast thresholds and motion duration thresholds-contribute to sex differences in mental rotation and interest in male-typed activities. We confirmed sex differences in vision, mental rotation, and activity interests in a sample of 132 college students. In novel findings, we showed that vision correlated with mental rotation performance in women, that vision was a better predictor of individual differences in mental rotation than sex, and that contrast thresholds correlated with women's interest in male-typed activities. These results suggest that sex differences in spatial cognition and activity interests may have their roots in basic perceptual processes.

Gendered occupational interests: prenatal androgen effects on psychological orientation to Things versus People.

There is considerable interest in understanding women's underrepresentation in science, technology, engineering, and mathematics careers. Career choices have been shown to be driven in part by interests, and gender differences in those interests have generally been considered to result from socialization. We explored the contribution of sex hormones to career-related interests, in particular studying whether prenatal androgens affect interests through psychological orientation to Things versus People. We examined this question in individuals with congenital adrenal hyperplasia (CAH), who have atypical exposure to androgens early in development, and their unaffected siblings (total N=125 aged 9 to 26 years). Females with CAH had more interest in Things versus People than did unaffected females, and variations among females with CAH reflected variations in their degree of androgen exposure. Results provide strong support for hormonal influences on interest in occupations characterized by working with Things versus People.

The benefits and drawbacks of gender typing: how different dimensions are related to psychological adjustment.

The benefits versus costs of gender typing are not clear: Is adjustment optimal when people identify and act in strongly gendered ways or when they embrace characteristics of both sexes? Previous findings are inconsistent, in part because they are derived from different conceptualizations of gender typing. A comprehensive understanding of the mental health consequences of gender typing requires recognition of the multidimensionality of gender typing and simultaneous consideration of these dimensions. On the basis of previous work on individual measures, we hypothesized that adjustment would be differentially associated with different aspects of gender typing: positively with sex-congruent gender identity and male-typed personality traits, negatively with rigid gender attitudes, and minimally with female-typed personality traits and gender-typed activity interests. Structural equation models were used to enable testing of all associations simultaneously. Results from a sample of 401 undergraduate students supported our hypotheses. For both women and men, adjustment was positively associated with gender-congruent identity, instrumentality, and flexible gender attitudes, and minimally related to activity interests and expressivity. These findings clarify the mental health benefits and costs of gender typing and highlight the multidimensionality of gender typing.