Melissa Hines

Human behavioral sex differences: a role for gonadal hormones during early development?

Evidence that gonadal hormones during prenatal and neonatal development influence behavior is reviewed. Several theoretical models of hormonal influences, derived from research in other species, are described. These models are evaluated on the basis of data from humans with either normal or abnormal hormonal exposure. It is concluded that the evidence is insufficient to determine which model best explains the data. Sexual differentiation may involve several dimensions, and different models may apply to different behaviors. Gonadal hormones appear to influence development of some human behaviors that show sex differences. The evidence is strongest for childhood play behavior and is relatively strong for sexual orientation and tendencies toward aggression. Also, high levels of hormones do not enhance intelligence, although a minimum level may be needed for optimal development of some cognitive processes. Directions for future research are proposed.

Masculinized finger length patterns in human males and females with congenital adrenal hyperplasia

The ratio of the length of the second digit (2D) to the length of the fourth digit (4D) is greater in women than in men. Since androgens are involved in most somatic sex differences and since the sexual dimorphism in 2D:4D is stable from 2 years of age in humans, it was hypothesized that finger length pattern development might be affected by early androgen exposure. Human females with congenital adrenal hyperplasia (CAH) are exposed prenatally to higher than normal levels of adrenal androgens, providing an opportunity to test the effects of early androgen exposure on digit ratios. The 2D:4D was calculated for females with CAH, females without CAH, males with CAH, and males without CAH. Females with CAH had a significantly smaller 2D:4D on the right hand than did females without CAH. Males with CAH had a significantly smaller 2D:4D on the left hand than did males without CAH. A subset of six males with CAH had a significantly smaller 2D:4D on both hands compared with their male relatives without CAH. These results are consistent with the idea that prenatal androgen exposure reduces the 2D:4D and plays a role in the establishment of the sex difference in human finger length patterns. Finger lengths may therefore offer a retrospective marker of perinatal androgen exposure in humans.

Sex differences in subregions of the medial nucleus of the amygdala and the bed nucleus of the stria terminalis of the rat

Sex differences are described in subregions of two nuclei of the rat brain: the medical nucleus of the amygdala (MA) and the bed nucleus of the stria terminalis (BNST). The volume of the posterodorsal region of the medial nucleus of the amygdala (MApd) is approximately 85% greater and the volume of the encapsulated region of the bed nucleus of the stria terminalis (BNSTenc) is approximately 97% greater in males than in females. The MApd and BNSTenc are distinct subregions of the MA and BNST. They exhibit intense uptake of gonadal hormones and are anatomically connected to each other and to other sexually dimorphic nuclei. The MA and BNST in general are involved in regulation of several sexually dimorphic functions, including aggression, sexual behavior, gonadotropin secretion and integration of olfactory information. Precise localization of sex differences in subregions of the MA and BNST, such as the MApd and BNSTenc, may facilitate understanding of the neural basis of such functions.

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.

Psychological outcomes and gender-related development in complete androgen insensitivity syndrome.

We evaluated psychological outcomes and gender development in 22 women with complete androgen insensitivity syndrome (CAIS). Participants were recruited through a medical database (n = 10) or through a patient support group (n = 12). Controls included 14 males and 33 females, of whom 22 were matched to women with CAIS for age, race, and sex-of-rearing. Outcome measures included quality of life (self-esteem and psychological general well-being), gender-related psychological characteristics (gender identity, sexual orientation, and gender role behavior in childhood and adulthood), marital status, personality traits that show sex differences, and hand preferences. Women recruited through the database versus the support group did not differ systematically, and there were no statistically significant differences between the 22 women with CAIS and the matched controls for any psychological outcome. These findings argue against the need for two X chromosomes or ovaries to determine feminine-typical psychological development in humans and reinforce the important role of the androgen receptor in influencing masculine-typical psychological development. They also suggest that psychological outcomes in women with CAIS are similar to those in other women. However, additional attention to more detailed aspects of psychological well-being in CAIS is needed.

Fetal Testosterone Predicts Sexually Differentiated Childhood Behavior in Girls and in Boys

Mammals, including humans, show sex differences in juvenile play behavior. In rodents and nonhuman primates, these behavioral sex differences result, in part, from sex differences in androgens during early development. Girls exposed to high levels of androgen prenatally, because of the genetic disorder congenital adrenal hyperplasia, show increased male-typical play, suggesting similar hormonal influences on human development, at least in females. Here, we report that fetal testosterone measured from amniotic fluid relates positively to male-typical scores on a standardized questionnaire measure of sex-typical play in both boys and girls. These results show, for the first time, a link between fetal testosterone and the development of sex-typical play in children from the general population, and are the first data linking high levels of prenatal testosterone to increased male-typical play behavior in boys.

Pre- and postnatal influence of testosterone propionate and diethylstilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats

The volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is several fold larger in males than in females. When female rats were treated pre- and postnatally with testosterone propionate (TP) or with diethylstilbestrol (DES) they became anovulatory and their SDN-POA developed equivalent in size to that of normal males. Identical treatment of male rats resulted in deficient testicular development, but had no influence on SDN-POA volume. The results indicate that the gross morphological sex difference in SDN-POA volume can exclusively be controlled by the hormonal environment during the critical period of sexual brain differentiation, and that non-steroidal estrogens are just as effective as convertible androgens in stimulating SDN-POA differentiation.

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.

Sex-related variation in human behavior and the brain

Male and female fetuses differ in testosterone concentrations beginning as early as week 8 of gestation. This early hormone difference exerts permanent influences on brain development and behavior. Contemporary research shows that hormones are particularly important for the development of sex-typical childhood behavior, including toy choices, which until recently were thought to result solely from sociocultural influences. Prenatal testosterone exposure also appears to influence sexual orientation and gender identity, as well as some, but not all, sex-related cognitive, motor and personality characteristics. Neural mechanisms responsible for these hormone-induced behavioral outcomes are beginning to be identified, and current evidence suggests involvement of the hypothalamus and amygdala, as well as interhemispheric connectivity, and cortical areas involved in visual processing.

Sex differences in response to children's toys in nonhuman primates (Cercopithecus aethiops sabaeus)

Sex differences in children’s toy preferences are thought by many to arise from gender socialization. However, evidence from patients with endocrine disorders suggests that biological factors during early development (e.g., levels of androgens) are influential. In this study, we found that vervet monkeys (Cercopithecus aethiops sabaeus) show sex differences in toy preferences similar to those documented previously in children. The percent of contact time with toys typically preferred by boys (a car and a ball) was greater in male vervets (n=33) than in female vervets (n=30) (P<.05), whereas the percent of contact time with toys typically preferred by girls (a doll and a pot) was greater in female vervets than in male vervets (P<.01). In contrast, contact time with toys preferred equally by boys and girls (a picture book and a stuffed dog) was comparable in male and female vervets. The results suggest that sexually differentiated object preferences arose early in human evolution, prior to the emergence of a distinct hominid lineage. This implies that sexually dimorphic preferences for features (e.g., color, shape, movement) may have evolved from differential selection pressures based on the different behavioral roles of males and females, and that evolved object feature preferences may contribute to present day sexually dimorphic toy preferences in children. D 2002 Elsevier Science Inc. All rights reserved.