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There is now good evidence that human sex-typed behavior is influenced by sex hormones that are present during prenatal development, confirming studies in other mammalian species. Most of the evidence comes from clinical populations, in which prenatal hormone exposure is atypical for a person's sex, but there is increasing evidence from the normal population for the importance of prenatal hormones. In this paper, we briefly review the evidence, focusing attention on the methods used to study behavioral effects of prenatal hormones. We discuss the promises and pitfalls of various types of studies, including those using clinical populations (concentrating on those most commonly studied, congenital adrenal hyperplasia, androgen insensitivity syndrome, ablatio penis, and cloacal exstrophy), direct measures of hormones in the general population (assayed through umbilical cord blood, amniotic fluid, and maternal serum during pregnancy), and indirect measures of hormones in the general population (inferred from intrauterine position and biomarkers such as otoacoustic emissions, finger length ratios, and dermatoglyphic asymmetries). We conclude with suggestions for interpreting and conducting studies of the behavioral effects of prenatal hormones. q

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Girls with congenital adrenal hyperplasia (CAH) who were exposed to high levels of androgen in the prenatal and early postnatal periods showed increased play with boys' toys and reduced play with girls' toys compared with their unexposed female relatives at ages 3 to 8~Boys with CAH did not differ from their male relatives in play with boys' or girls' toys. These results suggest that early hormone expoiure infemales has a masculinizing effeCt on sex-typed toy preferences.

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Our findings confirm the benefits of newborn screening for CAH and the importance of a second screening test, and suggest that programs for newborn CAH screening must consider complex issues in diagnosis and treatment. These results also confirm that CAH is a continuum of disorders, rather than a disorder with discrete subtypes. In addition, the difficulties in differentiating CAH subtypes in newborns, and thus deciding appropriate treatment, and the high incidence of NC CAH suggest that standard diagnostic criteria and treatment regimens for CAH may need modification. Where screening exists, physicians will encounter more cases of CAH than in the past.

Interest in biological substrates of sex-related variations in psychological and physiological characteristics has led to a search for biomarkers of prenatal hormone exposure that can be measured postnatally. There has been particular interest in digit ratio, the relative lengths of the second and fourth fingers (2D:4D), but its validity as a measure of prenatal androgen has not been established. We report the strongest evaluation of the value of 2D:4D as a biomarker for early androgen exposure. Individuals with 46,XY karyotype but no effective prenatal androgen exposure due to complete androgen insensitivity syndrome had digit ratios that were feminized: they were higher than those of typical men and similar to those of typical women. Nevertheless, the effect was modest in size, and there was considerable within-group variability and between-group overlap, indicating that digit ratio is not a good marker of individual differences in prenatal androgen exposure.

A battery of cognitive tests and a measure of early childhood activities were administered to 17 females and 8 males with congenital adrenal hyperplasia (CAH), an autosomal recessive disorder associated with elevated prenatal adrenal androgen levels. CAH females, as compared with unaffected female relatives, showed significantly enhanced performance on three tests of spatial ability -Hidden Patterns, Card Rotations, and Mental Rotations; no reliable differences in spatial ability were observed between male patients and controls. On the Early Life Activities Questionnaire (ELAQ), male patient and control groups did not differ significantly on any activity scales. In contrast, CAH females, relative to female control subjects, showed significantly lower frequencies of participation in activities involving verbal expression and a trend toward greater participation in spatial manipulation activities. Nevertheless, differences between female patient and control groups in early childhood activities did not account for observed differences in spatial ability, given the absence of a significant correlation between the spatial manipulation activity scale and spatial ability. These results are consistent with an effect of pre-and perinatal androgenizing hormones on the development of spatial ability.Sex hormone exposure during critical periods of development and central nervous system differentiation influences consequent patterns of sexually dimorphic behavior and neuroendocrine function. The organizational and/or sensitizing action of sex hormones on mating and non-mating behaviors has been documented in a variety of animals (