Human Studies of Behavioral Effects of Androgens and Estrogens

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In people, as in other species, behavior is affected by hormones in two ways: organizational changes to the brain during early development and activation of brain systems later in life.

Organizational effects of sex hormones occur during prenatal development. Sex differences in hormone concentrations are greatest during prenatal weeks 8 to 24, following the development of the genitalia. Because prenatal hormones cannot be manipulated, knowledge about human behavioral effects of hormones comes from "experiments of nature," in which hormones are altered by disease in the fetus or the mother's exposure to drugs. Studies of hormone effects on human behavior are consistent with studies in other species in suggesting that behavior is affected by androgen present early in development.

The best-studied experiment of nature is congenital adrenal hyperplasia (CAH), a genetic disease in which the fetus is exposed to high levels of androgen beginning early in gestation. If sexual differentiation of human behavior is affected by androgen present during critical periods of development (as occurs for human physical sexual differentiation and for both physical and behavioral sexual differentiation in other mammals), then females with CAH should be behaviorally more masculine and less feminine than a comparison group of females without CAH. And they are in many, but not all, ways. Compared to female controls, females with CAH are more interested in boys' toys and activities and less interested in girls' toys and activities in childhood and in adolescence, are more likely to report using physical aggression in conflict situations, have higher spatial ability, are less interested in infants and feminine appearance, and are less likely to engage in heterosexual activity and more likely to be sexually aroused by other women. However, most females with CAH have female-typical gender identity.

Findings from females with CAH have been confirmed in other ways. For example, girls exposed to masculinizing hormones because their mothers took medication during pregnancy are more likely than their unexposed sisters to report using aggression in conflict situations. Converging evidence for these special cases comes from normal individuals with typical variations in prenatal hormones: 7-year-old girls who had high testosterone in utero (determined from amniotic fluid at prenatal weeks 14 to 16) had better spatial ability than girls who had low testosterone.

The neural mechanisms mediating behavioral effects of prenatal androgen are currently not known. There are sex differences in brain structure and function, but these have not yet been well studied in relation to sex differences in behavior or to prenatal hormone exposure.

Sex hormones continue to affect behavior later in life, probably by activating neural circuits organized early in development. Androgen affects aggression, but the effect is small and bidirectional: That is, aggression itself can increase androgen. Androgen also facilitates spatial ability in a curvilinear fashion. High spatial ability is associated with relatively high androgen in females but relatively low androgen in males, but keep in mind that males on the low end of normal still have higher androgen than females on the high end of normal.

Estrogen also affects behavior later in life. Cognition changes with variations in estrogen levels resulting from the menstrual cycle, oral contraceptives, menopause, and estrogen treatment. Estrogen facilitates aspects of motor function, perhaps by modulating left-hemisphere regions involved in praxis. Estrogen also facilitates memory, so that postmenopausal women receiving estrogen supplementation have better memory than women not taking estrogen. There are associated changes in brain activity, especially in regions involved in memory, including frontal lobes and hippocampus.

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