The ambiguous sex characteristics associated with pseudohermaphroditism can also result from genetically induced biological errors that produce variations in prenatal hormonal processes. We consider three examples of disorders caused by hormonal errors: androgen insensitivity syndrome, fetally androgenized females, and DHT-deficient males.
Androgen Insensitivity Syndrome A rare genetic defect causes a condition known as androgen insensitivity syndrome (AIS), wherein the body cells of a chromosomally normal male fetus are insensitive to androgens (Zuloaga et al., 2008; Bertelloni et al., 2011). The result is feminization of prenatal development, so that the baby is born with normal-looking female genitals and a shallow vagina. Not surprisingly, babies with AIS are identified as female and reared accordingly. The anomaly is often discovered only in late adolescence, when a physician is consulted to find out why menstruation has not started (Gurney, 2007). Recent reviews of many AIS studies reveal that these individuals acquire a clear female gender identity and behave accordingly (Mazur, 2005; T’Sjoen et al., 2010). In one study, investigators compared psychological outcomes and gender development in a group of 22 women with AIS and a control group of 22 women without AIS. No significant differences were found between the women with AIS and the matched control subjects for any psychological outcome measures, including gender identity, sexual orientation, gender-role behaviors, and overall quality of life (Hines et al., 2003).
At first glance these observations seem to support the importance of social learning in shaping gender-identity formation. However, a case can also be made that these findings indicate the strong impact of biological factors in gender-identity formation. The lack of receptivity to androgen in individuals with AIS might prevent the masculiniza — tion of their brains necessary to develop a male identity, just as it results in failure to develop male genitals.
Fetally Androgenized Females In a second type of rare atypical sex differentiation, chromosomally normal females are prenatally masculinized by exposure to excessive androgens—the excess usually caused by a genetically induced malfunctioning of their own adrenal glands (adrenogenital syndrome) (Achermann et al., 2011). As a result, such babies are born with masculine-looking external genitals: An enlarged clitoris can look like a penis, and fused labia can resemble a scrotum. These babies are usually identified as female by medical tests, treated with minor surgery or hormone therapy to eliminate their genital ambiguity, and reared as girls.
Numerous studies have revealed that even though a substantial majority of fetally androgenized females develop a female gender identity, many engage in traditionally male activities and reject behavior and attitudes commonly associated with a female gender identity (Dessens et al., 2005; Rosario, 2011). A small number of these individuals experience such discomfort with the female sex of assignment that they eventually assume a male gender identity with commensurate male gender-role behaviors (Meyer — Bahlburg et al., 1996; Slijper et al., 1998). These various studies of fetally androgenized females appear to reflect the significant impact of biological factors in gender-identity formation.
DHT-Deficient Males A third variety of atypical prenatal differentiation is caused by a genetic defect that prevents conversion of testosterone into the hormone dihydrotestosterone (DHT), which is essential for normal development of external genitals in a male fetus. The testes of males with this disorder do not descend before birth, the penis and scrotum remain undeveloped so that they resemble a clitoris and labia, and a shallow
vagina is partially formed. Because their genitals look more female than male, DHT — deficient males are typically identified as female and reared as girls. However, because their testes are still functional, an amazing change occurs at puberty as accelerated testosterone production reverses the DHT deficiency. This causes the testes to descend and the clitoris-like organs to enlarge into penises. In short, these DHT-deficient males undergo rapid transformation, from apparently female to male! How do they respond?
Research has shown that a majority of DHT-deficient males make a switch from a female gender identity to a male gender identity, usually in adolescence or early adulthood (Cohen-Kettenis, 2005; Imperato-McGinley et al., 1979). These findings challenge the widely held belief that once gender identity is formed in the first few years of life, it cannot be changed.
These examples of atypical sex differentiation appear to provide contradictory evidence. In the first example of males with AIS, chromosomal males insensitive to their own androgens acquire a female gender identity consistent with the way they are reared. In the second example, prenatally masculinized chromosomal females tend to behave in a typically masculine manner even though they are reared female. Finally, in the third example, chromosomal males whose biological maleness is not apparent until puberty are able to switch their gender identity to male, despite early socialization as girls. Are these results at odds with one another, or is there a plausible explanation for their seeming inconsistencies?
As described earlier, some data suggest that prenatal androgens influence sex differentiation of the brain just as they trigger masculinization of the sex structures. The same gene defect that prevents masculinization of the genitals of males with AIS might also block masculinization of their brains, thus influencing the development of a female gender identity. Similarly, the masculinizing influence of prenatal androgens on the brain might also account for the tomboyish behaviors of fetally androgenized females. But what about DHT-deficient males who appear to make a relatively smooth transition from a female to a male gender identity? Perhaps these boys’ brains were prenatally programmed along male lines. Presumably, they had normal levels of androgens and, except for genital development, could respond appropriately to these hormones at critical stages of prenatal development. We cannot state with certainty that prenatal androgens masculinize the brain. However, this interpretation offers a plausible explanation for how DHT-deficient individuals, already hormonally predisposed toward a male gender identity despite being identified as female, can change to a male identity at adolescence in response to changes in their bodies.
These fascinating studies underscore the complexity of biological sex determination. We have seen that many steps, each susceptible to errors, are involved in sex differentiation before birth. There is substantial research evidence that biological factors, especially prenatal brain exposure to androgens, contribute to gender-identity formation. But there is more to the question, Just what makes us female or male? To help answer this question, we now turn to the role of social-learning factors in influencing gender — identity formation after birth.