ScienceDirect

Psychosocial factors

In the older literature on gender variant identity development cer- tain parental characteristics such as a maternal wish for a daughter, paternal absence, parental reinforcement patterns, or a symbiotic rela- tionship between mother and son have been considered to be the primary or even the single factor for the development of gender dys- phoria (e.g. Green, 1974; Stoller, 1968). Some of these hypotheses have been tested, but either no support for the hypotheses was found, or the interpretation of the outcome was problematic.

More recently, theories have been formulated that included multiple cumulative parent- and child-related risk factors responsible for the development of gender dysphoria (Coates, 1990; Zucker and Bradley, 1995). In these theories, gender dysphoria was hypothesized to develop
if both general child and parental factors (e.g. anxiety of the child, psy- chopathology of the parents) and specific factors (e.g. lack of limit set- ting of parents, fear of male aggression in mothers, and a feminine/ beautiful appearance in boys or a tough appearance in girls) converged during a critical period early in the child's life. Some support has been found for the role of a few of the general factors, such as elevated levels of psychopathology in parents (e.g., Marantz and Coates, 1991; Wolfe, 1990, but see Wallien, 2008), and the role of elevated anxiety of the child (e.g. Cohen-Kettenis et al., 2003; Zucker et al., 1996, but see Wallien et al., 2007). Evidence for the role of more specific child and parental factors for a gender dysphoric outcome is however scarcer. Some evidence supports the assumption that the appearance in gender dysphoric boys was more feminine and beautiful (e.g. Zucker et al., 1993) and mothers showed a lack of limit setting, particularly with respect to cross-gender behaviors (e.g. Zucker and Bradley, 1995).


Biological factors


Effects of gonadal hormones on sexual differentiation of the brain
A hypothesis for the etiology of gender dysphoria is that it is a central-nervous-system limited form of DSD: the brain may not have been sexually differentiated in line with the chromosomes, gonads and genitals. For example, gender dysphoria may be the result of a more or less feminized brain in an XY individual with testes and male genitals.
From animal studies we have learned that prenatal sex hormones not only direct the sex-typical development of the genitals, but also di- rect and organize the sexual differentiation of the brain (McCarthy et al., 2012), so called organizational effects. In animals, behaviors that show sex differences seem to be susceptible to influences of sex hormones (Hines, 2009): sex hormones are known to affect sex-typed behavior, but its effects on gender identity are for obvious reasons impossible to study in animals. Because the largest of all psychological sex differences in humans is gender identity (Hines, 2009), sex hormones likely con- tribute to its development.


DSD studies

In humans, studies in individuals with atypical prenatal hormonal levels, such as individuals with DSD could help to determine whether prenatal sex hormones affect gender identity development. Gender identity development in DSD has been most extensively studied in 46, XX individuals with congenital adrenal hyperplasia (CAH). CAH is caused by a deficiency in one or more of the enzymes required for syn- thesis of cortisol, aldosterone, and sex steroids in the adrenal gland. As a consequence, the brains are exposed prenatally to elevated levels of androgens (Merke and Bornstein, 2005) Female raised 46,XX indi- viduals with CAH show more masculine and less feminine interests, behaviors and preferences than control girls and women without CAH (Cohen-Bendahan et al., 2005). However, despite the increased male-typical behaviors and interests in these women, the effect of the prenatal androgen exposure on their gender identity seems to be less strong (Berenbaum and Bailey, 2003). The vast majority of women with CAH develop a female gender identity, although they may have a less strong female identification, and gender dysphoria occurs more often in this group than in women without CAH (de Vries et al., 2007; Dessens et al., 2005). A relationship between prenatal androgenization and the degree of masculinization on one hand and the prevalence of gender identity problems on the other hand was not found (Dessens et al., 2005).

In a critical review Jordan-Young (2012) suggests that other factors
like postnatal biological variables, medical interventions, and social context may be more important for differences between females with CAH and control women than the conventional explanation that early androgens have “masculinized” their brains (Jordan-Young, 2012). For example, a slightly more masculine appearance, caused by physiological

effects of CAH, might contribute to the somewhat higher prevalence of a masculine gender identity in girls and women with CAH.
In spite of the elevated androgen levels, gender dysphoria does not seem to occur more frequently in female raised patients com- pared to those raised male (Dessens et al., 2005) and gender identity development in these individuals thus seems remarkably adaptive.
Individuals with complete androgen insensitivity syndrome (CAIS) have 46,XY chromosomes, and produce androgens, but their external genitals develop in the female direction because of a receptor defect. At birth, the diagnosis is often missed, and they are assigned to the female sex. For long, it has been assumed that these girls develop a female gender identity throughout their lives (Mazur, 2005). In addi- tion to their physical appearance as a woman, the total absence of androgen effects on the brains of these XY-women with CAIS might lead to the development of the usually encountered female gender identity. However, they are generally reared unambiguously as females and perceived and treated as females. Therefore, socialization may con- tribute to their female gender identity as well (Hines, 2009). Despite the fact that all possible factors seem to support a female typical develop- ment, CAIS individuals scoring lower on a female gender identity scale than controls (Richter-Appelt et al., 2005) have been reported, as well as a case with such severe gender dysphoria that it lead to a female- to-male gender transition (T'Sjoen et al., 2011). It may, of course, be that these unexpected masculine features stem from a thus far undetected type of androgen receptors that are intact, but in this light the description by Cadet (2011), a woman with androgen insensitivity, about her gender identity is of interest. She describes it as “a malleable conviction, vulnerable to changes in perception of facts.” In her idea, information about the condition, social responses and other factors that can be perceived and evaluated, may result in gender identity changes. It may well be that some women with CAIS only need minor deviances from the norm to conclude that they do not want to live in their assigned gender, whereas others will not be dissatisfied about much larger discrepancies between their sex or gender characteristics. In contrast to individuals with CAIS, gender transitions are consid- erably more prevalent among persons born with partial androgen insensitivity syndrome (PAIS) (Mazur, 2005). Gender dysphoria seems to develop at similar rates in individuals with PAIS (nearly 25%), whether they are reared as boys or girls (Warne, 2008). Although the discrepancies between various elements of their sex and gender devel- opment differs (e.g. male raised individuals may not have adequate male genitalia, female raised individuals may be masculine appearing and do not have internal female reproductive organs) the related distress seems to be equally severe. Yet again, most individuals with PAIS, male and female raised, do not seem to be dissatisfied with their assigned
gender.
With regard to gender identity development, two other conditions are of particular interest. Five α-reductase-2 deficiency (5α-RD-2) and 17β-hydroxysteroid dehydrogenase-3 deficiency (17 β-HSD-3) are both conditions resulting from errors of androgen biosynthesis.
Forty six, XY children with 5α-RD-2 and 17 β-HSD-3, are usually born with female appearing or ambiguous genitalia. They are often raised as girls. Female raised individuals with 5α-RD-2 whose gonads are removed before puberty, generally maintain a female gender
identity (Hines, 2009), but a considerable percentage of the others with 5α-RD-2, as well as 17β-HSD-3, experience gender dysphoria to the extent that they decided to live as boys/men after puberty
(e.g. Cohen-Kettenis, 2005b), particularly if the condition is not diag- nosed before puberty and male secondary sex characteristics have developed. The occurrence of gender dysphoria after puberty might result from the hormonal changes of puberty with direct effects on brain and gender identity development. Like in PAIS, these persons may be somewhat masculine in appearance, preferences and interests. Masculine-looking and -behaving girls may develop a different sense of self and evoke different responses from family members and peers than feminine-looking and -behaving girls. Many known cases live in
societies that favor the male social role. Especially when there was already some gender discomfort present, it is likely that a masculinizing puberty increases distress to clinically significant levels into a full- blown gender dysphoria. Gender role changes occur at different rates in different societies (Hughes et al., 2006). We should therefore not overlook the impact of culture.
In conclusion, studies in individuals with DSD show that prenatal testosterone exposure of the brain influences the development of male-typical gender role behaviors. It is likely that it also increases the chance of a male gender identity development. However, even in cir- cumstances in which the person had been prenatally exposed to high levels of testosterone and has been reared as a girl from birth on, a female adult gender identity is the rule rather than the exception (e.g. Dessens et al., 2005), whereas, in the absence of prenatal testoster- one exposure, a male gender identity may develop (e.g. T'Sjoen et al., 2011). In contrast to what was long assumed, it is therefore unlikely that androgens influence gender identity in a very simple and direct way.
The timing of most of the self-initiated (patient instead of physician) gender transitions is after puberty. This does not mean that gender dys- phoria is absent in prepubertal children with DSD. Unfortunately, most studies report very little on the gender identity development of these children. The gender changes that were reported in childhood seemed to be more often physician imposed, after the diagnosis became appar- ent, than patient initiated (e.g., Dessens et al., 2005; Mazur, 2005; Meyer-Bahlburg, 2005). Gender transitions were generally not wel- comed by many parents, and patients' requests to change gender might only have been taken more seriously as the child grew older. Another reason for the relatively late patient initiated gender changes may be that the natural pubertal changes or hormone treatment in puberty make youth with DSD more aware of their bodies and their DSD. Although they may not have been troubled by their DSD in child- hood, their physical changes and the responses of the environment to their increasing male- or femaleness may become a new source of dis- tress. Once adolescents with DSD understand more about their condi- tion, they may start to feel uncomfortable and fear that there will be no suitable (sexual) partner for them (Warne, 2008), which may influ- ence their self esteem and make them question their position in society.