Hormonal effects

Many sex differences are developmentally organized, and then activated or revealed by the action of adult hormones (McCarthy et al., 2012). Hormones such as testosterone, estrogen and oxytocin (Chapter 4, 8), levels of which differ between sexes, are potential biomarkers for gender differences observed in ASD (Knickmeyer and Baron-Cohen, 2006; Schwarz et al., 2011).

Testosterone is made first in the fetal testes at about 9 weeks gestation; otherwise small amounts cross the placenta from the mother in both sexes. At 12–18 weeks, sex differences in serum testosterone are highest and sexual differentiation in the brain usually occurs, probably reflecting an important period for masculinization of the brain (Knickmeyer and Baron-Cohen, 2006). Small amounts of ovarian hormones are additionally required for active feminization of the female brain. It is understood that androgens organize male-type brain circuitry regardless of the genetic sex. If androgens were responsible for the development of autism, they would likely act via points of developmental sensitivity such as cognitive brain systems that are androgen-sensitive. Women with autism could be subjected to the masculinizing effect of more androgen-related molecules such as male sex hormones, usually present in small amounts in females. This hypothesis is supported by findings that women with autism have higher rates of androgen-related medical conditions such as polycystic ovarian syndrome (Ingudomnukul et al., 2007), late onset menarche (Knickmeyer et al., 2006b) and elevated serum testosterone levels with masculinized physical features (Schwarz et al., 2011). Furthermore, girls with congenital adrenal hyperplasia, characterized by an excess of steroid hormones, have been reported to have higher levels of autistic traits than their unaffected sisters (Knickmeyer et al., 2006a).

It has also been suggested that testosterone could drive male-specific ASD risks (Auyeung et al., 2009; Auyeung et al., 2010; Baron-Cohen et al., 2005). Instead of testosterone “causing” ASD, it could reduce a cognitive resilience factor, such as the ability to develop social communication skills. One longitudinal study suggested that variations in fetal testosterone are related to social cognition and attentional focus in typically developing children (Knickmeyer and Baron-Cohen, 2006). Preliminary evidence suggesting that sensitivity to prenatal sex steroid influence (indexed by second-and-fourth-finger length ratio) may be relevant for regions of the brain, such as anterior cingulate cortex and extrastriate cortex, could support the extreme male brain theory of autism (Lai et al., 2013).

Oxytocin and vasopressin are two neuropeptide hormones under scrutiny for their potential role in ASD (Carter, 2007; Francis et al., 2014). Both these hormones are known to be associated with social and repetitive behaviors (Carter, 2007). Oxytocin is involved in bonding, romantic attachment and other “pro-social” behaviors (Chapter 4). It influences social and repetitive behaviors in women and men (Kirsch, 2010). Furthermore, oxytocin administration has been shown to reduce repetitive behaviors temporarily in adults with ASD (Hollander et al., 2003) and to enhance social functioning. However, the evidence behind oxytocin as causative agent in ASD is inconclusive; it may be considered as one of several potentially relevant biomarkers which show sex-specificity with unclear clinical significance (Schwarz et al. 2011).

Neurobiological differences

Understanding gender differences in the brains of clinical populations with ASD remains limited by the focus of published research papers in predominantly male samples. It is increasingly highlighted that conclusions from studies including only one sex should not be extrapolated to another (Zucker and Beery, 2010). Innovative neuroimaging studies are beginning to elucidate underlying neurobiological influences on ASD (Philip et al., 2012; Via et al., 2011). Studies that examine the brains of women and men separately support possible differential risk and protective mechanisms that may lead to their development (Lai et al., 2013). Recent research using structural magnetic resonance imaging (MRI) examined whether neuroanatomy of ASD was different in female and male brains, and if neuroanatomical features fit predictions from the “extreme male brain” theory of ASD (Lai et al., 2013). They found that the neuroanatomy of ASD differed between females and males in a way that could not have occurred by chance and that atypical brain areas in females with ASD, in both grey and white matter, suggested neural “masculinization.” Lai et al (2013) also concluded that males with ASD showed gender-incoherence, representing possible “feminization” of the brain. However, this study included only participants with average or above-average IQ, meaning they cannot be generalized to all people with ASD. Furthermore, the differences could not be correlated with cognitive profiles, so do not explain how they might be causally linked to ASD. As well as gross anatomical differences, there may also be gender differences at the cellular level (e.g., in size, number of branches, parts of neurons, or distribution of neurotransmitters) and in variations of fiber connections between neurocognitive systems. Such investigations will be possible with future technological advances.

Implications for the gender disparities in girls

It is increasingly clear that girls with ASD may be missed by parents, teachers and clinicians, and receive the diagnosis relatively later than boys (Cheslack-Postava and Jordan-Young, 2012). It has been argued that girls with ASD are also often misdiagnosed with other mental health conditions. As a result, they do not often get adequate help or support for their ASD-specific needs. Low self-esteem, depression, vulnerability to relationship predators and abusive relationships have been reported in clinical settings (Attwood, 2007).

Children usually intrinsically fear strangers and learn social rules about interacting with others from a young age. Developing women will normally learn social rules about consensual sexual relationships as they progress through childhood and adolescence. Women with ASD may be more vulnerable to abuse both as children and adults, because they do not develop an understanding of social cues and rules in the same way. However, although girls with learning disability are well-recognized as being vulnerable to abuse (see Chapter 14), very little is known about the prevalence of sexual abuse in individuals with ASD. Clinical experience suggests that women with ASD have a high rate of adverse sexual experiences, even as children. Early life experiences of abuse will affect their expectations and understanding of sexual relationships later in life. For example, a woman who has been the victim of sexual abuse may have difficulty negotiating consensual sexual relationships in the future and understanding that she has the right to say no; if she has ASD, she may also lack the social skills to divert a predator. A developing personality is invariably harmed by childhood sexual abuse. Self-image may be distorted, often making the development of stable, reciprocal relationships even more challenging.

It is often suggested that women with ASD display increased masculine behavior and interests, and this may further contribute to social disadvantage faced by such women (Bejerot et al. 2012). Departure from gender norms in women with ASD may also place them at greater risk of social stigma as well as relationship difficulties. Bullying is reportedly more prevalent in girls with ASD, especially in childhood as female peer groups are more prone to psychological bullying, which may be less obvious to others (Baron-Cohen, 2002). Because they may be less well understood by others, girls with ASD may also be more likely to face discrimination. Girls may employ avoidance strategies, such as being well-behaved and polite, so as not to draw attention to themselves and to prevent social exclusion. The fact that girls may be able to camouflage their deficits may lead to symptoms being missed by parents as well as teachers. Women with ASD may only notice that they are different once they reach adulthood, and perhaps when they have children of their own. At this time, their mothering skills may be called into question, further worsening their self-esteem.

Conclusions

Girls and women are less likely to be diagnosed with ASD than boys and men. This may in part be related to a true protective effect of the biological differences between them. But it is increasingly acknowledged that underrecognition may also contribute. A delayed or misdiagnosis may have important implications and lead to poor outcomes for girls. There is still much to be learned about female presentations of autism, the explanations for this difference and how best they might access genuinely holistic and gender-specific care.