Testosterone and Male Gender Bias 11The leading popular hypothesis to explain why more males experience ASD
than females is the EMB theory, which proposes that children with ASD
show a heightened type of the male cognitive profile, and postulates that
gestational exposure to testosterone produces biological effects that are a
cause of autism. Some animal studies evidence indicates that testosterone
could mediate differences in cognitive ability between the sexes through its
organizational impact on the brain. Recent evidence that upholds the EMB
theory reported that the levels of sex steroid found in amniocentesis sam
ples were correlated with ASD diagnosis [61,62]. The ratio of index finger
(second digit) to ring finger (fourth digit) (2D:4D) has been extensively uti
lized in autism investigations as a proxy to determine levels of gestational
testosterone exposure.
One observation states that 2D:4D is sexually dimorphic, and explains
that ASD males tend to have a lower 2D:4D ratio than females. In other
words, normal males have an index finger (2D) that is shorter when com
pared with the ring finger (4D) than do females. This finding is not univer
sally accepted as valid [62]. EMB theory advocates usually argue that sexual
dimorphism is evident beginning with the first trimester of pregnancy, that
it seems later to be basically static following birth, and that it is not affected
by the androgen that accompanies puberty. The 2D:4D based evidence of
sexual dimorphism is also based on endocrine models with lower or higher
levels of fetal testosterone exposure, associated with complete androgen
insensitivity syndrome or congenital adrenal hyperplasia, respectively.
There appears to be strong evidence to link elevated fetal levels of testoster
one in amniotic fluid to autistic symptomatology, as well as an increase in
rightward asymmetry of the corpus callosum [57–61]. We will discuss this
in detail in Chapter 5. Figure 1.6 depicts a possible connection between fetal
testosterone and 2D:4D ratio.
Some of the most interesting studies, based on the research of various teams
led by Baron‐Cohen, focus on elevated fetal hormones in males and the result
ant development of autism. Taking advantage of the rich data available in the
Danish Historic Birth Cohort and Danish Psychiatric Central Register, these
researchers have analyzed the amniotic fluid samples of 128 males who were
born during the 1993–1999 period and who were given diagnoses, consistent
with the recommendations of the International Classification of Diseases,
10th Revision (ICD‐10), of autism, of Asperger syndrome, or of other related
conditions lumped together under the acronym PDD‐NOS (pervasive devel
opmental disorder not otherwise specified). These diagnosed individuals
were subsequently compared with a control group of typically developing
individuals. These investigators examined the concentration of four different
sex steroid hormones (testosterone, androstenedione, progesterone, and 17α‐
hydroxyprogesterone) in amniotic fluids, and determined how the levels of
these hormones correlated with later diagnosis of ASD. These findings have