Changes in the brain’s estrogen signaling may partly explain the higher rates of autism spectrum disorders among males, according to new research published in the journal Molecular Autism.

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Research has shown that there are three boys with autism for every girl with the condition.

Autism spectrum disorder (ASD) is an umbrella term encompassing the neurodevelopmental disorders autism, Asperger’s syndrome and childhood disintegrative disorder, among others. These disorders are usually characterized by impaired social interaction and communication and restricted or repetitive behavior.

Research has shown that there are three boys with autism for every girl with the condition, and 10 boys with Asperger’s syndrome for every girl with Asperger’s. These ratios have led researchers to suspect that sex hormones – such as high levels of testosterone – may play a part in influencing the disorder.

In 2004, researchers from Cambridge University, UK, analyzed testosterone levels in the wombs of 70 pregnant women. After the women’s children had reached the age of 4 years, their parents were asked to complete a checklist designed to pick up any behavioral or social difficulties associated with autism in their children.

The team reported that the children whose mothers had high levels of testosterone in their wombs while pregnant were less curious, less willing to make eye contact, and found it more difficult to fit into social groups than other children.

Although the children in that study were not autistic, the researchers were interested in testing a theory that autism “might be an extreme of the male brain.”

Now, researchers from Georgia Regents University in Augusta have analyzed brain tissue from 13 people who had ASD and 13 control subjects who did not have ASD. The researchers wanted to measure levels of aromatase and the estrogen receptor molecule ERβ in the brain tissue. Aromatase is an enzyme responsible for converting testosterone into the most potent estrogen – estradiol.

Although it seems like a low number of subjects, the authors explain that procuring the brain tissue samples of people with ASD for experimental use is very difficult.

The researchers report that they found 35% less ERβ mRNA and 38% less aromatase mRNA in the brain tissue from the people with ASD than in the control subject brain tissue.

The mRNA of estrogen receptor co-factors SRC1, CBP and P/CAF, was also lower in the ASD brains, at 34%, 77% and 52% respectively.

The researchers suggest that the lower levels of aromatase and these estrogen receptors could limit the conversion of testosterone to estradiol, which results in increased testosterone levels.

Lead author Anilkumar Pillai says that this is the first study to show that estrogen receptors in the brains of people with ASD may be different to other people. Though this difference could be a reason for the gender bias, Pillai cautions that the team still need to determine what causes the reduction in production of estrogen-related proteins.

Pillai says:

It is worth looking at whether drugs which modulate estrogen reception, but do not cause feminization, could allow for the long-term treatment of male patients with autism spectrum disorders. Current treatment involves the use of antipsychotics, which has long been a major concern as these patients are typically still in a stage of life where brain development is very rapid. However, additional studies are needed to test the estrogen mechanism.”