Males get more diagnoses of Autism Spectrum Disorders than females and it may be related to changes in the brain's estrogen signaling, writes a paper in Molecular Autism.

 Autism Spectrum Disorders are a broad category of diagnoses that include brain development and assessments of impaired social interaction, along verbal and non-verbal communication and restricted and repetitive behavior. The disorders may have a genetic basis and are around four times more common in men than in women. They have been associated with higher levels of the sex hormone testosterone, but whether there is a relationship between the disorders and estrogen signaling was not known. 

The authors examined the brains of people that had Autism Spectrum Disorders compared to controls, and found that they are linked with far lower levels of a key estrogen receptor and other estrogen-related proteins.

The group size is too small to be valid but the authors believe that even though they can't confirm a role for altered estrogen signaling in Autism Spectrum Disorders, it is worth pursuing.

Lead author Anilkumar Pillai says, "Our study is the first indicator that estrogen receptors in the brain of Autism Spectrum Disorder patients may be different to controls. Though this suggests a possible reason for the gender bias, we still need to determine what causes the reduced production of estrogen-related proteins."  

The group of researchers from Georgia Regents University measured the expression of proteins involved in the estrogen signalling pathway in brain tissue from 13 people that had Autism Spectrum Disorders and 13 controls. The low numbers involved in the study are because brain tissue for experimental use from individuals that had Autism spectrum Disorders is quite scarce. They looked for levels of ERβ - an estrogen receptor molecule, and aromatase, an enzyme which converts testosterone to estradiol, the most potent estrogen. 

They found 35% less ERβ mRNA and 38% less aromatase mRNA in autistic brain tissue in comparison with controls. They also found much less of the mRNA of estrogen receptor co-factors SRC1, CBP and P/CAF - 34%, 77% and 52% respectively. The lower levels of estrogen receptors and aromatase could lead to reduced conversion of testosterone to estradiol, resulting in increased levels of testosterone.

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."