Autism is seen four times as much in men than it is in women. This is a very odd phenomenon that has been hard to explain since it’s been observed. The reasoning behind it still isn’t well understood, but there were some interesting points brought up.
First off, the article Sex differences in autism spectrum disorders from NCBI discussed a possible diagnosing bias in Autism Spectrum Disorder (ASD). There may be a gender bias in diagnosing ASD that stems from how ASD is identified. ASD is diagnosed with many behaviors that violate traditional social norms and it is possible that males exhibit those signs for diagnosing in a more extreme fashion than females. Their main source of evidence of this was that in patients that fell just short of being diagnosed with ASD, the gender ratio was much more even, closer to 60:40.
After getting beyond this, multiple ideas were discussed to explain the ASD gender ratio. The most interesting one to me was about the role of testosterone and other hormones in the development of Autism and women’s genetic resistance. Since there is such a gender discrepancy, the first culprits looked at are what make us a boy or girl, sex chromosomes. A girl has two X chromosomes and a male has an X and Y chromosome. The first idea is that the Y chromosome is destructive, in that it leads to Autism. On the other hand, it could be that the X chromosome is protective against ASD. More than likely, it’s a little of both. Interesting evidence for this is that people with more than two chromosomes, their rates of Autism make sense in consideration to X being protective and Y being destructive. More X chromosomes and fewer Y chromosomes correlate with lower rates of ASD. This association makes sense in consideration with the role of testosterone in Autism.
Elevated levels of fetal testosterone and throughout development are seen in many who exhibit ASD. The exact role of testosterone in Autism isn’t well understood, but an interesting connection was made by the authors. Testosterone functions, on some levels, in a positive feedback loop. Testosterone inhibits the enzyme that changes is to estrogen. So naturally, the accumulation of testosterone leads to the inhibition of its own breakdown, leading to further accumulation. This is relevant to the gender discussion because, not only does the Y chromosome create more testosterone comparatively, but the X chromosome codes for the enzyme that changes testosterone to estrogen. This understanding might explain part of the gender story, as females with less natural testosterone and more enzymes to handle high amounts of it are more resistant to ASD. The most interesting piece of evidence for this hypothesis involves the siblings of those with ASD. When compared, siblings of a girl with Autism exhibit more symptoms of ASD than those with a brother with ASD. All these little pieces of evidence support the idea that women are resistant to ASD in a way that involves their additional X chromosome. An interesting analysis that comes to a funny conclusion, women having lower rates of ASD is due to their additional X chromosome or lack of a Y. Which is effectively saying, women are resistant to ASD because they are women, nonetheless, testosterone’s role in ASD will be important in the future for understanding and treating ASD.
The 4:1 Male to Female Ratio in Autism
