Is Estrogen the Culprit?

By Jordyn Hanover, Behavioral Neuroscience, 2017

Autism spectrum disorder is defined by the Center for Disease Control as “a developmental disability that can cause significant social, communication, and behavioral challenges.” Within the last two decades, the prevalence of autism has almost tripled. Approximately 1 in 150 children born twenty years ago were diagnosed with autism. Children born in 2002, however, had a rate of 1 in 68, making it an extremely prevalent disease. When a similar cohort of children was surveyed eight years later, the prevalence rate was found to be almost fifteen percent.

Additionally, statistics have shown that autism spectrum disorder is nearly five times greater in boys than in girls. The manifestation of the disease has risen almost 30 percent in the last two years, and as such, continues to receive increasing amounts of attention. Yet the reasons for this disorder’s increased prevalence, especially among males, is still unknown.

One suggested theory is that the sex hormones, testosterone and estrogen, are involved in the substantial difference between the proportion of males and females who have been diagnosed with autism. It has been proposed that estrogen in particular is, at least in part, the cause of the discrepancy between genders with respect to this disorder.

This was shown several years ago in a study published by Dr. Valerie Hu, which indicated that people with autism spectrum disorder have low levels of certain proteins. The protein in question, aromatase, is synthesized from a retinoic acid-related gene, and is directly related to the production of the sex hormones. Aromatase converts testosterone into estrogen, and when the gene is not functioning properly, testosterone levels build up. This implies that the gene causes an imbalance in sex hormones, which could possibly explain why autism is more common in males than in females.

In a recent study published in early September 2014, scientists at Georgia Regents University focused on the alpha and beta estrogen receptors. Alpha estrogen receptors are involved in various neurotransmitters, especially those involved in sexual behaviors, while beta-receptors can influence several behaviors correlated with autism spectrum disorder, such as anxiety and motor activity. This study focused on these receptors and several proteins that they regulate, and that are related to gene processing.

Using blotting techniques and reverse polymerase chain reactions on thirteen tissue samples (a dozen male and one female control), it was discovered that the RNA levels of beta-receptors in the middle frontal gyrus were lower in autistic brains.

These beta-receptors can influence the behaviors that estrogen impacts, many of which are not actually involved in reproduction but are used as identifiable signs of diagnosing autism. Additionally, the middle frontal gyrus is significant because it is an area that has been shown to be substantially different between males and females, and thus could partially account for the five to one difference.

The other important compound involved in this study was CYP19A1, an enzyme called aromatase, which is important for the production of estrogen in the cortex. This was also found to be significant decreased in patients with autism spectrum disorder. Both the decrease in the beta estrogen receptors and CYP19A1 are involved in the production of testosterone, the absence of which in various brain areas is suspected to be a potential cause of autism, or at least the imbalance of male versus female cases.

The next step in this research would be to determine whether adjusting levels of estrogen and testosterone would help to prevent autism or possibly reverse autistic behaviors. One possible way to test this would involve the use of estrogen receptor beta agonists, which essentially increase the binding of estrogen molecules to the beta receptor.

Beta agonists have been shown to improve memory in various animal trials, and Dr. Anilkumar Pillai, a neuroscientist who helped author the study, is hopeful that they can be used to reverse some of the behavioral effects of autism, such as shyness and anti-social behaviors. Additionally, he hopes to conduct follow up studies comparing the hormone levels of healthy and autistic children, using larger sample sizes and live patients.

By using various treatments to manipulate the amount of estrogen in the brain, it is not unreasonable to imagine that certain types of autism could potentially be largely eliminated or even cured within the next decade or two.

As a disorder that is largely behavioral in nature, finding a way to control or reverse these symptoms could allow millions of people, especially children, to control their own behaviors, and live a more social life.

This article was originally published in NUSci Issue 21.