Anavex Life Sciences Corp (AVXL)

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Genetic Mutations & Estrogen Metabolism (COMT)

Overview of Sex Hormones, COMT and MAO

Many of you reading this article may have already performed a genetic test and are aware of your COMT and MAO status – and if you haven’t done that yet no worries. Some of you may have inherited COMT and MAO genes which are slowed compared to the normal or “wild-type”. And at first blush these genes seem like they are going to ruin your life. But as I often tell my patients the genes you inherit from your parents are not your destiny, but they are your tendency. At the end of the day the body’s environment has the biggest impact on how our genes influence our lives. With that in mind let’s look at how the hormonal environment shapes our body’s genetic tendencies.

Women have higher estrogen levels and men have higher testosterone levels – this fact cannot be disputed. What isn’t as well known is how these two hormones impact the metabolism of our neurotransmitters by altering the speed of the COMT and MAO pathways. You will remember from my previous post that the COMT breakdown of dopamine has a major influence on how we react to stress. And you are about to learn that our sex hormones play a major role in determining our brain neurotransmitter levels.

Studies now show that sex hormones also play a critical role in how much dopamine we have in our brain. So logically it makes sense that men and women will react to stress differently. Because sex hormones have such a strong influence on our COMT and MAO pathways, men and women will have different COMT and MAO speeds, even if the genes and SNPs are identical.

In other words, the hormones have an epigenetic effect on the methylation of neurotransmitters that is occurring independently of the individual’s genetics – apart from that person’s genotype. A woman can be born with a fast COMT -/- genotype and yet experience all the symptoms of someone who is COMT +/+ when she is overly estrogen dominant. She experiences the symptoms not because of her genotype, but because the environment is interfering with her methylation pathways. Confused yet? Well keep reading it will all make sense shortly.

To help clarify this point I would like to ask you a question. And by asking this question I am not intending to offend anyone, but this question helps to illustrate an important point:

If you were to interview randomly 100 men and 100 women off the street, who would you expect to describe themselves as more anxious? Men or Women? And who would you expect to describe themselves as more angry or grumpy?

While I haven’t performed this study yet, I can assure you what the answers will be. More women will describe themselves as feeling anxious; and more men will describe themselves as feeling grumpy and angry. At first blush this information may not seem fair and it may sound like I am picking on one group or another. However that is far from the truth!

What this idea illustrates is that women have more anxiety and men have more anger – and you will soon see why. Because of recent research showing how sex hormones influence brain chemistry and methylation-related pathways, we have a new level of understanding WHY women and men react differently to stress. The answer to why women and men react to stress differently has everything to do with how estrogen and testosterone influence the methylation and breakdown of neurotransmitters. Figure 1 shows how our sex hormones interfere with key methylation

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These studies help to explain scientifically why women have a tendency towards anxiety and worry – more estrogen leads to more dopamine, adrenalin and catecholamines in the brain. And men (as you will see below) have a tendency towards anger and depression – since more testosterone leads to lower catecholamines. Estrogen has an anti-depressant effect, but too much of it can cause a woman to be unable to relax and calm down, and too little can lead to excessive crying and depression. The body doesn’t want too much and it doesn’t want too little – it wants a balanced amount! Figure 2 below illustrates the many problems associated with unbalanced estrogen levels:

Full article

http://www.beyondmthfr.com/treating-comt-and-mao-the-hormonal-cause-of-stress-and-anxiety/