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COMT Gene Mutation and Estrogen Dominance

In this article we will discuss COMT gene mutation and estrogen dominance. Specifically, we will look at:

  • How a COMT mutation can lead to estrogen dominance and hormone imbalance
  • Why this is not always going to happen and 
  • Which instances  COMT alterations will lead to estrogen dominance




So if you're curious about COMT gene and how it relates to estrogen dominance, keep reading.  We are going to discuss this in detail.


What is Estrogen Dominance

COMT is an acronym for catechol-o-methyl transferase and it is an enzyme  that allow us to break down catecholamines.  As it relates to estrogen dominance, this COMT enzyme basically helps us break down catechol-estrogens. It is a type of catecholamine and we want to look at how alterations in the COMT gene can lead to estrogen dominance. 

You might not be clear on what is estrogen dominance is.  So let's clear that up first.  Basically estrogen dominance is a phenomenon of excess estrogen in the presence of too low or too little progesterone.  There is a a relative imbalance with either too much estrogen or too little progesterone.  When it comes to COMT there can be an alteration in enzyme function that leads to higher levels of the estrogen. 


Read more on Hormones and Anxiety


COMT Gene Mutation and Estrogen Dominance

First a little bit more on COMT.  So COMT is the enzyme that breaks down catecholamines and many other things that we don't think of as necessarily catecholamines like estrogen.  Specifically it is the catechol estrogens and this process occurs through methylation.  Methylation is basically a process where your body adds a methyl group to other molecules. In this case the COMT enzyme uses SAMe as its methyl donor along with magnesium. These are the two cofactors for COMT. 

acne from estrogen dominance

What happens in the methylation process is your body turns hydroxy-estrogens into methoxy-estrogens or methylated estrogens.  Okay, you say, big deal?   

Well if you have an alteration in your COMT enzyme, this basically slows the process of turning that hydroxy-estrogen into methoxy-estrogen.  This leads to a buildup of more of these hydroxy-estrogens and estrogens in general. So that should makes sense, it is like an overflowing river.  When the levels get too high and the estrogens overflow and increase this tissue saturation with estrogens. This leads to increased estrogen activity and the symptoms of estrogen dominance. 


COMT Gene Mutations that Can Increase Estrogen

So how do know if you have a genetic alteration and your COMT gene or if your COMT enzymes are not working properly? Basically you have to do the genetic test to to look at SNP's in this gene. What you will find is that there are several points along the COMT enzyme that can be altered, several different SNP's.   What seems to stand out most to me clinically is one in particular.  Most of the research is done on this particular point mutation or single nucleotide polymorphism.  It is v158m.  If this specific point is altered on both of your chromosomes you have homozygous alteration.  This is also referred to as a Met Met alteration.  This alteration is what will produce a slowed estrogen breakdown.  The step from hydroxyl-estrogen to methoxy-estrogen is going to be slowed. This is the case for estradiol and any other estrogens that go through that pathway. 

When you have the normal functioning COMT or Val Val this process is going to work more efficiently or normal. You will have more efficient estrogen breakdown. 

Does that mean that everyone with the COMT homozygous SNP or Met/ Met will have estrogen dominance?  No, not at all. The reason is there are multiple pathways through which estrogen can be eliminated.  It is also important to note that the methylated forms provide an efficient way for elimination by the body. Still once the estrogens are methylated, they are still estrogens.  As such they may still bind to estrogen receptors and have an estrogen effect in the body (but likely much weaker). 

So be careful not to over emphasize one pathway or overemphasize looking at just one thing.  When we look at estrogen dominance and COMT, we also want to verify things with labs.  Is there excess estrogen or not?  If there is, we want to look at the other pathways through which estrogen is broken down.  COMT is just one and there are several that follow COMT and some that are separate from COMT.  I will post more on this topic in a future article.


So hopefully that was helpful in understanding a little bit more on COMT gene alterations and estrogen dominance.  In some cases it may lead to estrogen dominance, in some cases it may not this cause.  If you want help sorting out your hormone imbalance and think you might have estrogen dominance, click on the link below to get started. 


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