Optimizing methylation pathways means going further than just deciding how much B12 or folate a person needs. Seeking to optimize methylation pathways means you must go far beyond just looking at MTHFR and see all the genes and biochemicals that are impacting our health. And we cannot optimize genes without understanding how our sex hormones can impact our genetic pathways. This article will provide you with new insights into how our hormones impact our genetic pathways, while offering diet and nutritional ideas to properly support those pathways.

As we all know the differences between men and women are more than just skin deep. Our differences exist on a physical, genetic, emotional and hormonal level. In fact, our sex hormones are so powerful they don’t just change the size and shape of our bodies, they change how we respond to stress in our environment. An important thing about sex hormones is that not only do they influence how our bodies look; they also influence our brain and behavior! And you will soon see just how these sex hormones can influence brain function by altering the body’s COMT and MAO pathways.


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

COMT and MAO Estrogen Slows

Figure 1 – Estrogen and testosterone both influence the methylation and breakdown of neurotransmitters.


Estrogen, COMT and MAO

Compared to a healthy man, a healthy pre-menopausal woman should have much higher levels of estrogen and much lower levels of testosterone.  This elevated estrogen is a natural consequence of being female and of having the ability to conceive children.  In fact when a woman becomes pregnant her estrogen levels rise approx. 30-fold, providing the hormones her body needs to feed a growing baby. But that is only one type of estrogen, and in our environment estrogens come in many different flavors.

In addition to the estrogen made by the body, many women and men are exposed to toxic estrogens from chemicals like birth control, heavy metals, fire retardants, BPA, etc. which further increase the estrogen load. Many people are aware of the dangers of estrogenic toxins like BPA, but fewer people know that pesticides, herbicides, and fire retardants act like estrogen as well. In fact, science has now confirmed that heavy metals such as aluminum, arsenic, cadmium, lead, and mercury also activate estrogen receptors in our cells.1  These metalloestrogens as they are called create yet another burden for our detoxification systems and alter our hormone balance even more. Ultimately all this estrogen (both natural and man-made) causes problems for the COMT and MAO systems in the brain.

Key Concepts for COMT and Estrogen

Estrogen is broken down by the COMT gene – this reaction produces a calming, anti-cancer type of estrogen called 2-OH methoxy estrogen.2  2-OH methoxy estrogen is very important for health and it helps to prevent other symptoms of estrogen dominance such as PMS, heavy bleeding, fibroids, endometriosis, etc.

Even though the COMT gene breaks down estrogen, it is also epigenetically slowed down by estrogen. Meaning the more estrogen a woman or man has, the slower the COMT system will be working as cells will produce fewer copies of the enzyme. A research article from 2003 describes how hormonal therapy can be effective for dopamine-related diseases like Parkinson’s Disease. Because estrogen slows COMT pathways it may be of therapeutic value in Parkinson’s patients who need a more steady supply of dopamine in their brain.3

A recent review article published in 2015 shows how through environmental and epigenetic mechanisms, estrogen inhibits COMT pathways by about 30%. The researchers suggest this is why many women have a predisposition towards a phenotype of high anxiety and a lower tolerance for stress.4  So even if you aren’t born with a SNP in your COMT pathway, just being female or having too much estrogen can make it feel like you do have a +/- or +/+ SNP.

In addition to the epigenetic effects that estrogen has on COMT pathways, it also greatly impacts the MAO system. Because estrogen impacts both COMT and MAO pathways, it is capable of having a major impact on the levels of frontal-lobe dopamine and stress hormones throughout the body. Research has clarified that a woman’s mood is largely a reflection of how fast or slow her MAO-A system is working.

Key Concepts for MAO and Estrogen

In a study from the 1970’s, perimenopausal women with adrenal fatigue and depression were found to have a sped-up MAO system, leading to faster breakdown of dopamine and serotonin. When given oral estrogen replacement, the women were relieved of their depression symptoms.5  Menopause and adrenal fatigue both lower estrogen levels, so oral estrogen therapy helped slow down the MAO system, allowing the women to benefit from increased neurotransmitter levels.  While most women have too much estrogen and too much anxiety, women can experience the opposite problem of depression when their estrogen levels drop too low.

Interestingly a very recent study published in 2015 showed that post-partum depression is caused by a surge in the expression of MAO-A. Immediately after delivering a baby, a woman’s body goes through a profound decline in estrogen. This rapid loss of estrogen, no longer necessary since pregnancy has ended, causes a reflexive increase in the speed of MAO-A.6  As MAO-A speeds up it detoxifies neurotransmitters much faster leading to depression and other signs of post-partum depression such as apathy and excessive crying.

Another slightly older study published in 1995 confirms the relationship between estrogen levels and MAO pathways. When analyzing the effects of sex hormones the researchers found that estrogen inhibited the monoamine oxidase (MAO) pathway in brain cells.7  They concluded that this inhibition, this slowing down of the MAO system, was how estrogen creates its anti-depressant effect.  Remember a depressed woman might just be low in estrogen, while an anxious woman might have way too much.

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:

Estrogen Curve

Figure 2 – Bell curve showing reduced COMT/MAO activity with elevated levels of estrogen.

If you are born with or are exposed to more estrogen in your body (both natural and man-made) then you will have a tendency to have more dopamine in your brain because your COMT/MAO pathway has been slowed. This elevation of dopamine and catecholamines makes you much more likely to experience anxiety, worry, insomnia, chronic pain and other conditions associated with a slow COMT/MAO system.  A woman with too much estrogen may wake up and feel like she cannot handle another stressful thing at all.  And this woman with excess estrogen will also have a slowed COMT and MAO system that will tend to make her more sensitive to stress. 

Based on the information I have shared with you so far, we can see how being estrogen dominant will make it more difficult to deal with stressful life situations like a new job, new child, new relationship, relocating to a new town, etc. Excess estrogen will literally slow down your methylation pathways making you less able to tolerate even the slightest increase in stress. And if estrogen does one thing, you can bet that testosterone will probably do the opposite. So let’s now take a look at the testosterone research to see if that holds true.


Testosterone, COMT and MAO

In terms of the COMT and MAO pathways, the male sex hormone testosterone has the opposite effect of estrogen. Testosterone increases the genetic expression of COMT and MAO enzymes in the body leading to lower levels of dopamine, norepinephrine and epinephrine. If you are a man with healthy levels of testosterone in your body, you will tend to have a deficit of dopamine because your COMT and MAO enzymes are going faster.  This means men will gravitate towards activities which raise the catecholamine neurotransmitters, since these chemicals will help balance the brain and have a calming, soothing effect on the nervous system.

For many men, doing things labeled “stressful” or “risky” actually helps to balance their brain function. This is why men tend to feel a relaxed after going to the shooting range, attending a martial arts class, or riding a motorcycle at high speeds. Since men are supposed to have higher testosterone and lower estrogen, they tend to need more stress in their life in order to feel balanced and calm. Thus men often seek a riskier path in life due to the need for more dopamine and catecholamines in the brain.

If you look at our society objectively, you will notice that men tend to get into fist-fights, drive fast cars, shoot guns, rock climb, BASE jump, and do all kinds of other dangerous activities more frequently than women.  One big reason men are drawn to things which are dangerous is that these activities raise catecholamines, dopamine and adrenaline.  And when you become aware of how testosterone impacts brain function you will understand why.

Key Concepts for COMT, MAO and Testosterone

A recent study published in 2014 highlights how androgens like testosterone and DHT increase the speed of the MAO and COMT pathway in the substantia nigra and striatum where much of our brain dopamine is produced.This effect of testosterone helps to explain why men have a tendency to have lower dopamine and catecholamines; and why men seek risky behaviors in an effort to raise them. Since men have a tendency to breakdown dopamine and norepinephrine faster, they have developed an attraction for activities which are guaranteed to increase those neurochemicals.

In another related study from 2012, it was shown that testosterone increases the brain’s expression of estrogen receptor beta, the protective, calming type of estrogen receptor. Estrogen receptor beta is an important part of our hormone system because it helps to protect tissues like the breast, ovaries, uterus and prostate from the toxic effects of estrogens.  ER Beta as it is called acts like a toxic estrogen anti-dote in many tissues, including the brain. Thus testosterone not only speeds up a slow COMT and MAO system, it has many other benefits we are just beginning to learn about.

At the end of the day, men will compensate for lower dopamine by seeking behaviors which are higher risk.  I’m not saying all men do this, I’m just saying that as men we all have a tendency to behave this way.  And this tendency drives a lot of our behaviors.  Because testosterone increases the speed of COMT and MAO system, men spend a good deal of time being angry and grumpy. And to cure that persistent grumpiness and anger men seek out experiences which are stressful in order to raise dopamine/adrenalin. By raising their dopamine and adrenalin quickly, a man will actually calm down and be happy. This is self-medication at its best!


Diet and Supplement Recommendations

Now that it is clear how sex hormones influence our neurotransmitter and methylation cycle, we need to look at natural solutions for preventing and correcting these problems. In general, women need programs that help them to lower estrogen and raise progesterone. Men need programs that help them remove estrogen and raise testosterone. There are many safe, natural, and effective means for accomplishing this task. I have written down my favorite healing protocols for healthy detoxification of estrogen and estrogen-like toxins. You will find my detailed diet and supplementation protocols for men and women with hormone imbalance here.



What I see every day in my clinic is that estrogen dominance, toxins and hormone imbalances are a major cause of anxiety in both men and women. This fact doesn’t make sense until you understand how estrogen slows down the COMT and MAO pathways while testosterone speeds them up. Whether it is due to adrenal fatigue, birth control, hormone replacement, chemical toxins, etc. estrogen dominance will tend to cause imbalances in the brain and the methylation cycle. This also helps to explain why men and women deal with and react to stress so differently. Clearly when our hormones are imbalanced, our brain and methylation cycle will also become imbalanced. But it doesn’t have to be that way!

For those of you who are searching for answers to the root causes of your health problem, you are on the right track. But just learning about MTHFR genes is not enough.  To create lasting health we must understand how the environment talks to our genes. Only then will we have the opportunity to change the environment to promote a proper healing response. That road is challenging, but very rewarding. Yet, it is a hard road to travel alone.

If you would like assistance in your healing efforts please don’t hesitate to contact my office.   Working with our team of functional medicine and methylation experts will help you get better results in less time.



For more videos and learning about COMT, MAO and Methylation I recommend:

Treating COMT and MAO: How COMT Influences the Brain

How Blood Sugar Influences Dopamine/Adrenalin Levels – COMT and MAO

A Genetic Cause of Pain and Anxiety – COMT, MAO and MTHFR


In Health,

Dr. Rostenberg


By studying the current peer-reviewed research, Dr. Rostenberg has discovered powerful, natural strategies to optimize brain function and heal your body.  Using his knowledge of methylation and optimum health, he has helped patients from all over the world overcome their genetic imbalances.  He can help you uncover the genetic or root causes of your health problem and find a natural solution!  If you would like help with optimizing your genes to improve your methylation and reduce/eliminate your symptoms, please contact Dr. Rostenberg at Red Mountain Natural Medicine today. Phone 208-322-7755. Email Website



1 Darbre PD. Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast. J Appl Toxicol. 2006 May-Jun;26(3):191-7.

2 Tal R. The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis. Biol Reprod. 2012 Dec 13;87(6):134.

3 Jiang H, Xie T, Ramsden DB, et al. Human catechol-O-methyltransferase down-regulation by estradiol. Neuropharmacology. 2003 Dec;45(7):1011-8.

4 Dauvilliers Y, Tafti M, Landolt HP. Catechol-O-methyltransferase, dopamine, and sleep-wake regulation. Sleep Med Rev. 2015 Aug;22:47-53.

5 Klaiber EL, Broverman DM, Vogel W, et al. Effects of estrogen therapy on plasma MAO activity and EEG driving responses of depressed women. Am J Psychiatry. 1972 Jun;128(12):1492-8.

6 Sacher J, Rekkas PV, Wilson AA, et al. Relationship of monoamine oxidase-A distribution volume to postpartum depression and postpartum crying. Neuropsychopharmacology. 2015 Jan;40(2):429-35.

7 Ma ZQ, Violani E, Villa F, et al. Estrogenic control of monoamine oxidase A activity in human neuroblastoma cells expressing physiological concentrations of estrogen receptor. Eur J Pharmacol. 1995 Sep 15;284(1-2):171-6.

8 Godar SC, Bortolato M. Gene-sex interactions in schizophrenia: focus on dopamine neurotransmission. Front Behav Neurosci. 2014 Mar 6;8:71.

9 Purves-Tyson TD, Handelsman DJ, Double KL, et al. Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra. BMC Neurosci. 2012 Aug 6;13:95.



  • August 27, 2015 Reply


    i just reported to your webmaster that some links on the new design are broken….error 404

    i would not bother except i hyperlink to you!

    • August 28, 2015 Reply


      Lisa thank you for your help on this! Very much appreciated.

      Dr. Rostenberg

  • September 11, 2015 Reply


    Dr. Rostenberg, I have many symptoms on both sides of this scale: depression, chronic fibromiaglia, chronic vulvodynia and chronic sciatica pain, worry, anxiety, bad memory and focus, chronic fatigue and very poor energy levels. However, I sleep very deep without interruptions (although I can sleep 12 hr and will still crush right after breakfast and lunch). My COMTs are all good, but MAO is heterozygous. I’m diagnozed with Hashimoto’s and Adrenal Fatigue. How can I tell whether my problem is high or low estrogen? And how would you address this? (I already eat clean gluten free diet). Thanks.

    • September 14, 2015 Reply


      Hello Jena,

      Thank you for your comment! People can have symptoms from both sides of the catecholamine bell curve – sometimes the body just is unable to maintain a balanced supply of dopamine/catecholamines to the brain. To really know if you have high or low estrogen we perform a detailed history and consultation, discussing all the signs and symptoms related to estrogen imbalance. Also, saliva hormone tests are very good at showing the levels of estrogen which are actually getting into the cells. We can have a -/- COMT but still suffer like someone who is +/+ COMT. The reason is that the gut flora releases chemicals (phenols) which can slow down COMT and the hormonal imbalances due to estrogen and estrogen-like chemicals (BPA, etc.) also slow the COMT system. So the genes are part of the story, but the environment inside the body is most important. The best way to address this is to consult with our office. In this way we can learn all about your history and all the different struggles you’ve been through. Then we can build a plan and protocol to address your body’s unique needs.

      I would love to you help you move your health forward. Please contact my office so we can start to optimize your genes and change your life! and 208-322-7755.

  • September 11, 2015 Reply


    I should add that I don’t take any hormones. Only LDN and supps (Mag, Selenium, Molybdenum, Vit D3, TMG, Benfotiamine, Fish Oil).

  • November 13, 2015 Reply


    Dear Dr. Rostenberg,

    I am so confused and desperate. My daughter (27) has been ill for nearly 11 years and she suffers badly from stress, anxiety, rage, major depression, jaundice, brainfog, dizziness, headaches, OCD in the shape of checking, and intrusive horrible or worrying thoughts amongst other things. We had tons of tests performed and it is clear that her sex and stress hormones are way out of balance, steroid hormones as are her minerals, vitamins and amino acids. She has a very high level of free testosterone, low dopamine, low serotonin – organic acid test shows low 5-HIAA 0.91 mmol/mcr (reference 0.00 – 20.00), her saliva stress profile shows extremely high DHEA-S and her UAA test shows high levels of nearly everything, In plasma her RBC is way too low and I can go on and on. Just recently she had her genes tested at 23andMe and the results show +/+ for all the following: R297R/G492T/T941G MAO A R297R – TT, rs1137070 MAOA T1011C/1460C – CC, rs2072743 T89113C – CC and rs1799836 MAOB A118723G – CC, her COMT results from her MTHFR support variant report show 11 COMT results in the +/- range. Her resident gut flora is completely out of wack and she has virulence factor catalase. My daughter is soooo majorly stressed and has daily outbursts of rage. All the good advise she gets, get a job, start exercising, take up yoga or do breathing exercises seems way out of reach. We have been to see many specialists but no one really seems to be able to help. She has not been able to leave the house for more than a year and she seems to be getting worse every day. Would you be willing to have a look at her test results or after reading this would you have a clue what we should be looking for? We live in the Netherlands and I have not come across anyone here who is specialized in genetics and the link to all her other test results. Hope you can help us, although I try to help her, I am so worried that she will come towards the point of no return. Lara

    • November 16, 2015 Reply


      Hello Lara,

      Thank you for reaching out and contacting my office. Your daughter’s story sounds very challenging and frustrating, and I recognize you are feeling desperate to find some answers. First let me say that High Testosterone and High DHEA-S is are two indicators of insulin resistance, of a blood sugar problem. Blood sugar is one of those fundamental systems that must be working before other systems like hormone, brain, and immune system can be expected to work correctly. She cannot calm down until the chemical imbalances are corrected, since her behavior is a reflection of brain and body chemistry. Fix the chemistry, and behavior follows.

      I want to invite you to contact my front office at and 208-322-7755. Set up a new patient consultation with me and I will personally discuss and review all your daughter’s lab tests, etc. That consultation will provide us with an opportunity to meet via Skype and discuss what methylation and other tools are available to help your daughter. – In Health, Dr. Rostenberg

    • October 6, 2016 Reply


      Hi Lara, did you resolve or improve the situation for your daughter? Very interested to know.

  • February 9, 2016 Reply


    Interesting – thank you. My 9 year old son (who has troubles with anger when stressed) is COMT++ and MAO-A+. Does this means that once he’s an adult we can expect him to mellow out? (once we get through the testosterone swings of adolescence…)

    • February 10, 2016 Reply


      Hi Christina,

      Low dopamine is a main driver for feelings of anger. I suggest your son already has low dopamine based on your history. Testosterone will increase COMT but he will need stabilized blood sugar and healthy digestion in order to really balance his brain and prevent anger. That is a good thing to start doing even at this young age.

      In Health,

      Dr. Rostenberg

  • March 10, 2016 Reply


    Dr. Rostenberg, I am COMT V158M rs4 6 80 AG +/- and MAO-A R29 7R rs6 323 TT +/+. I have been struggling for many years with chronic crippling anxiety and insomnia. I have bad reactions (worsening anxiety and jitterriness) to all of the SSRIs, which now makes more sense in light of your observation that MAO-A +/+ slows down the breakdown of neurotransmitters so inhibiting their reuptake would be problematic. You say that testosterone will speed up a slow COMT and MAO-A system. Does it make sense then, even as a female, to take bioidentical testosterone? Would that help to increase the breakdown of my catecholamines? I have rock bottom Ievels of estrogen, progesterone, testosterone and DHEA after being on the pill for 30 years. This was prescribed in order to preserve bone density since I do not ovulate spontaneously (hypothalamic amenorrhea), possibly due to my very high levels of cortisol. Please let me know if you think bioidentical testosterone and/or DIM might be helpful. I would be extremely grateful for your advice- kind regards, Karen

    • March 13, 2016 Reply


      Hi Karen,

      Thanks for your comment! You’ve got some complicated health challenges as well as imbalanced genetic pathways. When we consider that our genes are influenced heavily by the environment inside our body, things can get complicated very quickly. In theory increasing testosterone will reduce anxiety, all things being equal. In addition, there are many nutritional factors that can help reduce anxiety and improve function of GABA receptors. Things like niacinamide, L-glycine, L-taurine and more can help reduce anxiety but its best work with an experienced practitioner. Please contact my office if you would like help unraveling your health challenges. We can be reached at 208-322-7755 and

      Yours in Health,

      Dr. Rostenberg

  • April 21, 2016 Reply


    Dr. Rostenberg, I’m 53 yrs old and just went into menopause as of three months ago I’ve stopped menstrating,, I can’t begin to tell you that this has been the worst experience of my life i think every symptom associated with menopause I got and then some, I’ve been watching you on utube and found all your information very helpful, I have one question I have been experiencing adrenal fatigue crashing and yawning almost all day long but I’ve recently started experiencing Tinnitus very high pitch ringing constantly it’s driving me crazy,,would you say that this is also a result of hormonal imbalance because it only started when I went in menopause, I do suffer from anxiety, panic attacks, and a really uncomfortable buzzing in my feet ,, I don’t know anymore what’s happening to me,,I just want to feel like myself again,,will these symptoms go away eventually when I’m not menopausing anymore or is this a life sentenece.?
    Appreciate any recommendations
    Regards, Anna

    • May 4, 2016 Reply


      Hello Anna,

      Thanks for your comment. Menopause is a particularly difficult time for women because the ovaries begin to shut down placing more stress on the adrenal glands. Low adrenal glands are particularly troublesome for women entering menopause. Tinnitus is related in the research to adrenal stress, and low cortisol levels. Remember that people with low cortisol have likely had a period of time with elevated cortisol, so each individual who ends up with low cortisol was previously a person with high cortisol. I can help you unravel your body’s hormone puzzle, rebuild your adrenal health, and balance your brain chemistry. To answer your question – No, this isn’t a life sentence. But it won’t just all get better by itself. You need to have a plan and I can help you with that. Please contact my office 208-322-7755 and if you would like to work with me to improve your health and overcome your challenges.

      Yours in Health,

      Dr. Rostenberg

  • May 9, 2016 Reply

    Rachel R.

    I’m having a little trouble processing the “directionality” of the information in this article, but I’d like to wrap my head around it because I suspect it may be highly relevant for me.

    I’m female. However, my personality is in the something like 1/2 a percent of women; I’m “weird.” lol I don’t know for sure my hormone levels, but by nature my personality is the most assertive/aggressive type, so I suspect perhaps I tend toward higher testosterone than the average woman. I also have MAO A mutations (homozygous) and several COMT mutations (heterozygous). Adrenal fatigue has been a problem for me for years and although I’m struggling with whether or not I’m following this article properly; I’m wondering if perhaps I’m addressing this backward from what my body needs. Am I understanding correctly that more aggressive endeavors will speed up MAO an COMT?

    • May 12, 2016 Reply


      Hi Rachel,

      People with COMT and MAO are accustomed to high(er) levels of dopamine/adrenalin. More aggressive endeavors are used as self-medication to maintain a higher level of dopamine/adrenalin. If the body is used to having high dopamine, and the dopamine drops lower, it can feel like there is an impulsive instinct to do something, anything, to raise the dopamine back up. Hope that helps!

      In Health,

      Dr. Rostenberg

  • May 14, 2016 Reply


    How does Wellbutrin affect the catecholemine levels? I have not been able to handle stress well, although at the same time, I function better under stress at my job. It’s bizarre….my doctor (who knows nothing about this stuff and told me to throw it away when I showed her my 23andme report years ago) just started me on Wellbutrin. Birth control in my younger years made me very “not nice” and I could not take them. I went through early menopause in my late 30’s ( unknown why….assumed it was my Hashimotos). I just read this article and it’s helping make sense of why I am how I am. Just curious if the Welbutrin will help or not. Thanks in advance. By the way…. I’m MAOA +\-, MAO b -/-, comt -61. -/-, comt h62h +\-, comt V1528m. +\-, comt -/-

  • May 19, 2016 Reply



    I just had thyroid function tests done and I have low free T3. My TSH is 0.98 which is considered good so wondering if it is secondary hypothyroidism where the problem is with my pituitary gland or hypothalamus.

    Is this something you can help with if I did a Skype consultation with your clinic? Already contacted your office a few months ago about the OAT but thyroid test just received last week. I had been waiting for all my results to come back before the consultation.

    Thank you

  • May 21, 2016 Reply


    But testosterone, especially exogenous, converts to estrogens. Many women are naturally higher in testosterone and feel more relaxed when doing the things listed above for men. My question is if exposed to either in supplement form, how does one rid them with a COMT/MTHFR and other mutations?

    • June 2, 2016 Reply


      Women with higher testosterone are actually insulin resistant. Higher insulin causes higher testosterone and given the rampant blood sugar problems we all face, its no wonder women are having such high levels.

  • June 30, 2016 Reply


    What about progesterone? It rises when pregnant & drops after delivery, using progrsterone cream helped my peri menopausal depression, estrogen did nothing for me.

  • August 12, 2016 Reply


    Would you suggest to take a small amount of estrogen (topical) during the luteal phase if someone has fast MAO activity esp when someone is in peri-menopause ???

    • August 28, 2016 Reply


      Hi Bernadette,

      Thanks for your comment! Estrogen will SLOW DOWN the MAO system, so theoretically improving estrogen levels will slow it down and lead to a calming, anti-depressant effect. There are other options besides estrogen hormones, some plants like Siberian Rhubarb have phytoestrogen that can also be helpful when people have estrogen-related deficiencies. Black cohosh and phytoestrogens from soy are also very, very helpful with peri-menopausal symptoms as they too have a mild estrogen activity that supports healthy mood during menopause. The rhubarb product is called Estrovera and the black cohosh product is called Black Cohosh Plus. These are available through our online Metagenics web store – Hope that helps!

      In Health,

      Dr. Rostenberg

  • May 11, 2017 Reply


    I battle with COMPT/ Estrogen methylation.
    Would the Nuvaring be an option as a contraception?

    • May 11, 2017 Reply

      Dr. Rostenberg

      Hi Megan,

      In general the less exposure we have to estrogen the lower our chances or risks of cancer. So birth control needs to be understood as a toxin that while useful, is still a cancer-causing agent. IUD’s use lower doses or zero doses of hormones to be effective so in general we recommend these for our patients as they are safer than taking oral birth control. Hope that helps.

      In Health,

      Dr. Rostenberg

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