Dr. Frank-Chris Schoebel
Dr. Frank-Chris Schoebel
Dr. Frank-Chris Schoebel has been working as a cardiologist in Düsseldorf for 25 years and was a member of staff at the Clinic for Cardiology, Pneumology and Angiology at the University Hospital Düsseldorf for more than 16 years, including 6 years as senior physician. To the profile.

COMT & MAO - estrogen, testosterone and aromatase


Enzymes,Activating neurotransmitters,COMT,MAO,estrogen,testosterone,degradation,degradation enzymes in body

Modulation of COMT and MAO by estrogen, testosterone and aromatase.

Via the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), the activating neurotransmitters dopamine, norepinephrine, epinephrine and serotonin are broken down. As a result, these two enzymes not only have an influence on your behavior and state of mind, but also on your cardiovascular system, for example on heart rhythm and blood pressure.

Enzymes,Activating neurotransmitters,COMT,MAO,estrogen,testosterone,degradation,degradation enzymes in body

Enzymes,Activating neurotransmitters,COMT,MAO,estrogen,testosterone,degradation,degradation enzymes in body

We distinguish people with genetically different variants of COMT and MAO:

  • Low-COMT or -MAO = slow degradation
  • Intermediate-COMT or -MAO = medium-fast degradation
  • High-COMT or -MAO = fast degradation

The formation of COMT and MAO is decisively influenced epigenetically, i.e. directly by the switching on and off of genes, by the hormones estrogen and testosterone. Estrogen inhibits the genetic formation of COMT and MAO, testosterone increases it.

Enzymes,Activating neurotransmitters,COMT,MAO,estrogen,testosterone,degradation,degradation enzymes in body

COMT, MAO and dopamine in women - normal ovarian cycle and the pill.

Estrogen inhibits the formation of COMT and MAO, thus indirectly INCREASING the neurotransmitters dopamine, norepinephrine, epinephrine, and serotonin.

Enzymes,Activating neurotransmitters,COMT,MAO,estrogen,testosterone,degradation,degradation enzymes in body


The influence of estrogen on COMT and MAO is particularly clear in women with a normal ovarian cycle. Accordingly, there are usually very impressive differences between the 1st and 2nd half of the cycle.

In the estrogen-dominated 1st half of the cycle, i.e. before ovulation, women are usually more active, socially more open and consequently happier. This is essentially due to increased dopamine levels, because estrogen indirectly inhibits the breakdown of dopamine via its effect on COMT. The positive radiance associated with estrogen and dopamine is also called "glow.

The "Glow" makes evolutionary biological sense, since the 1st half of the cycle is geared towards fertilization and thus towards bringing about a pregnancy. Women in the 1st half of the cycle thus have a higher attraction for men, while the "Glow" tends to provoke competitive behavior in other women.

In the progesterone-dominated 2nd half of the cycle, which is geared towards a possible pregnancy, the "glow" then recedes into the background. The cause here is an increase in progesterone in relation to estrogen. Progesterone indirectly prevents the inhibitory effect of estrogen on the formation of COMT and MAO.

In short, these connections between estrogen and the reduced formation of COMT or MAO explain the changes in mood during the ovarian cycle. Estrogen thus has a decisive influence on the concentration of the activating neurotransmitters dopamine, noradrenaline, adrenaline and serotonin.

Women who take the "Pill" for contraception must be aware that the "Pill" with its progesterone component simulates the 2nd half of the cycle. This basically means that good mood, feelings of happiness and a good appearance are less likely than if they did not take the pill.

COMT, MAO and dopamine in women - pregnancy and postpartum depression and menopause.

During pregnancy, not only progesterone but also estrogen levels are significantly increased, in some cases by about 30 times. This means that women usually feel happier during pregnancy. To what extent there are differences here when a woman is pregnant with a boy or a girl is still unclear to us.

Changes in hormonal status around childbirth, especially the drop in estrogen with the termination of pregnancy, increase the risk for peripartum depression, which occurs in 10-16% of all births. After birth, we call this form of depression postpartum depression.

In our view, pregnant women who are genetically predisposed to an increased depletion of activating neurotransmitters, especially those with high-COMT and high-MAO gene polymorphisms, are particularly at risk for postpartum depression. This assumption is indirectly supported by scientific data showing that women who had a depressive episode before pregnancy have a doubly increased risk for postpartum depression.

Knowing the gene polymorphisms for COMT and MAO, precautions can be taken early while still pregnant in women who are at increased risk for postpartum depression, and then implemented after delivery to prevent the depression.

Unless there is a desire to breastfeed, temporary estrogen substitution after termination of pregnancy may be considered. Vitamin D should be given in higher doses of 40,000 to 60,000 units per week. Vitamin D indirectly increases the formation of dopamine via epigenetic induction of tyrosine hydroxylase. Aim for vitamin D valley levels in the blood of 50-80 µg per l. Specific temporary administration of antidepressants must also be considered. Consequently, close coordination between the pregnant woman, obstetrician, gynecologist, neurotransmitter specialists and also a psychiatrist is necessary.

COMT, MAO and dopamine in women - Menopause in high-COMT and/or high-MAO.

With menopause around the age of 50, hormone production in the ovaries decreases; estrogen and progesterone are then hardly produced here. This increases the risk of depression, especially in women with a high rate of neurotransmitter degradation (high-COMT, high-MAO). Here, too, the substitution of hormones and vitamin D can be considered.

Especially in the case of menopausal symptoms, we can alleviate them through the administration of estrogen, which consequently also lifts the general mood. Since the risk of uterine cancer, for example, is fundamentally increased with increasing age, especially in women after menopause, estrogen should never be administered alone over a longer period of time. Therefore, a combination of estrogen and progesterone is always given.

However, when using a hormonal approach to modulate depression in women with high-COMT or high-MAO, care should be taken to balance the ratio in favor of the estrogen dose so that the desired effect occurs. As a rule, the balance usually plays a greater role than the absolute amount of estrogen added.

COMT, MAO and dopamine in women - Menopause in low-COMT and/or low-MAO.

On the other hand, women who have a low-COMT metabolism as a genetic prerequisite find menopause quite pleasant. Due to the decreasing estrogen level, excess activating neurotransmitters are better eliminated. Consequently, circling thoughts, inner restlessness and feelings of anxiety can become more manageable or disappear. Experienced gynecologists know this very well.

We also observe that especially women with low-COMT gene polymorphism "save" the "glow", i.e. the positive radiance, which usually occurs regularly in the 1st half of the cycle before menopause, to a certain extent into postmenopause. In short, women with low-COMT gene polymorphism often retain a more youthful glow in postmenopause.

Incidentally, if hormone therapy is being considered in menopause in a woman with low-COMT gene polymorphism, for example to treat hot flashes, then we must proceed with particular caution. We know from experience that in such a case an excess of estrogen can provoke anxiety and panic attacks. Therefore, it makes sense if in such cases the balance of estrogen and progesterone is more in favor of progesterone.

COMT and MAO in men - Testosterone

Testosterone increases the formation of COMT and MAO and thus indirectly REDUCES the concentration of the neurotransmitters dopamine, norepinephrine, epinephrine and serotonin.

Compared to women, men are first of all considered to be less capable of vibration, i.e. less emotional. In social behavior, this can also be associated with less empathy. This certainly also has to do with the fact that testosterone in men, particularly in young and middle age, indirectly causes the activating neurotransmitters to be increasingly reduced.

It is precisely the combination of high-COMT and high-MAO, in conjunction with higher testosterone levels in younger and middle age, that can lead to risk-taking behavior. To get the "adrenaline kick," men then do some daredevil things, for example, on tests of courage, in traffic, and in the popular extreme sports.

It cannot be denied that men (and women) with an increased depletion of activating neurotransmitters are more likely to be at risk of depression, especially in high-COMT. Above all, these men should be cautious in dealing with the medicinal supply of testosterone, since testosterone enhances the pre-existing High-COMT metabolism and can thus provoke depressive moods.

Enzymes,Activating neurotransmitters,COMT,MAO,estrogen,testosterone,degradation,degradation enzymes in body

COMT and MAO - testosterone and estrogen in the course of life

Finally, with increasing age, approximately between the ages of 40 and 50, testosterone levels decrease in men and estrogen levels decrease in women, respectively. In a sense, this leads to a decrease in vibratory capacity in women and an increase in vibratory capacity in men. Consequently, women basically tend to become less emotionally vibratory and men more vibratory.

Enzymes,Activating neurotransmitters,COMT,MAO,estrogen,testosterone,degradation,degradation enzymes in bodyEnzymes,Activating neurotransmitters,COMT,MAO,estrogen,testosterone,degradation,degradation enzymes in body

Consequently, the decrease in testosterone with increasing age in men may well be associated with an increase in empathy. However, this is complicated by the fact that especially in men with low-MAO gene polymorphism, irritability may increase, which may be associated with early exhaustion, latent aggressive and socially avoidant behavior in later life due to overstimulation.

Enzymes,Activating neurotransmitters,COMT,MAO,estrogen,testosterone,degradation,degradation enzymes in body

COMT and MAO in men - Aromatase

Aromatase plays a special role in the formation of estrogen, and thus also in the control of COMT and MAO. The enzyme aromatase causes the conversion of testosterone into 17ß-estradiol also outside the ovaries or the testes. We are dealing here with both quantitative and qualitative aspects.

The quantitative importance of aromatase is revealed by the high content of aromatase in adipose tissue. Abdominal fat is the main site for the extragonadal formation of 17ß-estradiol, i.e. outside the ovaries or testes. In short, the more abdominal fat, the more 17ß-estradiol. Likewise, we always see this quite clearly from the high estrogen levels in overweight men. Thus, overweight also has a clear influence on the emotional state and the circulation in men via an estrogen-mediated reduction of COMT and MAO.

Qualitatively, we need to know that there are genetic variants for the formation of aromatase, also called CYP19A1 (cytochrome P450 19A1), which contribute to an increased formation of 17ß-estradiol. This "fast metabolism", also called "high-aromatase", is not only relevant for an increased formation of 17ß-estradiol independent of the amount of abdominal fat, but also for the metabolism of drug-supplied testosterone (gel, injection). Consequently, in "fast metabolizers" the supplied testosterone is rapidly and in excess converted into 17ß-estradiol.

The genetically determined different metabolic rates of aromatase also explain influences on the rates of degradation of COMT and MAO: the faster aromatase and thus estrogen production, the slower the degradation of activating neurotransmitters via COMT and MAO due to estrogen inhibition.

Enzymes,Activating neurotransmitters,COMT,MAO,estrogen,testosterone,degradation,degradation enzymes in body

Special case - degradation of estrogen via COMT

When evaluating estrogen, it should also be considered that estrogen itself is partly degraded by COMT. Consequently, especially in women with low-COMT metabolism, the metabolism of activating neurotransmitters is disturbed via 2 pathways, once via the epigenetic inhibition of the formation of COMT and additionally also via the additional burden of the weakened enzyme pathway by estrogen.

Moreover, the constellation of "low-COMT+high-aromatase" is in a sense a self-reinforcing process, a positive feed-back loop. This can therefore lead to significant health consequences not only via an increase in activating neurotransmitters, but also through the side effects of estrogen independent of neutransmitter metabolism. Finally, a connection between these mechanisms and autoimmune diseases, which occur in about 80% of the cases in women, is conceivable.

Furthermore, progesterone-sensitive acne is also interesting in this context. Many, especially young women, have acne that can be well controlled by taking the pill, i.e. a surplus of progesterone. We have the clear impression here that the combination of "low-COMT+high aromatase" plays a role.

Therapeutic benefit COMT and MAO - gynecologist, urologist, psychiatrist and cardiologist.

As is clear from the above, an isolated determination of COMT and MAO accordingly makes little sense. Finally, only the synopsis of the gene polymorphisms for COMT and MAO in conjunction with the individual hormone status and the co-factors of the individual enzymes allows meaningful therapeutic decisions.

Knowledge of the metabolism of activating neurotransmitters is of particular therapeutic benefit for medical specialties dealing with emotional, hormone-dependent and cardiovascular disorders, in short for psychiatrists, gynecologists, urologists and cardiovascular physicians. Accordingly, more targeted and thus better treatment becomes possible for the people affected. Consequently, people with certain symptoms may particularly benefit:

  • inner restlessness, for example circling thoughts, fear up to panic attacks
  • depressive mood up to depressions
  • Cardiac arrhythmias, for example, palpitations, heart palpitations
  • Increases in blood pressure, for example, also strongly fluctuating blood pressure

We know that even for physicians, the relationships between activating neurotransmitters, COMT and MAO in relation to the hormones estrogen and testosterone, including the co-factors, are not easy to understand at first. However, the effort is worthwhile, because we have learned in the Cardiopraxis that we simply know people better this way and can target the treatment of cardiovascular diseases more individually.

Literature for all

Aromatase literature

Behavioral Biology Literature

Pregnancy literature

Literature on estrogen and testosterone

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