When One Gene Turns Up the Volume: COMT, Mood & Hormones

Have you ever felt like stress, mood swings, and PMS symptoms hit you harder than other people? You’re not imagining it. One of the reasons can be a gene called COMT (catechol-o-methyltransferase).

Think of COMT as your body’s “volume knob.” It helps turn down the intensity of stimulating brain chemicals like dopamine and adrenaline, and it also helps your body process estrogen by-products.

When COMT runs a little slower (because of a common genetic difference called COMT Val158Met, especially in the Met/Met version), that volume knob doesn’t work as well. This can shape how you respond to stress, how you process hormones, and how conditions like PCOS or PMDD affect you.

COMT 101—What It Does

COMT’s job is to “quiet down” certain brain chemicals and to help clear estrogen. It does this by adding a methyl group (from a nutrient called SAMe) to chemicals in the body that contain catechol..

Here’s what COMT works on:

• Neurotransmitters (brain chemicals): dopamine, norepinephrine, and epinephrine (adrenaline)

• Catechol estrogens: 2-hydroxy and 4-hydroxy estrogen by-products (from Phase II estrogen metabolism)

When COMT is slow, those brain chemicals and estrogen by-products stick around longer than they should.

How Slow COMT Shows Up

1. Mood and Stress

In certain parts of the brain, COMT is the main “off switch” for dopamine and norepinephrine. While these brain chemicals are essential for things like focus and energy, if COMT is sluggish:

• You may feel anxious, irritable, or easily overstimulated, especially under stress.

• Caffeine or lack of sleep can make you feel “wired but tired.”

• You may notice overthinking, racing thoughts, or sensitivity to stress.

• Tension headaches, tight muscles, or even heightened pain sensitivity can also show up.

It doesn’t mean anything is “wrong” — it just means your brain chemistry lingers in the “on” position longer.

2. Estrogen Processing

Estrogen breakdown happens in two steps:

• Phase I (liver): estrogen is converted into by-products like 2-OH, 4-OH, and 16-OH.

• Phase II (COMT’s role): COMT helps neutralize the 2-OH and 4-OH forms so they can be cleared.

When COMT is slow, 2-OH and 4-OH can build up instead of moving into the calmer 2-methoxy form. That backlog can tip the balance toward more problematic forms of estrogen.

You may feel this as:

• Breast tenderness

• Water retention/bloating

• Mood swings

• Heavier PMS

COMT and PCOS

In PCOS, many people don’t ovulate regularly, which means progesterone often runs lower. That can create relative estrogen dominance — estrogen is higher compared to progesterone.

If you also have slow COMT, the load is heavier:

• Estrogen by-products (2-OH and 4-OH) don’t clear well.

• Stronger estrogen signals (4-OH and 16-OH) dominate.

• This can feel like breast tenderness, bloating, mood swings, fluid retention, or heavier cycles.

Anything that slows down the liver–bile–gut axis (alcohol, processed foods, low fiber, constipation, gut imbalances like SIBO) can make the problem worse.

What PCOS Looks Like in Teens/Young Adults

Young Women With PCOS

Picture a teen or young adult with PCOS:

• Physical symptoms: acne, irregular cycles, stubborn weight gain, cravings.

• Add slow COMT: anxiety, irritability, mood swings (especially before periods), poor sleep, caffeine dependence that backfires.

• Even with “clean eating,” symptoms may cycle back unless liver, bile, and gut support are added.

  
  

  Supporting blood sugar, estrogen clearance, methylation nutrients, and gut health often improves skin, cycles, and mood together.

COMT and PMDD

With PMDD (premenstrual dysphoric disorder), mood symptoms get intense in the second half of the cycle (the luteal phase). Hormones are rising and falling quickly. If COMT is slow, those shifts feel louder:

• Catechol estrogens don’t clear as smoothly.

• Stress chemicals linger longer.

• Anxiety, irritability, or emotional reactivity get amplified.

Not everyone with PMDD has COMT variants, but slow COMT often shows up in people with stronger premenstrual mood symptoms.

Practical Ways to Support COMT

(Always discuss with your clinician before starting supplements or big changes.)

1. Nutrients for COMT

• Foods first: leafy greens (folate), eggs/beans/soy (choline), fish/meat (B12), nuts/seeds (B6, magnesium).

• Supplements if needed: methyl-folate, B12, B6 (as P5P), choline, magnesium.

• SAMe: sometimes used short-term for mood or estrogen support. Must be monitored carefully if you’re anxious or on medications.

2. Support Estrogen Clearance

• Cruciferous veggies (broccoli, arugula, cabbage).

• DIM (if clearly estrogen dominant — ask your clinician).

• Calcium D-glucarate to help move estrogen out.

• Fiber + hydration for regular bowel movements.

• Limit alcohol and processed foods that slow detox.

3. Gut and Bile Support

• Treat constipation (magnesium, fiber, movement).

• Consider SIBO testing if bloating, reflux, or gas are present.

• Support digestion with bitter foods or bile support if recommended.

4. Stress and Lifestyle

• Regular exercise (both strength and aerobic).

• 7–9 hours of sleep.

• Stress-management tools: deep breathing, yoga, walks.

• Limit caffeine, especially if it worsens anxiety.

5. Helpful Labs (to personalize your plan)

• Sex hormones (testosterone, DHEA-S, SHBG, progesterone).

• Metabolic markers (fasting glucose, insulin, HbA1c, lipids).

• Liver health (ALT/AST, GGT; ultrasound if needed).

• Gut health (SIBO breath testing, stool tests in some cases).

Bottom Line

Having the COMT Met/Met gene doesn’t cause PCOS or PMDD by itself. But it can turn up the volume on anxiety, irritability, and hormone-related symptoms by slowing how your body clears stress chemicals and estrogen by-products.

The good news? With the right food, nutrients, lifestyle, and gut/liver support, you can help COMT do its job better — and bring the mood–hormone loop back into balance.

Wondering if this could be you? Contact us for a free 10-minute consult with one of our doctors.