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How COMT Affects PMS and What You Can Do

Premenstrual syndrome (PMS) involves emotional, physical, and mental symptoms that occur before menstruation, such as mood swings, irritability, anxiety, and cramps. One gene that influences PMS risk is COMT (catechol-O-methyltransferase). COMT makes an enzyme that helps break down brain chemicals like dopamine and norepinephrine and also participates in estrogen metabolism. Variations in COMT change how quickly these chemicals are cleared, which can affect mood, stress resilience, and how the body responds to hormonal shifts in the luteal phase.

What this means biologically

  • Fast COMT activity lowers levels of dopamine and norepinephrine more quickly and speeds estrogen breakdown. This can reduce mood-stabilizing signals and contribute to PMS symptoms.
  • Slow COMT activity allows neurotransmitters to remain active longer and slows estrogen clearance, which is generally associated with more stable mood during the premenstrual window.
  • Your rs4680 genotype (AA, AG, or GG) predicts COMT activity level and can help personalize lifestyle and nutrition strategies to reduce symptom severity.

Practical recommendations

The following diet, supplement, lifestyle, and monitoring suggestions aim to support hormone balance and mood regulation across the menstrual cycle. These are educational recommendations only. PlexusDx does not provide medical advice. Always discuss changes with your healthcare provider before starting new supplements, medications, or major lifestyle changes.

Diet and nutrition

  • Prioritize whole foods: vegetables, fruits, lean protein, legumes, whole grains, nuts, and seeds to support steady blood sugar and neurotransmitter production.
  • Moderate carbohydrate intake in the luteal phase to avoid blood sugar dips that can worsen mood swings. Favor complex carbs and fiber-rich choices.
  • Choose low-histamine foods if you notice sensitivity (fresh meats, most fresh vegetables, gluten-free whole grains). Reduce aged cheeses, processed meats, alcohol, and fermented foods that can raise histamine and worsen symptoms in some people.
  • Include sources of omega-3 fats (fatty fish, flaxseed, chia) to support inflammation balance and mood.
  • Ensure adequate protein and amino acid variety to support neurotransmitter synthesis (tryptophan and tyrosine precursors).

Supplements to consider

  • Zinc: supports neurotransmitter regulation and can help mood and PMS symptoms when levels are low. Follow dosing guidance from your provider.
  • Vitamin B6: involved in serotonin synthesis and may reduce premenstrual mood symptoms. Use the active form (pyridoxal-5-phosphate) if recommended by your clinician.
  • Vitex (chasteberry): commonly used for cyclical breast tenderness and mood-related PMS symptoms. Take under supervision from a provider, especially if on hormonal treatments.
  • Saffron: may improve mood and reduce irritability in the premenstrual period for some people.
  • Calming nutrients: low-dose GABA, magnesium, and L-theanine can support relaxation and sleep. Discuss interactions with medications and appropriate dosages with your clinician.

Lifestyle and behavioral strategies

  • Track symptoms across at least two cycles to identify patterns and the specific days when symptoms peak. Use a simple app, journal, or calendar.
  • Practice mindfulness and brief daily stress-reduction techniques such as breathing exercises, progressive muscle relaxation, or short guided meditations to improve stress resilience.
  • Engage in gentle aerobic exercise and restorative movement during the luteal phase—walking, yoga, and swimming can reduce tension and improve mood.
  • Prioritize consistent sleep timing and create a calming bedtime routine; disrupted sleep worsens emotional regulation and PMS severity.
  • Build social support: talk with trusted friends or family about cyclical changes and consider peer groups or counseling when mood symptoms are impactful.

Monitoring and tests to discuss with your clinician

  • Consider testing vitamin D, zinc, magnesium, and ferritin levels if symptoms are moderate to severe, and correct deficiencies under medical supervision.
  • Thyroid function tests can rule out hypothyroidism, which can mimic or worsen mood symptoms around the cycle.
  • Hormone testing may be appropriate in select cases to assess luteal phase progesterone and estrogen patterns. Interpret results in the context of symptoms and cycle timing.
  • Keep a symptom diary to help clinicians evaluate treatment response and to distinguish PMS from other mood disorders.

Genetic interpretation: rs4680 (COMT)

Below are explanations of how each rs4680 genotype is commonly interpreted relative to COMT activity and PMS risk. Use the accordion to expand the section that matches your genotype.

2 effect alleles (GG) — Fast COMT activity

If you have the GG genotype, your COMT enzyme works rapidly to break down dopamine, norepinephrine, and estrogen. Faster clearance of mood-supporting neurotransmitters and quicker estrogen metabolism are associated with a higher likelihood of premenstrual mood changes, irritability, and anxiety in the luteal phase.

Practical steps:

  • Focus on steady blood sugar and frequent small meals with protein to support neurotransmitter availability.
  • Emphasize zinc and vitamin B6 intake, and discuss supplements like saffron or vitex with your clinician.
  • Prioritize sleep, stress management, and gentle exercise to support neurotransmitter balance.
  • Track your cycle closely so you can implement extra self-care measures in the week before your period.
1 effect allele (AG) — Intermediate COMT activity

With the AG genotype, your COMT enzyme activity is intermediate. You may clear neurotransmitters and estrogen faster than people with two non-effect alleles, but not as quickly as those with two effect alleles. This can mean a moderate increase in PMS risk or symptom severity, but individual experience varies.

Practical steps:

  • Adopt balanced meals with quality protein and complex carbohydrates, especially in the luteal phase.
  • Consider zinc and vitamin B6 if dietary intake is low, and discuss herbs like vitex or saffron with your provider if symptoms are bothersome.
  • Use stress reduction tools and consistent sleep to buffer mood swings during hormonal changes.
  • Monitor symptoms across cycles and adjust lifestyle strategies when premenstrual symptoms begin.
0 effect alleles (AA) — Slow COMT activity

If you have the AA genotype, your COMT enzyme works more slowly. Neurotransmitters like dopamine and norepinephrine stay active longer and estrogen is cleared more gradually. This pattern is generally associated with more stable mood and a lower genetic risk for PMS compared to faster COMT variants.

Practical steps:

  • Maintain a nutrient-dense whole food diet and adequate protein to support steady neurotransmitter synthesis.
  • Continue sleep hygiene, stress-reduction practices, and regular exercise to support emotional balance.
  • Even with lower genetic risk, track symptoms so you can identify and address any cyclical changes early.

Other considerations

  • Genetics is one part of the picture. Environment, sleep, stress, nutrition, and hormonal history also strongly influence PMS.
  • If symptoms are severe or impair daily functioning, consult a healthcare provider. Treatment options may include cognitive behavioral therapy, hormonal therapies, or targeted nutrient correction guided by a clinician.
  • Be cautious with herbal supplements if you are pregnant, breastfeeding, on hormonal contraception, or taking medications. Always check with your healthcare provider.

PlexusDx provides educational genetic information only and does not provide medical advice. Use this report to inform discussions with your healthcare provider, who can make personalized recommendations and diagnose or treat medical conditions.