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CYP19A1 (rs4646) and Estrogen: What Your Genotype May Mean for Health

Estrogen is a central hormone for reproductive health, menstrual cycle regulation, bone strength, brain function, and cardiovascular protection. The CYP19A1 gene encodes the aromatase enzyme, which converts androgens like testosterone into estrogens in tissues such as the ovaries, adipose tissue, brain, and bone. Variations at rs4646 in CYP19A1 affect aromatase activity and therefore influence how much estrogen your body produces. Understanding your genotype can help you focus on lifestyle, diet, and monitoring choices that support hormone balance and long-term health.

How aromatase activity affects health

  • Lower aromatase activity tends to reduce overall estrogen levels. This can be protective in some hormone-sensitive contexts but may increase risk for lower bone density and metabolic changes over time.
  • Higher aromatase activity increases estrogen production, which supports stronger bones and some cardiovascular benefits but can raise the likelihood of estrogen-related conditions such as fibroids or other hormone-sensitive issues.
  • Fat tissue produces estrogen. Body weight and body fat distribution therefore influence circulating estrogen irrespective of genotype.

Practical recommendations to support balanced estrogen

These general strategies support healthy estrogen metabolism regardless of genotype. Tailor them with your healthcare provider based on your personal health history and test results.

  • Nutrition
    • Eat a variety of fruits, vegetables, whole grains, legumes, and lean proteins.
    • Include cruciferous vegetables (broccoli, cauliflower, Brussels sprouts, kale) to support estrogen metabolism through compounds that influence hormone pathways.
    • Prioritize fiber from whole foods to help bind and remove excess estrogen via the gut.
    • Limit high-fat processed foods and reduce added sugars to support metabolic and hormonal health.
  • Weight and body composition
    • Maintaining a healthy weight helps regulate estrogen because adipose tissue produces estrogen.
    • Combine resistance training and aerobic activity to support bone health and body composition.
  • Exercise
    • Aim for regular physical activity: at least 150 minutes of moderate aerobic activity per week plus two strength sessions to support bones, metabolism, and hormone balance.
  • Lifestyle habits
    • Limit alcohol intake; alcohol can increase estrogen levels and affect liver clearance of hormones.
    • Avoid smoking, which negatively affects bone and cardiovascular health.
    • Prioritize sleep and stress management since chronic stress can disrupt hormonal balance.
  • Liver and gut health
    • Support liver detoxification with a balanced diet, adequate hydration, and limiting excess alcohol and medications when possible.
    • Maintain a healthy gut microbiome through fiber, fermented foods, and a varied diet to aid estrogen excretion.
  • Targeted nutrients and supplements to discuss with your healthcare provider
    • Calcium and vitamin D to support bone density (dosing individualized by age, sex, and lab values).
    • Magnesium to support bone and metabolic health.
    • Consider a multivitamin if dietary intake is inadequate.
    • Use supplements only under medical guidance, especially if you have or suspect hormone-sensitive conditions.
  • Monitoring and tests to consider
    • Bone density screening (DEXA) if risk factors for low bone mass are present or if prolonged low estrogen is suspected.
    • Basic metabolic panel, fasting glucose or A1c, and lipid panel to monitor metabolic effects.
    • Discuss hormone testing with your clinician only when results would change management.

Genetic interpretation: CYP19A1 rs4646

2 effect alleles (AA) — Lower aromatase activity, lower estrogen

If your genotype is AA at rs4646, you carry two copies of the effect allele associated with reduced aromatase enzyme activity. Aromatase converts testosterone into estrogen in tissues such as the ovaries, fat, brain, and bone. Reduced activity typically leads to lower circulating estrogen compared with other genotypes.

Potential implications

  • May have lower lifetime estrogen exposure; in some contexts this can be protective against certain estrogen-driven conditions.
  • Increased attention to bone health is important because estrogen supports bone density.
  • Monitor metabolic health since changes in estrogen can affect fat distribution, insulin sensitivity, and lipids.

Practical actions

  • Ensure adequate dietary calcium and vitamin D; discuss supplementation with your provider based on labs and risk factors.
  • Include weight-bearing and resistance exercise to maintain bone strength.
  • Focus on a nutrient-dense diet with fiber, lean protein, and healthy fats.
  • Regularly review bone health and metabolic labs with your clinician if clinically indicated.
1 effect allele (AC) — Intermediate aromatase activity, moderate estrogen

If your genotype is AC at rs4646, you carry one copy of the effect allele and one copy of the non-effect allele, giving intermediate aromatase activity. Your estrogen production is likely between the higher and lower activity groups.

Potential implications

  • Generally consistent estrogen synthesis supporting reproduction, bone density, cognitive health, and cardiovascular function.
  • Lower relative risk for extremes related to very high or very low estrogen, but individual factors still matter.

Practical actions

  • Maintain a balanced diet rich in vegetables (including cruciferous vegetables), fiber, and lean protein.
  • Stay active with a mix of aerobic and resistance training to support bones and metabolic health.
  • Limit alcohol and avoid smoking to help keep estrogen at healthy levels and protect liver function.
  • Discuss routine health maintenance and any specific concerns with your clinician.
0 effect alleles (CC) — Higher aromatase activity, higher estrogen

If your genotype is CC at rs4646, you carry two copies of the non-effect allele linked to higher aromatase activity. This is the most common genotype and is associated with greater conversion of androgens to estrogen, leading to higher estrogen levels across tissues.

Potential implications

  • Higher estrogen can support stronger bone health and may provide some cardiovascular benefits.
  • May increase susceptibility to estrogen-related conditions such as uterine fibroids or other hormone-sensitive concerns.

Practical actions

  • Focus on weight management because adipose tissue contributes to estrogen production.
  • Include cruciferous vegetables and fiber to support estrogen metabolism and elimination.
  • Limit alcohol intake and avoid smoking to reduce excess estrogen exposure and support liver clearance.
  • Discuss with your clinician any symptoms suggestive of hormone-sensitive conditions and consider appropriate monitoring.

Important note from PlexusDx

PlexusDx provides educational information about genetic predispositions only. This content is not medical advice and should not replace consultation with a qualified healthcare professional. Always discuss your genetic results, symptoms, and any changes to diet, supplements, or medications with your healthcare provider before starting them. Your provider can interpret genetic findings in the context of your personal and family medical history and recommend appropriate testing or interventions.