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How CYP3A4 Variations Affect Estrogen Metabolism and Men’s Hormone Health

Estrogen is commonly thought of as a female hormone, but it plays important roles in men too. Proper estrogen balance supports bone health, brain function, libido, and sperm production. The liver enzyme CYP3A4 helps break down estrogen into different metabolites. Certain genetic variations in the CYP3A4 gene can change how quickly estrogen is converted into specific metabolites, including 16α-hydroxyestrone (16α-OHE1). When 16α-OHE1 is produced in excess it may contribute to hormone imbalances and increase risk for prostate-related problems or other estrogen-related concerns.

What this means for you

Your genotype at rs2740574 in the CYP3A4 gene influences enzyme activity and the relative production of estrogen metabolites.

CC — Two effect alleles (higher CYP3A4 activity)

You carry two copies of the effect allele. This genotype is associated with increased CYP3A4 enzyme activity, which can speed conversion of estradiol toward 16α-hydroxyestrone (16α-OHE1). Elevated 16α-OHE1 over time may be linked to higher risk for prostate issues and hormone imbalances.

  • Diet: Aim to include cruciferous vegetables daily — broccoli, cabbage, Brussels sprouts, cauliflower and kale — to support healthier estrogen pathway balance.
  • Supplements to consider: DIM (diindolylmethane), sulforaphane-rich extracts, N-acetylcysteine (NAC), and antioxidant support such as resveratrol. These can support liver detoxification and favorable estrogen metabolism. Discuss doses with your provider.
  • Lifestyle: Limit alcohol, stop smoking, and reduce exposure to environmental estrogens such as BPA, phthalates, and some personal care chemicals. Maintain a healthy weight and regular physical activity to support hormone balance.
  • Gut and elimination: Consume high-fiber foods and consider probiotic-supporting foods to encourage estrogen excretion through bowel movements.
  • Medication interactions: Avoid grapefruit if you are taking medications metabolized by CYP3A4, and always check with your prescriber before combining supplements and prescription drugs.
  • Monitoring: Regular hormone panels and prostate health screening (PSA and clinical exams as recommended by your provider) are advised to track changes over time.
CT — One effect allele (moderately increased CYP3A4 activity)

You carry one copy of the effect allele. This genotype is associated with increased CYP3A4 activity compared with the non-effect genotype, tending to push estrogen metabolism toward 16α-OHE1 to a lesser degree than two copies would. This may slightly raise risk for prostate issues or hormone shifts.

  • Diet: Regularly include cruciferous vegetables and plenty of fiber. Aim for a colorful whole-food pattern rich in vegetables, lean proteins, and healthy fats.
  • Supplements to consider: DIM, sulforaphane-containing foods or extracts, and NAC may support balanced estrogen metabolism. Antioxidants such as vitamin C and polyphenols can aid detox pathways.
  • Lifestyle: Limit alcohol intake, do not smoke, minimize exposure to endocrine-disrupting chemicals, and maintain consistent exercise and sleep patterns.
  • Gut and elimination: Maintain a fiber-rich diet and supportive gut health practices to encourage estrogen clearance.
  • Medication interactions: Grapefruit can alter CYP3A4-mediated drug levels. Avoid grapefruit if you are on medications that list interactions, and consult your provider.
  • Monitoring: Consider periodic hormone testing and prostate health evaluations with your healthcare provider so any trends can be caught early.
TT — Zero effect alleles (typical CYP3A4 activity)

You carry two copies of the non-effect allele. This genotype is associated with typical CYP3A4 enzyme function. Your body metabolizes estrogen at a standard rate without genetically increased conversion toward 16α-OHE1. This baseline supports typical hormone balance and lowers genetic predisposition to estrogen-related concerns tied to excess 16α-OHE1.

  • Diet: Continue a balanced diet with regular intake of vegetables, fiber, and diverse nutrients to support natural hormone processing.
  • Supplements: Not routinely required solely for this genetic result. Use targeted supplements only when indicated by symptoms or lab results and under guidance from your provider.
  • Lifestyle: Maintain healthy habits—regular exercise, moderate alcohol use, no smoking, and reduced exposure to environmental estrogens—to preserve hormone health.
  • Monitoring: Routine health care, prostate exams and hormone testing as advised by your clinician remain appropriate.

Practical recommendations to support healthy estrogen metabolism

  • Eat cruciferous vegetables daily: These foods provide compounds that support estrogen detoxification enzymes and promote a more favorable balance of estrogen metabolites.
  • Prioritize fiber and gut health: Soluble and insoluble fiber, along with fermented foods or targeted probiotics, support removal of estrogens through the digestive tract.
  • Consider targeted supplements only after professional discussion: DIM, sulforaphane extracts, NAC, and antioxidant support can be helpful for some people but are best used under clinical supervision to avoid interactions or unintended effects.
  • Minimize exposure to environmental estrogens: Reduce use of plastics with BPA, avoid heating food in plastic containers, choose fragrance-free personal care products when possible, and be cautious with processed foods that may contain endocrine-disrupting additives.
  • Limit alcohol and stop smoking: Both can impair liver detoxification and worsen hormone balance.
  • Be aware of drug interactions: Grapefruit and certain supplements can affect CYP3A4 activity and alter levels of medications. Always check with your prescribing clinician or pharmacist.
  • Maintain regular medical surveillance: Work with your healthcare provider on appropriate hormone panels and prostate health checks based on age, family history, symptoms, and this genetic information.

Tests and monitoring to discuss with your healthcare provider

  • Serum hormone panel: total and free testosterone, estradiol, SHBG, and other hormones as indicated by symptoms.
  • Prostate monitoring: PSA testing and digital rectal exam as recommended for age and risk factors.
  • Liver function tests: if you plan to start supplements or medications that affect liver metabolism.
  • Comprehensive medication review: identify drugs metabolized by CYP3A4 to avoid interactions with grapefruit or supplements.

Important disclaimer

PlexusDx provides genetic education and information only. This content is not medical advice. Genetic results describe potential predispositions and do not diagnose disease or guarantee outcomes. Always discuss genetic results, new supplements, major diet changes, or medical screening plans with your healthcare provider before making changes to your health care or treatment plan.