HSA | FSA CARDS ARE NOW ACCEPTED

How CYP3A4 and Progesterone Metabolism Affect Your Health

Progesterone is a hormone that plays important roles in reproductive health, mood regulation, sleep, and fertility for people of all sexes. The CYP3A4 gene makes an enzyme in the liver that helps break down progesterone and many commonly used medications. Variations in CYP3A4 can change how quickly your body clears progesterone and certain drugs. That can influence hormone balance, mood, sleep, fertility, and how you respond to medications.

Why this matters

  • Slower progesterone metabolism can lead to higher circulating progesterone for longer periods, which may affect mood, sleep patterns, menstrual cycles, and fertility.
  • Changes in CYP3A4 enzyme activity can alter how medications are processed, potentially increasing side effects or changing how effective a drug is.
  • Lifestyle, diet, and environmental exposures can further raise or lower CYP3A4 activity and influence overall hormone and liver health.

General recommendations to support healthy progesterone and liver metabolism

  • Eat cruciferous vegetables regularly: broccoli, kale, Brussels sprouts, cauliflower and cabbage support liver enzyme pathways and promote balanced hormone metabolism.
  • Include polyphenol-rich foods: berries, green tea, and colorful fruits and vegetables support antioxidant defenses and liver health.
  • Avoid known CYP3A4 inhibitors: grapefruit and bergamot can significantly slow CYP3A4 activity and raise levels of hormones and some medications.
  • Limit exposure to endocrine-disrupting chemicals: avoid heating food in plastic, reduce use of BPA and phthalate-containing products, and prefer glass or stainless steel for food and drink storage.
  • Support detoxification pathways: consider whole-food sources or clinically validated supplements with care and under provider guidance (see supplement section).
  • Prioritize sleep, regular physical activity, and stress management to support balanced hormones and liver function.

Diet and nutrition strategies

Small, consistent dietary choices can meaningfully support progesterone metabolism and liver health:

  • Daily servings of cruciferous vegetables to provide natural glucosinolates and sulforaphane precursors.
  • Regular intake of berries, green tea, and other polyphenol-rich foods to support antioxidant systems and reduce oxidative stress on the liver.
  • Adequate protein and healthy fats to support hormone synthesis and cytochrome P450 enzyme function.
  • Reduce processed foods, excessive alcohol, and high-sugar meals, which can stress the liver and alter hormone balance.

Supplements to consider with provider approval

Before starting any supplement, discuss with your healthcare provider, especially if you take medications metabolized by CYP3A4.

  • Sulforaphane or broccoli seed extract: may help support phase II detoxification and antioxidant defense.
  • N-acetylcysteine (NAC): supports glutathione production, a key liver antioxidant.
  • Resveratrol: a polyphenol that may modulate enzyme activity and support metabolic health.
  • Calcium D-glucarate: may support elimination of hormones and reduce reabsorption in the gut.

Lifestyle and environmental strategies

  • Exercise regularly: moderate aerobic and resistance training support hormone balance and liver function.
  • Prioritize sleep: aim for consistent high-quality sleep to support hormone rhythms and repair.
  • Manage stress: practices such as mindfulness, breathing exercises, and gentle movement reduce cortisol and support hormone balance.
  • Reduce exposures: choose BPA-free and phthalate-free products, avoid microwaving food in plastic, and limit inhalation/exposure to pollutants and certain household chemicals.

Medication and monitoring considerations

If you take medications that are primarily processed by CYP3A4, altered enzyme activity can change drug levels. Work with your healthcare provider to:

  • Review all prescription and over-the-counter medications, supplements, and herbal products for interactions.
  • Consider therapeutic drug monitoring where appropriate to check serum levels of medications or hormones.
  • Track symptoms related to hormone changes such as mood shifts, sleep disturbances, menstrual irregularities, or fertility concerns.
  • Order baseline and follow-up lab tests if recommended by your provider, such as liver function tests, hormone panels, and medication level checks.

Genetic interpretations for rs4986907 (CYP3A4*15A)

2 effect alleles — TT (reduced CYP3A4 activity)

You carry two copies of the effect allele (TT), a variant called CYP3A4*15A, which is associated with decreased CYP3A4 enzyme activity. Reduced enzyme activity may slow progesterone breakdown in the liver, causing progesterone to remain in circulation longer.

  • Potential effects: altered hormone balance that could influence mood, sleep, menstrual cycle regularity, and fertility. Increased sensitivity or altered response to medications metabolized by CYP3A4.
  • Diet: emphasize cruciferous vegetables (broccoli, kale, Brussels sprouts), polyphenol-rich foods (berries, green tea), and adequate protein and healthy fats to support hormone production and liver enzymes.
  • Supplements: under provider guidance, consider sulforaphane, N-acetylcysteine (NAC), resveratrol, and calcium D-glucarate to support liver detox pathways.
  • Avoid: grapefruit and bergamot, as they can further inhibit CYP3A4. Limit exposure to BPA and phthalates.
  • Lifestyle: regular exercise, consistent sleep, stress management, and reduced alcohol intake to support liver and hormone health.
  • Medical monitoring: discuss medication reviews and possible drug level monitoring with your healthcare provider. Consider periodic hormone panels and liver function tests as indicated.
1 effect allele — CT (intermediate CYP3A4 activity)

You carry one copy of the effect allele (CT), which indicates intermediate CYP3A4 enzyme activity. Progesterone breakdown may be moderately slower compared to typical function.

  • Potential effects: progesterone may stay elevated longer than average, with possible mild impacts on mood, sleep, fertility, or menstrual patterns. Some medications may be processed more slowly.
  • Diet: include cruciferous vegetables and polyphenol-rich foods such as berries and green tea to support liver detoxification.
  • Supplements: options like sulforaphane, NAC, resveratrol, and calcium D-glucarate may help support detox pathways when used under clinical guidance.
  • Avoid: grapefruit and bergamot; minimize exposure to endocrine-disrupting chemicals.
  • Lifestyle: maintain regular physical activity, prioritize quality sleep, and engage in stress reduction practices.
  • Medical monitoring: review medications with your provider; consider monitoring if you start new drugs metabolized by CYP3A4 or if you experience symptoms.
0 effect alleles — CC (typical CYP3A4 activity)

You carry two copies of the non-effect allele (CC), indicating normal CYP3A4 enzyme function. Your body is likely to metabolize progesterone and CYP3A4-processed medications at standard rates.

  • Potential effects: typical hormone clearance and medication processing.
  • Diet: continue a balanced diet rich in cruciferous vegetables and polyphenol-rich foods to maintain liver and hormone health.
  • Supplements: generally not required specifically for CYP3A4 support, but consider general liver-supportive nutrients under provider guidance.
  • Avoid: ongoing avoidance of grapefruit and bergamot if you take medications affected by CYP3A4.
  • Lifestyle: regular exercise, adequate sleep, and stress management to support sustained hormone balance.
  • Medical monitoring: routine care as advised by your healthcare provider; review medications for interactions when appropriate.

Important considerations and next steps

  • PlexusDx provides genetic information to help you understand potential predispositions. This information is educational and not medical advice.
  • Always consult your healthcare provider before changing medications, starting supplements, or making major diet or lifestyle changes. Your provider can interpret this information in the context of your medical history, symptoms, and current treatments.
  • Consider sharing your genetic result with your provider, and discuss targeted monitoring such as hormone testing, liver panels, or medication level checks if relevant.

PlexusDx does not provide medical advice. For personalized medical recommendations, diagnosis, or treatment, consult your healthcare provider.