Progesterone | CYP3A4 (rs4986910)

If your genotype at rs4986910 is GG, you carry two copies of the effect allele. This variant, called CYP3A4*3, is associated with reduced CYP3A4 enzyme activity. Reduced activity slows progesterone metabolism and may lead to higher circulating progesterone. Potential impacts include changes in mood, sexual function, sleep, and fertility.

Practical steps to support progesterone processing and liver health

• Diet: Eat cruciferous vegetables such as broccoli, kale, cauliflower, and Brussels sprouts. Include polyphenol rich foods like berries, green tea, and colorful vegetables to support liver phase II pathways.
• Supplements to consider: sulforaphane (from broccoli sprout extracts), N acetyl cysteine (NAC) to support glutathione, resveratrol for polyphenol support, and calcium D glucarate to aid clearance of hormone metabolites. Discuss doses with your healthcare provider before starting any supplement.
• Avoid CYP3A4 inhibitors: grapefruit and bergamot can further inhibit CYP3A4 and increase hormone levels or alter drug metabolism.
• Limit liver stressors: reduce or avoid alcohol, stop smoking, and minimize exposure to endocrine disrupting chemicals such as BPA and phthalates in plastics.
• Lifestyle: regular aerobic exercise and strength training support metabolic health and hormonal balance. Maintain healthy body weight to reduce aromatization and inflammatory stress.
• Monitoring: regular hormone blood tests and medication reviews with your clinician can help detect and manage elevated progesterone or drug interactions.

If your genotype at rs4986910 is AG, you carry one effect allele and one non effect allele. This typically indicates intermediate CYP3A4 function. Progesterone and some medications may be broken down more slowly than in individuals with typical function, which can lead to modestly higher progesterone levels in some people. Effects on mood, sexual function, sleep, and fertility may occur in certain situations.

Practical steps to support progesterone processing and liver health

• Diet: emphasize cruciferous vegetables like broccoli and kale, plus polyphenol rich foods such as berries, green tea, leafy greens, and brightly colored vegetables to enhance liver detox pathways.
• Supplements that may help: consider polyphenol sources and nutrients that support liver detoxification, including sulforaphane, NAC, and calcium D glucarate. Talk with your healthcare provider before use.
• Avoid grapefruit and bergamot because they inhibit CYP3A4 and can further slow hormone and medication clearance.
• Reduce liver burden by limiting alcohol intake, avoiding tobacco, and minimizing exposure to environmental toxins.
• Maintain regular physical activity, balanced sleep, and a healthy weight to support hormone balance.
• Work with your clinician to monitor hormone levels and review prescription or over the counter medications for potential interactions.

If your genotype at rs4986910 is AA, you carry two copies of the non effect allele. This indicates typical CYP3A4 enzyme function. Your liver is likely to process progesterone and many medications at standard rates and you do not have the increased hormone retention associated with the G allele.

Recommended general habits to maintain healthy hormone metabolism

• Balanced diet: continue eating a variety of vegetables and fruits, including cruciferous vegetables and polyphenol rich foods, to support liver health.
• Healthy lifestyle: regular exercise, adequate sleep, stress management, and maintaining a healthy weight support hormone balance.
• Limit alcohol and avoid smoking to reduce liver stress.
• Monitor exposures: reduce use of plastics with BPA, avoid unnecessary environmental toxins, and be mindful of herbal or supplemental products that can influence liver enzymes.
• Continue routine medical care: periodic hormone testing and medication reviews help maintain optimal health.