Living with MTHFR: Estrogen Dominance (Hormone Imbalance)

Living with MTHFR: Estrogen Dominance (Hormone Imbalance)

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Jamie Hope - Founder of Methyl-Life

Medical Reviewer:

Jamie Hope - Founder of Methyl-Life
Kari Asadorian - Bachelor of Science in Nursing

Edited By:

Kari Asadorian - Bachelor of Science in Nursing

Updated On:

February 18, 2025

Table of Contents

    Weight gain, bloating, crazy mood swings, abnormal periods… no, it’s not just part of ‘being a woman’. These unpleasant symptoms are far from normal and are certainly not something that any woman should put up with.


    Unfortunately, that’s exactly what many women do. We blame ourselves for our symptoms, even when we’re doing our best to eat a healthy diet, live a clean lifestyle, and exercise regularly. And if we’re not doing these things, we feel doubly responsible.


    Well, here’s the important news: hormonal imbalances are not our fault. In many cases, our discomfort and suffering come down to estrogen dominance and MTHFR.  


    And guess what, guys? You’re affected, too. 

    What is estrogen dominance?

    To understand estrogen dominance, it’s important to first understand estrogen and its many roles in the body - for both men and women.


    Estrogen is known as the ‘female hormone’ because it’s largely responsible for women’s physiology and biochemistry. It’s one of the most important female reproductive hormones and plays a crucial role in normal daily functioning. It gives women their feminine characteristics, such as breasts and a wider pelvis, and tells the body to store excess fat reserves in the hips and thighs.


    Along with regulating menstruation, estrogen is also involved with cholesterol production in the liver, bone health, skin repair and integrity, mood, and much more.

    Low levels of estrogen can lead to symptoms of menopause, like vaginal changes, hot flashes, irregular periods, and reduced bone density.


    In men, the predominant form of estrogen is estradiol. It plays an important role in male sexual function, particularly in modulating libido, erectile function, and spermatogenesis.


    Like anything in the body, hormones can get out of balance. And when your body has too much estrogen in comparison to progesterone, a whole host of problems can begin. This is estrogen dominance.


    It’s important to understand that estrogen dominance isn’t necessarily about having high estrogen. It can occur even with low or normal levels. The problem is simply that you don’t have enough counterbalancing hormones to mitigate the effect of estrogen in your body: that is, estrogen is higher than progesterone.


    It’s hard to believe just how much power one little hormone can have! For example, many women find it difficult to manage their weight, especially as they get older. But we now know that weight gain is less about ‘calories in, calories out’ - and more about hormonal balance. In fact, only about 30% of weight gain comes down to the food you’re eating. The rest is to do with your hormones.

    Symptoms of estrogen dominance in women

    In women, estrogen dominance is associated with a huge array of debilitating symptoms, including:

    • Recurring PMS
    • Weight gain, particularly around the tummy, hips, and thighs
    • Fibrocystic breasts
    • Fibroids
    • Endometriosis
    • Irregular menstrual cycle
    • Low energy and/or fatigue
    • Reduced sex drive
    • Low mood or depression
    • Anxiety
    • Bloating
    • Breast tenderness
    • Mood swings
    • Brain fog
    • Sleeping problems and/or insomnia

    Estrogen dominance is also linked to much more serious long-term health conditions. These include:

    • Cancer: High levels of estrogen can put women at a higher risk of breast cancer, ovarian cancer, and endometrial cancer.
    • Autoimmune conditions: Elevated estrogen can increase your body’s inflammatory response, causing your immune system to produce antibodies that attack your own tissues.
    • Thyroid issues: Excess estrogen can block thyroid hormones from reaching their receptor sites in order to do their job.
    • Diabetes: Progesterone is a natural diuretic and helps to stabilize blood sugar. When estrogen is dominant, however, your risk of insulin resistance and diabetes may increase

    Symptoms of estrogen dominance in men

    Although estrogen plays a different role in men’s bodies, it can also get out of balance and cause problems. After the age of 40, declining progesterone levels lead to a fall in testosterone levels. This can lead to higher levels of estrogen because testosterone and progesterone levels can’t balance the amount of estrogen.Symptoms of estrogen dominance in men include:


    • “Man boobs” - softer tissue or inflammation around your chest and armpits.
    • Increased body fat in the upper chest and obliques
    • Abdominal weight gain
    • Lethargy/fatigue
    • Brain fog
    • Mood swings
    • Irritability
    • Low libido
    • Depression
    • Anxiety


    Long term, excess estrogen in men can trigger abnormal cell growth and prostate enlargement. This increases the risks for cancer, as well as cardiovascular disease, bone density loss, high cholesterol, and urinary and prostate disease.

    What causes estrogen dominance?

    Estrogen dominance has a lot to do with hormonal imbalance, which in turn has a lot to do with liver function. Estrogen is broken down in the liver via three different pathways. The particular pathway will determine whether estrogen will be converted into good or bad metabolites.


    The 2-hydroxy metabolic pathway is considered the ‘normal’ or ‘good’ pathway, as it allows your body to produce good estrogen metabolites that support healthy mood, libido, breast tissue, and reproductive health. This pathway has the lowest risk of cancer and other health issues.


    The 16-hydroxy and 4-hydroxy pathways are considered ‘bad’ as they are linked to higher risks of breast cancer. Converting too many hormones with this pathway can lead to symptoms of estrogen dominance such as irritability, vaginal dryness, and PMS.

    What determines which metabolic pathway will be used?

    There are many factors involved in how estrogen is metabolized in your body. Your diet, nutritional profile, liver health, stress levels, and the amount of sleep you get each night all play a part.


    Gene mutations such as COMT and MTHFR also influence your ability to methylate and detoxify your hormones. Environmental and lifestyle factors also have a significant impact on hormone metabolism.

    Diet

    Many animal products now contain growth hormones that are injected into animals to make them grow bigger or boost milk production. These hormones can disrupt your natural hormone balance. Pesticides, herbicides, and fungicides used on fresh produce can disrupt endocrine function and interfere with hormone activity and metabolism.

    Environment

    Exposure to chemicals that mimic estrogen (known as xenoestrogens) has reduced our ability to deal with estrogen. Xenoestrogens are present in man-made chemical compounds such as BPA in plastic water bottles, parabens, and phytates in skincare products, cosmetics, and sunscreens.


    Xenoestrogens sit on estrogen receptor sites in the body, creating an excess of estrogen in relation to our other hormones. If your liver is already burdened with other toxins - such as poor diet, stress, alcohol, and caffeine - the job of clearing this extra estrogen can become too much.

    Body fat

    Excess fat around your midsection and thighs is a major contributor to estrogen dominance. Fat tissue is like a magnet for estrogen, absorbing and storing much of what is circulating in the bloodstream. Fat is also able to synthesize estrogen from your other hormones.


    Elevated levels of estrogen encourage your body to make more fat cells, which leads to more estrogen: quite the vicious cycle.

    Genes

    Variations or mutations of certain hydroxylation genes - particularly CYP1B1 and CYP3A4 - are known for the increased production of potentially harmful estrogens such as 4OHE1 and 16aOHE1.


    Other genetic factors, such as those related to GSTM1 (glutathione transferase) can reduce your ability to eliminate harmful free radicals made from certain hydroxylated estrogens.

    Methylation issues

    Methylation is central to the function of every cell in your body, including endocrine and hormone function. Problems with your methylation can have a significant impact on hormone-related issues, particularly estrogen clearance.


    Methylation is key to the inactivation and detoxification of a number of molecules, particularly catechol estrogens. The methylation of harmful estrogens 4OH E1 and E2 inactivates and effectively neutralizes the volatile 4OH molecule. Phase II methylation of estrogen requires the COMT enzyme (catechol oxygen methyltransferase).


    A mutation of the MTHFR gene can reduce your ability to methylate - and therefore inactivate - any potentially harmful estrogens circulating in the blood.


    There are 2 major MTHFR variants: 677 and 1298. The status of either of these can have a direct impact on the entire methylation cycle.


    A mutation in the MTHFR gene means your body will make less of the active MTHFR enzyme, which in turn means you make fewer methyl groups. A mutation in two MTHFR genes will result in even fewer methyl groups. It’s estimated that around 60%+ of people in the United States have this genetic mutation.


    Estradiol is deactivated when a methyl group attaches to it. Without enough methyl groups, estradiol and its metabolites (which still have estrogenic activity) will remain elevated. Estrone (E1) also needs a methyl group to attach to it to deactivate. Estrone has less estrogenic activity than estradiol, but it is still a potent estrogen.


    This means that someone with the MTHFR gene can end up with two different kinds of estrogen and their hormonally active metabolic breakdown products circulating in their bloodstream.

    How to treat estrogen dominance

    Balancing estrogen and supporting methylation processes in the body involves an individualized approach. There should be a focus on diet, vitamins/minerals, and certain herbs that have been shown to influence genetic expression as well as the metabolism of hormones and their subsequent detoxification.


    Effective nutritional protocols can improve the function of the enzymes required in the methylation process. This can help the body to make the hormones that you need and remove (inactivate) the ones you don’t, while also supporting the genes required for good health.

    Improve your diet

    Cut out foods that are likely to contain hidden estrogens from added hormones, pesticides, and fertilizers used in conventional farming methods. This includes processed meats, dairy products, and produce.


    Stick to grass-fed meats and organic foods whenever possible. Drink only pure filtered water.

    Ditch the toxins

    Check the labels on your skincare products and avoid those with synthetic compounds. Use glass or stainless steel bottles and containers for food.

    Minimize stress

    Take some time out for yoga or meditation, or at least 30 minutes of gentle exercise. Make sure you’re getting adequate sleep at night to allow your body to recover from daily stresses.

    Support methylation and detoxification

    Healthy liver function is the first step in correcting and/or preventing poor estrogen metabolism and rebalancing estrogen levels. Specific nutrients can help to clear excess estrogen from the body and restore hormonal balance, while also supporting optimal estrogen metabolism and detoxification.

    Recommended nutrients for balancing estrogen

    Calcium-D-Glucarate

    This form of calcium promotes phase 2 glucuronidation; a phase II biotransformation reaction that helps to make molecules more water-soluble. It’s also believed to be a beta-glucuronidase inhibitor, which helps prevent the reabsorption of detoxified estrogens through second-pass metabolism. 


    Simply put, calcium-d-glucarate binds to circulating estrogen that would otherwise be reabsorbed by your body, then allows it to be flushed out.  

    Diindolylmethane (DIM)

    Diindolylmethane is a compound formed in the body from plant substances of cruciferous vegetables such as cabbage, Brussels sprouts, cauliflower, and broccoli.


    DIM supplementation helps to metabolize estrogen into more good metabolites than the potentially harmful metabolites. It also appears to help destroy cancer cells and reduce inflammation.

    Glutathione promoters and/or cofactors

    Proper glutathione function is essential for the removal of harmful free radicals inside cells which can damage DNA. Mutations can lead to insufficient DNA repair, a major risk in the development of cancer.


    N-Acetyl-L-Cysteine (NAC) and resveratrol are two important antioxidants that can help reduce the formation of estrogen-DNA adducts and prevent several cancers. Vitamin D supplementation is also effective in inhibiting breast cancer cell growth.


    MTHFR enzymes are crucial components of glutathione synthesis. Proper function of glutathione also requires mineral cofactors such as selenium (to form glutathione peroxidase) and magnesium (to activate the glutathione synthetase enzyme). Several B-vitamins play a central role here, especially vitamins B6 and B2.

    Additional herbs and nutrients

    Milk thistle, dandelion, Alpha-Lipoic acid all support healthy liver function and the safe detoxification and clearance of excess estrogens.

    Methylation support

    As explained previously, certain MTHFR mutations compromise the methylation cycle, leading to hormone imbalances – as is the case in estrogen dominance. MTHFR and COMT mutations can reduce methylation activity and result in the accumulation of harmful estrogens.


    To ensure efficient methylation in the body, supplementation with L-Methylfolate is highly recommended.


    A comprehensive methylfolate supplement can go a long way in supporting proper liver detoxification and the methylation processes involved in repairing DNA, turning genes on and off, estrogen clearance, and getting around the MTHFR gene mutation.


    Methyl-Life’s™ Methylated Multivitamin is a delicious Chocolate Raspberry chewable multi that contains many of the nutrients required for optimal methylation in the body.


    Methyl-Life’s™ Methylated Multivitamin contains the purest L-Methylfolate available: Magnafolate® PRO. This form of L-Methylfolate the closest to the pharmaceutical version of methylfolate and has been tested as three times purer in a recent study. 


    This research-based formulation includes methylfolate and hydroxocobalamin to promote your body’s production of glutathione, your most powerful antioxidant.

    This special formula helps to support healthy hormonal balance and methylation processes by:

    • Supplying L-Methylfolate (active B9) and active B12 (as well-tolerated hydroxocobalamin)
    • Supporting energy and healthy detoxification with other active B vitamins and methylation cofactors
    • Boosting serotonin, an important neurotransmitter
    • Reducing harmful homocysteine levels in the body
    • Supporting fertility, pregnancy and fetal health
    • Helping repair the myelin sheath for nerve health


    Methyl-Life’s™ Methylated Multivitamin promotes energy production with a host of B vitamins and their cofactors, TRAACS® minerals, Vitamins A, D3, E, and bioactive K2. It also contains a new ATP energy formula (Panmol® NADH + MicroActive® CoQ10).


    It includes TMG for lowering homocysteine levels in the body, and a specialized, soy-free form of choline that crosses the blood-brain barrier (Citicoline) for improved cognitive health. Soy-free Phosphatidylserine which contains essential phospholipids also supports cognitive function.


    The Chewable Methylated Multi can be taken along with other Methyl-Life™ products containing methylfolate as a means of increasing your daily nutrition intake.

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    References

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    Katie Stone - Naturopath

    About the Author

    Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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