The link between estrogen and uterine cancer is significant and well-established. While estrogen itself is not “bad” and we need it for many reasons, when it is out of balance, bad things can happen like cancer. Estrogen encourages cell growth and division. When estrogen is chronically elevated, or not properly balanced by progesterone, it can create a hormonal environment that increases the risk for uterine cancer and cancer recurrence.
Uterine cancer, often called endometrial cancer, is hormonally sensitive in most women, meaning it is fueled by estrogen. Therefore, lowering estrogen levels after surgery can be crucial for preventing recurrence.
Many pathologists will check for estrogen receptor positivity on your biopsy sample. You should know what your result is. Approximately 70-80% of women diagnosed with endometrial cancer will be estrogen receptor positive.
Type 1 endometrial cancer (grades 1 and 2) is the most common type, accounting for approximately 80-85% of all uterine cancers. Type 1 tumors are highly estrogen receptor positive (80-90+%). These cancers are more likely to respond to therapies that block hormones.
Type 2 endometrial cancer (serous cell, clear cell, grade 3 endometrial and carcinosarcomas) are less common and only about 10-20% of these tumors are estrogen receptor positive.
Targeted drugs like aromatase inhibitors, progestins and selective estrogen receptor modulators (tamoxifen) all carry undesirable side effects and have mixed results when it comes to preventing cancer recurrence. Therefore, we want to try to lower estrogen levels naturally to minimize side effects and long-term damage to our bodies.
ESTROGEN IN POST-MENOPAUSAL WOMEN
Most of us have undergone a radical hysterectomy after being diagnosed with uterine cancer. You would think without ovaries we would not produce estrogen anymore, but that is not the case. After menopause, estrogen is still produced and even small increases in estrogen levels can have significant effects.
The adrenal glands produce androgens (male hormones), primarily androstenedione, testosterone and dehydroepiandrosterone (DHEA). These androgens can be converted into estrogens in other tissues.
To convert androgens to estrogens, a key enzyme is involved called aromatase. This conversion occurs in various tissues including fat, muscle, skin and even the brain. However, the most significant site of this process is in fat tissue.
Once estrogen is produced, the liver is the primary site for estrogen metabolism. It converts estrogens into various metabolites. This process involves hydroxylation and conjugation, which makes estrogens water-soluble. Conjugation, particularly with glucuronic acid, is essential for excretion of the estrogens.
Some of the water-soluble estrogens are excreted through the kidneys in urine, which is why estrogen levels can be measured in urine.
Some of the estrogen metabolites are excreted into the bile, which then passes into the intestines. Within the gut is a collection of bacteria that metabolize estrogens, called the estrobolome. However, certain bacteria produce an enzyme called beta-glucuronidase. This enzyme deconjugates estrogens, allowing them to be reabsorbed back into the bloodstream instead of being excreted. This recirculation can raise estrogen levels.
WHAT CAUSES ELEVATED ESTROGEN LEVELS?
YOU’RE MAKING TOO MUCH
Fat tissue is the major site of peripheral estrogen production. The enzyme aromatase, present in the fat tissues, converts androgens from the adrenal glands into estrogens. Therefore, increased body fat leads to increased aromatase activity and higher estrogen levels. It’s also a vicious cycle. The more estrogen you have, the more it stimulates fat deposition and weight gain! Insulin resistance can also lead to increased aromatase activity and more estrogen production and many women who are obese have insulin resistance.
YOU’RE BEING OVERLY EXPOSED TO IT
Unfortunately, our exposure to estrogen today is significantly higher than it was in the past due to xenoestrogens, environmental toxins, pharmaceuticals and dietary factors that were far less common in previous generations.
Xenoestrogens
Xenoestrogens are man-made chemicals that act like estrogen in the body. They interfere with our hormonal signals by either blocking or mimicking our natural hormones. Often called endocrine disruptors, these chemicals can have serious health consequences including cancer growth.
Exogenous Estrogens
These come from hormone replacement therapy, a direct source of estrogens.
Phytoestrogens
These are plant compounds that can have estrogen-like effects by binding to estrogen receptors. Foods that are high in phytoestrogens include, flaxseeds, soybeans and soy products, grains, legumes, dried fruits, berries and cruciferous vegetables. There is some controversy around the role of phytoestrogens in hormonally driven cancers, more on this later.
YOU MAY NOT BE METABOLIZING AND EXCRETING IT PROPERLY
Gut Microbiome Imbalance (Dysbiosis)
As I mentioned earlier, the estrobolome plays a very important role in estrogen metabolism and excretion. Dysbiosis can disrupt the balance of certain bacteria and lead to increased reabsorption of estrogens from the gut back into the bloodstream.
Liver Function
If the liver is not functioning optimally, it may not be able to metabolize and eliminate estrogen as efficiently, leading to higher circulating levels.
STRESS CAN IMPACT ESTROGEN LEVELS
Progesterone is the main hormone that balances estrogen. Progesterone opposes the proliferative effects of estrogen by calming tissue growth, supporting proper cell differentiation and preventing excessive cell division. Without progesterone, even small amounts of estrogen can lead to “estrogen dominance” in the body.
The ovaries are the main source of progesterone production. After a radical hysterectomy, progesterone levels drop significantly. Unlike estrogen, progesterone is not produced in fat tissue. The adrenal glands produce progesterone from a precursor hormone that makes both progesterone and cortisol. When there is stress, the body prioritizes the production of cortisol over progesterone, leading to even lower levels.
CARCINOGENIC EFFECTS OF ESTROGEN
Estrogen, in excess, can become carcinogenic in the following ways.
- Estrogen stimulates uncontrolled cellular proliferation
- It opposes progesterone and disrupts thyroid function
- Estrogen metabolites can damage DNA
- It deprives tissues of oxygen
- Estrogen disrupts metabolic processes and mitochondrial function in healthy cells
- It increases prostaglandins, which cause pain and inflammation
- Estrogen disrupts immune function
- It promotes fat storage, which increases its own production
TESTING HORMONE LEVELS
Hormone testing is commonly done with a blood or saliva sample. However, these standard tests only measure estrogen circulating in the blood so it’s possible to have high estrogen in the body, but get a normal or even low reading. They are also only a single point in time and hormones fluctuate throughout the day, another reason for inaccuracy.
The most accurate and comprehensive test you can get is called the Dutch Test. This stands for dried urine test for comprehensive hormones.
This test measures estrogen, progesterone, testosterone, cortisol, DHEA, dopamine, melatonin and more. You collect multiple urine samples throughout the day, making this a much more accurate test and easy to do.
This comprehensive test gives a detailed picture of how much you are producing, how you are detoxing the different metabolites, how you are responding to stress and so much more. Unfortunately, this test is not commonly done by regular doctors, some of whom have never heard of it. You can order the test yourself, but it is best to have a naturopathic doctor to help you interpret it and develop a treatment plan based on your results.
NATURAL WAYS TO LOWER ESTROGEN
Lowering estrogen naturally can be done in several ways.
DIINDOLYLMETHANE (DIM)
DIM is a phytochemical found in cruciferous vegetables like broccoli, cauliflower and cabbage. These vegetables contain a substance called indole-3 carbinol, which is converted to DIM in the stomach. DIM primarily works not by blocking estrogen receptors, but by influencing estrogen metabolism.
Modulation of Estrogen Metabolism
Estrogen, once produced undergoes several metabolic transformations in the liver. These pathways lead to the formation of different estrogen metabolites, some of which are considered more beneficial (“good” estrogens) and others that are potentially harmful (“bad” estrogens).
The two main metabolites are:
2-hydroxyestrone (2-OHE1): This “good” metabolite is considered less potent and may have protective effects against hormone-sensitive cancers.
16⍺-hydroxyestrone (16⍺-OHE1): This “bad” metabolite is more potent and has been linked to an increased risk of some hormone-sensitive cancers due to its stronger estrogenic effects and potential to promote cancer cell proliferation.
DIM promotes the conversion of estrogen towards the “good” metabolite, 2-OHE1 pathway and reduces the production of the “bad” 16⍺-OHE1 metabolite. This shift in the ratio of 2-OHE1 to 16⍺-OHE1 is beneficial for maintaining a healthier estrogen balance.
Influence on Cytochrome P450 Enzymes
The conversion of estrogen to its different metabolites is done by a family of liver enzymes called cytochrome P450 (CYP enzymes). DIM can influence certain CYP enzymes, which can alter the rate of estrogen metabolism in the liver. In this way, DIM indirectly affects the levels of circulating estrogen and the balance of its metabolites.
HOW TO TAKE DIM
You would have to eat about 2 1/2 pounds of cruciferous vegetables per day just to get 25mg of DIM. Any form of cooking these vegetables reduces the absorption of DIM in the body.
It is better to take DIM as a supplement directly instead of Indole-3 Carbinol (IC3). IC3 is much less bioavailable and has to be converted to DIM in the stomach to have any effect.
A common dose for DIM supplementation is 100mg – 300mg daily.
CHRYSIN
Chrysin is a flavonoid that is found in passionflower, honey and bee propolis. It acts as a natural aromatase inhibitor, which can block the conversion of testosterone into estrogen. There are oral and topical forms and the dose varies. The topical form may be better absorbed through the skin and is 100 – 300mg per day. Do some research into this or talk to your naturopathic doctor about the best way to use it. Read More
GRAPESEED EXTRACT
This is another natural supplement that can act as an aromatase inhibitor. Dosages range from 200mg to as high as 2000mg per day. Here is a phase 1 prevention trial in healthy post-menopausal women using grapeseed extract as a natural aromatase inhibitor for women at risk for breast cancer. Read More
ASHWAGANDA
Ashwaganda is an adaptogenic herb that has been used in Ayurvedic medicine for centuries. There is some evidence showing it exerts a balancing effect on the endocrine system to reduce the amount of estrogen in the body by inhibiting aromatase. It is also anti-inflammatory, anti-oxidant and reduces stress, all of which can help prevent estrogen dominance. A typical dose is 250-500mg per day. Do not take this if you have hyperthyroidism. Read More
WEIGHT LOSS
If you are overweight or obese, this is probably the number one way to reduce estrogen levels in your body.
Adipose tissue is a major site of estrogen production and higher body weight is often associated with higher circulating levels of estrogen.
Being overweight or obese can be an indicator of insulin resistance and metabolic syndrome. Insulin resistance can lead to increased aromatase activity, which converts androgens into estrogens. It also lowers levels of sex hormone binding globulin. This is a protein that binds to estrogen reducing its level in the bloodstream. By losing weight, you will improve insulin sensitivity and lower estrogen levels.
EXERCISE
Exercise can have a big impact when it comes to lowering estrogen and balancing hormones. It improves insulin sensitivity and helps with weight loss and reducing body fat.
In this study of healthy young adult women, they found that aerobic exercise improved the ratio of 2 OHE1 to 16⍺-OHE1, similar to what DIM does. They concluded that exercise led to favorable changes in estrogen metabolism, which would explain how it lowers the risk of breast cancer. Read More
HEALTHY DIET
Dietary choices can significantly influence estrogen metabolism and excretion.
More than 3000 preservatives, flavorings, colors and other ingredients are added to food in the United States, and none of them are required to undergo testing for estrogenic activity. Some studies however, have shown that some of these additives could be endocrine disruptors or estrogen mimicking substances and are most often found in processed foods. Low doses of these chemicals can lead to significant changes.
The best way to avoid problems is to eat real, whole foods and stay away from processed, packaged and ultra-processed foods. If it has a label with lots of ingredients, you don’t want it. You also want to avoid sugar and sugar in all its forms is added to everything that is packaged and processed. A healthy ketogenic diet with fresh organic meats, eggs, low-carbohydrate vegetables and leafy greens, nuts, seeds water, tea or coffee is best.
AVOID ALCOHOL
The liver is the main organ responsible for metabolizing estrogen. When you consume alcohol, the liver has to prioritize processing the alcohol, which can interfere with its ability to metabolize estrogen. Also, alcohol may influence the activity of the CYP enzymes involved in estrogen synthesis. Studies have shown that women who consume alcohol tend to have higher estrogen levels compared to non-drinkers even with moderate alcohol consumption. Read More
REDUCE EXPOSURE TO XENOESTROGENS
Xenoestrogens are a big cause of elevated estrogen levels. Unfortunately, xenoestrogens are hidden all around us. They are in our water, soil, air, household building materials, food, personal care products, cleaning products and even store receipts!
- Researchers in Germany found traces of an unknown estrogenic substance leaching into mineral water stored in a commonly used plastic for water bottles.
- In another example, scientists tested 20 brands of mineral water and found that 60% of the samples tested positive for estrogenic substances.
- BPA (bisphenyl A) is a known endocrine disruptor and is found in plastic food storage containers and water bottles.
- Propyl gallate is another example. This is a preservative used to prevent fats and oils from spoiling that can be found in a wide range of foods, including baked goods, shortening, dried meats, mayonnaise and candy. You will not see this listed in the ingredients as it is a GRAS substance (generally recognized as safe).
With xenoestrogens all around us, how do we avoid them? Here are ways to reduce your exposure.
- Filter your water
- Eat wild-caught and organic foods
- Filter the air in your home
- Eat real whole food and not packaged, processed food
- Eliminate plastic
- Ditch non-stick cookware, use stainless steel instead
- Get rid of scented products (candles, air fresheners, perfume)
- Avoid or minimize touching store receipts
- Use natural fiber clothing, bedding and furniture in your home as much as possible. Avoid stain-resistant fabrics, carpet and upholstery
- Choose safe cosmetics and personal care products that do not contain endocrine disruptors (phthalates, parabens)
- Use vinegar, water and baking soda for cleaning and avoid toxic household products that contain a long list of chemicals
- Avoid using pesticides or herbicides
AVOID THE USE OF HORMONES
It’s best to avoid any hormone replacement therapy with exogenous estrogens. Progestins are synthetic hormones and their actions more closely mimic estrogen/androgens on the cell. They are not the same as natural progesterone.
SUPPORT YOUR GUT AND LIVER HEALTH
Your gut and liver are crucial for metabolizing and excreting excess estrogen. Therefore it is important that you take measures to improve gut health and liver function.
MILK THISTLE
Milk thistle or silymarin is a potent anti-oxidant. It helps protect the liver from damage caused by free radicals, which are unstable molecules produced during the body’s normal metabolism and exposure to toxins. The liver is exposed to a lot of toxins and free radicals and silymarin helps neutralize them.
Some studies suggest silymarin can promote regeneration of liver cells by enhancing protein synthesis. It can also prevent toxins from binding to liver cells by altering the structure of the outer cell membrane.
Look for the content of silymarin in any milk thistle products. The higher the silymarin the better, as this is the active component.
Dosing ranges from 200-600 mg per day divided into 2-3 doses.
PROBIOTICS
Probiotics can support the estrobolome, the gut bacteria that help with the excretion of excess estrogen. They can also reduce the bacteria that produce beta-glucuronidase, which leads to estrogen being recirculated in the blood. Beneficial bacteria that help with this include Lactobacillus rhamnosus, Lactobacillus reuteri and Bifidobacteria longum species.
WHAT ABOUT PHYTOESTROGENS?
There is some controversy around phytoestrogens. Phytoestrogens are plant-derived compounds that have a chemical structure similar to estrogen. They can bind to estrogen receptors in the body, exerting weak estrogenic or anti-estrogenic effects. Some research suggests that they may be beneficial by binding to estrogen receptors and blocking estrogen. Other studies suggest that they may increase the risks of hormonally driven cancers.
After reviewing several of these studies, the bottom line is that phytoestrogens from common foods like cruciferous vegetables, berries and flaxseeds is likely not a risk factor for uterine cancer. Moderation is key here. High-dose supplementation with phytoestrogens and/or excessive consumption of soy products or grains is not recommended. Read More
The same Lord is Lord of all and richly blesses all who call on Him. ~ Romans 10:12