Published August 22 2016
Many people with thyroid and autoimmune thyroid conditions have problems with estrogen metabolism. This can lead to many different problems, including thyroid nodules, weight gain, and different types of cancers. And so the primary goal of this article is to discuss how to modulate estrogen metabolism in a positive manner so that you will have a decreased risk of developing these and other health conditions.
Although the main goal of this article is to discuss how to modulate estrogen metabolism, I’d first like to explain why problems with estrogen metabolism occur in the first place. After all, it of course is important to address those factors which can lead to estrogen metabolism issues. After discussing this I will then cover some of the more common conditions which develop when there is an imbalance of estrogen metabolism. And finally, I will conclude this article by discussing seven things you can do to positively influence estrogen metabolism.
Understanding The Basics of Estrogen Metabolism
Before talking about some of the factors which can cause imbalances in estrogen metabolism, it probably is a good idea to briefly discuss some of the basic facts regarding estrogen. If this section gets a little too advanced for you then feel free to skip to the next section entitled “How Do Estrogen Metabolism Problems Develop?” There are three main types of estrogen, which includes estradiol, estrone, and estriol. Estradiol is considered to be the dominant estrogen, and it can be converted into estrone, and estrone in turn can convert into estradiol. Both of these hormones can convert into estriol, which is primarily produced during pregnancy by the placenta.
During premenopause, most estrogens are produced in the ovaries. In postmenopause, estrogen production from the ovaries greatly decreases, and most of the estrogen is produced through the aromatization of androgens (i.e. testosterone) in the fat cells, although this conversion can also take place in other tissues such as the skin and bone. Testosterone is converted into estradiol, while androstenedione is converted into estrone.
Estrogens bind to certain receptors, and there are two main types of estrogen receptors…estrogen alpha and estrogen beta. I’ll briefly talk about these receptors later in this article. Estradiol and estrone both lead to the formation of estrogen metabolites, which include 2-hydroxyestrone (2-OH), 4-hydroxyestrone (4-OH), and 16α-hydroxyestrone (16α -OH). These metabolites have different biological activity, as the 2-OH metabolite has weak estrogenic activity, and thus is labeled as being the “good” estrogen. On the other hand, the 4-OH and 16α-OH metabolites have a greater amount of estrogenic activity. These metabolites can be tested through the urine, and there is evidence that those with higher amounts of 4-OH and 16α-OH metabolites have an increased risk of developing certain types of cancers, although this is controversial.
The enzyme catechol-o-methyltransferase (COMT) is involved in the detoxification and excretion of estrogens. As a result, supporting detoxification/methylation can help with the elimination of estrogens. Not surprisingly, if someone has a genetic polymorphism of the COMT gene then this can affect the methylation of estrogens. In addition, certain cofactors are necessary to support the methylation of estrogen, including S-adenosylmethionine (SAMe) and magnesium. A process called glucuronidation is also involved in the detoxification of estrogen, and there is an enzyme called beta-glucuronidase that can prevent the excretion of estrogen and allow it to re-enter the circulation. Some stool panels test for this enzyme, and if someone has elevated levels of beta-glucuronidase then they will want to support the gut flora and increase their fiber intake. Calcium D-glucarate can also reduce beta-glucuronidase activity.
How Do Estrogen Metabolism Problems Develop?
There are numerous ways in which people develop problems with estrogen metabolism.
Poor diet. What you eat can affect estrogen metabolism. For example, eating a lot of nonorganic meat and dairy products over a prolonged period of time can affect estrogen metabolism. Also, eating a diet low in fiber and vegetables can have a negative effect on estrogen metabolism. As for how eating meat can affect estrogen metabolism, while non-organic cows are usually given bovine growth hormone, exogenous estrogen in the form of estradiol is also a factor (1) (2) (3). It’s important to understand that consuming dairy from cows not given hormones can also affect estrogen metabolism, and the reason for this is because most dairy cows continue to lactate throughout their entire pregnancy, which leads to large amounts of estrogen in the milk (4). One study showed that urine concentrations of estone, estradiol, and estriol were significantly increased in adults and children after drinking cow’s milk (4). Another study showed that organic and conventional dairy products had similar concentrations of estrone and estradiol (5).
On the other hand, eating a high fiber diet can have a positive effect on estrogen metabolism (6) (7). There is plenty of evidence which shows that eating cruciferous vegetables such as broccoli can have a positive effect on estrogen metabolism by increasing the ratio of 2-hydroxyestrone to 16-hydroxyestrone (8) (9) (10). Flaxseed can also have a positive effect on estrogen metabolism, which I discussed in an article entitled “The Truth About Soy, Flaxseed, And Other Phytoestrogens“. In this article I discussed some studies which showed that flaxseed can decrease the risk of developing hormone-dependent cancers, and can increase concentrations of 2-hydroxyestrone, which as I mentioned earlier, is considered to be the “good” estrogen metabolite.
In this article I also spoke about the two main types of estrogen receptors, which are estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). Of these two estrogen receptors, ERα is considered to be the “bad” estrogen receptor, whereas ERβ is the “good” estrogen receptor. And while most phytoestrogens bind to both ERα and ERβ, they seem to have a higher binding affinity for ERβ, whereas estradiol and estrone have higher binding affinities to ERα.
Xenoestrogens. There are many studies which show that xenoestrogens can have a negative effect on estrogen metabolism. Bisphenol A (BPA) is one of the xenoestrogens we’re commonly exposed to, and this is a known endocrine disruptor (11) (12) (13). Drinking out of BPA-free plastic bottles doesn’t necessary mean you aren’t being exposed to endocrine-disrupting chemicals, as bisphenol S (BPS) and bisphenol F (BPF) are two commonly used BPA substitutes which also have endocrine-disrupting effects (14) (15). And while many people realize that plastic water bottles are a big source of BPA, many aren’t aware that thermal paper receipts are a major source as well (16). Phthalates are another common xenoestrogen, and these can also affect estrogen metabolism (17) (18) (19).
Bioidentical hormones. Not surprisingly, taking bioidentical estrogen can affect estrogen metabolism. This is why you need to be very careful when taking hormones, even when they are bioidentical. Hormones are very powerful, and it’s not uncommon to see high estradiol levels in patients who are taking estradiol. Since saliva tests for the free form of the hormone this elevation of estradiol is more commonly seen with saliva testing, but I’ve also seen numerous patients with high levels of estradiol in the blood.
Oral contraceptives. Not all oral contraceptives include estrogen, as some only include progestin. Others include a combination of estrogen and progestin, and these can affect estrogen metabolism. One effect of oral contraceptives is that they can increase the incidence of gallbladder disease (20), and one factor could be that estrogen leads to bile that is thick and sluggish. A few studies also show that use of certain oral contraceptives is associated with a slight increase in breast cancer risk (21) (22), although this once again depends on the formulation. There is evidence that oral contraceptives can potentially reduce the risk of developing ovarian cancer (23).
Iodine deficiency. Although there is controversy over iodine and thyroid health, iodine has an anti-estrogenic effect, and therefore can play a role in preventing breast cancer (24) (25). One potential mechanism in which iodine/iodide can inhibit the effects of estrogen is by modulating the cytochrome P450 pathway (25), which plays a role in detoxification. This data shows that treatment with iodine and iodide increases the levels of cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1), which are two phase I estrogen metabolizing enzymes (24). I spoke about the cytochrome P450 enzymes in a blog post I wrote entitled “Understanding The Detoxification Pathways“. But what’s important to understand is that iodine can help with the detoxification of estrogens. So while some people don’t do well when taking iodine, an iodine deficiency can be problematic in some people, and correcting this iodine deficiency can benefit estrogen metabolism.
What Health Issues Can Estrogen Metabolism Imbalances Cause?
There are many different health conditions that can be caused by estrogen metabolism imbalances. Keep in mind that not everyone with a condition such as estrogen dominance will develop these conditions. But if you have one or more of the following conditions, there is a good chance that an estrogen imbalance is a factor.
Certain Types of Cancers. There are a number of different cancers that are dependent on estrogen. In other words, increased estrogen levels will increase the proliferation of cancer cells. Two of the most common estrogen-dependent cancers are breast cancer and prostate cancer (26) (27) (28). This doesn’t mean that all cases of breast and prostate cancer are dependent on estrogen, although approximately 70% of breast cancer cells are hormone dependent (29). This is why the drug Tamoxifen is frequently given to those with breast cancer, as it blocks the estrogen receptors. There are other types of estrogen-dependent cancers as well, such as endometrial and ovarian cancer. There is also evidence that some cases of thyroid cancer are caused by problems with estrogen metabolism (30) (31) (32).
Thyroid Nodules. Estrogen not only can increase the risk of thyroid cancer, but it can also increase the risk of developing thyroid nodules (33) (34). Thyroid nodules are four times more common in women than men and their frequency increases with age and low iodine intake (35) (36). And remember that I mentioned earlier how iodine plays a role in estrogen metabolism. As a result, having an iodine deficiency can greatly increase one’s risk of developing thyroid nodules.
Gallstones. Estrogen increases biliary cholesterol secretion, which in turn causes cholesterol supersaturation of bile (42) (43) (44). In other words, higher levels of estrogen can lead to bile that is thick and sluggish, which in turn can increase the risk of developing gallstones.
Weight Gain. Although having healthy levels of estrogen is important for the regulation of fat mass, fat deposition and differentiation, and fat cell metabolism (45), increased levels of estrogen can cause weight gain and a resulting increase in inflammation. As I mentioned earlier, adipose tissue is a source of estrogen biosynthesis, and is the main source of estrogen in postmenopausal women. In other words, the more fat tissue you have, the more circulating estrogens you will have, and this can lead to a vicious cycle of adipose tissue formation. Part of the problem is related to excessive aromatase activity, as adipose tissue is the greatest peripheral source of aromatase.
How To Modulate Estrogen Metabolism
There are a few different things you can do to modulate estrogen metabolism in a positive way, and I’m going to discuss seven of them here:
1. Decrease exposure to xenoestrogens and other exogenous estrogens. Of course you want to do everything you can to minimize your exposure to xenoestrogens. So where should you start? Well, the best place is in your home, as many household products and cosmetics include xenoestrogens, and so you want to make sure to use natural household products and cosmetics. Since bottled water is a source of xenoestrogens you want to minimize your consumption of bottled water. Pesticides and herbicides are sources of xenoestrogens, and while you won’t be able to completely eliminate your exposure to these chemicals, you can do things to reduce your exposure. With regards to dairy, I mentioned earlier how most dairy cows lactate during pregnancy, and so you will be exposed to estrogens in the dairy products you consume, even if the dairy is organic. And since conventional cows are sometimes given estradiol you also want to try to eat organic beef whenever you can.
2. Support detoxification and methylation. Supporting detoxification and methylation can help with the elmination of estrogens, which I’ve discussed in other articles and blog posts. Earlier in this article I also mentioned how increased activity of the enzyme beta-glucuronidase can prevent the excretion of estrogen, and thus doing things to help reduce beta-glucuronidase activity can help. This includes supporting the gut flora through prebiotics and probiotics, making sure you eat enough fiber, and taking calcium D-glucarate can also help.
3. Consume phytoestrogens. There is a great deal of controversy over phytoestrogens, which are compounds that have weak estrogenic or antiestrogenic activity. Flax and soy are two of the more well known foods which have phytoestrogens, but there are others as well. Phytoestrogens have the ability to bind to the estrogen receptors, and as a result are classified by some sources as being endocrine disruptors. However, as I mentioned earlier, it appears that phytoestrogens mostly bind to the estrogen receptor beta (ERβ), which is the “good” estrogen receptor. If you eat soy then you want to make sure it’s organic and fermented, but even if this is the case I think it’s a good idea to minimize your consumption of soy.
4. Supplement with Diindolylmethane (DIM). 3,3′-diindolylmethane (DIM) is derived from indole-3-carbinol, which is found in cruciferous vegetables. And numerous studies show that DIM can positively affect estrogen metabolism (46) (47) (48). While one can take a supplement that has DIM, I recommend getting most of the DIM from eating cruciferous vegetables.
5. Correct an Iodine Deficiency. As I mentioned earlier, iodine has an anti-estrogenic effect, and one can test for an iodine deficiency, and if iodine is deficient you will eventually want to correct this. However, while an iodine deficiency can have a negative effect on estrogen metabolism, not everyone does well on iodine. This is especially true with many people who have Hashimoto’s Thyroiditis. There is a lot of controversy surrounding iodine and thyroid health, and I’ll be releasing an updated blog post on iodine in the near future, and so before supplementing with iodine you might want to check this out.
7. Be cautious about taking bioidentical hormones and oral contraceptives. Since bioidentical estradiol and certain types of oral contraceptives affect estrogen metabolism, you want to be cautious about taking these. This doesn’t mean that there isn’t a time and place for hormone replacement or oral contraceptives. However, with regards to hormone deficiencies, the goal should be to address the cause of the hormone imbalance whenever possible. And if someone needs to be on bioidentical estradiol they should be tested first, and then monitored on a regular basis. In addition, those with a family history of breast cancer might want to consider testing the urinary estrogen metabolites I discussed earlier (2-OH, 4-OH, 16α-OH).
Too Much Estrogen Isn’t A Good Thing, But…
Although this article mainly focuses on the problems associated with excess estrogen, it’s important to understand that estrogen isn’t inherently bad. In fact, while too much estrogen can cause a lot of health issues, too little estrogen isn’t a good thing. For example, while there is evidence that xenoestrogens can trigger autoimmunity (52), the natural estrogen in your body can have a positive effect on immune system health (53), and also seems to have a protective effect against cardiovascular disease (54). And it’s well known that low levels of estrogen can lead to unpleasant symptoms such as hot flashes. So just like any other hormone, estrogen is important, but elevated or depressed levels of estrogen can be problematic.
In summary, it’s common for people with thyroid and autoimmune thyroid conditions to have estrogen metabolism imbalances. Some of the reasons why these imbalances in estrogen metabolism occur include poor diet, exposure to xenoestrogens, taking bioidentical hormones, and having an iodine deficiency. Estrogen metabolism imbalances can cause numerous health conditions, including certain types of cancer, thyroid nodules, fibrocystic breasts, uterine fibroids, endometriosis, metabolic inflammation, and gallstones. In order to modulate estrogen metabolism in a positive manner you want to decrease your exposure to xenoestrogens, minimize your consumption of dairy and non-organic meat, exercise regularly, correct an iodine deficiency, be cautious about taking bioidentical hormones, and consider consuming phytoestrogens and/or Diindolylmethane. And remember that supporting detoxification and methylation will also help with estrogen metabolism, as well as doing things to reduce beta-glucuronidase activity. While elevated levels of estrogen can be problematic, having normal levels of estrogen is important for optimal health.