Are Phytoestrogens Good or Bad for Endometriosis?

A few months ago I asked my Facebook group to tell me what supplements they use to help them improve their endometriosis. I’ve sometimes seen women using herbs that might not be appropriate for their situation (e.g. black cohosh or red clover), and I had in mind that I’d review each herb for their potential estrogenic-activity, then present it in a handy-dandy chart for easy reference. However, my question produced an astonishing list of sixty-three different herbs in response. (I wondered, did I bite off more than I could chew?) And that was just the herbs. This didn’t include vitamins, minerals and a variety of enzymes, too. In the meantime, several women brought up the hotly-debated question: are phytoestrogens good or bad for endometriosis?

Some people are adamant that they are. Others avoid any kind of estrogen like it’s the next coronavirus. But what if I told you the answer was “both, and”? As I will explain below, it’s just too complex to make a blanket statement that phytoestrogens as a whole are either good or bad for endometriosis. It depends on so many factors. That’s why I wanted to make that handy-dandy chart, and I promise I will finish it one of these days—I’m about a third of the way through researching each herb. But first, I thought it would be better to get a basic understanding of phytoestrogens and how they work.

What is estrogen?

As you probably know, estrogen is a sex hormone known for its role in the female reproductive system. Its produced primarily in the ovaries during the first half of your cycle, although it can be produced in smaller amounts in tissues outside the ovaries, such as the liver, pancreas, adrenal glands, adipose tissue, and breast (as well as testes in men). There are several different forms of estrogen, with estradiol being the main estrogen circulating in humans. Meanwhile, estriol and estretrol are found more during pregnancy, and estrone is usually associated with menopause.

As you also probably know, estrogen is what builds up the lining of the uterus, the endometrium, in preparation for egg implantation—important for endometriosis sufferers. But aside from its role in the female reproductive system, estrogen also helps maintain bone density, has a protective effect on the heart and blood vessels, and has a positive affect on mood, cognitive ability, and pain perception. It also maintains the health and appearance of your skin. Estrogen gives you that healthy glow and makes you feel happy and sexy, attracting your partner to you in the first half of your cycle. (So you guys can fertilize that egg).

So let’s get one thing straight, my endo friends. We *need* estrogen! Yes, estrogen also leads to proliferation of endometrial lesions in endometriosis, and this is where it gets its bad rap from. BUT we still need a normal amount of circulating estrogen for proper functioning. So before you go crazy in trying to avoid estrogen completely (which is close to impossible), you might want to get your hormone levels checked. If you are estrogen dominant and you have endo symptoms, then by all means, reduce your exposure to xenoestrogens such as plastics and pesticides, rethink your need for hormonal birth control and eliminate dairy. Also consume dandelion root tea to help your liver break down excess estrogen, and magnesium to help move it through your system. As for what to do about phyto-estrogens, read on.

What are phytoestrogens?

Phytoestrogens are chemical compounds found in plants that are structurally similar to the estrogen found in humans (and other mammals). This is important. They are “structurally” similar, but that doesn’t mean they always have an estrogenic effect on the body. More on that in a minute.

Phytoestrogens have all kinds of non-hormonal benefits such as anti-inflammatory and anti-oxidant activity, but in others instances, they’ve been recognized as endocrine disruptors—chemicals either natural or man-made that “mimic or interfere with the body’s hormones.” For women with endometriosis, an estrogen-dependent disease, this is important to take note of.

There are hundreds of types of phytoestrogens, from reservatrol to flavones and so many more that haven’t been studied in much detail or perhaps even identified yet. Given this large variety, its a wonder everyone places them all under the same catch-all name. Not all phytoestrogens are created equal. Nor do they all act the same way.

Lignans are “the most prevalent phytoestrogens in the diet”¹ and are found in many fiber-rich foods such as berries, nuts and whole grains. Flaxseeds are particularly high in lignans.

Coumestans are another type of phytoestrogen and are found in legumes such as alfalfa and clover. This phytoestrogen first received attention in the 1940’s when it was found that female sheep grazing on clover-dominant pastures had high rates of infertility, still-borns, uterine prolapse and “the frequent occurrence of a cystic endometrium.”² It was eventually discovered that the coumestrol in the clover was having an estrogenic effect on the ewes.

Of all the phytoestrogens, isoflavones are probably the most studied. That’s because they’re found in high amounts in soybeans and soy-based products, and there’s been a lot of interest in soy’s benefits to women in menopause, as well as their potential (and controversial) cancer-reducing effects. Isoflavones are also present in smaller amounts in other legumes, as well as wine, berries, grains, and nuts.

However even all isoflavones are not created equal. The isoflavones in soy are made up of glycitein, daidzein and genistein. Red clover also has isoflavones (in addition to the coumestans) and they’re made up of biochanin A, formononetin, and genistein (again). Each of these phytoestrogens can have different reactions in the body, and some of the forms are biologically inactive. The proportion of bioactive to inactive forms “varies substantially among foods,” and the amount of isoflavones in food can also vary by season.³

Add to all this, some phytoestrogens, such as genistein have higher “estrogenic potency” than others, such as biochanin A.¹ This is why, again, one can’t just say “phytoestrogens” are good or bad. We have to get more specific. Which phytoestrogen? Or really, considering that most plants are made up of more than one phytoestrogen, it would be better to ask, if [this specific plant] is good or bad for endometriosis. (Most of us aren’t consuming isolated phytoestrogens on their own.)

Much of what determines whether a plant is estrogenic or anti-estrogenic depends on its ability to bind with and modulate the activity of estrogen receptors.

What are estrogen receptors?

Estrogen functions by binding to specific receptors in cells. Much like a key to a lock, estrogen fits into its receptor and activates it, allowing it in most cases to bind directly to specific DNA sequences (called estrogen response elements). Sometimes it can also affect the DNA indirectly, through a series of signals sent between proteins. Either way, this binding leads to activation or blocking of the estrogen receptor, which ultimately leads to changes in gene expression and the physiological responses associated with that receptor.

There are two main Estrogen Receptors (ERs): ER alpha (ERα), and ER beta (ERβ). ERα and ERβ have different expression patterns and functions, and the balance between the two can affect the way estrogen acts in different tissues. Both are “markedly” expressed in the cardiovascular and central nervous systems, and share in the development and function of the ovaries. Meanwhile, ERα is predominantly expressed in the breast, uterus, and bones, and helps regulate metabolism and ERβ is more widely expressed in the immune system.⁴ However, the distribution of the receptors “can change over the lifespan,” likely causing their roles to change too.³

Because phytoestrogens are structurally similar to estrogen, as already mentioned, they, too can often bind to estrogen receptors, although usually with much lower affinities,⁵ Different phytoestrogens have affinities for binding to different estrogen receptors,⁶ and it appears most have a higher affinity for ERβ.¹

In case you missed it when I said it earlier, estrogen or estrogen-like compounds can block OR activate the estrogen receptor. This is important because proponents for the use of phytoestrogens tend to generalize and say that phytoestrogens block estrogen receptors, and thus are anti-estrogenic. (They also tend to generalize and lump all phytoestrogens together). This is not always the case. As we’ve seen, coumestans are definitely estrogenic in the reproductive tract. But both lignans and isoflavones have been shown to be both estrogenic AND anti-estrogenic at times. This is why many researchers liken phytoestrogens to selective estrogen receptor modulators (although maybe in a limited capacity).¹

What are Selective Estrogen Receptor Modulators?

The term “Selective Estrogen Receptor Modulator” (SERM) refers to a group of synthetic drugs designed to target estrogen receptors in specific (selective) tissues and either activate or block the receptors, depending on the tissue type and location. The most well known example is tamoxifen used to treat breast cancer. It acts as an antagonist (is anti-estrogenic) in the breast and agonist (estrogenic) in bone. This has made researchers hopeful about its use as an effective treatment for ER-positive breast cancer, without the risk of osteoporosis.⁷ However, unfortunately, tamoxifin can also be estrogenic in the uterus and “stimulate endometrial cell growth leading to uterine cancer.”⁸

The same kind of selective actions have been found in phytoestrogens. Brzezinski and Debi reviewed studies on the effects of genistein and daidzein on cancer, cardiovascular disease and osteoporosis and found them to be both estrogenic and anti-estrogenic “depending on the specific tissue and the concentrations of circulating endogenous estrogens.”⁹ However, while their review saw this selective modulation as a positive benefit of soy, they did find that “paradoxically, low concentrations of genistein stimulated cell growth.” Whether or not genistein is estrogenic or anti-estrogenic, depended on how much was consumed, how much estrogen was already present in the patient, what stage of life they were in and even what kind of tumor they had. This led the researchers to state that soy phytoestrogens present “SERM-like activity.”

So we have hundreds of different types of phytoestrogens and many more combinations of them, plus different estrogen receptors playing different roles in the body. Add to this, the fact that different phytoestrogens have different affinities for different receptors. And even the same phytoestrogen can act selectively, being either estrogenic or anti-estrogenic depending on certain factors.

Ultimately, whether or not phytoestrogens are beneficial or harmful depends on the phytoestrogen, in which part of the body it binds too, what function it performs, and the presence of other compounds in the plant that may interact with it. It also depends on the age, health status, current hormone levels and gut composition of the patient, as well as how many other phytoestrogens they’re consuming regularly.¹⁰

So how do we know which phytoestrogens are beneficial for endometriosis?

That being said, it’s not like we don’t know anything about phytoestrogens and their role in endometriosis—this blog post is just scratching at the surface of the research out there. We just have to get specific. (That’s why I’m working on that chart for you.) In the meantime, here are a few things we do know.

Avoid clover

(and high concentrations of coumestens). I already mentioned the horrifying effects of sheep eating too much clover, above. There have been many more studies corroborating its estrogenic activity.

Avoid soy

(and high concentrations of isoflavones). While soy has been touted as a possible remedy for menopause, breast cancer, and cardiovascular disease (and it isn’t wholly clear that it is)¹¹, it doesn’t mean it will also be anti-estrogenic in the uterus or the site of endometrial lesions.

The fact that it’s widely touted as beneficial for vasomotor symptoms of menopause (e.g. hot flashes, night sweats) should be a red flag, because menopause symptoms are usually associated with a decrease in circulating estrogen. Thus, it follows that soy is probably acting as an estrogen agonist. Anecdotally, many women in our group have felt relief (myself included) when eliminating soy from the diet. And Chandrareddy et al.¹² found the same in their case studies of three separate women, each suffering from abnormal uterine bleeding, endometriosis, and/or severe dysmenorrhea. “All three women improved after withdrawal of soy from their diet.”

Soy isoflavones have also been show to cause infertility and liver disease in captive cheetahs. Even more worrisome is that fetuses exposed to soy in the womb, as well as infants fed soy-formula have shown “malformations in the ovary, uterus, mammary gland and prostate, early puberty, reduced fertility, disrupted brain organization, and reproductive tract cancers,”³ specifically uterine cancer.¹³ Soy also contains goitrogens that can interfere with proper thyroid functioning.¹⁴ This is particularly important for women with autoimmune thyroid disease, a common co-morbidity in endometriosis. Patisaul and Jefferson³ list many more detrimental affects of soy, although they do point out that most Asians have a specific intestinal microbe that allows them to metabolize soy, which may explain why they don’t usually experience the same adverse effects.

If you’re concerned about isoflavones and coumestens in your diet, you can visit the USDA’s Database for the Isoflavone Content of Selected Foods here.

Do your research

As for the rest of the phytoestrogens out there, some can be beneficial for a variety of reasons, but not necessarily for direct effects on endometriosis. Personally, the only herb I took while healing from adenomyosis was dandelion, which is why I wrote an entire post about it. I won’t go into detail on the pros and cons here of each of the sixty-three herbs my Facebook members mentioned, but I will tell you how to go about finding out what works for you.

When deciding to add a new phytoestrogen (whether tea, supplement or food) to your diet, do your best to research it. See if you can determine if it has estrogenic and anti-estrogenic activities or is highly estrogenic only. Now that you know a phytoestrogen could act anti-estrogenic in the breast but still be estrogenic in the uterus, for instance, see if you can find out how it affects the reproductive tract, fertility, or the endometrium. (And hopefully my one-day chart will help with that).

If the papers in PubMed are too complicated to understand (and they most certainly can be at times!) or there simply isn’t much peer-reviewed research on the herb, take what we do know about it and extrapolate. For instance, black cohosh has been traditionally used to make missing periods reappear. So it’s a good chance you wouldn’t want to take it for a condition like adenomyosis. The same could be said of foods that help with menopause, such as with soy, as I mentioned above. And be careful with statements such as “supports the uterus,” as many say of raspberry leaf. What exactly does “support” mean? Estrogen also supports the uterus. (And several women in our group have had adverse reactions to raspberry leaf).

You can also ask for people’s experience in our Facebook group, and feel free to tag me as I already may know something about it.

But remember, what works for one woman may not work for you. Flax seeds, for instance, make me bleed mid-cycle. Other women, on the other hand, find flax seeds during the first half of their cycle are beneficial. If you’re an Asian woman, soy might actually be beneficial for you—or at the very least, not harmful. So in the end you still have to be your own scientist and keep track of your symptoms.

Don’t over-consume phytoestrogens

If you’ve found an herb with phytoestrogens that’s working for you, be careful about adding more phytoestrogens. They could bioaccumulate.¹⁵ And because the combination of herbs and foods you’re consuming has most likely not been studied in detail, we don’t know for sure what the effects of those different types of phytoestrogens in your body might be. If you do add another phytoestrogenic food to your diet, be sure to monitor your symptoms for a couple of weeks afterwards. And only add one herb at a time. How else can you be sure which herb is working for you, and which isn’t?

Know why you’re taking that herb

There may be other herbs that can perform the same function without being estrogenic. For instance dandelion is just as powerful at cleaning the liver as milk thistle, but may be less estrogenic. Lemon balm is good for anxiety but it affects the thyroid (again, acting as an endocrine disruptor), which can also affect women with endometriosis. So maybe another herb with non-hormonal action or magnesium might be a better bet for relaxation and pain relief.

Finally, the subject of phytoestrogens is vast and complex. I’ve tried to simplify it as much as possible here, but I wouldn’t be surprised if I missed something! If you have more questions, would like to add to this discussion, or share research you’ve come across, please feel free to comment below. There’s always more to learn about this subject! In the meantime, stay tuned for that handy-dandy chart. 😊

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References

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