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The Gut–Hormone Connection: How Gut Microbes Influence Estrogen Levels

on November 15, 2017

by Chris Kresser

Emerging research indicates that the gut microbiome plays a central role in the regulation of estrogen levels within the body and thus influences the risk of developing estrogen-related diseases such as endometriosis, polycystic ovary syndrome, breast cancer, and prostate cancer. Read on to learn about the connection between gut microbes and estrogen levels and why correcting dysbiosis may be key for preventing and reversing estrogen-related conditions.


Gut microbes regulate estrogen

Scientific research has demonstrated that gut microbes regulate many aspects of human physiology, including intestinal permeability, the absorption of nutrients from food, and immunity. However, recent studies suggest that gut microbes play another crucial role in the human body by regulating circulating estrogen levels. 

The estrobolome is the collection of microbes capable of metabolizing estrogens. (1) The estrobolome modulates the enterohepatic circulation of estrogens and affects circulating and excreted estrogen levels. Microbes in the estrobolome produce beta-glucuronidase, an enzyme that deconjugates estrogens into their active forms. Beta-glucuronidase activity produces active, unbound estrogen that is capable of binding to estrogen receptors and influencing estrogen-dependent physiological processes.

Could balancing the microbiome be a new way to treat estrogen-related diseases?

When the gut microbiome is healthy, the estrobolome produces just the right amount of beta-glucuronidase to maintain estrogen homeostasis. However, when gut dysbiosis is present, beta-glucuronidase activity may be altered. This produces either a deficiency or an excess of free estrogen, thus promoting the development of estrogen-related pathologies. (2)

Estrogen plays many vital roles in the human body. It regulates body fat deposition and adipocyte differentiation, female reproductive function, cardiovascular health, bone turnover, and cell replication. Gut dysbiosis has the potential to alter the estrobolome, disrupt estrogen homeostasis, and impair these processes, promoting the development of chronic diseases.

Obesity, cardiovascular disease, and osteoporosis

In postmenopausal women, estrobolome disruption is associated with an increased risk of obesity, cardiovascular disease, and osteoporosis. Estrogens regulate glucose and lipid metabolism, adipocyte differentiation, bone formation, and the inflammatory response in atherosclerosis. Research indicates that the normal reductions in estrogen that occur at menopause impair these estrogen-dependent processes, triggering obesity, cardiovascular disease, and osteoporosis. (3, 4, 5, 6)

Gut dysbiosis resulting in decreased beta-glucuronidase activity may exacerbate the low-estrogen state in postmenopausal women, further increasing the risk of these chronic diseases. (7) Indeed, a high prevalence of gut dysbiosis has been observed in obese patients and those with cardiovascular disease and osteoporosis. (8, 9, 10) Taken together, this research suggests that an important relationship exists between the estrobolome, estrogen deficiency, and the incidence of obesity, cardiovascular disease, and osteoporosis.

Endometriosis

Endometriosis, an estrogen-driven condition characterized by the growth of endometrial tissue outside the uterus, has been associated with gut dysbiosis. (11) The estrobolome of women with endometriosis may have larger numbers of beta-glucuronidase-producing bacteria, leading to increased levels of circulating estrogen, which drives endometriosis. Dysbiosis of the vagina and endometrium, including a decrease in Lactobacilli and an increase in pathogenic gram-negative bacteria, has also been detected in women with endometriosis and may further contribute to hormonal imbalance. These findings indicate that perhaps the term “estrobolome” should be expanded to encompass microbes in both the gut and the female reproductive tract. (12, 13)

PCOS

Polycystic ovary syndrome (PCOS) may also be influenced by estrobolome disruption. Women with PCOS have an excess of androgens in relation to estrogen, as well as an altered gut microbiota. Researchers theorize that the altered gut microbiota in PCOS women may promote increased androgen biosynthesis and decreased estrogen levels through lowered beta-glucuronidase activity. (14, 15) Interestingly, modulation of the gut microbiota with fecal microbiota transplantation (FMT) has been found to improve estrous cycles and decrease androgen biosynthesis in an animal model of PCOS, indicating that modulation of the estrobolome may be beneficial in the treatment of PCOS. (16)

Breast, endometrial, cervical, and ovarian cancer

In recent years, an abundance of research has emerged linking dysbiosis of the gut microbiota to various forms of cancer. Researchers have discovered that cancer patients have a significantly altered gut microbiota compared to healthy controls, as well as imbalances in the microbiota of tissues such as the breast and endometrium. The altered gut microbiota of cancer patients may lead to increased beta-glucuronidase activity and increased levels of circulating estrogen, which binds to estrogen receptors and promotes cell proliferation in estrogen-sensitive tissues. (17) The microbial milieu of the gut may also affect the microbiome of distant estrogen-sensitive tissues, such as the breast, through direct transference of microbes; in one fascinating example of this phenomenon, probiotic Lactobacilli ingested by women were found to reach breast tissue, where they exert anticarcinogenic effects. (18) Clearly, an intricate relationship exists between the estrobolome, estrogen levels, estrogen-sensitive tissues, and cancer.

Prostate cancer

Dysbiosis of the prostate gland has been associated with prostate cancer, and despite a current lack of studies on the topic, researchers hypothesize that the gastrointestinal microbiota may also be markedly different in men with this disease. (19, 20) Furthermore, elevated estrogen levels have been implicated in the development of prostate cancer, providing further support for the hypothesis that the estrobolome plays an important role in prostate cancer development. (21)

What factors disrupt the estrobolome?

Diet and lifestyle factors that are commonly known to disrupt the gut microbiome also have the potential to disrupt the estrobolome. Antibiotics and hormonal contraceptives have been found to alter both the gut microbiota and estrogen levels within the body, suggesting that they may have an adverse impact on the estrobolome. (22, 23)

Diet is another important factor that may affect the estrobolome. A large body of research demonstrates that diet significantly impacts the gut microbiota; considering that the estrobolome is part of the overall microbiota, it is also likely to be affected by the foods we choose to consume. Notably, the consumption of phytoestrogens in foods has been found to significantly impact the gut microbiota and the risk of estrogen-related diseases. Phytoestrogens can be estrogenic or antiestrogenic and can, therefore, have either a protective or causative effect on the development of cancer and chronic diseases. (24) The estrobolome may be the key mediator determining the effects of phytoestrogens on endogenous estrogen levels. (25)

Could balancing the microbiome be a new way to treat estrogen-related diseases? #womenshealth #microbiome

Probiotics can restore a healthy estrogen balance

Research indicates that it may be possible to modulate the estrobolome and reverse estrogen-related pathologies through probiotic supplementation.

  • Supplementation with a broad-spectrum Lactobacillus probiotic has been found to normalize the estrous cycle and decrease testosterone biosynthesis in an animal model of PCOS. (26)
  • In an animal model of endometriosis, Lactobacillus gasseri suppressed ectopic tissue growth, which is an estrogen-driven process. (27)
  • In a menopausal mouse model of osteoporosis, Lactobacillus reuteri prevented bone loss resulting from low estrogen. (28)
  • Lactobacilli have anticarcinogenic effects in breast tissue, suggesting that supplementation may be useful for the prevention of breast cancer. (29)

While research on the relationship between probiotic supplementation and the estrobolome is still in its infancy, this shouldn’t stop practitioners from recommending probiotics to their patients with estrogen-related conditions. Reversing dysbiosis appears to be key for modulating the estrobolome, and probiotic supplementation is a relatively simple and inexpensive way to accomplish this. Practitioners may just find that probiotics have been the missing tool in their toolbox for treating estrogen-related conditions!

Now I want to hear from you. Have you observed an association between gut dysbiosis and estrogen-related conditions in your patients? Have you ever used probiotic therapies for treating estrogen-related disorders? Let me know in the comments below.

28 Comments

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  1. I was diagnosed with endometriosis many years ago in my early 30’s and had TERRIBLE menstrual cramps (along with many other symptoms that at the time I did not know was related but was indeed such as headaches, eczema). During my worst days of my cycle it would not be uncommon to take 10 OTC pain pills per day. We also tried prescription pain meds which did not solve the problem. [As an aside, not even once did my physician ever mention diet or lifestyle changes that could be helpful.] In my early 40’s, our family went AIP/Paleo and my painful cramps (along with the other related symptoms) ceased by my first cycle and have remained under control without the use of any prescription pain meds (zero/nada/zilch). Unfortunately, by the time I learned about these lifestyle changes and got my endometriosis under control I was past the “safe” age for getting pregnant. I wish I had known 10 yrs ago what I know now. Hopefully this will help others. Chris — Thank You for the amazing work you do and for this article.

  2. Chris, I’m a personal trainer and group exercise leader, and after listening to a Robb Wolf podcast talk with you, I hope soon to be a health coach as well. But, with this article, I have to wonder if there is more I can do for my clients, especially my female clients, with respect to gut health.

    Is there a simple list of things I can give to my clients to take to their doctor to check for and measure with regard to relevant gut hormone levels that we can then begin to address before it causes more serious issues?

    Being a guy, I’m just not as well versed in female health as I’d like to be but I also realize that diet plays a huge role in general health as well as has an impact on hormones. Thanks. -ts

  3. Specifically what lab tests do you order for SIBO,parasites,fungal overgrowth and levels fo beneficial gut bacteria. Do 3rd party payor’s pay for the tests and if not what is the cost to the patient? In the clinical situations described above, what percentage of time do the lab results end up being usefull in your clinical action plan?

    Thank you for your response.
    Sincerely, Eliseo Perez M.D.
    P.S. i am enjoying your new book!

  4. I’m at my first IFM meeting as I write. Saw a lecture on that subject this week. I find it interesting. I have a PCOS pt I have been treating and picked up a specimen collection kit with this pt in mind and will try a Functional approach to treating this pt and see what happens. She has had a botch gastric bypass as well. I’m looking forward to see how she does with the different treatment.

    P.S. I got a copy of your book 3 days before the IFM conference and I have been reading it while trying to cover all the new material from the conference. Just finished Chapter 11.

  5. I suspect micro biome imbalances are at the root of my ME/CFS, inflammatory polyarthropathy, and now I wonder about my recent peri menopausal weight gain. I’m on a broad spectrum probiotic (Garden of Life Women’s formula), but I wonder about adding a probiotic with specifically lactobacilli. Are there certain brands you could recommend? Thanks!

  6. Why are their only animal studies on this subject? Surely this is an easy thing to study in human subjects? When there are conclusive studies done on humans, I may be more inclined to believe the results.

  7. I am not a practitioner. However, I can say 100% that I was not surprised to see this article, because this has been my exact experience as a patient – I have suffered from both oestrogen dominance and gut dysbiosis for many years – and mine seems to be a particularly stubborn case – I worked with a naturopath for 2.5 years very strictly adhering to diet, supplementation etc. STILL I did not manage to solve my gut issues. Now, of course, I don’t have the money to pay to see someone else. My gut dysbiosis commenced after a conventional doctor put me on broad spectrum antibiotics for a period of 4 months following a kidney infection (pylonephritis) at age 20! I have been unable to remediate this situation – and now it is almost 30 years later. Sadly, we do not appear to have any decent practitioners here in Australia and nobody seems to do ANY actual testing. Whilst my practitioner was able to normalize my hormones somewhat, she knew NOTHING about the gut and basically followed the protocol set by the Metagenics company in relation to my gut. This simply didn’t work, and in fact I’ve been left with the impression that their products aren’t that great, to be honest.

    So, I’ll be very interested to read your digestive package, and I’ll be nicely surprised if I learn anything about the gut, because I’ve read everything I can lay my hands on about this. I even attempted, in the 80s, to talk about what would later become known as “gut dysbiosis” (in the early days it was merely a discussion about yeasts) with a conventional doctor and her reaction to me showing her the book “The Yeast Connection” was hilarious (or would have been if it was funny).

    So, yes, I can attest personally to the fact that there is a definite connection. I would suggest the connection may go far further than oestrogen also. Oestrogen dominance was what I determined was behind a large uterine polyp that I had cut out in 2010. After 2.5 years on chaste tree tablets, I managed to get the ‘replacement polyp’ to stop growing! So there was something at least.

    Now, I’m afraid I won’t go anywhere near a conventional doctor or a hospital – not even if my life depends on it. Our medical “system” is absolutely criminal IMHO.

    I hear all these stories about how people get over this – well all I can say is that if you’ve had this condition as long as almost 30 years, then getting rid of it appears to be almost impossible.

    Sadly, it appears as though the natural health stage is now teeming with people flogging sub-standard supplements and products that simply don’t work. It is also exceptionally annoying to people who are suffering to be constantly told that you can resolve this condition quickly and easily – pick the wrong practitioner and you are stuffed – all your money has gone and you still have the problem.

    Anyway, clearly I’m not in a positive mood about all this today, so I’ll leave it there.

    • Hi, Sorry to hear about your gut problems. But wanting to ask if you have had the specific PCR stool test for parasites available in Australia. (as i see that is where your from) Google the Feacal Mutliplex PCR test. Its free on medicare and we do it 3 times a year as you can pick up common gut parasites anywhere. Clearing myself of this and also constantly working on ‘leaky gut’ and going AI Paleo really helped me a lot. If you have any gut parasites you cannot heal your gut. x

    • There definitely are subpar supplements on the market but there are also fantastic ones that have clinical trials backing their efficiency. I was incredibly sick post cancer treatment and clearly has a radical imbalance of my microbiome but came across products that helped me get my body and health back. I am happy to share more if you are interested.

  8. Having a healthy gut impacts all the bodily functions and its importance to really stay healthy should be emphasized. Would like to know more about the quality of probiotics we have in the market that can really help us maintain a healthy gut. What are the lactobacilli and bifidobacteria strains that we should look for to help us stay healthy?Are there unbiased info on what kind of reliable technologies to preserve the viability of the good bugs until they reach the large intestines.

  9. Fascinating and needed information! Dr. Kresser, Thank You!

    Being postmenopausal, I can identify with the significant hormone change related effects,
    I believe I’m one of those “complex cases” as no integrative practitioner, to date, has been able to nail down the “lets try this” recommendations to improve my hormone related imbalances.
    Becomes very costly, time, money, and health wise, as well as, disappointing when progress is insignificant.
    I used to be a consistent probiotic consumer.
    While there is never a magic bullet fix, upping my pre/probiotic intake can begin immediately.
    Time to find a reputable brand/product that provides the above mentioned probiotic strains
    along with the intake of more fermented vegetables.

    I applaud Chris for he and his team to dedicate time to stay informed, site the research and
    share with his subscribers. There is so much research and information, even with our instant-age-access to information, I still believe, practitioners do not have enough time to keep current with all of it. I’m always grateful what I’ve learned from Dr. K’s articles, and often times incorporate into my self care well being journey.

  10. I just got back results from a uBiome microbiome fecal test.
    It said my lacto and bifido levels were normal so does this mean I don’t have SIBO?
    I also didn’t have any pathogens which surprised me since I’ve had IBS for 40 years

    • Hi Steve… not sure if you are still looking here, but wanted to share that my Ubiome tests said same, even having some lacto strains which were uncommon and beneficial. I had regained 74% diversity by using Prescript Assist after antibiotics for Lyme (which I had previously had but was not active) which nearly killed me. Even with Prescript Assist my total numbers were low, and Genova test showed low butyrate. Anyway, I did have SIBO most likely as ended up with small intestinal ulcers and horrible IBS. My IBS began with menopause. So with all that said, I am having luck with large amounts of Prebiotics (I am working my way up to a 20 gm dose) in addition to my already high fiber diet. Digestion is poor, stomach acid low most of the time (had a reflux test done and was negative but acid levels mostly low). I had tried low FODMAP diet (sort of paleo like) to slow SIBO but this actually made me worse as I could not tolerate many of the veggies on it. I had/have gastritis and gut is extremely sensitive, most likely due to low estrogen. Currently the prebiotics (acacia, banana flour, FOS, Jerusalem artichoke, psyllium) are helping and I am rotating large amounts of several different multi strain probiotics plus making my own yogurt with a Walmart version of Align (bifido infants). Having some luck. Also using Nutritional (brewers) Yeast from Blubonnet which is unfortified. Don’t laugh, but I am basing this protocol on what has helped my horses with their gut issues. Horses are notorious for gut problems, but sometimes there is more research into maintaining gut health in food species animals more so than in humans. My fasting glucose went from 90 last year to 76 this year, A1C dropped by .1 point (5.0) and hsCRP dropped from 1.8 to 1.2. So although insulin rose a little to 8.4 from 6.5 (my current diet is excessively high in healthy fats as they are soothing to my sore gut) I am going to stick with this approach and see what happens in 6 mos. I am also going to try to cut some of the fats down a bit which when things settle should be easy. Already I am tolerating a few more foods and have only been at this for a few weeks. Your mileage may vary, but sharing in case something here helps you! 🙂

  11. How I wish that this information was available 20 years ago. I’ve had a hysterectomy to “fix” endometriosis, but since then have been plagued by gut health problems. Gone Paleo, then AIP, have had a measure of success, but feel I’m flying blind.

  12. So, after reading all this and please excuse my older brain, is it safe for people that have had oestrogen positive breast cancer and are taking Tamoxifen, to eat yogurt made with l.reuteri?

  13. Due to exercise and diet last year I lost 10 lbs. I’m 17, 5’2 and went from 133 to 122 in a matter of 7 months which seemed very healthy to me. My estrogen levels drastically dropped. During this 7 month time frame, my period disappeared. After those 7 months, the periods continued to be absent and I gained weight despite low calorie diet and intense exercise. Now I’m at 135 even though I’ve been exercising and dieting still. I have GI issues such as bloating and consstipation also. These started after my weight loss as well, same time my estrogen levels dropped. No doctors can figure out how to treat me and help me lose weight despite my intense exercise and healthy diet.

  14. I used to need 100mg DIM twice daily plus topical treatments for persistent moderate acne that began when I was 16. 25 years later I had FMT at Taymount, for gut restoration post chemo (testicular cancer, pure teratoma), autoimmunity, antibiotic usage, stress etc. Since FMT I am 99% acne free without DIM or even needing to wash my face, however, to be 100% acne free I need to eat cruciferous veggies 3-4 times per week, probably because I have a deleted GSTM1 gene, that and better gut flora seem to be supporting my liver well. Plus, I had difficulty passing water previous to commencing DIM which seemed to reverse that in a matter of months.

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