Gut health during perimenopause (the months and years of a woman’s life leading up to menopause) can be essential to a woman’s ongoing and future health.
Perimenopause usually begins when a woman reaches her mid-40s and ends when she reaches menopause, on average, at age 51.
Hormonal changes and the gut microbiome
Gradually diminishing levels of estrogen are the hallmark of perimenopause. The body also produces less progesterone. During this time, declining ovarian function leads to irregular menstruation and symptoms, such as hot flashes. At the same time, the number of follicles and the number of viable eggs in the ovaries decreases, leading to fewer ovulations. By the time a woman is in her 40s, her estrogen levels become less predictable. Especially in the early years of perimenopause, they may spike higher than normal as the body tries to stimulate ovulation. Later, estrogen levels may drop very low. These hormonal changes result in irregular menstrual periods that eventually stop.1 Perimenopause officially ends a year after a woman has her last menstrual period. On average, this time lasts about four years.
Estrogen metabolism
The body makes three main types of estrogen: estrone (E1), estradiol (E2) and estriol (E3). Before perimenopause, estradiol, produced primarily in the ovaries, is the most potent form of estrogen and the most abundant in the body. Estriol (E3) is the weakest estrogen; it’s made primarily during pregnancy.
Estrone is made in both the ovaries and in adipose tissue. It’s sometimes called menopause estrogen because it continues to be produced in fat tissue and from endogenous testosterone, even after the ovaries have stopped making it. Higher levels of blood estrogen from estrone after menopause are linked to an increased risk of breast cancer.2
All forms of estrogen are metabolized in the liver. In phase 1, the cytochrome P450 enzyme system converts all forms of estrogen into three possible metabolites: 2-hydroxy estrone (2-OH), 4-hydroxy estrone (4-OH) and 16-hydroxy estrone (16-OH).3
- 2-OH (2-hydroxyestradiol) is the weakest metabolite in terms of estrogenic activity in the body. It blocks more potent estrogens that promote cell proliferation. Because the stronger estrogens may promote cancer in the breast, ovary or uterus, all tissues high in estrogen receptors, 2-OH is the safest estrogen metabolite. About 80% of estrogen is converted to 2-OH.
- 4-OH (4-hydroxyestradiol) is a much stronger estrogen metabolite. It has been shown to alter DNA, which can promote cancer in estrogen-sensitive tissues. About 20% of estrogen is converted to 4-OH.
- 16-OH (16-hydroxyestradiol) has also been shown to promote cancer in estrogen-sensitive tissues, particularly in the breast. This metabolite is also associated with inflammation and obesity in perimenopause and menopause. Small amounts of estrogen are converted to this form.
During phase 2 conjugation and detoxification, estrogen metabolites are further transformed through methylation, glucuronidation and sulfation. These processes inactivate estrogen and make the metabolites water-soluble so they can be excreted through the bile into the gut for elimination in the stool. The methylation process activates the beneficial properties of the 2-OH metabolite and decreases the harmful properties of the dangerous 4-OH metabolite.
A healthy estrogen balance favoring the production of 2-OH is vital for a woman’s health. Efficient liver detoxification pathways are needed to influence estrogen metabolism toward 2-OH production and away from 4-OH and 16-OH production.
Gut health and estrogen metabolism
Once the conjugated estrogen metabolites reach the gut, more than half are deconjugated and returned to circulation by the estrobolome bacteria. These are a suite of 60 gut bacteria genera4 that produce the enzyme beta-glucuronidase, which cleaves the conjugated estrogen metabolites and reactivates them. Most deconjugated estrogen is released back into the enterohepatic circulation in biologically active form. The estrobolome helps balance estrogen in the body, regulating the levels during the regular increases and decreases of the menstrual cycle.
At the start of the perimenopause years, estrogen levels naturally fluctuate more between high and low levels. The estrobolome helps even out the estrogen levels during this time, but dysbiosis can disrupt balance and reduce beta-glucuronidase production. This keeps estrogen from recirculating and reduces overall estrogen levels.
Many researchers believe dysbiosis affecting the estrobolome plays a role in perimenopausal and menopausal symptoms, such as hot flashes, vaginal dryness, insomnia and emotional disturbances, such as depression. Alterations in the estrobolome may also accelerate osteoporosis.5
Support estrogen metabolism in the liver
Helping the liver metabolize estradiol and estrone more efficiently minimizes the time the OH-4 and OH-16 metabolites spend in circulation, giving them less opportunity to damage estrogen-sensitive tissues. One way to improve the process is by ensuring the liver has plenty of the cofactors needed to conjugate the estrogen metabolites. Essential cofactors for estrogen conjugation include N-acetyl cysteine (NAC), choline, folate and vitamin B12.
To support the methylation and glucuronidation pathways, women in the perimenopause years should consume a high-fiber diet rich in cruciferous vegetables, particularly brassica vegetables, such as broccoli, Brussels sprouts, cabbage, cauliflower, collards, kale and turnips. The brassicas are high in fiber, and fiber alone positively affects estrogen metabolism.6 These vegetables are also high in indoles, including indole-3-carbinol, which help shift estrogen metabolism away from the dangerous forms.7 Brassicas are also an excellent dietary source of diindolylmethane (DIM), a compound shown to affect estrogen metabolism and shift it toward 2-OH production positively.8
Other foods that support estrogen metabolism in the liver include dandelion leaves, rooibos tea, rosemary, curcumin (turmeric) and ellagic acid from berries, pomegranates, grapes and walnuts. Supplements of resveratrol, a phenol found in the skin of grapes, blueberries, raspberries, mulberries and peanuts, can be helpful. Supplements of astaxanthin, a xanthophyll carotenoid found in some kinds of algae and salmon, trout, krill and shrimp, may also help. Isoflavones, such as soy and flaxseed, omega-3 fatty acids and green tea polyphenols, may also help shift estrogen metabolism toward 2-OH.
Aerobic exercise can help reduce high circulating estrogen levels and shift the estrogen pathways in the liver toward a healthier ratio. For example, exercise has improved healthy premenopausal women’s 2-OH/16-OH ratio.9
Accumulated toxins from common drugs, including statins, steroids, some antibiotics, some arthritis drugs, acetaminophen and antifungal drugs, can also slow liver pathways. Alcohol, food additives and environmental toxins (pesticides, agricultural chemicals, household chemicals, personal care products and many other sources) can also slow the estrogen metabolism pathways by competing for the same detoxification enzymes.
Support estrogen metabolism in the gut
During the perimenopause years, decreasing estrogen and progesterone gradually reduce the diversity of the gut microbiome. The microbiome composition starts to become similar to that of a man of the same age. Because beneficial bacteria thrive in environments with estrogen, declining hormone levels mean the microbiome community may shift toward containing more harmful bacteria.
The decline in estrogen and progesterone and the associated shift in the gut microbiome composition may lead to increased gut barrier permeability, allowing microbial translocation. This may be an underlying cause of the increased frequency of bacterial vaginosis, yeast infections and urinary tract infections during the perimenopausal years.
Continuing a diet with the same food components that lead to a healthy gut microbiome will help modulate the natural shift in the gut microbiome and support gut barrier integrity. It will also lead to a healthy estrobolome and safer circulating estrogen levels.
Fiber is essential for gut health and supporting the microbiome. Many studies suggest dietary fiber may be even more important for the estrobolome bacteria than the overall microbiota.10 Similarly, higher fiber intake may naturally lower estrogen levels, particularly estrone levels, in postmenopausal women by as much as 47%.11
Adding prebiotic dietary fiber provides the most support for the estrobolome bacteria. Good dietary sources of prebiotic fiber include almonds, bananas, beans, whole grains, oats, flaxseed, peas, artichokes, soy foods, leafy greens and cabbage. These foods are all high in inulin, a prebiotic soluble fiber. Inulin supplements can help increase prebiotic intake.
Phytoestrogens are plant nutrients found in many foods, including soy products, whole grains, beans and some fruits and vegetables. These phenolic compounds, including isoflavones and lignans,12 are structurally similar to estrogen and can bind to estrogen receptors throughout the body, mimicking the effects of estrogen. By blocking estrogen metabolites from estrogen-sensitive tissues, phytoestrogens may help prevent some cancers.
The efficacy of phytoestrogens for relieving perimenopause and menopause symptoms has been extensively studied. Overall, the research finds a plant-based approach is helpful for mild to moderate symptoms.13
Some women find a diet high in phytoestrogens, especially lignans, helps relieve perimenopause symptoms, such as hot flashes. Good phytoestrogen food choices include beans and legumes, soy foods (tofu, soy milk, soy protein powder), flaxseed, oats, pears, broccoli and carrots. Foods rich in lignans include flaxseeds (the most concentrated dietary source), cashew nuts, vegetables and fruits, legumes and whole grains.14 Dark chocolate contains phytoestrogen compounds in the form of catechins. All these foods are also high in prebiotic fiber that support the estrobolome and the rest of the gut microbiome.
Phytoestrogens in supplement form are usually sourced from soy, red clover, flaxseed and hops. Soy and red clover supplements contain large amounts of the isoflavones genistein and daidzein, which may have estrogen-like effects. Vitamin D, DHEA and garlic oil supplements also help support estrogen.
Constipation is a common problem that can develop in the perimenopause years. It’s partly caused by decreased estrogen and progesterone, which can slow down the passage of food through the digestive system and cause more water reabsorptions, leading to constipation.
The perimenopausal years are also when many women start needing medication for health issues, such as high blood pressure and low thyroid function. Some of these drugs, such as calcium channel blockers for hypertension, can cause constipation.
An additional factor is the natural weakening of the pelvic floor muscles, which comes from childbearing and simply from age. Weakened pelvic floor muscles make passing stool more difficult.
Increasing fiber and fluid intake is essential to help relieve frequent constipation during this time. Plain water or water with lemon is a good, simple choice. Drinking coffee can help; aloe vera juice is also helpful. Increasing physical activity helps increase colon activity and strengthens pelvic and abdominal muscles. If the pelvic floor muscles are weak, exercises designed to improve bowel function can be beneficial.
Heal the gut
A healthy gut microbiome is vital for efficient estrogen metabolism. If the gut wall is damaged and has increased permeability, conjugated estrogens can escape into the circulation before the estrobolome can recycle them. In addition, decreasing estrogen levels cause changes in the composition of the gut microbiome associated with weight gain in the perimenopause and menopause years.15 In addition, estrogen-related microbiome changes are related to metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), osteoporosis and coronary artery disease.16
To help make sure the gut microbiome is balanced and reduce gut permeability, I recommend following my Super 7(R) Action Plan:
- Reset diet/lifestyle/mindset
- Remove triggers, such as food sensitivities and pathogens
- Replace digestive enzymes and stomach acid
- Regenerate damaged intestinal mucosa
- Re-inoculate with quality pre- and probiotics
- Reintroduce certain foods removed in step 2
- Retain your health and GI integrity
The recently introduced supplement BPC 157 can be beneficial for treating leaky gut syndrome. This peptide, found naturally in gastric secretions, helps regenerate cells in the intestinal walls and helps seal up damaged areas. It also helps stabilize the microbiome and helps treat dysbiosis.17
Final thoughts
In wrapping up our exploration of the nuanced relationship between perimenopause and gut health, it’s clear this is a dynamic and complex interaction with significant implications for women’s health. The shifts in gut microbiota composition and function during perimenopause underscore the physiological changes women experience and highlight the connection between gut health and prevalent symptoms, from mood swings to weight shifts. Most natural changes during the perimenopause transitional time can be efficiently and effectively managed by maintaining a healthy lifestyle and a healthy gut.
Understanding the bidirectional nature of this relationship holds the key to unlocking targeted, effective interventions that can support women through perimenopause.
ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a doctor of chiropractic, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller Inside-Out Health and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a master’s degree in human nutrition. The American Chiropractic Association Sports Council named Silverman Sports Chiropractor of the Year in 2015. He is on the advisory board for Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A thought leader in his field and practice, he is a frequently published author in peer-reviewed journals and other mainstream publications and was the principal investigator in two Level 1 FDA laser studies. His book, Amazon best-seller Immune Reboot, was released in December 2022. For more information, visit drrobertsilverman.com.
References
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- Key TJ, et al. Circulating sex hormones and breast cancer risk factors in postmenopausal women: Reanalysis of 13 studies. Endogenous Hormones and Breast Cancer Collaborative Group. Br J Cancer. 105(5):709-22, 2011. NCBI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188939/. Accessed May 7, 2024.
- Tsuchiya Y, et al. Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett. 2005;227(2):115-124. PubMed. https://pubmed.ncbi.nlm.nih.gov/16112414/. Accessed May 7, 2024.
- Plottel CS, Blaser MJ. Microbiome and malignancy. Cell Host Microbe. 2011;10:324–335. PubMed. https://pubmed.ncbi.nlm.nih.gov/22018233/. Accessed May 7, 2024.
- Hu S, et al. Gut microbial beta-glucuronidase: A vital regulator in female estrogen metabolism. Gut Microbes. 2023;15(1):2236749. NCBI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10416750/. Accessed May 7, 2024.
- Rose DP, et al. High-fiber diet reduces serum estrogen concentrations in premenopausal women. Am J Clin Nutr. 1991;54(3):520‐525. PubMed. https://pubmed.ncbi.nlm.nih.gov/1652197/. Accessed May 7, 2024.
- Fowke JH, et al. Brassica vegetable consumption shifts estrogen metabolism in healthy postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2000;9(8):773‐779. PubMed. https://pubmed.ncbi.nlm.nih.gov/10952093/. Accessed May 7, 2024.
- Reyes-Hernández OD, et al. 3,3′-Diindolylmethane and indole-3-carbinol: Potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways. Cancer Cell Int. 2023;23(1):180. PubMed. https://pubmed.ncbi.nlm.nih.gov/37633886/. Accessed May 7, 2024.
- Smith AJ, et al. The effects of aerobic exercise on estrogen metabolism in healthy premenopausal women. Cancer Epidemiol Biomarkers Prev. 2013;22(5):756‐764. PubMed. https://pubmed.ncbi.nlm.nih.gov/23652373/. Accessed May 7, 2024.
- Farvid MS, et al. Fiber consumption and breast cancer incidence: A systematic review and meta-analysis of prospective studies. Cancer. 2020;126(13):3061-3075. PubMed. https://pubmed.ncbi.nlm.nih.gov/32249416/. Accessed May 7, 2024.
- Monroe KR, et al. Dietary fiber intake and endogenous serum hormone levels in naturally postmenopausal Mexican American women: The Multiethnic Cohort Study. Nutr Cancer. 2007;58(2):127-135. PubMed. https://pubmed.ncbi.nlm.nih.gov/17640158/. Accessed May 7, 2024.
- Desmawati D, Sulastri D. Phytoestrogens and their health effect. Maced J Med Sci. 2019;7(3):495-499. PubMed. https://pubmed.ncbi.nlm.nih.gov/30834024/. Accessed May 7, 2024.
- Franco OH, et al. Use of plant-based therapies and menopausal symptoms: A systematic review and meta-analysis. JAMA. 2016;315(23):2554-2563. PubMed. https://pubmed.ncbi.nlm.nih.gov/27327802/. Accessed May 7, 2024.
- Rodríguez-García C, et al. Naturally lignan-rich foods: A dietary tool for health promotion? Molecules. 2019;24(5):917. NCBI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429205/. Accessed May 7, 2024.
- Peters BA, et al. Menopause is associated with an altered gut microbiome and estrobolome with implications for adverse cardiometabolic risk in the Hispanic Community Health Study/Study of Latinos. mSystems. 2022;7(3). PubMed. https://pubmed.ncbi.nlm.nih.gov/35675542/. Accessed May 7, 2024.
- Peters BA, et al. Spotlight on the gut microbiome in menopause: Current insights. Int J Womens Health. 2022;14:1059-1072. PubMed. https://pubmed.ncbi.nlm.nih.gov/35983178/. Accessed May 7, 2024.
- Sikiric P, et al. Novel cytoprotective mediator, stable gastric pentadecapeptide BPC 157. Vascular recruitment and gastrointestinal tract healing. Curr Pharm Des. 2018;24(18):1990-2001. PubMed. https://pubmed.ncbi.nlm.nih.gov/29879879/. Accessed May 7, 2024.