Phytoestrogens and Hormonal Modulation

Applications in Menopause Management and Breast Cancer Prevention

By Artemis Morris, ND

Exploring the benefits of phytoestrogens in managing menopause symptoms and reducing breast cancer risks.

This article examines the role of phytoestrogens, particularly soy, in managing menopausal symptoms and supporting breast cancer prevention. It discusses the scientific evidence behind these plant-derived compounds and their impact on women’s health.

Is Soy Good or Bad for Me, Doc?

Most of us have had this question from our patients: How we respond can impact their health, hormones, and the menu of their plant-based diet. There is a lot of misinformation, even among holistic healthcare practitioners, about phytoestrogens and, in particular, soy. 

Soy (Glycine Max) is complex- it is the most well-known plant food containing phytoestrogens; its production in the US is mostly genetically modified (GMO), it’s in most animal feed, a common food allergy, contains a high nutrient profile of complete protein, is the most widely consumed vegan source of protein worldwide and has multiple health benefits including in women’s health.¹Phytoestrogens, including soy, are plant-derived compounds that mimic the hormone estrogen and has potential benefits in managing hormonal imbalances, alleviating menopausal symptoms, osteoporosis, cognitive health, and preventing hormone-related cancers such as breast cancer.

What Are Phytoestrogens?

Categories and Sources of Phytoestrogens

There are three main categories of plant-derived phytoestrogens: mycotoxins, phytoalexins, and the non-estrogenic compounds (equol and enterolignans) requiring gut microbes for their estrogenic effect.² Phytoalexins, such as isoflavones from soy and lignans from flax seeds, are produced as part of a plant’s defense mechanism and, therefore, can vary in concentrations depending on the plant’s response to stress, infection, or physical injury.²

Phytoestrogens are also characterized by the phytochemicals in various amounts of many plants consumed as food, spices, and teas. The chemical constituents called phytoestrogens include coumestans, resorcylic acid lactones,  isoflavones, flavanones, and enterolignans.  For example, Red Clover is a plant that contains multiple phytoestrogenic components, including coumestans, resorcylic acid lactones, isoflavones, flavonoids, and enterolignans. ^2,3

How Phytoestrogens Work

The endocrine activity of phytoestrogens depends on their affinity for estrogen receptor binding—both the nuclear and membrane receptors—and on their ability to induce estrogen-dependent gene transcription. In addition, they can also act on other cell physiological pathways that exhibit other health properties that vary in health effects depending on the dose, subject, gender, age, and physiological status.^2,3

The Gut Microbiota’s Role in Phytoestrogen Metabolism

The gut microbiota plays a role in enterolignan, isoflavone metabolism, and phytoestrogen compounds.² It was proposed that people consuming soy with gut microbes capable of converting the isoflavone daidzein into equol are more likely to benefit from soyfood consumption.² Equol, a metabolite with a stronger binding affinity for estrogen receptors than its precursor daidzein, may enhance the health effects of phytoestrogens, including potential benefits for bone, cardiovascular, and menopausal health. Approximately 50% of Japanese individuals can produce equol compared to 30% of Westerners, with vegetarians being more likely to be equol producers than non-vegetarians. However, both equol and isoflavones have phytoestrogenic properties, and it remains unclear whether equol confers additional benefits independent of isoflavones^.²

Phytoestrogenic plants have unique phytochemical, nutrient, physiological, and energetic properties that vary depending on their environment and how they interact with their consumers’ unique and estrogen-binding variables. The mechanisms by which phytoestrogens exert their physiological effects and interact with estrogen receptors are complex, and research in this area is ongoing.

Estrogen Primer

Types of Estrogen

Estrogen, primarily produced in the ovaries and other tissues depending on the stage in a woman’s life, includes three forms: estrone (E1), estradiol (E2), and estriol (E3). Estradiol (E2) is the most potent, regulating reproductive, bone, and cardiovascular health, while estrone (E1) predominates post-menopause and can enzymatically convert to estradiol. Estriol (E3), significant during pregnancy, may have protective benefits in non-pregnant women against estrogen-sensitive conditions such as breast cancer. ^3,4 While the affinity of phytoestrogens to the three estrogen receptors ((ERα, ERβ, and GPER1) is relatively low, and their structure is different from that of natural estrogens, research is still uncovering the mechanism by which their varying effects occur.^3,4 Phytoestrogens, like isoflavones from soy, interact with estrogen receptors favoring ERβ, associated with anti-inflammatory, anti-proliferative, and potentially cancer-protective effects.

Receptor Specificity

ERα (Estrogen Receptor Alpha) is found in reproductive tissues and is implicated in estrogen receptor-positive breast cancers, promoting cell proliferation. ERβ (Estrogen Receptor Beta), expressed in many tissues like the brain and immune system, often acts as a protective factor, inhibiting the pro-growth effects of ERα.⁸ GPER1 (G-protein-coupled estrogen receptor 1) is involved in various cancers, including breast cancer. It displays a dual role as both an estrogen agonist and antagonist, offering potential as a target for cancer prevention and treatment.^5,6,7,9

Phytoestrogens, such as isoflavones (from soy) and lignans (from flaxseed), mimic natural estrogens by binding to these receptors with lower affinity, acting as natural selective estrogen receptor modulators (SERMs). ⁹ This dual activity—estrogenic and anti-estrogenic—positions soy as a potential dietary ally in breast cancer prevention and management. Unlike synthetic endocrine disruptors, phytoestrogens are associated with beneficial health effects, offering a natural, safe approach to modulating estrogen function in hormone-sensitive conditions.⁹

The interactions between estrogen types, the enzymes influencing their production (aromatase, 17β-hydroxysteroid dehydrogenase (17β-HSD), and their receptor interaction are key to understanding phytoestrogens’ potential effects and uses. The biosynthesis of human and animal hormones can be impacted by factors such as diet (e.g., nutrient deficiency), genetics, and stress. In contrast, stressors, ultraviolet light, and climate variation also impact the biosynthesis of phytoestrogens.⁶

Three commonly studied phytoestrogens are isoflavones, lignans, and coumestans. Isoflavones (e.g., Genistein and Daidzein) are found primarily in soy-based foods and can potentially manage menopausal symptoms and reduce breast cancer risk. In preclinical studies, genistein was shown to reduce tumor growth in breast cancer models, likely by modulating the activity of ERβ and decreasing the inflammatory environment in the breast tissue.¹⁰

The gut microbiota metabolizes lignans in flaxseeds, whole grains, legumes, and vegetables into enterolignans, such as enterodiol and enterolactone. Lignans have antioxidant and anti-inflammatory properties, which help reduce oxidative stress—an essential factor in cancer development. Lignans have been shown to lower the risk of hormone-related cancers, including breast cancer.¹¹Coumestans are in alfalfa and other legumes. Coumestans have weaker estrogen-like effects compared to isoflavones and lignans. Coumestans can potentially contribute to cancer prevention and hormone balance in postmenopausal women.¹²

Phytoestrogens in Menopause

Relieving symptoms

Phytoestrogens can aid in managing menopausal symptoms, such as hot flashes, night sweats, mood swings, vaginal dryness, and other menopausal symptoms associated with the natural decline in estrogen production and cessation of menstruation. Phytoestrogens, with their mild estrogen-like activity, have been explored as a natural, safer alternative to synthetic hormone replacement therapy (HRT). A meta-analysis confirmed that soy isoflavones, such as genistein, significantly reduce the frequency and severity of hot flashes and other menopausal symptoms.¹³ By interacting with estrogen receptors,  particularly ERβ, in tissues that are sensitive to hormonal fluctuations, such as the hypothalamus and breast, phytoestrogens may alleviate symptoms without the adverse effects and risks typically associated with synthetic HRT.¹³

Bone Health

Phytoestrogens also have beneficial effects on bone health and postmenopausal osteoporosis. Phytoestrogens, particularly isoflavones, have been shown to help maintain bone density by interacting with estrogen receptors in bone tissue, thereby reducing the risk of fractures. ¹⁴

Phytoestrogens and Breast Cancer Prevention

Protective Mechanisms

The potential of phytoestrogens in breast cancer prevention is the subject of ongoing research. Since many breast cancers are estrogen receptor-positive (ER+), a primary concern has been whether phytoestrogens might stimulate estrogen receptors and promote cancer growth. However, research suggests that phytoestrogens may offer protective benefits against breast cancer.^3,18Isoflavones, particularly genistein, have been shown to inhibit the growth of estrogen-dependent breast cancer cells. Phytoestrogens also possess antioxidant and anti-inflammatory properties that help protect cells from DNA damage and prevent chronic inflammation, which is essential in cancer development¹². A cohort study in Asia found that women who consumed higher levels of phytoestrogens, particularly from soy, had a significantly lower risk of developing breast cancer. ^3,18 

Research Highlights

Observational studies in the U.S. and China, summarized in meta-analyses published in 2013 and 2019, further confirmed these findings, showing protective effects in ER-positive and ER-negative patients. This suggests that phytoestrogens may offer protective effects by modulating estrogen receptor activity and reducing the impact of environmental estrogens.¹⁵

Several major health organizations, including the American Cancer Society, the American Institute for Cancer Research, and the World Cancer Research Fund International, have concluded that women diagnosed with breast cancer can safely consume soy.^7-10 

The European Food Safety Authority (EFSA) concluded in 2015 that isoflavone supplements do not affect breast tissue in postmenopausal women. Beginning in 1999, clinical trials consistently showed that neither soy nor isoflavone consumption affected markers of breast cancer risk, including mammographic density and in vivo breast cell proliferation.¹⁸ Research supports the idea that phytoestrogens have a safer profile than synthetic hormone replacement therapies in cancer prevention.

Phytoestrogens have been suggested as hormonal substitutes or complementary in breast cancer treatments.¹⁹ Research indicates that GPER1 may be involved in dual effects of phytoestrogens, where they may act protectively in some tissues while promoting cancer growth in others. This underscores the complexity of phytoestrogens’ interaction with estrogen receptors and the need for further study into their role in breast cancer prevention and treatment.¹¹ 

In gynecological cancers, selective estrogen receptor modulators (SERMs) and Aromatase Inhibitors (AIs) control high estrogen hormone production. However, the SERM-based endocrine therapy using Tamoxifen has been shown to result in tumor resistance to the drug and relapse into the disease. Phytoestrogens are an exciting area of research in cancer as they act as natural SERMs.^19,21

New research found that treatment with estrogens elicits anti-cancer effects in ~30% of patients with advanced endocrine-resistant estrogen receptor alpha (ER)-positive breast cancer.²¹ Phytoestrogens offer a new territory of nutritional potential with anti-proliferative benefits that may serve as hormonal substitutes or complement conventional breast cancer care.¹²

Phytoestrogens and Uterine Cancer

Soy isoflavones at doses above 20 mg/day have been shown to increase endometrial thickness through endometrial cell proliferation. However, there is no compelling evidence to suggest that these effects lead to an increased risk of endometrial cancer. This contrasts with hormonal replacement therapies, which are known to have differing effects on breast and uterine cancers.² One possible explanation for this difference is that the uterus, ovaries, and vagina are rich in estrogen receptor beta (ERβ) subtypes, to which isoflavones have a greater affinity than estrogen receptor alpha (ERα). ERβ is involved in cell differentiation, which may counteract the cell proliferation induced by ERα. Studies in postmenopausal women suggest that isoflavones may have a vaginal effect, while no apparent endometrial effects have been demonstrated despite numerous trials.²

Phytoestrogens: A Natural Ally for Women’s Health

Phytoestrogens, such as those found in soy, offer a natural, low-risk approach to supporting hormone balance and women’s health. These plant compounds can alleviate menopausal symptoms, lower the risk of estrogen-sensitive cancers, and provide antioxidant and anti-inflammatory benefits, making them a valuable alternative or complement to synthetic hormone therapies.

Their potential to regulate estrogen levels and reduce the risks of hormone-related conditions—including menstrual irregularities, Polycystic Ovarian Syndrome (PCOS), Menopause, osteoporosis, and cancer risk—highlights their role in women’s health throughout life. Phytoestrogen-rich foods like soy influence hormone activity and contribute essential nutrients and bioactive compounds that promote heart, bone, and brain health.

Considerations for the safety and effectiveness of soy and other phytoestrogens include quality (non-GMO, organic), preparation, nutrigenomics/ nutrigenetics, microbiome, and individual factors. Moderation and personalization are key—making these foods a cornerstone of a holistic, Naturopathic approach to hormone balance and wellness.

In answer to the question, “Is soy good for me?” the best response remains: “It depends.” But when thoughtfully incorporated into a balanced diet, soy and phytoestrogens are a safe and beneficial ally, especially for women navigating hormonal changes or seeking preventive and complementary care.

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