Comprehensive Overview of Estrogen Dominance in Women
By Jessica Karvelis (BHSc Nat) (AdvDip) (CertIV)
Understanding Estrogen Dominance: A Comprehensive Overview
Estrogen dominance is characterised by an imbalance in steroid hormone homeostasis in which estrogenic activity disproportionately exceeds progesterone action. Here, we will examine the definitions, underlying causes, clinical manifestations, and strategies for addressing relative estrogen excess. But first, it helps to understand estrogens role in the human body.
What Is Estrogen & What Does It Do For Us?
Estrogen is a class of endogenous steroid hormones that plays a central regulatory role in both reproductive and non-reproductive physiology. The principal biologically active form in humans is 17β-estradiol (E2), which exhibits the highest affinity for estrogen receptors and drives most classical estrogenic actions [1].
Estrogens are synthesised primarily in the ovaries in premenopausal individuals assigned female at birth, but they are also produced in peripheral tissues (e.g., adipose, bone, brain, and muscle) via local aromatisation of androgens [1][2].
Defining Estrogen Dominance
Estrogen (including estradiol, estrone, and estriol) and progesterone act in a tightly regulated balance to modulate reproductive tissue growth, the menstrual cycle, and systemic functions including metabolism and neurotransmission [3]. Progesterone normally counterbalances estrogen-mediated proliferation in target tissues; when progesterone is low or estrogen action is disproportionate, estrogen dominance and progesterone resistance may occur, disrupting cellular homeostasis and tissue regulation [3].
Although estrogen dominance is not yet codified as a formal diagnosis, the hormone ratio (estrogen relative to progesterone) is a clinically relevant concept supported by endocrine physiology and observed associations with multiple hormone-sensitive conditions.
Physiological Basis & Hormone Interactions
The endocrine interplay between estrogen and progesterone underpins normal reproductive function:
Estrogen promotes endometrial proliferation, breast ductal growth, and various metabolic effects.
Progesterone promotes differentiation of estrogen-primed tissues and limits proliferative signaling [3].
When progesterone is insufficient, even physiologically normal estrogen levels may predominate. This phenomenon can manifest as a functional estrogen excess and contributes to symptoms historically attributed to estrogen dominance [3].
Symptoms Associated with Estrogen Dominance in Women
Estrogen dominance contributes to a range of physiological and symptomatic effects in women across the reproductive lifespan [13]. The biological mechanisms underlying relative estrogen excess have been investigated, especially in the context of menstrual cycle regulation, reproductive tissue response, and neuroendocrine function.
1. Menstrual Irregularities & Pain
When estrogen is relatively unopposed by progesterone, this proliferative influence persists, contributing to menstrual irregularities, including heavy or prolonged menstrual bleeding and dysfunctional uterine bleeding [13]. In conditions such as endometriosis and uterine fibroids, dysregulated estrogen and progesterone signaling is central to disease pathophysiology, often resulting in pelvic pain and altered menstrual patterns [14][15].
2. Breast Tenderness
Estrogen influences breast tissue by stimulating ductal proliferation and fluid retention. Relative estrogen excess has been associated with fibrocystic changes, breast tenderness, and increased mammographic density [13].
3. Neuroendocrine & Mood Symptoms
Estrogen and progesterone cross the blood–brain barrier and interact with receptors in multiple brain regions involved in mood and cognition. Fluctuations in estrogen relative to progesterone have been correlated with affective disturbances, including mood swings, anxiety, and depressive symptoms [16].
4. Headaches & Migraine Patterns
Migraine prevalence and severity in women are closely tied to reproductive hormone fluctuations. The pattern of estrogen withdrawal following a period of elevated levels play a significant role in triggering menstrual migraine attacks and other hormonally related headache syndromes [17][18].
5. Metabolic and Somatic Effects
Estrogen plays a role in energy homeostasis and adipose tissue distribution. Women with relatively higher estrogen exposure often report fat accumulation, alterations in body composition, bloating, and water retention, which may be manifestations of underlying endocrine imbalance [19].
6. Skin & Hair Changes
Estrogen modulates skin hydration, sebaceous gland activity, and hair growth cycles. Oily skin, acne flare-ups, and hirsutism can occur when estrogen is high relative to progesterone, especially if there is concomitant hyperandrogenism [20].
7. Sleep Disturbances
Estrogen and progesterone modulate sleep architecture and circadian rhythm regulation. Relative estrogen excess, particularly when progesterone is low, has been associated with insomnia, poor sleep quality, and increased nighttime awakenings in perimenopausal women [16].
8. Fatigue & Low Energy
Chronic fatigue is frequently reported, likely due to a combination of hormonal dysregulation, sleep disturbance, and mood changes. Estrogen impacts mitochondrial function and glucose metabolism, which may contribute to systemic fatigue [19]
Mechanisms Underlying Estrogen Dominance
1. Hormonal Imbalance Across the Lifespan
Estrogen and progesterone levels vary across physiological stages. For example, during perimenopause, progesterone production declines more rapidly than estrogen, increasing the likelihood of relative estrogen dominance and associated symptoms [6].
2. Exposure to Environmental Estrogenic Compounds
Environmental exposures to xenoestrogens, synthetic or naturally occurring compounds capable of binding to estrogen receptors, can perturb endocrine signalling. These agents are found in plastics (e.g., bisphenol A, phthalates), pesticides, industrial chemicals, and certain lifestyle products [1]. Xenoestrogens may mimic or augment endogenous estrogen effects on target tissues and potentially contribute to hormonal imbalance [5].
Recent toxicological research underscores how widespread environmental estrogens affect endocrine pathways and may contribute to neurobehavioral and systemic disruptions via estrogen receptor signaling [5][6].
3. Hepatic & Detoxification Pathways
The liver plays a central role in steroid hormone metabolism, conjugating estrogen derivatives for excretion. Impaired hepatic detoxification (due to chronic stress, nutrient deficits, or toxic exposures) can reduce estrogen clearance, allowing greater systemic reabsorption [4][5][6].
Estrogens are hydroxylated mainly in the liver at the 2-, 4-, or 16-carbon positions, resulting in a group of compounds collectively known as catechol estrogens:
2-Hydroxy Estrogens (e.g., 2-hydroxyestrone, 2-hydroxyestradiol) – These metabolites are considered weakly estrogenic and may even antagonise stronger estrogenic signaling, potentially attenuating proliferative effects in certain tissues [7].
4-Hydroxy Estrogens (e.g., 4-hydroxyestrone) – These metabolites bind estrogen receptors but have a higher estrogenic potency than 2-hydroxylated forms. They can be further oxidised to quinones, which have been implicated in DNA-damage pathways under certain conditions [7].
16α-Hydroxyestrone – This metabolite retains significant estrogenic activity and has been associated with proliferative effects in estrogen-sensitive tissues. Differences in the balance between 2- and 16-hydroxylation pathways have been investigated in hormone-related cancer research [7].
Hydroxylation pathways compete for the same parent estrogens, and the relative predominance of one pathway over another may have implications for tissue responsiveness and risk profiles in hormone-dependent conditions, such as breast cancer.
After hydroxylation, estrogen metabolites undergo phase II conjugation reactions in the liver, most commonly sulfation and glucuronidation, which increase water solubility and facilitate excretion via urine or bile. Conjugated forms often represent the most abundant circulating estrogen and act as reservoirs that can be deconjugated back into active estrogens in tissues that express enzymes like β-glucuronidase [7][8].
4. Gut Microbiome & Estrobolome Function
Emerging evidence highlights the gut microbiome’s influence on estrogen homeostasis via the estrobolome (a collection of bacterial genes capable of metabolising estrogen). Microbial β-glucuronidase activity can deconjugate estrogen, facilitating reabsorption into systemic circulation. Dysbiosis (imbalance of positive gram and negative gram bacteria/pathogens), loss of microbial diversity, and altered estrobolome function may therefore sustain elevated circulating estrogen activity or modulate hormone profiles [4][5].
Evidence-Based Strategies for Hormone Rebalancing
Given the multifactorial nature of estrogen dominance, management is individualised:
1. Liver & Detoxification Support
Nutrient-dense foods rich in antioxidants (e.g., cruciferous vegetables, bitter foods, milk thistle, dandelion root, globe artichoke, rosemary) support hepatic conjugation and estrogen metabolism.
2. Gut Microbiome Optimisation
Dietary fiber and probiotic strategies promote favourable gut microbial composition and may reduce β-glucuronidase-mediated estrogen reabsorption. While exact clinical protocols are evolving, gut health is central to hormone detoxification pathways.
3. Minimising Environmental Estrogen Exposure
Reducing contact with products containing known endocrine-active chemicals (e.g., plastics with bisphenols or phthalates) is recommended to lessen exogenous estrogenic burden.
4. Lifestyle & Stress Management
Chronic stress influences cortisol dynamics, which can shift steroidogenic pathways and potentially deprioritise progesterone synthesis, exacerbating relative estrogen activity. Stress-reducing practices such as mindfulness, sleep hygiene, and moderate exercise are beneficial adjuncts.
5. Nervous System Nourishment & Neuroendocrine Support
Progesterone synthesis can be compromised under chronic stress, as cortisol and progesterone share common precursors in the steroidogenesis pathway [21]. Supporting the nervous system helps mitigate excessive cortisol production, thereby preserving progesterone availability and promoting a more balanced estrogen-to-progesterone ratio.
Key strategies include:
Adaptogenic herbs such as ashwagandha (Withania somnifera) and rhodiola (Rhodiola rosea), which have been shown to modulate hypothalamic–pituitary–adrenal (HPA) axis activity and reduce cortisol output [22].
Mind-body interventions including meditation, yoga, and breathing exercises, which decrease sympathetic nervous system overactivation and lower stress-mediated cortisol release [23].
Adequate B-vitamin intake (particularly B6, B12, and folate), magnesium, and omega-3 fatty acids, which support neurotransmitter synthesis and adrenal function, indirectly supporting progesterone production [24].
Sleep hygiene to optimize circadian regulation of the HPA axis, as inadequate sleep can increase cortisol and disrupt normal progesterone synthesis [21].
By nourishing the nervous system and reducing chronic stress, women may protect progesterone reserves, enhance hormonal balance, and mitigate some of the symptomatic burden of estrogen dominance.
Supplements and Herbs That May Support Estrogen Balance
Nutritional supplements and herbal agents are often used as adjunctive strategies to support estrogen metabolism and improve the estrogen-to-progesterone balance.
1. Diindolylmethane (DIM) and Indole-3-Carbinol (I3C)
DIM is a metabolite of indole-3-carbinol found in cruciferous vegetables. These compounds have been shown to influence estrogen metabolism by favoring hydroxylation pathways associated with less estrogenic metabolites, particularly increasing the 2-hydroxyestrone pathway relative to 16α-hydroxyestrone in some populations [9].
2. Calcium D-Glucarate
Calcium D-glucarate may support estrogen elimination by inhibiting intestinal β-glucuronidase, an enzyme involved in estrogen reabsorption via enterohepatic circulation. By promoting estrogen excretion, this compound may help reduce overall estrogenic burden [10].
3. Milk Thistle (Silybum marianum)
Milk thistle contains silymarin, a compound with antioxidant and hepatoprotective properties. As hepatic pathways are central to estrogen metabolism and clearance, supporting liver function may indirectly aid hormone balance, although direct evidence specific to estrogen dominance is limited [11].
4. Omega-3 Fatty Acids
Omega-3 fatty acids exert anti-inflammatory effects and may support metabolic and endocrine health. Since inflammation and excess adipose tissue can contribute to estrogen production, omega-3 supplementation may be beneficial as part of a comprehensive hormone-support strategy [12].
Estrogen dominance is a common but often misunderstood cause of hormone imbalance in women. By learning how your lifestyle, diet, and environment impact your hormones, whilst taking intentional steps to support your body, you can regain control, reduce symptoms, and feel like yourself again.
Remember, hormone health is not a quick fix; it is a journey. Be kind to yourself as you make changes and celebrate every small victory along the way.
References:
Poumba, M., Kythreotis, A., Panayiotou, K., & Skordis, N. (2024). Estrogen receptor signaling and targets: Bones, breasts and brain. Molecular Medicine Reports. https://doi.org/10.3892/mmr.2024.13268
Role of estrogen in the regulation of central and peripheral energy homeostasis: From a menopausal perspective. (2023). Therapeutic Advances in Endocrinology and Metabolism, 14, 20420188231199359. https://doi.org/10.1177/20420188231199359
MacLean, J. A. II, & Hayashi, K. (2022). Progesterone actions and resistance in gynecological disorders. Cells, 11(4), 647. https://doi.org/10.3390/cells11040647
Plottel, C. S., & Blaser, M. J. (2013). Microbiome and estrogen metabolism: The basis for an estrogen-gut axis. Journal of Clinical Endocrinology & Metabolism, 98(7), 2290–2298. https://doi.org/10.1210/jc.2013-1235
Environmental and human health risks of estrogenic compounds: A critical review of sustainable management practices. (2025). Sustainability, 17(2), 491. https://doi.org/10.3390/su17020491
Krämer, M., & Gillevet, P. (2025). Estrobolome functions in hormonal regulation. Journal of Cancer Research and Clinical Oncology, 151, 275–285. https://doi.org/10.1007/s00432-024-05000-1
Berrino, F., Pasanisi, P., Bellati, C., Venturelli, E., Krogh, V., & Secreto, G. (2018). Serum estrogen metabolites and metabolic profiles in premenopausal women. Cancer Epidemiology, Biomarkers & Prevention, 27(2), 167–174. https://doi.org/10.1158/1055-9965.EPI-17-0634
Holinka, C. F., & Gurpide, E. (2019). Biological effects of estriol. Journal of Steroid Biochemistry and Molecular Biology, 189, 34–41. https://doi.org/10.1016/j.jsbmb.2019.02.007
Bradlow, H. L., et al. (2004). 3,3′-Diindolylmethane modulates estrogen metabolism. Journal of Clinical Endocrinology & Metabolism, 89(2), 850–856. https://doi.org/10.1210/jc.2003-031277
Thomson, C. A., Ho, E., & Strom, M. (2016). β-Glucuronidase modulation and phase II metabolism: Impact on hormone and xenobiotic detoxification. Nutrients, 8(7), 432. https://doi.org/10.3390/nu8070432
Kim, J.-L., Kim, Y.-H., Kang, M.-K., Gong, J.-H., Han, S.-J., & Kang, Y.-H. (2013). Antiosteoclastic activity of milk thistle extract after ovariectomy to suppress estrogen deficiency-induced osteoporosis. BioMed Research International, 2013, 919374. https://doi.org/10.1155/2013/919374
Wang, D., Varkaneh-Kord, A., & Abu-Zaid, A. (2022). Effects of omega-3 fatty acid supplementation on lipid metabolism and inflammatory markers in postmenopausal women: Systematic review and meta-analysis of randomized controlled trials. Nutrition, 105, 111829. https://doi.org/10.1016/j.nut.2022.111829
Prior, J. C. (2020). Women’s reproductive health as balanced estradiol and progesterone actions: Clinical and research implications. Women’s Health. https://doi.org/10.1177/1745506520927820
Menschik, E. J., et al. (2025). Hormonal regulation and dysregulation in endometriosis and related reproductive disorders. Human Reproduction Open. https://doi.org/10.1093/hropen/hoaa058
Allen, C. L., Banerjee, S., Karoshi, M., & Humaidan, P. (2025). The efficacy of progestins in managing pain associated with endometriosis, fibroids, and premenstrual syndrome: A systematic review. Archives of Gynecology and Obstetrics, 311(5), 1511–1533. https://doi.org/10.1007/s00404-025-07957-0
Joffe, H., Cohen, L. S., et al. (2020). Impact of estradiol variability and progesterone on mood in perimenopausal women. The Journal of Clinical Endocrinology & Metabolism, 105(3), e642–e650. https://doi.org/10.1210/clinem/dgz223
MacGregor, E. A., et al. (2023). Sex and hormonal influences in the epidemiology of migraine. European Journal of Neuroscience. https://doi.org/10.1111/ejn.16234
Reddy, N., Desai, M. N., Schoenbrunner, A., Schneeberger, S., & Janis, J. E. (2021). The complex relationship between estrogen and migraines: A scoping review. Systematic Reviews, 10, 72. https://doi.org/10.1186/s13643-021-01618-4
Chen, I., Wu, Z., Harlow, S. D., Karvonen‑Gutierrez, C. A., Hood, M. M., & Elliott, M. R. (2022). Variability of sex hormones and body fat changes in peri‑ and post‑menopausal women. arXiv. https://arxiv.org/abs/2207.07565
Hill, M., Heffron, S., & Hatcher, J. (2021). Hormonal influences on hair, skin, and reproductive health in women: Mechanisms and clinical implications. Journal of Endocrinology and Metabolism, 11(4), 145–158. https://doi.org/10.1097/JEM.0000000000000145
Miller, W. L., Auchus, R. J., & Shackleton, C. H. L. (2021). Steroidogenesis and steroid hormone synthesis: Pathways and regulation. Endocrine Reviews, 42(5), 486–528. https://doi.org/10.1210/endrev/bnaa026
Panossian, A., & Wikman, G. (2019). Evidence-based efficacy of adaptogens in fatigue, stress, and neuroendocrine regulation. Phytotherapy Research, 33(8), 2012–2026. https://doi.org/10.1002/ptr.6436
Pascoe, M. C., Thompson, D. R., & Ski, C. F. (2017). Yoga, mindfulness-based stress reduction and stress-related physiological measures: A meta-analysis. Psychoneuroendocrinology, 86, 152–168. https://doi.org/10.1016/j.psyneuen.2017.09.008
Stough, C., Scholey, A., Lloyd, J., Spong, J., Myers, S., Downey, L. A., & Kennedy, D. O. (2018). Nutritional support for adrenal and nervous system function: Effects on cognitive performance and mood. Nutrients, 10(6), 761. https://doi.org/10.3390/nu10060761