Kaitlyn Zorn, HBSc, ND

Vis Medicatrix Naturae

“Estrogen dominance” is a term used in naturopathic medicine to describe a high ratio of estrogen to progesterone. Different factors in our Western lifestyle, such as high stress and synthetic hormone exposure, contribute to the etiology of excess estrogen and estrogen dominance. Other factors involved in the development of this condition are anovulatory cycles due to irregular menses, dysinsulinemia, hyperprolactinemia, and calcium and magnesium deficiency.¹ Environmental exposures to xenoestrogens and alcohol consumption may also be contributors. A cross-sectional analysis of premenopausal women showed a positive association between total alcohol intake and estradiol levels: Women who consumed greater than 5 alcoholic drinks per week had higher urinary estradiol levels compared with non-drinkers.² Xenoestrogens or other endocrine disruptors have been demonstrated to act as estrogen receptor (ER)-alpha ligands, increasing estrogenic activity.³ It is also thought that diets high in processed foods and animal products can further increase estrogen dominance.

Related Conditions

Even when absolute estrogen levels are normal, if the ratio of estrogen to progesterone is high, symptoms of excess estrogen levels can occur. This is quite common in young and middle-aged women, yielding symptoms ranging from insomnia, mood swings, anxiety, depression, and weight gain, to menstrual issues, brain fog, and infertility and miscarriages.¹ According to the American Associations of Naturopathic Physicians, estrogen dominance has been associated with a variety of other conditions including fatigue, fibrocystic breasts, headaches and uterine fibroids.³ Hypothetical risks of hormonal cancers related to estrogen dominance are also of concern to patients and practitioners.

High absolute estrogen levels have been correlated with increased rates of hormonal cancers such as breast and endometrial cancers.⁴ The concept of estrogen dominance, however, has not been a known risk factor for hormonal cancers in the literature. Adding to the complexity is the notion that there are “bad” circulating estrogen metabolites (2-hydroxyestrone) and “good” estrogen metabolites (4-hydroxyestrone and 16-hydroxyestrone). It has been proposed in the naturopathic community that, by decreasing estrogen metabolism to 2-hydroxy (-OH) estrone and supporting the safer estrogen metabolism to 4-OH- and 16-OH-estrone, these cancer risks may be reduced.⁴ Despite acceptance of this hypothesis, clinical studies showing a significant association between the estrogen metabolite type and breast cancer are lacking, as reported in a Townsend Letter examining this topic.⁵ On the contrary, a relationship between high total estrogen levels and increased risks of breast cancer has been demonstrated. Thus, naturopathic practice may benefit from a focus on overall estrogen imbalance, rather than on types of estrogen metabolism. The European Prospective Investigation into Cancer and Nutrition (EPIC) found that, in post-menopausal women, those with the highest estrogen levels had a greater than 2-fold increase in breast cancer risk.⁶ The Nurses’ Health Study II found that, in premenopausal women, follicular (menstrual cycle days 3-5) estrogen levels were associated with breast cancer risk.⁷ This may be due to the fact that, during the follicular phase, estrogen promotes breast cancer cell growth. If it is not counterbalanced by adequate progesterone, as in estrogen dominance, the risk of breast cancer may potentially be increased, but there remains no literature supporting this hypothesis.

Diagnosis

Salivary and blood tests can be used to measure levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P), and thyroid stimulating hormone (TSH). A normal mid-follicular E2 level in a cycling woman is 27-123 pg/mL, and a normal post-menopausal level is 0-40 pg/mL.⁸ Progesterone is best measured during the luteal phase in premenopausal women and is normal at 5–20 ng/mL.⁹ Although there is no standard reference range for estrogen to progesterone ratio, there are suggested optimal E2:P ranges as seen in various salivary lab testing. For example, Genova Diagnostics uses a P:E2 range of 23-159 in the follicular phase, 25-141 in the luteal phase, and 33-116 after menopause to help in the diagnosis of estrogen dominance.¹⁰

From a Traditional Chinese Medicine (TCM) approach, the Liver, Kidney, Penetrating (PV), Conception (CV), Spleen, Heart, Governing (GV) and Belt (BV) channels are involved in regulating gynecology.¹¹ Symptoms of Liver Qi stagnation are very similar to those of estrogen dominance, featuring premenstrual syndrome (PMS), mood swings, and irritability. Various symptoms of Qi blockages may occur along the Liver meridian as well, such as fibrocystic breast masses, as well as cysts and masses in the uterus.

Treatment

Whether treating estrogen dominance or high absolute estrogen, there are many naturopathic strategies that have been shown to promote healthy estrogen levels and metabolism and that may alleviate correlated symptoms and potentially reduce risks of hormonal cancers.

An intervention that promotes hormonal clearance from the liver may be advisable. The cytochrome P450 phase I and phase II enzymes are necessary for proper estrogen metabolism and clearance. In order for estrogen metabolites to be effectively cleared from the body, phase II cytochrome P450 reactions convert harmful metabolites into compounds that are water-soluble and can then be excreted via the kidneys.¹² Certain sulfur-containing foods such as those from the brassica family (eg, broccoli, Brussels sprouts, kale, and cabbage) as well as garlic and onions have been shown to upregulate phase II reactions, thereby promoting estrogen clearance. Preliminary research has shown that supplementation with indole-3-carbinol (I3C, a compound found in brassicas) can promote 2-hydroxylation of estrogen, suggesting a beneficial effect on estrogen metabolism and a potential reduction in estrogenic stimulation and breast cancer risk.^13,14 As previously discussed, the form of estrogen metabolite may not be as important as once thought. However, there is adequate evidence to suggest that overall estrogen metabolism and clearance can be enhanced with dietary and supplemental interventions.

Vitamin B6 (pyridoxine) and magnesium are both involved in estrogen metabolism, specifically in the hepatic conversion of 2-OH-hydroxyestrone to 2-methoxyestrone.¹⁵ A study found that supplementation with 250 mg of magnesium plus 40 mg of vitamin B6 daily led to significant reductions in mean PMS scores.¹⁶

From a TCM perspective, promoting a smooth flow of Liver Qi can help clear the meridian, and alleviate PMS symptoms such a breast tenderness, mood swings, irritability and headaches. In a randomized clinical study, acupuncture sessions performed twice weekly for 2 menstrual cycles resulted in a 58.9% reduction in anxiety on the Hamilton Anxiety (HAM-A) scale and a 52.0% reduction in depression as seen on the Hamilton Depression (HAM-D) scale), indicating its usefulness in premenstrual dysphoric disorder.¹⁷

From a lifestyle perspective, it is thought that reducing environmental exposures to xenoestrogens like bisphenol-A (BPA) in plastics, and eating a diet low in saturated and trans-fatty acids, as well as simple carbohydrates, may help to support healthy estrogen levels. Postmenopausal vegetarian women without breast cancer were found to have significantly lower levels of plasma estrone-sulfate, estradiol, and free estradiol, and higher levels of sex-hormone-binding-globulin compared with an omnivorous group with breast cancer.¹⁸ Reducing caffeine and alcohol and incorporating adequate physical activity may further support proper estrogen metabolism. An exercise level of 300 minutes per week was shown to reduce urine estrogen levels by 18.9%, thus reducing breast cancer risk in high-risk premenopausal women.¹⁹

Overall, an integrative approach involving dietary and lifestyle interventions, as well as acupuncture and TCM, can help promote healthy estrogen levels, reducing symptoms of PMS, and potentially lowering risks of hormone- related cancers, especially in postmenopausal women. From a naturopathic perspective, balancing progesterone levels, in relation to estrogen, may also be clinically effective in managing hormone-related symptoms and conditions, but was not a focus of this paper. The theory of estrogen dominance and excess estrogen is widely prevalent in naturopathic practice, and future research in this field will help NDs to create ideal treatment recommendations for patients.

References:

1. Friedman M. Fundamentals of Naturopathic Endocrinology. Lady Lake, Florida: Muskeegee Medical Publishing Company; 2014.
2. Hartman TJ, Sisti JS, Hankinson SE, et al. Alcohol Consumption and Urinary Estrogens and Estrogen Metabolites in Premenopausal Women. Horm Cancer. 2016;7(1):65-74.
3. La Rosa P, Pellegrini M, Totta P, et al. Xenoestrogens Alter Estrogen Receptor (ER) alpha Intracellular Levels. PLOS One. 2014; 9(2):e88961.
4. Lucille H. Estrogen Dominance: Too much of a good thing can certainly be bad. [Web page]. Naturopathic Physicians: Natural Medicine. Real Solutions. AANP Website. http://www.naturopathic.org/content.asp?contentid=401. Accessed November 28, 2016.
5. Schor J. Estrogen Metabolite Ratios: Time for Us to Let Go [Web page]. Townsend Letter: The Examiner of Alternative Medicine Website. http://www.townsendletter.com/Jan2013/estrogen0113.html. Accessed November 28, 2016.
6. Kaaks R, Rinaldi S, Key TJ, et al. Postmenopausal serum androgens, oestrogens and breast cancer risk: The European prospective investigation into cancer and nutrition. Endocr Relat Cancer. 2005;12:1071-1082.
7. Eliassen AH, Missmer SA, Tworoger SS, et al. Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst. 2006; 98(19):1406-1415.
8. Sofronescu AG. Estradiol [Web page]. Medscape Website. http://emedicine.medscape.com/article/2089003-overview#a1. Accessed November 28, 2016.
9. White C. Serum progesterone: MedlinePlus Medical Encyclopedia. [Web page]. MedlinePlus. https://medlineplus.gov/ency/article/003714.htm. Accessed January 5, 2017.
10. Rhythm Sample Report. Genova Diagnostics [Web page]. https://www.gdx.net/core/sample-reports/Rhythm-Sample-Report.pdf. Accessed January 5, 2017
11. Kassam N . Comprehensive Notes. Asian Medicine III, ASM302. Toronto, Ontario: Canadian College of Naturopathic Medicine; 2015
12. Nutritional Influences on Estrogen Metabolism. Applied Nutritional Science Reports. [Web page]. Advanced Nutrition Publications, Inc. http://www.afmcp-sa.com/ansr/MET451%20Endocrine%20ANSR.pdf. Accessed November 28, 2016.
13. Bradlow HL, Michnovicz JJ, Halper M, et al. Long-term responses of women to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prev. 1994;3(7):591-595. https://www.ncbi.nlm.nih.gov/pubmed/7827590
14. Michnovicz JJ, Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst. 1997;89(10):718-23
15. Hall, DC. Nutritional Influences on Estrogen Metabolism [Web page]. Applied Nutritional Science Reports Website. http://www.afmcp-sa.com/ansr/MET451%20Endocrine%20ANSR.pdf. Accessed November 28, 2016.
16. Fathizadeh N, Ebrahimi E, Valiani M, et al. Evaluating the effect of magnesium and magnesium plus vitamin B6 supplement on the severity of premenstrual syndrome. Iran J Nurs Midwifery Res. 2010;15(Suppl 1):401-405.
17. Carvalho, Weires K, Ebling M, et al. Effects of acupuncture on the symptoms of anxiety and depression caused by premenstrual dysphoric disorder. Acupunct Med. 2013;31(4):358-363.
18. Aubertin-Leheudre M, Hamalainen E, Adlercreutz H. Diets and hormonal levels in postmenopausal women with or without breast cancer. Nutr Cancer. 2011;63(4):514-524.
19. Kossman DA, Williams NI, Domchek SM, et al. Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer. J Appl Physiol. 2011;111(6):1687-1693.

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Kaitlyn Zorn, HBSc, ND, practices in Guelph at Healing Foundations Naturopathic Clinic. Kaitlyn has a general family naturopathic practice, however, she has a keen interest in treating mental health conditions such as stress, anxiety, and depression; conditions related to hormone imbalances such as gynecological problems, adrenal, and thyroid conditions; and, digestive concerns, such as food sensitivities, bloating, and indigestion. She graduated from the Canadian College of Naturopathic Medicine (CCNM) in 2016. In her 4^th year internship at CCNM, Dr. Zorn gained experience in Adjunctive Cancer Care. In her spare time, she loves cooking, being in nature and doing yoga.