Differentiating Between PLANT PHYTOESTROGENS & ESTROGEN
Soyfoods do not contain human estrogen. Soybean isoflavones are not the same as human estrogen.
Hormones are chemical messengers produced by the body that cause tissues to behave in a certain way. For hormones to exert effects they need to bind to and activate receptors in cells.
Estrogen is referred to as the female sex hormone. It is primarily produced by the ovaries and travels in the bloodstream to interact with tissues.
Estrogen is crucial to the reproductive function and menstrual cycle of a woman. In premenopausal women, estrogen levels rise suddenly halfway through the cycle, which triggers the release of an egg. This level then quickly decreases after ovulation.
Estrogen is also responsible for the growth of breasts during adolescence. Other functions include helping to preserve bone strength and improving the thickness and quality of the skin. After menopause, the ovaries produce very little estrogen, so blood estrogen levels markedly decrease. That which is present in the blood comes mainly from estrogen production in fat tissue.
Despite its designation as the female sex hormone, men also produce estrogen. Estrogen in males is secreted by the adrenal glands and by the testes. Although throughout much of life estrogen levels are higher in women than men, blood estrogen levels in older men are actually higher than levels in older women.1
Isoflavones are naturally occurring compounds widely found within the plant kingdom and especially in legumes. However, among commonly consumed foods, soybeans and most foods made from soybeans are uniquely rich sources.2
Isoflavones serve two roles in plants. They are defense molecules; that is, isoflavones ward off disease-causing pathogenic fungi and other microbes.3 In addition, the soybean uses isoflavones to stimulate soil-microbe rhizobium to form nitrogen-fixing root nodules.4 Nitrogen fixation is the process by which molecular nitrogen in the air is converted into ammonia, which can be used by the plant to make compounds it requires for its survival, such as amino acids.
Isoflavones have been rigorously studied by health scientists over the past 30 years when the U.S. National Cancer Institute first expressed interest in understanding the role isoflavones in cancer prevention and treatment.5
Isoflavones have similar chemical structure to estrogen and are classified as plant estrogens because in certain situations, they exert effects similar to the hormone estrogen. However, isoflavones are very different from estrogen.
It is not unusual for compounds with similar chemical structures to have very different effects. For example, cholesterol and phytosterols have almost identical structures and yet the former modestly raises blood cholesterol6 whereas the latter lower it.7
Interaction with Estrogen Receptors
There are two receptors in cells to which estrogen binds – estrogen receptor alpha (ER-alpha) and estrogen receptor beta (ER-beta). The binding of estrogen to these receptors triggers a cascade of reactions within the cell that affects function. Estrogen has equal affinity for both receptors.
Isoflavones also bind to both estrogen receptors but in contrast to estrogen, preferentially bind to and activate ER-beta.8 This difference in binding preference between estrogen and isoflavones is important because when activated, ER-alpha and ER-beta can have very different and even opposite effects on cells.9 Compounds that specifically target ER-beta are viewed as potential anti-cancer agents.10,11
Use of estrogen therapy has been associated with an increased proliferation of cells in the breast, which can increase risk of breast cancer.12 Clinical studies show that isoflavones do not stimulate breast cell proliferation in women13-18 and population studies show exposure to isoflavones has either a neutral effect on breast cancer risk or is protective against this disease.19,20
In women, estrogen stimulates the proliferation of cells in the endometrium (lining the uterus), which can increase risk of endometrial cancer.21 Isoflavones do not stimulate endometrial cell proliferation in women22 and population studies show isoflavone exposure is associated with a decrease in endometrial cancer risk.23
Hormone Levels in Women
Estrogen therapy increases blood estrogen levels.24 Isoflavones do not affect levels of estrogen in the blood.25
Sperm and Semen
Research shows that in men estrogen reduced sperm motility and sperm density.26 Clinical studies show that isoflavones do not affect sperm or semen.27,28
Hormone Levels in Men
Isoflavones do not increase blood estrogen levels29 or lower testosterone levels.30
Muscle Mass and Strength
Supplementation with soy protein rich in isoflavones leads to increases in muscle mass and strength in individuals engaged in resistance exercise training, such as weightlifting, to the same extent as supplementation with animal protein including whey protein.31
1.Simpson ER. Sources of estrogen and their importance. J Steroid Biochem Mol Biol. 2003; 86(3-5):225-30. https://www.ncbi.nlm.nih.gov/pubmed/14623515.
2. Franke AA, Custer LJ, Wang W, et al. HPLC analysis of isoflavonoids and other phenolic agents from foods and from human fluids. Proc Soc Exp Biol Med. 1998;217(3):263-73. https://www.ncbi.nlm.nih.gov/pubmed/9492334.
3. Subramanian S, Hu X, Lu G, et al. The promoters of two isoflavone synthase genes respond differentially to nodulation and defense signals in transgenic soybean roots. Plant Mol Biol. 2004;54(5):623-39. https://www.ncbi.nlm.nih.gov/pubmed/15356384.
4. Long SR. Rhizobium-legume nodulation: life together in the underground. Cell. 1989;56(2):203-14. https://www.ncbi.nlm.nih.gov/pubmed/2643474.
5. Messina M, Barnes S. The role of soy products in reducing risk of cancer. J Natl Cancer Inst. 1991;83(8):541-6. https://www.ncbi.nlm.nih.gov/pubmed/1672382.
6. Vincent MJ, Allen B, Palacios OM, et al. Meta-regression analysis of the effects of dietary cholesterol intake on LDL and HDL cholesterol. Am J Clin Nutr. 2019;109(1):7-16. https://www.ncbi.nlm.nih.gov/pubmed/30596814.
7. Talati R, Sobieraj DM, Makanji SS, et al. The comparative efficacy of plant sterols and stanols on serum lipids: a systematic review and meta-analysis. J Am Diet Assoc. 2010; 110(5):719-26. https://www.ncbi.nlm.nih.gov/pubmed/20430133.
8. Takeuchi S, Takahashi T, Sawada Y, et al. Comparative study on the nuclear hormone receptor activity of various phytochemicals and their metabolites by reporter gene assays using Chinese hamster ovary cells. Biol Pharm Bull. 2009;32(2):195-202. https://www. ncbi.nlm.nih.gov/pubmed/19182375.
9. Oseni T, Patel R, Pyle J, et al. Selective estrogen receptor modulators and phytoestrogens. Planta Med. 2008;74(13):1656-65. https://www.ncbi.nlm.nih.gov/pubmed/18843590.
10. Ma R, Karthik GM, Lovrot J, et al. Estrogen receptor beta as a therapeutic target in breast cancer stem cells. J Natl Cancer Inst. 2017;109(3):1-14. https://www.ncbi.nlm.nih.gov/ pubmed/28376210.
11. Gallo D, De Stefano I, Grazia Prisco M, et al. Estrogen receptor beta in cancer: an attractive target for therapy. Curr Pharm Des. 2012;18(19):2734-57. https://www.ncbi.nlm.nih.gov/ pubmed/22390760.
12. Hofseth LJ, Raafat AM, Osuch JR, et al. Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast. J Clin Endocrinol Metab. 1999;84(12):4559-65. https://www.ncbi.nlm.nih.gov/pubmed/10599719.
13. Hargreaves DF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab. 1999;84(11):4017-24. https://www.ncbi.nlm.nih.gov/pubmed/10566643.
14. Sartippour MR, Rao JY, Apple S, et al. A pilot clinical study of short-term isoflavone supplements in breast cancer patients. Nutr Cancer. 2004;49(1):59-65. https://www.ncbi.nlm.nih.gov/pubmed/15456636.
15. Palomares MR, Hopper L, Goldstein L, et al. Effect of soy isoflavones on breast proliferation in postmenopausal breast cancer survivors. Breast Cancer Res Treatment. 2004;88 (Suppl 1)4002 (Abstract).
16. Cheng G, Wilczek B, Warner M, et al. Isoflavone treatment for acute menopausal symptoms. Menopause. 2007;14(3 Pt 1):468-73. https://www.ncbi.nlm.nih.gov/ pubmed/17290160.
17. Khan SA, Chatterton RT, Michel N, et al. Soy isoflavone supplementation for breast cancer risk reduction: A randomized phase II trial. Cancer Prev Res (Phila). 2012;5(2):309-19. https://www.ncbi.nlm.nih.gov/pubmed/22307566.
18. Shike M, Doane AS, Russo L, et al. The effects of soy supplementation on gene expression in breast cancer: a randomized placebo-controlled study. J Natl Cancer Inst. 2014;106(9). https://www.ncbi.nlm.nih.gov/pubmed/25190728.
19. Xie Q, Chen ML, Qin Y, et al. Isoflavone consumption and risk of breast cancer: a dose- response meta-analysis of observational studies. Asia Pacific journal of clinical nutrition. 2013;22(1):118-27. https://www.ncbi.nlm.nih.gov/pubmed/23353619.
20. Zhao TT, Jin F, Li JG, et al. Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies. Clin Nutr. 2019;38(1):136-45. https://www.ncbi.nlm.nih.gov/pubmed/29277346.
21. Woodruff JD, Pickar JH. Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group. Am J Obstet Gynecol. 1994;170(5 Pt 1): 1213-23. https://www.ncbi.nlm.nih.gov/pubmed/8178840.
22. Mareti E, Abatzi C, Vavilis D, et al. Effect of oral phytoestrogens on endometrial thickness and breast density of perimenopausal and postmenopausal women: A systematic review and meta-analysis. Maturitas. 2019;12481-8. https://www.semanticscholar. org/paper/Effect-of-oral-phytoestrogens-on-endometrial-and-of-Mareti-Abatzi/ d562204ead8a485909e3a1e985700c88b8632e6f.
23. Myung SK, Ju W, Choi HJ, et al. Soy intake and risk of endocrine-related gynaecological cancer: a meta-analysis. BJOG : an international journal of obstetrics and gynaecology. 2009;116(13):1697-705. https://www.ncbi.nlm.nih.gov/pubmed/19775307.
24. Edlefsen KL, Jackson RD, Prentice RL, et al. The effects of postmenopausal hormone therapy on serum estrogen, progesterone, and sex hormone-binding globulin levels in healthy postmenopausal women. Menopause. 2010;17(3):622-9. https://www.ncbi.nlm.nih. gov/pubmed/20215977.
25. Hooper L, Ryder JJ, Kurzer MS, et al. Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis. Hum Reprod Update. 2009;15(4):423-40. https://www.ncbi.nlm.nih.gov/ pubmed/19299447.
26. Lubbert H, Leo-Rossberg I, Hammerstein J. Effects of ethinyl estradiol on semen quality and various hormonal parameters in a eugonadal male. Fertil Steril. 1992;58(3):603-8. https://www.ncbi.nlm.nih.gov/pubmed/1387850.
27. Beaton LK, McVeigh BL, Dillingham BL, et al. Soy protein isolates of varying isoflavone content do not adversely affect semen quality in healthy young men. Fertil Steril. 2010;94(5):1717-22. https://www.ncbi.nlm.nih.gov/pubmed/19819436.
28. Mitchell JH, Cawood E, Kinniburgh D, et al. Effect of a phytoestrogen food supplement on reproductive health in normal males. Clin Sci (Lond). 2001;100(6):613-8. https://www.ncbi.nlm.nih.gov/pubmed/11352776.
29. Messina M. Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence. Fertil Steril. 2010;93(7):2095-104. https://www.ncbi.nlm.nih.gov/pubmed/20378106.
30. Hamilton-Reeves JM, Vazquez G, Duval SJ, et al. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. Fertil Steril. 2010;94(3):997-1007. https://www.ncbi.nlm.nih.gov/pubmed/19524224.
31. Messina M, Lynch H, Dickinson JM, et al. No difference between the effects of supplementing with soy protein versus animal protein on gains in muscle mass and strength in response to resistance exercise. International journal of sport nutrition and exercise metabolism. 2018;28(6):674-85. https://www.ncbi.nlm.nih.gov/pubmed/29722584.