The Safety of Phytoestrogens in Menopause, Prostate and Breast Cancer
Jill Stansbury
Paul R Saunders
David Winston
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Keywords

Phytoestrogens
Prostate cancer
Breast cancer
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Abstract

Plant based natural products have been proposed as alternatives to the use of hormones for the treatment of menopausal symptoms, which has been associated with an increased risk of breast cancer and coronary artery disease. Specific herbal compounds such as Thai Kudzu root (Pueraria mirifica) have shown beneficial effects in the treatment of peri-menopausal symptoms and menopausal-related osteoporosis when used as an adjunct or as a single medicine. Pueraria mirifica has been used in conjunction with Vitex Berry (Vitex agnus-castus), Red Clover (Trifolium pratense) Sage (Salvia officinalis and S. miltiorrhiza), and Black Cohosh (Actaea racemosa), with the optional addition of natural progesterone and soy milk. Clinically, these compounds require careful dosing and are associated with variable times to efficacy. No known drug interactions exist, although research on the effects of phytoestrogens is limited. Phytoestrogens have not been associated with increased risk of cancer and therefore provide a safe alternative to standard treatment modalities.

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References

Birnbaum, LS and Fenton, SE. Cancer and developmental exposure to endocrine disruptors. Environ Health Perspect. 2003 Apr; 111(4): 389–94.
Ho, M-S, Tang, W-Y, de Frausto, JB, et.al. Developmental Exposure to Estradiol and Bisphenol A Increases Susceptibility to Prostate Carcinogenesis and Epigenetically Regulates Phosphodiesterase Type 4 Variant 4. Cancer ResJun, 2006 66; 5624
Wu AH, Wan P, Hankin J, et.al. Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis 23:1491–6, 2002.
Jakes RW, Duffy SW, Ng FC, et.al. Mammographic parenchymal patterns and self reported soy intake in Singapore Chinese women. Cancer Epidemiol Biomarkers Prev 11:608–13, 2002.
Parkin DM, Bray F, Ferlay J, et.al. Global Cancer Statistics, 2002. CA Cancer J. Clin. 55, 74–108 ( 2005).
Hwang YW, Kim SY, Jee SH, et.al. Soy food consumption and risk of prostate cancer: a meta-analysis of observational studies. Nutr. Cancer61(5), 598–606 ( 2009).
Zhao E and Mu Qing. Phytoestrogen Biological Actions on Mammalian Reproductive System and Cancer Growth. Sci Pharm. 2011 March; 79(1):1–20.
Low YL, Dunning AM, Dowsett M, et.al. Phytoestrogen exposure is associated with circulating sex hormone levels in postmenopausal women and interact with ESR1 and NR1I2 gene variants. Cancer Epidemiol Biomarkers Prev. 2007 May; 16(5):1009–16.
Subramanian A, Salhab M, Mokbel K. Oestrogen producing enzymes and mammary carcinogenesis: a review. Breast Cancer Res Treat. 2008; 111(2):191–202.
Auricchio F, Migliaccio A, Castoria G. Sex-steroid hormones and EGF signalling in breast and prostate cancer cells: Targeting the association of Src with steroid receptors. Steroids. 2008; 73(9–10):880–4.
Cassidy A, Bingham S, Setchell K. Biological effects of isoflavones in young women – importance of the chemical composition of soybean products. Br J Nutr. 1995; 74(4):587–601.
Li L, Andersen ME, Heber S, Zhang Q. Non-monotonic dose-response relationship in steroid hormone receptor-mediated gene expression. J Mol Endocrinol. 2007; 38(5–6):569–85.
Payen L, Sparfel L, Courtois A, Vernhet L, Guillouzo A, Fardel O. The drug efflux pump MRP2: Regulation of expression in physiopathological situations and by endogenous and exogenous compounds. Cell Biol Toxicol. 2002; 18(4):221–33.
Bliedtner A, Zierau O, Albrecht S, Liebhaber S, Vollmer G. Effects of genistein and estrogen receptor subtype-specific agonists in ArKO mice following different administration routes. Mol Cell Endocrinol. 2010; 314(1):41–52.
Hsieh T, Wu JM. Targeting CWR22R nu 1 prostate cancer cell proliferation and gene expression by combinations of the phytochemicals EGCG, genistein and quercetin. Anticancer Res. 2009; 29(10):4025–32.
Doerge DR, Sheehan DM. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect. 2002 Jun; 110 Suppl 3:349–53.
Sosic-Jurjević B, Filipović B, Ajdzanović V, Savin S, Nestorović N, Milosević V, Sekulić M. Suppressive effects of genistein and daidzein on pituitary-thyroid axis in orchidectomized middle-aged rats. Exp Biol Med (Maywood). 2010 May; 235(5):590–8.
Son HY, Nishikawa A, Ikeda T, Imazawa T, Kimura S, Hirose M. Lack of effect of soy isoflavone on thyroid hyperplasia in rats receiving an iodine-deficient diet. Jpn J Cancer Res. 2001 Feb; 92(2):103–8.
Morani A, Warner M, Gustafsson J-. Biological functions and clinical implications of oestrogen receptors alfa and beta in epithelial tissues. J Intern Med. 2008; 264(2):128–42.
Hermann RM, Wolff HA, Jarry H, Thelen P, Gruendker C, Rave-Fraenk M, et al. In vitro studies on the modification of low-dose hyper-radiosensitivity in prostate cancer cells by incubation with genistein and estradiol. Radiation Oncology. 2008; 3:19.
Geller J, Sionit L, Partido C, et.al. Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture. The Prostate 1998; 34:75–9.
Kikuno N, Shiina H, Urakami S, Kawamoto K, Hirata H, Tanaka Y, et al. Genistein mediated histone acetylation and demethylation activates tumor suppressor genes in prostate cancer cells. International Journal of Cancer. 2008; 123(3):552–60.
Kumar NB, Krischer JP, Allen K, Riccardi D, Besterman-Dahan K, Salup R, et al. Safety of purified isoflavones in men with clinically localized prostate cancer. Nutrition and Cancer–an International Journal. 2007; 59(2):169–75.
Pendleton JM, Tan WW, Anai S, Chang M, Hou W, Shiverick KT, et al. Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy. BMC Cancer. 2008; 8:132.
Jackson RL, Greiwe JS, Schwen RJ. Emerging evidence of the health benefits of S-equol, an estrogen receptor β agonist. Nutr Rev. 2011 Aug; 69(8):432–48.
Branca F, Lorenzetti S. Health effects of phytoestrogens. Diet Diversification and Health Promotion. 2005; 57:100–111.
Fritz WA, Eltoum IE, Cotroneo MS, Lamartiniere CA. Genistein alters growth but is not toxic to the rat prostate. J Nutr. 2002; 132(10):3007–11.
Strom SS, Yamamura Y, Duphorne CM, Spitz MR, Babaian RJ, Pillow PC, et al. Phytoestrogen intake and prostate cancer: A case-control study using a new database. Nutrition and Cancer–an International Journal. 1999; 33(1):20–5.
Almstrup K, Fernandez MF, Petersen JH, Olea N, Skakkebaek NE, Leffers H. Dual effects of phytoestrogens result in U-shaped dose-response curves. Environ Health Perspect. 2002; 110(8):743–8.
Sasano H, Nagasaki S, Miki Y, Suzuki T. New Developments in Intracrinology of Human Breast Cancer Estrogen Sulfatase and Sulfotransferase. Steroid Enzymes and Cancer. 2009; 1155:76–9.
Frenette G, Leclerc P, D’Amours O, Sullivan R. Estrogen Sulfotransferase Is Highly Expressed Along the Bovine Epididymis and Is Secreted Into the Intraluminal Environment. J Androl. 2009; 30(5):580–9.
Pasqualini JR. Estrogen Sulfotransferases in Breast and Endometrial Cancers. Steroid Enzymes and Cancer. 2009; 1155:88–98.
Day JM, Tutill HJ, Purohit A, Reed MJ. Design and validation of specific inhibitors of 17 beta-hydroxysteroid dehydrogenases for therapeutic application in breast and prostate cancer, and in endometriosis. Endocr Relat Cancer. 2008; 15(3):665–92.
Krazeisen A, Breitling R, Moller G, Adamski J. Phytoestrogens inhibit human 17 beta-hydroxysteroid dehydrogenase type 5. Mol Cell Endocrinol. 2001; 171(1-2):151–62.
Le Bail JC, Champavier Y, Chulia AJ, Habrioux G. Effects of phytoestrogens on aromatase, 3 beta and 17 beta-hydroxysteroid dehydrogenase activities and human breast cancer cells. Life Sci. 2000; 66(14):1281–91.
Spires TE, Fink BE, Kick EK, You D, Rizzo CA, Takenaka N, et al. Identification of novel functional inhibitors of 17 beta-hydroxysteroid dehydrogenase type III (17 beta-HSD3). Prostate. 2005; 65(2):159–70.
Zhu YS, Sun GH. 5alpha-Reductase Isozymes in the Prostate. J Med Sci. 2005; 25(1):1–12.
Cai LQ, Imperato-McGinley J, Zhu YS. Regulation of prostate 5-alpha-reductase-2 gene expression and prostate weight by dietary fat and caloric intake in the rat. Prostate. 2006 May 15; 66(7):738–748.
Cai LQ, Cai J, Wu W, et.al. 17α-Estradiol and genistein inhibit high fat diet induced prostate gene expression and prostate growth in the rat. J Urol. 2011 Oct; 186(4):1489–96.
Drsata J. [Enzyme inhibition in the drug therapy of benign prostatic hyperplasia]. Casopis lekarǔ cěskych. 2002; 141(20):630–5.
Wadsworth TL, Worstell TR, Greenberg NM, Roselli CE. Effects of dietary saw palmetto on the prostate of transgenic adenocarcinoma of the mouse prostate model (TRAMP). Prostate. 2007; 67(6):661–73.
Habib FK, Ross M, Ho CKH, Lyons V, Chapman K. Serenoa repens (Permixon (R)) inhibits the 5 alpha-reductase activity of human prostate cancer cell lines without interfering with PSA expression. International Journal of Cancer. 2005; 114(2):190–4.
Rhodes L, Primka RL, Berman C, Vergult G, Gabriel M, Pierre-Malice M, Gibelin B. Comparison of finasteride (proscar®), a 5α reductase inhibitor, and various commercial plant extracts in in vitro and in vivo 5α reductase inhibition. Prostate. 1993; 22:43–51.
Pelletier G. Expression of steroidogenic enzymes and sex-steroid receptors in human prostate. Best Practice & Research Clinical Endocrinology & Metabolism. 2008; 22(2):223–8.
Onsory K, Sobti RC, Al-Badran AI, Watanabe M, Shiraishi T, Krishan A, et al. Hormone receptor-related gene polymorphisms and prostate cancer risk in North Indian population. Mol Cell Biochem. 2008; 314(1-2):25–35.
Balunas MJ, Kinghorn AD. Natural Compounds with Aromatase Inhibitory Activity: An Update. Planta Med. 2010; 76(11):1087–93.
Musa MA, Cooperwood JS, Khan MOF. A Review of Coumarin Derivatives in Pharmacotherapy of Breast Cancer. Curr Med Chem. 2008; 15(26):2664–79.
Paoletta S, Steventon GB, Wildeboer D, Ehrman TM, Hylands PJ, Barlow DJ. Screening of herbal constituents for aromatase inhibitory activity.Bioorg Med Chem. 2008; 16(18):8466–70.
Tempfer CB, Froese G, Heinze G, Bentz E, Hefler LA, Huber JC. Side Effects of Phytoestrogens: A Meta-analysis of Randomized Trials. Am J Med. 2009; 122(10):939–U133.
Roberts H. Safety of herbal medicinal products in women with breast cancer. Maturitas. 2010; 66(4):363–9.

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