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Soy

Soy

Common Names

  • Soybean
  • Soya
  • Tofu
  • Miso
  • Tempeh

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For Patients & Caregivers

How It Works

Whether soy helps relieve menopausal symptoms is still unclear. It may reduce risk of some cancers.

Soy contains large amounts of substances known as isoflavones, also called phytoestrogens. These substances act in a similar way as estrogen in the body and may also be antioxidants. The effects are weak in younger women because estrogen is abundant. At menopause, however, the effects may increase due to the decrease in estrogen. Studies in animals suggest that soy can prevent or reduce bone loss by acting like estrogen and by reducing loss of calcium.

In laboratory studies, isoflavones slowed down the growth of several different types of cancer cells, including breast and prostate cancers. Animal studies showed that genistein, one of the isoflavones, may interfere with tamoxifen that is used for breast cancer. But a new study showed that soy foods can benefit women with breast cancer.

Patients should consult their physicians about use of soy supplements.

Purported Uses
  • To prevent cancer
    Laboratory and some clinical studies suggest that women with high soy intake have a lower risk of developing breast cancer. High intake of isoflavones can also reduce risk of lung cancer.
  • To prevent heart disease
    Clinical trials show that soy protein, not pills, reduces LDL (bad) cholesterol levels, which may help prevent heart disease.
  • To reduce high cholesterol
    Clinical trials show that soy protein, not pills, reduces LDL (bad) cholesterol levels and may increase HDL (good) cholesterol levels.
  • To treat menopause symptoms such as hot flashes, vaginal dryness, sleep disturbances, mood problems
    Clinical studies have conflicting results.
  • To prevent bone loss
    Some clinical trials and animal studies support this use.

Patient Warnings

Consumption of home-fermented tofu resulted in two cases of botulism.

Do Not Take If
  • You are hypersensitive to soy products.
  • You are taking tamoxifen: Animal studies have shown that genistein may reduce the effects of tamoxifen on estrogen-dependent breast cancer.
  • You are taking aromatase Inhibitors: Soy-based supplements may reduce the effects of aromatase inhibitors used in breast cancer treatment.
  • You are taking cytochrome P450 substrate drugs: Soymilk and miso may make them less effective.
  • You are taking P-Glycoprotein substrate drugs: Soymilk and miso may make them less effective.
  • You are taking UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrate drugs: Soy can increase the side effects of these drugs.

Side Effects
  • Flatulence
  • Allergic reactions

Case Reports

  • Breast enlargement: In a 60-year-old man following consumption of soy milk over a period of 6 months. Symptoms resolved after discontinuing use.
  • Abnormal uterine bleeding: In 3 women after a high intake of soy products. Symptoms improved following withdrawal of use.
  • Loss of sex drive and erectile dysfunction: In a 19-year-old diabetic man who was otherwise healthy, following intake of large amounts of soy-based products in a vegan-style diet. Symptoms improved 1 year after discontinuing the diet.
  • Death related to salt poisoning: A 55-year-old woman died following ingestion of a large quantity of Japanese shoyu soy sauce.
  • Seizure-like activity from elevated blood sodium levels: In a 19-year-old man 2 hours after ingesting a quart of soy sauce.
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For Healthcare Professionals

Scientific Name
Glycine max

Clinical Summary

Soybeans, derived from Glycine max, are rich in protein and other essential nutrients and are widely consumed as food. Soy also contains significant amounts of isoflavones — genistein (4’,5,7-trihydroxyisoflavone), daidzein (4’,7-dihydroxyisoflavone), and glycitein (4’,7-dihydroxy-6-methoxyisoflavone) (1). They are marketed as dietary supplements to treat hot flashes, high cholesterol, and for cancer prevention. Isoflavones are thought to exhibit both selective estrogen receptor modulator activity and non-hormonal effects. Studies on the effect of soy for menopausal symptoms are inconclusive (2) (3) (4) (5) (6) (7) (8) (9). While some studies indicate slower bone density loss (10) (11), others report no such effects in postmenopausal women (12) (13). It was shown to reduce low-density-lipoprotein (LDL) (14) in postmenopausal women (15) and blood pressure in hypertensive postmenopausal women (16), suggesting a benefit for cardiovascular health (17). Genistein reduced fasting blood glucose and insulin levels as well as improving insulin resistance (18). Soy intake also reduced proteinuria in type 2 diabetic patients with nephropathy (19). However, conflicting data suggest no such protective effects against diabetes (20).

Soy may reduce risk of prostate (21) (22) (23), lung (24) (80), and endometrial (25) (26) cancers, but can increase the risk of bladder cancer (27) and endometrial hyperplasia (28). It was also shown to prevent breast cancer (29) (30) but conflicting data suggest that supplementation may have adverse effects (31) (32). A study done in mice suggests that consumption of soy products may increase metastasis (33), and daidzin-rich extracts may promote ER-positive breast cancer growth ().

Genistein, the most estrogenic isoflavone (34), demonstrates antiproliferative effects in multiple cell lines, including breast cancer (ER-positive and negative) (35), prostate cancer (androgen-dependent and independent) (36), nasopharyngeal carcinoma (37), neuroblastoma, sarcoma, and retinoblastoma cells (36). Animal studies also show that genistein antagonizes the effects of tamoxifen (38) (39) and promotes tumor progression in advanced prostate cancer (40). Soy supplements may decrease serum PSA levels in prostate cancer patients before prostatectomy (41), but this effect is not observed in patients after prostatectomy (82) . Further research is needed to evaluate the role of genistein in cancer prevention.

Soy consumption reduced mortality and recurrence in breast cancer patients, regardless of tamoxifen use (42). However new data suggest that supplementation may stimulate overexpression of breast cancer genes in patients with invasive breast cancer (87).

In other studies, soy prolonged survival among women with lung cancer (81). Supplementation with isoflavones may reduce the adverse effects associated with chemotherapy (43) and radiotherapy (44), but when used together with vitamin E and selenium, did not prevent prostate cancer progression (45). It was also ineffective in reducing hot flashes in patients with prostate cancer (83).

Patients should consult their physicians about the use of soy supplements.

Food Sources

Raw soybeans, low-fat soy flour, roasted soybeans, dry-roasted soy beans, soy milk, tofu, and soy protein isolate. There are no isoflavones in soy sauce or soy oil.

Purported Uses
  • Cancer prevention
  • Cardiovascular disease
  • High cholesterol
  • Menopausal symptoms
  • Osteoporosis

Mechanism of Action

Animal studies suggest that genistein and daidzein have an ability to prevent or reduce bone loss in a manner similar to synthetic estrogen due to increased beta versus alpha estrogen receptor (ER) binding (10). Both isoflavones may modulate bone remodeling through ERs by regulating target gene expression (50). Soy may also contribute to maintaining bone density by causing less calcium to be excreted in the urine (35).

Proposed mechanisms of soy’s cholesterol-lowering effect include phytoestrogen-induced hyperthyroid state and increased excretion of bile acids, which may enhance removal of LDL. Isoflavones may inhibit oxidation of LDL and may alter hepatic metabolism with enhanced removal of LDL and VLDL by hepatocytes (17). Serum lipids may also be regulated through modified transcription factor and downstream gene expression and by promoting antioxidant enzyme activity (51).

The phytochemicals in soybeans also exhibit anticarcinogenic activity, for which many mechanisms have been proposed. Genistein affects microRNA expression—targeted translation inhibitors for multiple proteins implicated in the regulation of various pathobiological processes in cancer (52). In addition, genistein demonstrated an anti-minichromosome maintenance (MCM) effect, a gene family frequently upregulated in various cancers and considered a promising anticancer drug target (53).

In breast cancer, genistein acts as an agonist to estrogen receptor (ER)-alpha in ER-alpha-predominant breast cancer cells, but likely acts as an antiestrogen in cells with ER-beta alone, suggesting therapeutic potential for premenopausal women with ER-alpha-negative/ER-beta-positive tumors (54). However, in an in vitro breast model, genistein also induced estrogen-dependent MCF-7 tumor cell growth and increased breast cancer-associated aromatase expression and activity, suggesting that soy-based supplements may affect the efficacy of aromatase inhibitors used in breast cancer treatment (55). Genistein is also known to negate the inhibitory effect of tamoxifen on MCF-7 tumor growth and increase expression of estrogen-responsive genes (38). Alternatively, soy isoflavones may reduce breast cancer risk by decreasing endogenous ovarian steroid levels (56). Studies suggest that some benefits ascribed to dietary isoflavones may depend on early life exposure, thereby impacting gene expression at an epigenetic level. (47) (48) (49)

In prostate cancer, soy protein extracts appear to influence the progression of established tumors rather than inhibit etiologic factors. Furthermore, soy protein consumption reduces androgen receptor expression in prostate tumors (57). Other proposed prevention mechanisms include genistein-induced prostate cancer cell adhesion, direct growth inhibition, and induction of apoptosis (22). Growth inhibition appears to be independent of genistein’s estrogenic effects. In human prostate cancer cell lines, both genistein and daidzein affect microRNA regulation (58) and induce decreased methylation of gene promoters including BRCA1 (59). In tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant prostate cancer cells, soy isoflavones enhance TRAIL-mediated apoptosis by engaging apoptotic pathways and regulating NF-κB activity (60) (61). However, in a patient-derived prostate cancer xenograft model, increased proliferation and metastasis in genistein-treated groups were linked to enhanced activities of tyrosine kinases, the epidermal growth factor receptor, and its downstream Src (40). Both genistein and daidzein also act as radiosensitizers for prostate cancer in vitro and in vivo, but pure genistein increased lymph node metastasis, whereas the combination of genistein, daidzein, and glycitein did not. Daidzein may protect against genistein-induced metastasis, and its ability to inhibit cell growth and potentiate radiation appears to be androgen-receptor-independent (62). In addition, soy isoflavones radiosensitized human A549 NSCLC cells, and decreased hemorrhages, inflammation, and fibrosis caused by radiation suggesting protection of normal lung tissue (63). The combination of genistein, daidzein, and glycitein also mediated growth-suppressive effects via ER-beta in DLD-1 human colon adenocarcinoma cells (64). 7,3’,4’-trihydroxyisoflavone (THIF), a daidzein metabolite, targets Cot and MKK4 to inhibit UVB-induced skin cancer (65) and cyclin-dependent kinases and phosphatidylinositol 3-kinase to inhibit EGF-induced proliferation and transformation in JB6 P+ mouse epidermal cells (66).

The intestinally derived isoflavone metabolite R-equol, but not S-equol, was also found to be potently chemopreventive (67). However, neonatal and prepubertal exposure to equol showed no long-term chemoprevention against DMBA-induced mammary tumors even though an equol-exposure ’imprinting’ effect resulted in a decrease in immature terminal end structures and an increase in mature lobules (68).

The soy peptide lunasin exhibits chemopreventive properties via gene expression upregulation (69) and cell adhesion (70), apoptosis (71), and anti-inflammatory activity (72).

Warnings

Consumption of home-fermented tofu resulted in two cases of botulism (84).

Contraindications
  • Contraindicated in patients who are hypersensitive to soy products.

Adverse Reactions
  • Flatulence, allergic reactions

Case Reports

  • Gynecomastia: In a 60-year-old man following consumption of soy milk over a period of 6 months. Symptoms resolved after discontinuing use (76).
  • Abnormal uterine bleeding: With endometrial pathology in 3 women after a high intake of soy products. Symptoms improved following withdrawal of use (77).
  • Loss of libido and erectile dysfunction: In a 19-year-old diabetic man who was otherwise healthy, following intake of large amounts of soy-based products in a vegan-style diet. Symptoms improved 1 year after discontinuing the diet (78).
  • Death from massive pulmonary edema: A 55-year-old woman died following ingestion of a large quantity of Japanese shoyu soy sauce  (79).
  • Seizure-like activity due to acute hypernatremia: In a 19-year-old man 2 hours after ingesting a quart of soy sauce. Symptoms improved following treatment with large quantities of water (85).

Herb-Drug Interactions
  • Tamoxifen: Animal studies suggest that genistein may antagonize the effects of tamoxifen on estrogen-dependent breast cancer (MCF-7) (38) (39).
  • Aromatase inhibitors: Genistein also induced MCF-7 tumor cell growth and increased breast cancer-associated aromatase expression and activity in an in vitro breast model, suggesting that soy-based supplements may affect the efficacy of aromatase inhibitors used in breast cancer treatment (55).
  • Cytochrome P450 substrates: Soymilk and miso were shown to induce CYP3A4 in vivo, and can affect the intracellular concentration of drugs metabolized by this enzyme (86).
  • P-Glycoprotein: Soymilk and miso were shown to induce P-Gp in vivo, and can affect the intracellular concentration of certain drugs (86).
  • UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrates: Soy modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (75).

Dosage (OneMSK Only)

References

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  2. Van Patten CL, Olivotto IA, Chambers GK, et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol. Mar 15 2002;20(6):1449-1455.

  3. Cassidy A, Bingham S, Setchell KD. Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. Am J Clin Nutr. Sep 1994;60(3):333-340.

  4. Han KK, Soares JM, Jr., Haidar MA, et al. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol. Mar 2002;99(3):389-394.

  5. Newton KM, Reed SD, LaCroix AZ, et al. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. Dec 19 2006;145(12):869-879.

  6. Scambia G, Mango D, Signorile PG, et al. Clinical effects of a standardized soy extract in postmenopausal women: a pilot study. Menopause. Mar-Apr 2000;7(2):105-111.

  7. Upmalis DH, Lobo R, Bradley L, et al. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study. Menopause. Jul-Aug 2000;7(4):236-242.

  8. Brink E, Coxam V, Robins S, et al. Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: a randomized, double-blind, placebo controlled study. Am J Clin Nutr. Mar 2008;87(3):761-770.

  9. Jacobs A, Wegewitz U, Sommerfeld C, et al. Efficacy of isoflavones in relieving vasomotor menopausal symptoms - A systematic review. Mol Nutr Food Res. Sep 2009;53(9):1084-1097.

  10. Potter SM, Baum JA, Teng H, et al. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr. Dec 1998;68(6 Suppl):1375S-1379S.

  11. Marini H, Minutoli L, Polito F, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. Jun 19 2007;146(12):839-847.

  12. Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA. Jul 7 2004;292(1):65-74.

  13. Alekel DL, Van Loan MD, Koehler KJ, et al. The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Am J Clin Nutr. Jan 2010;91(1):218-230.

  14. Rideout TC, Chan YM, Harding SV, et al. Low and moderate-fat plant sterol fortified soymilk in modulation of plasma lipids and cholesterol kinetics in subjects with normal to high cholesterol concentrations: report on two randomized crossover studies. Lipids Health Dis. 2009;8:45.

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  16. Welty FK, Lee KS, Lew NS, et al. Effect of soy nuts on blood pressure and lipid levels in hypertensive, prehypertensive, and normotensive postmenopausal women. Arch Intern Med. May 28 2007;167(10):1060-1067.

  17. Lissin LW, Cooke JP. Phytoestrogens and cardiovascular health. J Am Coll Cardiol. May 2000;35(6):1403-1410.

  18. Atteritano M, Marini H, Minutoli L, et al. Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: a two-year randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. Aug 2007;92(8):3068-3075.

  19. Azadbakht L, Esmaillzadeh A. Soy-protein consumption and kidney-related biomarkers among type 2 diabetics: a crossover, randomized clinical trial. J Ren Nutr. Nov 2009;19(6):479-486.

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  26. Goodman MT, Wilkens LR, Hankin JH, et al. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol. Aug 15 1997;146(4):294-306.

  27. Sun CL, Yuan JM, Arakawa K, et al. Dietary soy and increased risk of bladder cancer: the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev. Dec 2002;11(12):1674-1677.

  28. Unfer V, Casini ML, Costabile L, et al. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Fertil Steril. Jul 2004;82(1):145-148, quiz 265.

  29. Cline JM, Hughes CL, Jr. Phytochemicals for the prevention of breast and endometrial cancer. Cancer Treat Res. 1998;94:107-134.

  30. Butler LM, Wu AH, Wang R, et al. A vegetable-fruit-soy dietary pattern protects against breast cancer among postmenopausal Singapore Chinese women. Am J Clin Nutr. Apr 2010;91(4):1013-1019.

  31. Trock BJ, Hilakivi-Clarke L, Clarke R. Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst. Apr 5 2006;98(7):459-471.

  32. Steinberg FM, Murray MJ, Lewis RD, et al. Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women. Am J Clin Nutr. Feb 2011;93(2):356-367.

  33. Martinez-Montemayor MM, Otero-Franqui E, Martinez J, et al. Individual and combined soy isoflavones exert differential effects on metastatic cancer progression. Clin Exp Metastasis. Oct 2010;27(7):465-480.

  34. Muthyala RS, Ju YH, Sheng S, et al. Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta. Bioorg Med Chem. Mar 15 2004;12(6):1559-1567.

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  36. Setchell KD. Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr. Dec 1998;68(6 Suppl):1333S-1346S.

  37. Han H, Zhong C, Zhang X, et al. Genistein induces growth inhibition and G2/M arrest in nasopharyngeal carcinoma cells. Nutr Cancer. 2010;62(5):641-647.

  38. Ju YH, Doerge DR, Allred KF, et al. Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice. Cancer Res. May 1 2002;62(9):2474-2477.

  39. Liu B, Edgerton S, Yang X, et al. Low-dose dietary phytoestrogen abrogates tamoxifen-associated mammary tumor prevention. Cancer Res. Feb 1 2005;65(3):879-886.

  40. Nakamura H, Wang Y, Kurita T, et al. Genistein increases epidermal growth factor receptor signaling and promotes tumor progression in advanced human prostate cancer. PloS one. 2011;6(5):e20034.

  41. Lazarevic B, Boezelijn G, Diep LM, et al. Efficacy and safety of short-term genistein intervention in patients with localized prostate cancer prior to radical prostatectomy: a randomized, placebo-controlled, double-blind Phase 2 clinical trial. Nutr Cancer. 2011;63(6):889-898.

  42. Shu XO, Zheng Y, Cai H, et al. Soy food intake and breast cancer survival. JAMA. Dec 9 2009;302(22):2437-2443.

  43. Tacyildiz N, Ozyoruk D, Yavuz G, et al. Soy isoflavones ameliorate the adverse effects of chemotherapy in children. Nutr Cancer. 2010;62(7):1001-1005.

  44. Ahmad IU, Forman JD, Sarkar FH, et al. Soy isoflavones in conjunction with radiation therapy in patients with prostate cancer. Nutr Cancer. 2010;62(7):996-1000.

  45. Fleshner NE, Kapusta L, Donnelly B, et al. Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium. J Clin Oncol. Jun 10 2011;29(17):2386-2390.

  46. Schultz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physician’s Guide to Herbal Medicine. 4th ed. New York: Springer.

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  49. Korde LA, Wu AH, Fears T, et al. Childhood soy intake and breast cancer risk in Asian American women. Cancer Epidemiol Biomarkers Prev. Apr 2009;18(4):1050-1059.

  50. Tang X, Zhu X, Liu S, et al. Isoflavones suppress cyclic adenosine 3’,5’-monophosphate regulatory element-mediated transcription in osteoblastic cell line. J Nutr Biochem. Sep 2011;22(9):865-873.

  51. Marsh TG, Straub RK, Villalobos F, et al. Soy protein supports cardiovascular health by downregulating hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein-2 and increasing antioxidant enzyme activity in rats with dextran sodium sulfate-induced mild systemic inflammation. Nutr Res. Dec 2011;31(12):922-928.

  52. American Menopause Society. The role of soy isoflavones in menopausal health: report of The North American Menopause Society/Wulf H. Utian Translational Science Symposium in Chicago, IL (October 2010). Menopause. Jul 2011;18(7):732-753.

  53. Majid S, Dar AA, Saini S, et al. Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer. Cancer Res. Apr 1 2010;70(7):2809-2818.

  54. Rajah TT, Du N, Drews N, et al. Genistein in the presence of 17beta-estradiol inhibits proliferation of ERbeta breast cancer cells. Pharmacology. 2009;84(2):68-73.

  55. van Duursen MB, Nijmeijer SM, de Morree ES, et al. Genistein induces breast cancer-associated aromatase and stimulates estrogen-dependent tumor cell growth in in vitro breast cancer model. Toxicology. Nov 18 2011;289(2-3):67-73.

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  58. Rabiau N, Trraf HK, Adjakly M, et al. miRNAs differentially expressed in prostate cancer cell lines after soy treatment. In Vivo. Nov-Dec 2011;25(6):917-921.

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  65. Lee DE, Lee KW, Byun S, et al. 7,3’,4’-Trihydroxyisoflavone, a metabolite of the soy isoflavone daidzein, suppresses ultraviolet B-induced skin cancer by targeting Cot and MKK4. J Biol Chem. Apr 22 2011;286(16):14246-14256.

  66. Lee DE, Lee KW, Song NR, et al. 7,3’,4’-Trihydroxyisoflavone inhibits epidermal growth factor-induced proliferation and transformation of JB6 P+ mouse epidermal cells by suppressing cyclin-dependent kinases and phosphatidylinositol 3-kinase. J Biol Chem. Jul 9 2010;285(28):21458-21466.

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  77. Chandrareddy A, Muneyyirci-Delale O, McFarlane SI, et al. Adverse effects of phytoestrogens on reproductive health: a report of three cases. Complement Ther Clin Pract. May 2008;14(2):132-135.

  78. Siepmann T, Roofeh J, Kiefer FW, et al. Hypogonadism and erectile dysfunction associated with soy product consumption. Nutrition. Jul-Aug 2011;27(7-8):859-862.

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