Skip to main content
SpringerLink
Log in

Endokrinologie der Phytoöstrogene

Hintergrund und klinische Implikationen

  • Leitthema
  • Published:
Gynäkologische Endokrinologie Aims and scope

Zusammenfassung

Viele Hinweise sprechen dafür, dass eine Ernährung mit phytoöstrogenreichen Lebensmitteln möglicherweise mit einem erniedrigten Risiko für Brust- und Prostatakrebs assoziiert ist. Darüber hinaus ist vermutet worden, dass sie auch eine vorbeugende Rolle bei kardiovaskulären Erkrankungen, postmenopausaler Osteoporose und klimakterischem Syndrom spielen könnte. Es wird spekuliert, ob Phytoöstrogenen eine Rolle bei der Prophylaxe von Altersdemenzkrankheiten zukommen könnte. Bis jetzt gibt es keine direkten Beweise einer nützlichen Wirkung von Pflanzenöstrogenen beim Menschen. Die gefundenen protektiven Assoziationen sind nicht definitiv mit der phytoöstrogenen Bioverfügbarkeit verbunden, sondern könnten auch auf andere biologisch aktive Substanzen in diesen Pflanzen zurückgehen. Kausale Schutzeffekte und die Mechanismen einer phytoöstrogenen Aktivität beim Menschen sind also noch zu beweisen. Mögliche nachteilige Wirkungen von Phytoöstrogenen sind bisher nicht ausreichend abgeschätzt worden, eine Überprüfung auf mögliche endokrine Störwirkungen ist notwendig.

Abstract

Herbal estrogens are substances found in food, i.e., lignans or isoflavonoids, that induce biological responses in mammals including the human and can imitate or modulate the activity of endogenous estrogens. The intake of phytoestrogens might be associated with a lower risk of developing breast and prostate cancer. Furthermore, they might have positive preventive effects in cardiovascular disease, postmenopausal osteoporosis, climacteric symptoms, and cognitive disorders. Up to now there is no direct evidence for these postulated effects in humans supported by long-term intervention studies. Most if not all information is based on intake of herbal estrogen-enriched food in Asian populations or short-term interventions in Western populations. However, food products associated with lowered disease risk might contain other antioxidative or anticancer substances besides herbal estrogens, which might be responsible for the postulated protective effects. There are insufficient data concerning negative side effects of herbal estrogens. Further studies are needed to clarify the role of these drugs in prophylaxis and treatment of cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1.
Abb. 2.
Abb. 3.
Abb. 4.
Abb. 5.
Abb. 6.
Abb. 7.
Abb. 8.

Literatur

  1. Adlercreutz H, Fotsis T, Lampe J et al. (1993) Quantitative determination of lignans and isoflavonoids in plasma of omnivorous and vegetarian women by isotope dilution gas chromatography-mass spectrometry. Scand J Clin Lab Invest Suppl 215:5–18

    Google Scholar 

  2. Allred CD, Ju YH, Allred KF et al. (2001) Dietary genistin stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein. Carcinogenesis 22:1667–1673

    Google Scholar 

  3. Anstead GM, Carlson KE, Katzenellenbogen JA (1997) The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids 62:268–303

    Google Scholar 

  4. Anthony MS, Clarkson TB, Hughes CL Jr et al. (1996) Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. J Nutr 126:43–50

    Google Scholar 

  5. Arai Y, Uehara M, Sato Y et al. (2000) Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake. J Epidemiol 10:127–135

    Google Scholar 

  6. Barnes S, Sfakianos J, Coward L, Kirk M (1996) Soy isoflavonoids and cancer prevention. Underlying biochemical and pharmacological issues. Adv Exp Med Biol 401:87–100

    Google Scholar 

  7. Blair RM, Fang H, Branham WS et al. (2000) The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol Sci 54:138–153

    Google Scholar 

  8. Boker LK, Van der Schouw YT, De Kleijn MJ et al. (2002) Intake of dietary phytoestrogens by Dutch women. J Nutr 132:1319–1328

    Google Scholar 

  9. Breithofer A, Graumann K, Scicchitano MS et al. (1998) Regulation of human estrogen receptor by phytoestrogens in yeast and human cells. J Steroid Biochem Mol Biol 67:421–429

    Google Scholar 

  10. Brzozowski AM, Pike AC, Dauter Z et al. (1997) Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389:753–758

    Google Scholar 

  11. Chen S, Kao YC, Laughton CA (1997) Binding characteristics of aromatase inhibitors and phytoestrogens to human aromatase. J Steroid Biochem Mol Biol 61:107–115

    Google Scholar 

  12. Chen Z, Zheng W, Custer LJ et al. (1999) Usual dietary consumption of soy foods and its correlation with the excretion rate of isoflavonoids in overnight urine samples among Chinese women in Shanghai. Nutr Cancer 33:82–87

    Google Scholar 

  13. Cline JM, Paschold JC, Anthony MS et al. (1996) Effects of hormonal therapies and dietary soy phytoestrogens on vaginal cytology in surgically postmenopausal macaques. Fertil Steril 65:1031–1035

    Google Scholar 

  14. Coldham NG, Sauer MJ (2001) Identification, quantitation and biological activity of phytoestrogens in a dietary supplement for breast enhancement. Food Chem Toxicol 39:1211–1224

    Google Scholar 

  15. Coward L, Barnes NC, Setchell KDR, Barnes S (1993) Genistein, daidzein and their beta-glycoside conjugates: antitumor isoflavones in soybean foods from American and Asian diets. J Agric Food Chem 41:1961–1967

    Google Scholar 

  16. Collins BM, McLachlan JA, Arnold SF (1997) The estrogenic and antiestrogenic activities of phytochemicals with the human estrogen receptor expressed in yeast. Steroids 62:365–372

    Google Scholar 

  17. Collins P, Webb C (1999) Estrogen hits the surface. Nat Med 5:1130–1131

    Google Scholar 

  18. Cowley SM, Hoare S, Mosselman S, Parker MG (1997) Estrogen receptors alpha and beta form heterodimers on DNA. J Biol Chem 272:19858–19862

    Google Scholar 

  19. Divi RL, Chang HC, Doerge DR (1997) Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. Biochem Pharmacol 54:1087–1096

    Google Scholar 

  20. Fang H, Tong W, Shi LM et al. (2001) Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens. Chem Res Toxicol 14:280–294

    Google Scholar 

  21. Gehm BD, McAndrews JM, Chien PY, Jameson JL (1997) Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci USA 94:14138–14143

    Google Scholar 

  22. Graumann K, Breithofer A, Jungbauer A (1999) Monitoring of estrogen mimics by a recombinant yeast assay: synergy between natural and synthetic compounds? Sci Total Environ 225:69–79

    Google Scholar 

  23. Hawkins MB, Thornton JW, Crews D et al. (2000) Identification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts. Proc Natl Acad Sci USA 97:10751–10756

    Google Scholar 

  24. Hunter DS, Hodges LC, Vonier PM et al. (1999) Estrogen receptor activation via activation function 2 predicts agonism of xenoestrogens in normal and neoplastic cells of the uterine myometrium. Cancer Res 59:3090–3099

    Google Scholar 

  25. Joannou GE, Kelly GE, Reeder AY et al. (1995) A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids. J Steroid Biochem Mol Biol 54:167–184

    Google Scholar 

  26. Kao YC, Zhou C, Sherman M et al. (1998) Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: a site-directed mutagenesis study. Environ Health Perspect 106:85–92

    Google Scholar 

  27. Kaufmann WK (1998) Human topoisomerase II function, tyrosine phosphorylation and cell cycle checkpoints. Proc Soc Exp Biol Med 217:327–334

    Google Scholar 

  28. Kikuchi Y, Shimamura Y, Hirokado M et al. (2001) Daily intake of isoflavones based on the market basket method. Shokuhin Eiseigaku Zasshi 42:122–127 (Abstract)

    Google Scholar 

  29. Kitaoka M, Kadokawa H, Sugano M et al. (1998) Prenylflavonoids: a new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure-activity relationship. Planta Med 64:511–515

    Google Scholar 

  30. Krazeisen A, Breitling R, Moller G, Adamski J (2002) Human 17beta-hydroxysteroid dehydrogenase type 5 is inhibited by dietary flavonoids. Adv Exp Med Biol 505:151–61

    Google Scholar 

  31. Kuiper GG, Enmark E, Pelto-Huikko M et al. (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93:5925–5930

    Google Scholar 

  32. Kuiper GG, Carlsson B, Grandien K et al. (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138:863–870

    Google Scholar 

  33. Kuiper GG, Lemmen JG, Carlsson B et al. (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139:4252–4263

    Google Scholar 

  34. Kulling SE, Rosenberg B, Jacobs E, Metzler M (1999) The phytoestrogens coumoestrol and genistein induce structural chromosomal aberrations in cultured human peripheral blood lymphocytes. Arch Toxicol 73:50–54

    Google Scholar 

  35. Kulling SE, Metzler M (1997) Induction of micronuclei, DNA strand breaks and HPRT mutations in cultured Chinese hamster V79 cells by the phytoestrogen coumoestrol. Food Chem Toxicol 35:605–613

    Google Scholar 

  36. Kurzer MS, Xu X (1997) Dietary phytoestrogens. Annu Rev Nutr 17:353–381

    Google Scholar 

  37. Makela S, Poutanen M, Lehtimaki J et al. (1995) Estrogen-specific 17 beta-hydroxysteroid oxidoreductase type 1 (E.C. 1.1.1.62) as a possible target for the action of phytoestrogens. Proc Soc Exp Biol Med 208:51–59

    Google Scholar 

  38. Makela S, Poutanen M, Kostian ML et al. (1998) Inhibition of 17beta-hydroxysteroid oxidoreductase by flavonoids in breast and prostate cancer cells. Proc Soc Exp Biol Med 217:310–316

    Google Scholar 

  39. Matsuzaki S, Fukaya T, Suzuki T et al. (1999) Oestrogen receptor alpha and beta mRNA expression in human endometrium throughout the menstrual cycle. Mol Hum Reprod 5:559–564

    Google Scholar 

  40. Meagher LP, Beecher GR, Flanagan VP, Li BW (1999) Isolation and characterization of the lignans, isolariciresinol and pinoresinol, in flaxseed meal. J Agric Food Chem 47:3173–3180

    Google Scholar 

  41. Mei J, Yeung SS, Kung AW (2001) High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 86:5217–5221

    Google Scholar 

  42. Milligan S, Kalita J, Pocock V et al. (2002) Oestrogenic activity of the hop phyto-oestrogen, 8-prenylnaringenin. Reproduction 123:235–242

    Google Scholar 

  43. Milligan SR, Kalita JC, Pocock V et al. (2000) The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J Clin Endocrinol Metab 85:4912–4915

    Google Scholar 

  44. Miodini P, Fioravanti L, Di Fronzo G, Cappelletti V (1999) The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function. Br J Cancer 80:1150–1155

    Google Scholar 

  45. Nagata C, Takatsuka N, Inaba S et al. (1998) Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women. J Natl Cancer Inst 90:1830–1835

    Google Scholar 

  46. Nagel SC, vom Saal FS, Welshons WV (1998) The effective free fraction of estradiol and xenoestrogens in human serum measured by whole cell uptake assays: physiology of delivery modifies estrogenic activity. Proc Soc Exp Biol Med 217:300–309

    Google Scholar 

  47. Ogawa S, Inoue S, Watanabe T et al. (1998) The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitro. Biochem Biophys Res Commun 243:122–126

    Google Scholar 

  48. Paige LA, Christensen DJ, Gron H et al. (1999) Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta. Proc Natl Acad Sci USA 96:3999–4004

    Google Scholar 

  49. Paech K, Webb P, Kuiper GG et al. (1997) Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites. Science 277:1508–1510

    Google Scholar 

  50. Pagliacci MC, Smacchia M, Migliorati G et al. (1994) Growth-inhibitory effects of the natural phyto-oestrogen genistein in MCF-7 human breast cancer cells. Eur J Cancer 30A:1675–1682

    Google Scholar 

  51. Peterson TG, Ji GP, Kirk M et al. (1998) Metabolism of the isoflavones genistein and biochanin A in human breast cancer cell lines. Am J Clin Nutr 68 [6 Suppl]:1505S–1511S

  52. Pettersson K, Grandien K, Kuiper GG, Gustafsson JA (1997) Mouse estrogen receptor beta forms estrogen response element-binding heterodimers with estrogen receptor alpha. Mol Endocrinol 11:1486–1496

    Google Scholar 

  53. Pike AC, Brzozowski AM, Hubbard RE et al. (1999) Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist. EMBO J 18:4608–4618

    Google Scholar 

  54. Pujol P, Rey JM, Nirde P et al. (1998) Differential expression of estrogen receptor-alpha and -beta messenger RNAs as a potential marker of ovarian carcinogenesis. Cancer Res 58:5367–5373

    Google Scholar 

  55. Qian Y, Deng C, Song WC (1998) Expression of estrogen sulfotransferase in MCF-7 cells by cDNA transfection suppresses the estrogen response: potential role of the enzyme in regulating estrogen-dependent growth of breast epithelial cells. J Pharmacol Exp Ther 286:555–560

    Google Scholar 

  56. Roberts-Kirchhoff ES, Crowley JR, Hollenberg PF, Kim H (1999) Metabolism of genistein by rat and human cytochrome P450 s. Chem Res Toxicol 12:610–616

    Google Scholar 

  57. Rowland I, Wiseman H, Sanders T et al. (1999) Metabolism of oestrogens and phytoestrogens: role of the gut microflora. Biochem Soc Trans 27:304–308

    Google Scholar 

  58. Rowland IR, Wiseman H, Sanders TA et al. (2000) Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut microflora. Nutr Cancer 36:27–32

    Google Scholar 

  59. Rudel R (1997) Predicting health effects of exposures to compounds with estrogenic activity: methodological issues. Environ Health Perspect 105 [Suppl 3]:655–663

    Google Scholar 

  60. Sathyamoorthy N, Wang TT (1997) Differential effects of dietary phyto-oestrogens daidzein and equol on human breast cancer MCF-7 cells. Eur J Cancer 33:2384–2389

    Google Scholar 

  61. Pawson T, Scott JD (1997) Signaling through scaffold, anchoring, and adaptor proteins. Science 278:2075–2080

    Google Scholar 

  62. Saunders PT, Millar MR, Williams K et al. (2000) Differential expression of estrogen receptor-alpha and -beta and androgen receptor in the ovaries of marmosets and humans. Biol Reprod 63:1098–1105

    Google Scholar 

  63. Seow A, Shi CY, Franke AA et al. (1998) Isoflavonoid levels in spot urine are associated with frequency of dietary soy intake in a population-based sample of middle-aged and older Chinese in Singapore. Cancer Epidemiol Biomarkers Prev 7:135–140

    Google Scholar 

  64. Setchell KDR, Adlercreutz H (1998) Mammalian lignans and phytoestrogens. In: Rowland I (ed) The role of the gut flora in toxicity and cancer. Academic Press, London, pp 315–346

  65. Song TT, Hendrich S, Murphy PA (1999) Estrogenic activity of glycitein, a soy isoflavone. J Agric Food Chem 47:1607–1610

    Google Scholar 

  66. Speirs V, Skliris GP, Burdall SE, Carder PJ (2002) Distinct expression patterns of ER alpha and ER beta in normal human mammary gland. J Clin Pathol 55:371–374

    Google Scholar 

  67. Speirs V, Parkes AT, Kerin MJ et al. (1999) Coexpression of estrogen receptor alpha and beta: poor prognostic factors in human breast cancer? Cancer Res 59:525–528

    Google Scholar 

  68. Stahl S, Chun TY, Gray WG (1998) Phytoestrogens act as estrogen agonists in an estrogen-responsive pituitary cell line. Toxicol Appl Pharmacol 152:41–48

    Google Scholar 

  69. Twaddle GM, Turbov J, Liu N, Murthy S (1999) Tyrosine kinase inhibitors as antiproliferative agents against an estrogen-dependent breast cancer cell line in vitro. J Surg Oncol 70:83–90

    Google Scholar 

  70. Wang C, Kurzer MS (1997) Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutr Cancer 28:236–247

    Google Scholar 

  71. Wang H, Mao Y, Zhou N et al. (2001) Atp-bound topoisomerase II as a target for antitumor drugs. J Biol Chem 276:15990–15995

    Google Scholar 

  72. Wei H, Wei L, Frenkel K et al. (1993) Inhibition of tumor promoter-induced hydrogen peroxide formation in vitro and in vivo by genistein. Nutr Cancer 20:1–12

    Google Scholar 

  73. Wei H, Bowen R, Cai Q et al (1995) Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med 208:124–130

    Google Scholar 

  74. Wong CK, Keung WM (1997) Daidzein sulfoconjugates are potent inhibitors of sterol sulfatase (EC 3.1.6.2). Biochem Biophys Res Commun 233:579–583

    Google Scholar 

  75. Wood JR, Greene GL, Nardulli AM (1998) Estrogen response elements function as allosteric modulators of estrogen receptor conformation. Mol Cell Biol 18:1927–1934

    Google Scholar 

  76. Xu X, Harris KS, Wang HJ et al. (1995) Bioavailability of soybean isoflavones depends upon gut microflora in women. J Nutr 125:2307–2315

    Google Scholar 

  77. Zava DT, Duwe G (1997) Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro. Nutr Cancer 27:31–40

    Google Scholar 

  78. Zhang Y, Song TT, Cunnick JE et al. (1999) Daidzein and genistein glucuronides in vitro are weakly estrogenic and activate human natural killer cells at nutritionally relevant concentrations. J Nutr 129:399–405

    Google Scholar 

  79. Duncan AM, Underhill KE, Xu X, Lavalleur J, Phipps WR, Kurzer MS (1999) Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab 84(10):3479–3484

    Google Scholar 

  80. Pino AM, Valladares LE, Palma MA, Mancilla AM, Yanez M, Albala C (2000) Dietary isoflavones affect sex hormone-binding globulin levels in postmenopausal women. J Clin Endocrinol Metab 85(8):2797–2800

    Google Scholar 

  81. Harper A, Kerr DJ, Gescher A, Chipman JK (1999) Antioxidant effects of isoflavonoids and lignans, and protection against DNA oxidation. Free Radic Res 31(2):149–160

    Google Scholar 

  82. Petit F, Le Goff P, Cravedi JP, Valotaire Y, Pakdel F (1997) Two complementary bioassays for screening the estro-genic potency of xenobiotics: recombinant yeast for trout estrogen receptor and trout hepatocyte cultures. J Mol Endocrinol 19(3):321–335

    Google Scholar 

  83. Foth D, Cline JM (1998) Effects of mammalian and plant estrogens on mammary glands and uteri of macaques. Am J Clin Nutr 68(6 Suppl):1413S–1417S

    Google Scholar 

  84. Thompson LU, Robb P, Serraino M, Cheung F (1991) Mammalian lignan production from various foods. Nutr Cancer 16(1):43-52

    Google Scholar 

  85. Milligan SR, Khan O, Nash M (1998) Competitive binding of xenobiotic oestrogens to rat alpha-fetoprotein and to sex steroid binding proteins in human and rainbow trout (Oncorhynchus mykiss) plasma. Gen Comp Endocrinol 112(1):89–95

    Google Scholar 

  86. Brzezinski A, Adlercreutz H, Shauol R, Rosler A, Shmueli A, Tanos V, Schenker JG (1997) Short-term effects of phytoestrogen-rich diet on postmenopausal women. J North American Menopause Soc 4:89–94

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abteilung Gynäkologische Endokrinologie und Fertilitätsstörungen, Frauenklinik, Universitätsklinikum Heidelberg

    K. H. Adzersen & T. Strowitzki

  2. , Universitätsfrauenklinik, Voßstraße 9, 69115, Heidelberg

    K. H. Adzersen

Authors
  1. K. H. Adzersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Strowitzki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. H. Adzersen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adzersen, K.H., Strowitzki, T. Endokrinologie der Phytoöstrogene. Gynäkologische Endokrinologie 1, B15–B25 (2003). https://doi.org/10.1007/s10304-003-0016-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10304-003-0016-7

Schlüsselwörter

Keywords

Search

Navigation