Fertility and Sterility
Volume 82, Issue 1 , Pages 145-148 , July 2004

Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study

  • Vittorio Unfer, M.D.

      Affiliations

    • A.G.UN.CO., Obstetrics and Gynecology Centre, Rome, Italy
    • Corresponding Author InformationReprint requests: Prof. Vittorio Unfer, A.G.UN.CO. Obstetrics and Gynecology Centre, Via G. Cassiani, 15-00155 Rome, Italy (FAX: 39-06-3241284).
  • ,
  • Maria Luisa Casini, Ph.D.

      Affiliations

    • Department of Human Physiology and Pharmacology “Vittorio Erspamer,” University “La Sapienza,” Rome, Italy
  • ,
  • Loredana Costabile, M.D.

      Affiliations

    • A.G.UN.CO., Obstetrics and Gynecology Centre, Rome, Italy
  • ,
  • Marcella Mignosa, M.D.

      Affiliations

    • Centre of Perinatal and Reproductive Medicine, Department of Gynecological, Obstetrical, and Pediatric Sciences, University of Perugia, Perugia, Italy
  • ,
  • Sandro Gerli, M.D.

      Affiliations

    • Centre of Perinatal and Reproductive Medicine, Department of Gynecological, Obstetrical, and Pediatric Sciences, University of Perugia, Perugia, Italy
  • ,
  • Gian Carlo Di Renzo, M.D., Ph.D.

      Affiliations

    • Centre of Perinatal and Reproductive Medicine, Department of Gynecological, Obstetrical, and Pediatric Sciences, University of Perugia, Perugia, Italy

Received 14 July 2003 ,Revised 12 November 2003 ,Accepted 12 November 2003.

References 

  1. Loprinzi CL, Michalak JC, Quella SK, O'Fallon JR, Hatfield AK, Nelimark RA, et al.  Megestrol acetate for the prevention of hot flashes. N Engl J Med. 1994;331:347–352
  2. Xu X, Wang HJ, Murphy PA, Hendrich S. Neither background diet nor type of soy food affects short-term isoflavone bioavailability in women. J Nutr. 2000;130:798–801
  3. Adlercreutz H. Phyto-oestrogens and cancer. Lancet Oncol. 2002;3:364–373
  4. Barnes S, Peterson TG, Coward L. Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. J Cell Biochem Suppl. 1995;22:181–187
  5. Mueller SO, Kling M, Arifin Firzani P, Mecky A, Duranti E, Shields-Botella J, et al.  Activation of estrogen receptor alpha and ERbeta by 4-methylbenzylidene-camphor in human and rat cells (comparison with phyto- and xenoestrogens). Toxicol Lett. 2003;142:89–101
  6. Rickard DJ, Monroe DG, Ruesink TJ, Khosla S, Riggs BL, Spelsberg TC. Phytoestrogen genistein acts as an estrogen agonist on human osteoblastic cells through estrogen receptors alpha and beta. J Cell Biochem. 2003;89:633–646
  7. Lee Y, Jin Y, Lim W, Ji S, Choi S, Jang S, et al.  A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen receptor in human breast carcinoma MCF-7 cells. J Steroid Biochem Mol Biol. 2003;84:463–468
  8. Pearce V, Nawaz Z, Xiao W, Wiedenfeld D, Boyle N, Smith D. 4-Ethoxymethylphenol (a novel phytoestrogen that acts as an agonist for human estrogen receptors). J Steroid Biochem Mol Biol. 2003;84:431–439
  9. Jefferson WN, Padilla-Banks E, Clark G, Newbold RR. Assessing estrogenic activity of phytochemicals using transcriptional activation and immature mouse uterotrophic responses. J Chromatogr B Analyt Technol Biomed Life Sci. 2002;777:179–189
  10. Diel P, Smolnikar K, Schulz T, Laudenbach-Leschowski U, Michna H, Vollmer G. Phytoestrogens and carcinogenesis-differential effects of genistein in experimental models of normal and malignant rat endometrium. Hum Reprod. 2001;16:997–1006
  11. Markaverich BM, Webb B, Densmore CL, Gregory RR. Effects of coumestrol on estrogen receptor function and uterine growth in ovariectomized rats. Environ Health Persp. 1995;103:574–581
  12. Balk JL, Whiteside DA, Naus G, DeFerrari E, Roberts JM. A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium. J Soc Gynecol Invest. 2002;9:238–242
  13. Penotti M, Fabio E, Modena AB, Rinaldi M, Omodei U, Vigano P. Effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries. Fertil Steril. 2003;79:1112–1117
  14. Upmalis DH, Lobo R, Bradley L, Warren M, Cone FL, Lamia CA. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women (a multicenter, double-blind, randomized, placebo-controlled study). Menopause. 2000;7:422
  15. Johnson EB, Muto MG, Yanushpolsky EH, Mutter GL. Phytoestrogen supplementation and endometrial cancer. Obstet Gynecol. 2001;98:947–950
  16. Sammartino A, Di Carlo C, Mandato VD, Bifulco G, Di Stefano M, Nappi C. Effects of genistein on the endometrium (ultrasonographic evaluation). Gynecol Endocrinol. 2003;17:45–49
  17. Cornier E. The Pipelle (a disposable device for endometrial biopsy). Am J Obstet Gynecol. 1984;148:109–110
  18. Hofmeister FJ, Vondrak B, Barbo DM. The value of the endometrial biopsy. A study of 14,655 office endometrial biopsies. Am J Obstet Gynecol. 1966;95:91–98
  19. Heikaus S, Winterhager E, Traub O, Grummer R. Responsiveness of endometrial genes Connexin26, Connexin43, C3 and clusterin to primary estrogen, selective estrogen receptor modulators, phyto- and xenoestrogens. J Mol Endocrinol. 2002;29:239–249
  20. Wober J, Weisswange I, Vollmer G. Stimulation of alkaline phosphatase activity in Ishikawa cells induced by various phytoestrogens and synthetic estrogens. J Steroid Biochem Mol Biol. 2002;83:227–233
  21. Duncan AM, Underhill KE, Xu X, Lavalleur J, Phipps WR, Kurzer MS. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab. 1999;84:3479–3484
  22. Murray MJ, Meyer WR, Lessey BA, Oi RH, DeWire RE, Fritz MA. Soy protein isolate with isoflavones does not prevent estradiol-induced endometrial hyperplasia in postmenopausal women (a pilot trial). Menopause. 2003;10:456–464
  23. Hale GE, Hughes CL, Robboy SJ, Agarwal SK, Bievre M. A double-blind randomized study on the effects of red clover isoflavones on the endometrium. Menopause. 2001;8:338–346
  24. Morito K, Hirose T, Kinjo J, Hirakawa T, Okawa M, Nohara T, et al.  Interaction of phytoestrogens with estrogen receptors alpha and beta. Biol Pharm Bull. 2001;24:351–356
  25. Pike AC, Brzozowski AM, Hubbard RE, Bonn T, Thorsell AG, Engstrom O, et al. Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist. EMBO J 19991;18:4608–18
  26. Lecce G, Meduri G, Ancelin M, Bergeron C, Perrot-Applanat M. Presence of estrogen receptor beta in the human endometrium through the cycle (expression in glandular, stromal, and vascular cells). J Clin Endocrinol Metab. 2001;86:1379–1386

PII: S0015-0282(04)00530-8

doi: 10.1016/j.fertnstert.2003.11.041

Fertility and Sterility
Volume 82, Issue 1 , Pages 145-148 , July 2004