Zusammenfassung
Isoflavone als Phytoestrogene werden heute zunehmend im Rahmen der Selbstsupplementation eingesetzt. Phytoestrogene wie Isoflavone und Lignane können funktionell in Abhängigkeit von ihrer Konzentration, der Konzentration der endogenen Hormone und dem spezifischen Endorgan estrogene und antiestrogene Eigenschaften entfalten. Als Sicherheitsaspekt für den praktischen Einsatz ist das Wirkpotenzial von Phytoestrogenen am Endometrium von entscheidender klinischer Bedeutung. Der Artikel gibt einen Überblick über den aktuellen Wissensstand der Wirkung von Isoflavonen am Endometrium. Nach Wirkmechanismus, relevanten tierexperimentellen und der Mehrheit der klinischen Untersuchungen zeigen Isoflavone keine estrogene Wirkung am postmenopausalen Endometrium. Langzeituntersuchungen und große plazebokontrollierte Studien, wie sie z. B. zur Hormonersatztherapie vorliegen, fehlen jedoch. Gerade für höhere Dosierungen von 100 mg Isoflavonen/d und mehr fehlen aussagekräftige Untersuchungen. In der Praxis sollte deshalb Frauen mit Selbstsupplementation eine regelmäßige Vorsorgeuntersuchung einschließlich Vaginalsonographie empfohlen werden.
Abstract
Use of self-supplementation with phytoestrogens is increasing today. Isoflavones interact with the mammalian ER and appear to have both estrogen-agonist and estrogen-antagonist effects, depending on the tissue involved and the amounts circulating. For safety reasons possible effects of phytoestrogens on the endometrium are of clinical importance. This paper reviews epidemiological, experimental and clinical studies on the effects of isoflavones on the endometrium. Nearly all of the available trials with postmenopausal women have suggested an absence of endometrial growth in response to isoflavone supplementation. But for higher dosages of 100 mg isoflavones/d and above and for long-term supplementation limited data are available on the effects of isoflavones on the uterine endometrium. In women using self-supplementation gynaecological screening and vaginal ultrasound are recommended.
Schlüsselwörter
Key words
Endometrium - isoflavones
Literatur
-
1
Adams N R.
Organizational and activational effects of phytoestrogens on the reproductive tract of the ewe.
Proc Soc Exp Biol Med.
1995;
208
87-91
-
2
Adlercreutz H, Fotsis T, Bannwart C, Wahala K, Makela T, Brunow G, Hase T.
Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets.
J Steroid Biochem.
1986;
25
791-797
-
3
Balk J L, Whiteside D A, Naus G, DeFerrari E, Roberts J M.
A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium.
J Soc Gynecol Investig.
2002;
9
238-242
-
4
Barbone F, Austin H, Partridge E E.
Diet and endometrial cancer: a case-control study.
Am J Epidemiol.
1993;
137
393-403
-
5
Bennetts H W, Underwood E J, Shier F L.
A specific breeding problem of sheep on subterranean clover pastures in Western Australia.
Aust J Agric Res.
1946;
22
131-138
-
6
Cassidy A, Bingham S, Setchell K DR.
Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women.
Am J Clin Nutr.
1994;
60
333-340
-
7
Clifton-Bligh P B, Baber R J, Fulcher G R, Nery M L, Moreton T.
The effect of isoflavones extracted from red clover Rimostil on lipid and bone metabolism.
Menopause.
2001;
8
259-265
-
8
Cline J M, Franke A A, Register T C, Golden D L, Adans M R.
Effect of dietary isoflavone aglycones on the reproductive tract of male and female mice.
Toxicol Pathol.
2004;
32
91-99
-
9
Crisafulli A, Marini H, Bitto A. et al .
Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT‐and placebo-controlled study.
Menopause.
2004;
11
400-404
-
10
De Cecco L, Leone M, Gerbaldo D, Venturini P L, Rissone R, Messeni Leone M.
Steroid therapy and the endometrium: biological and clinical implications.
Ann NY Acad Sci.
1991;
622
296-301
-
11
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 malignat rat endometrium.
Human Reprod.
2001;
16
997-1006
-
12
Duncan A M, Underhill K E, Xu X, Lavalleur J, Phipps W R, Kurzer M S.
Modest hormonal effects of soy isoflavones in postmenopausal women.
J Clin Endocrinol Metab.
1999;
84
3479-3484
-
13
Foth D, Cline J M, Römer T.
Die Wirkung von Isoflavonen auf das Endometrium und Brustdrüsengewebe von Makaken (Macaca fascicularis).
Zentralbl Gynakol.
2000;
122
96-102
-
14
Foth D, Cline J M.
Effects of mammalian and plant estrogens on mammary glands and uteri of macaques.
Am J Clin Nutr.
1998;
68
1413-1417
-
15
Fung H Y, Wong Y L, Wong F W, Rogers M S.
Study of oestrogen and progesterone receptors in normal human endometrium during the menstrual cycle by immunocytochemical analysis.
Gynecol Obstet Invest.
1994;
38
186-190
-
16
Goodman M T, Wilkins L R, Hankin J H, Lyu L C, Wu A H, Kolonel L N.
Association of soy and fiber consumption with the risk of endometrial cancer.
Am J Epidemiol.
1997;
146
294-306
-
17
Hale G E, Hughes C L, Agarwal S K, Robboy S J, Bievre M.
A double blind placebo controlled trial on the effect of an isoflavone on the endometrium.
Menopause.
2001;
8
338-346
-
18
Johnson E B, Muto M G, Yanushpolsky E H, Mutter G L.
Phytoestrogens and endometrial cancer.
Obstet Gynecol.
2001;
98
947-950
-
19
Kayisli U A, Aksu C A, Berkkanoglu M, Arici A.
Estrogenicity of isoflavones on human endometrial stromal and glandular cells.
J Clin Endocrinol Metab.
2002;
87
5539-5544
-
20
Key T J, Chen J, Wang D Y, Pike M C, Boreham J.
Sex hormones in women in rural China and in Britain.
Br J Cancer.
1990;
62
631-636
-
21
Koshiyama M, Yoshida M, Takemura M, Yura Y, Matsushita K, Hayashi M, Tauchi K, Konishi I, Mori T.
Immunohistochemical analysis of distribution of estrogen receptors and progesterone receptors in the postmenopausal endometrium.
Acta Obstet Gynecol Scand.
1996;
75
702-706
-
22
Krenn L, Unterrieder I, Ruprechter R.
Quantification of isoflavones in red clover by HPLC.
J Chromatography.
2002;
777
1230-1268
-
23
Kurman R J, Kaminski P F, Norris H J.
The behavior of endometrial hyperplasia: a long term study of “untreated” hyperplasia in 170 patients.
Cancer.
1985;
56
402-412
-
24
La Vecchia C, Francheschi S, Decarli A, Gallus G, Tognoni G.
Risk factors for endometrial cancer at different ages.
J Natl Cancer Inst.
1984;
73
667
-
25
Levi F, Francheschi S, Negri E, La Vecchia C.
Dietary factors and the risk of endometrial cancer.
Cancer.
1993;
71
3575-3581
-
26
Lu L J, Anderson K E, Grady J J, Kohen F, Nagamani M.
Decreased ovarian hormones during a soya diet: implications for breast cancer prevention.
Cancer Res.
2000;
60
4112-4121
-
27
Markiewicz L, Garey J, Aldercreutz H, Gurpide E.
In vitro bioassays of non-steroidal phytoestrogens.
J Steroid Biochem Mol Biol.
1993;
45
399-405
-
28
Murray M J, Meyer W R, Lessey B A, Oi R H, DeWire R E, Fritz M A.
Soy protein isolate with isoflavones does not prevent estradiol-induced endometrial hyperplasia in postmenopausal women: a pilot trial.
Menopause.
2003;
10
456-464
-
29
Nagata C, Kabuto M, Kuriso Y, Shimizu H.
Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women.
Nutr Cancer.
1997;
29
228-233
-
30
NAMS .
The role of isoflavones in menopausal health: consensus opinion of The North American Menopause Society.
Menopause.
2000;
7
215-229
-
31
NAMS .
Treatment of menopausal-associated vasomotor symptoms: position statement of The North American Menopause Society.
Menopause.
2004;
11
11-33
-
32
Neis K J, Brandner P, Ulrich-Winkelspecht K.
The oestrogen receptor (ER) in normal and abnormal uterine tissue.
Eur J Cancer.
2000;
36
30-31
-
33 Neis K J, Ulrich-Winkelspecht K, Riehm S, Ulrich U. Rezeptorexpression des prä- und postmenopausalen Endometriums. Römer T, Mueck AO Endometrium und Hormonsubstitution. Stuttgart; Thieme 1998
-
34
Nikander E, Rutanen E M, Nieminen P, Wahlstrom T, Ylikorala O, Tiitinen A.
Lack of effect of isoflavonoids on the vagina and endometrium in postmenopausal women.
Fertil Steril.
2005;
83
137-142
-
35
Noci I, Borri P, Chieffi O.
Aging of the human endometrium: a basic morphological and immunohistochemical study.
Eur J Obstet Gynecol Reprod Biol.
1995;
63
181-185
-
36
Parkin D M.
Cancers of the breast, endometrium and ovary: geographic correlations.
Eur J Cancer Clin Oncol.
1989;
25
1917-1925
-
37
Penotti M, Fabio E, Modena A B, Rinaldi M, Omodei U, Vigano P.
Effect of soy-derived isoflavones on hot-flashes, endometrial thickness, and the pulsatility index of the uterine arteries.
Fertil Steril.
2003;
79
1112-1117
-
38
Potischman N, Swanson C A, Brinton L A, McAdams M, Barrett R J, Berman M L, Mortel R, Twiggs L B, Wilbanks G D, Hoover R N.
Dietary associations in a case-control study of endometrial cancer.
Cancer Causes Control.
1993;
4
239-250
-
39
Rohr U D. et al .
Phytoestrogene - was ist bei der Anwendung am Menschen gesichert.
Gynäkologie und Geburtshilfe.
2004;
5
1-13
-
40
Sammartino A, Di Carlo C, mandato V D, Bifulco G, Di Stefano M, Nappi C.
Effects of genistein on the endometrium: ultrasonographic evaluation.
Gynecol Endocrinol.
2003;
17
45-49
-
41
Santell R C, Chang Y C, Nair M G, Helferich W G.
Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats.
J Nutr.
1997;
127
263-269
-
42
Scambia G, Mango D, Signorile P G, Angeli R A, Palena C, Gallo D, Bombardelli E, Morazzoni P, Riva A, Mancuso S.
Clinical effects of a standardized soy extract in postmenopausal women: a pilot study.
Menopause.
2000;
7
105-111
-
43
Shu X O, Zheng W, Potischman N, Brinton L A, Hatch M C, Gao Y T, Fraumeni Jr J F.
A population based case-contol study of dietary factors and endometrial cancer in Shanghai, People's Republic of China.
Am J Epidemiol.
1993;
137
155-165
-
44
Snijders M, de Goeij A, Koudstaal J, Bosman F.
Oestrogen and progestogen receptor content in human endometrium.
Eur J Obstet Gynecol Reprod Biol.
1996;
70
9-10
-
45
Tang B Y, Adams N R.
Effect of equol on oestrogen receptors and on synthesis of DNA and protein in the immature rat uterus.
J Endocrinol.
1980;
85
291-297
-
46
Terakawa N, Kigawa J, Takenati Y. et al .
The behavior of endometrial hyperplasia: a prospective study. Endometrial Hyperplasia Study Group.
J Obstet Gynaecol Res.
1997;
23
223-230
-
47
The Writing Group for the PEPI Trial .
Effects of hormonal replacement therapy on endometrial histology in postmenopausal women.
JAMA.
1996;
275
370-375
-
48
Unfer V, Casini M A, Costabile L, Mignosa M, Gerli S, Di Renzo G C.
Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study.
Fertil Steril.
2004;
82
145-148
-
49
Unfer V, Casini M L, Costabile L, Mignosa M, Gerli S, Di Renzo G C.
High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial.
J Soc Gynecol Investig.
2004;
11
323-328
-
50
Upmalis D H, Lobo R, Bradley L, Warren M, Cone F L, Lamia C A.
Vasomotoric symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomised, placebo-controlled study.
Menopause.
2000;
7
236-342
-
51
Villani C, Pucci G, Pietrangeli D, Pace S, Tomao S.
Role of diet in endometrial cancer patients.
Eur J Gynecol Oncol.
1986;
7
139-143
-
52
Wang Hong Xu, Wei Zheng, Yong Bing Xiang, Zhi Xian Ruan, Jia Rong Cheng, Qi Dai, Yu Tang Gao, Xiao Ou Shu.
Soya food intake and risk of endometrial cancer among Chinese women in Shanghai: population based case-control study.
BMJ.
2004;
328
1285
-
53
Wang D Y, Key T J, Pike M C, Boreham J, Chen J.
Serum hormone levels in British and rural Chinese females.
Breast Cancer Res Treat.
1991;
18
41-45
-
54
Watanabe S, Terashima K, Sato Y, Arai S, Eboshida A.
Effects of isoflavone supplement on healthy women.
Biofactors.
2000;
12
233-241
-
55
Whitten P L, Lewis C, Russell E, Naftolin F.
Potential adverse effects of phytoestrogens.
J Nutr.
1995;
125
771-776
-
56
Whitten P L, Naftolin F.
Effects of a normal, human-concentration, phytoestrogen diet on rat uterine growth.
Steroids.
1992;
57
98-106
-
57
Whitten P L, Naftolin F.
Effects of a phytoestrogen diet on estrogen-dependent reproductive processes in immature female rates.
Steroids.
1992;
57
56-61
-
58
Wood C E, Register T C, Anthony M S, Kock N D, Cline J M.
Breast and uterine effects of soy isoflavones and conjugated equine estrogens in postmenopausal female monkeys.
J Clin Endocrinol Metab.
2004;
89
3462-3468
-
59
Wu A H, Pike M C.
Dietary soy protein and hormonal status in femals.
Am J Clin Nutr.
1995;
62
51-53
-
60
Wynder E L, Fujita Y, Harris R E, Hirayama T, Hiyama T.
Comparative epidemiology of cancer between the United States and Japan: A second look.
Cancer.
1991;
67
746-763
-
61
Xu X, Duncan A M, Merz B E, Kurzer M S.
Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women.
Cancer Epidemiol Biomarkers Prev.
1998;
7
1101-1108
-
62
Zheng W, Kushi L H, Potter J D, Sellers T A, Doyle T J, Bostick R M, Folsom A R.
Dietary intake of energy and animal foods and endometrial cancer incidence: the Iowa Women's Study.
Am J Epidemiol.
1995;
142
388-394
PD Dr. med. Dolores Foth
Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe der Universität zu Köln
Kerpenerstr. 34
50931 Köln
Email: dolores.foth@uk-koeln.de
