CoChat
Sign Up
Cited by 15Phytoestrogen effects and researchEstrogen and related hormone effectsPhytochemicals and Antioxidant Activities

Urinary estrogen metabolites in two soy trials with premenopausal women

Open access
Maskarinec, G, Morimoto, Y, Heak, S, Isaki, M, Steinbrecher, A, Custer, L, Franke, A A·2012·European Journal of Clinical Nutrition
DOI 10.1038/ejcn.2012.71PMC PMC3437012
Open this paper in CoChat — free account

Abstract

Background Soy consumption may protect against breast cancer through modification of estrogen metabolism. Objectives We examined the effect of soy foods on urinary estrogens and the 2-hydroxy (OH)/16α-OH estrone (E(1)) ratio in two dietary interventions with premenopausal women. Subjects/methods The Breast, Estrogens, And Nutrition (BEAN1) study was a 2-year randomized trial and BEAN2 a 13-month randomized crossover study. In both interventions, study participants consumed a high-soy diet with 2 soy food servings/day and a low-soy diet with <3 servings of soy/week. Urine samples were collected at baseline and at the end of the diet periods, analyzed for nine estrogen metabolites by liquid chromatography mass spectrometry, and adjusted for creatinine levels. For BEAN1, two samples for 188 participants and for BEAN2, three samples for 79 women were analyzed. We applied mixed-effects regression models with log-transformed values of estrogen metabolites and soy intake as the exposure variable. Results In BEAN1, no effect of the high-soy diet on individual estrogen metabolites or hydroxylation pathways was observed. The median 2-OH/16α-OHE(1) ratio decreased non-significantly in the intervention group from 6.2 to 5.2 as compared with 6.8 and 7.2 in the control group (P=0.63). In BEAN2, only 4-OHE(1) was significantly lower after the high-soy diet. Interaction terms of the high-soy diet with equol producer status, ethnicity and weight status revealed no significant effect modification. Conclusions Contrary to our hypothesis and some previous reports, the results from two well-controlled dietary interventions do not support an effect of a high-soy diet on a panel of urinary estrogen metabolites and the 2-OH/16α-OHE(1) ratio.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/ejcn.2012.71

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Of nine RCTs assessing impact of soy on estrogen metabolism via urinary metabolites, five reports of six studies found no significant change in 2-hydroxyestrone, 16α-hydroxyestrone, or 2:16α hydroxyestrone ratio compared to control.

    “Of these, five reports of six studies found no significant change in 2-hydroxyestrone, 16α-hydroxyestrone, or 2:16α hydroxyestrone ratio compared to the control group (p>0.05 for all) [148,149,156,161,164].”

    From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [161]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 32

  1. [1]Wu AH Yu MC Tseng CC Pike MC Epidemiology of soy exposures and breast cancer risk Br J Cancer 2008 98 9 14 18182974 PMC2359677
  2. [2]Setchell KD Soy isoflavones--benefits and risks from nature’s selective estrogen receptor modulators (SERMs) J Am Coll Nutr 2001 20 354S 362S 11603644
  3. [3]Hooper L Ryder JJ Kurzer MS Lampe JW Messina MJ Phipps WR Cassidy A Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis Hum Reprod Update 2009 15 423 440 19299447 PMC2691652
  4. [4]Zhu BT Conney AH Functional role of estrogen metabolism in target cells: review and perspectives Carcinogenesis 1998 19 1 27 9472688
  5. [5]Yager JD Liehr JG Molecular mechanisms of estrogen carcinogenesis Annu Rev Pharmacol Toxicol 1996 36 203 232 8725388
  6. [6]Obi N Vrieling A Heinz J Chang-Claude J Estrogen metabolite ratio: Is the 2-hydroxyestrone to 16alpha-hydroxyestrone ratio predictive for breast cancer? Int J Womens Health 2011 3 37 51 21339936 PMC3039007
  7. [7]Eliassen AH Spiegelman D Xu X Keefer LK Veenstra TD Barbieri RL Willett WC Hankinson SE Ziegler RG Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer among Premenopausal Women Cancer Res 2012 72 696 706 22144471 PMC3271178
  8. [8]Moon YJ Wang X Morris ME Dietary flavonoids: effects on xenobiotic and carcinogen metabolism Toxicol In Vitro 2006 20 187 210 16289744
  9. [9]Wood CE Register TC Cline JM Soy isoflavonoid effects on endogenous estrogen metabolism in postmenopausal female monkeys Carcinogenesis 2007 28 801 808 17032659
  10. [10]Xu X Duncan AM Merz BE Kurzer MS Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women Cancer Epidemiol Biomarkers Prev 1998 7 1101 1108 9865428
  11. [11]Lu LJ Cree M Josyula S Nagamani M Grady JJ Anderson KE Increased urinary excretion of 2-hydroxyestrone but not 16alpha- hydroxyestrone in premenopausal women during a soya diet containing isoflavones Cancer Res 2000 60 1299 1305 10728690
  12. [12]Teas J Hurley TG Hebert JR Franke AA Sepkovic DW Kurzer MS Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women J Nutr 2009 139 939 944 19321575
  13. [13]Falk RT Xu X Keefer L Veenstra TD Ziegler RG A liquid chromatography-mass spectrometry method for the simultaneous measurement of 15 urinary estrogens and estrogen metabolites: assay reproducibility and interindividual variability Cancer Epidemiol Biomarkers Prev 2008 17 3411 3418 19064556 PMC4158914
  14. [14]Eliassen AH Ziegler RG Rosner B Veenstra TD Roman JM Xu X Hankinson SE Reproducibility of fifteen urinary estrogens and estrogen metabolites over a 2- to 3-year period in premenopausal women Cancer Epidemiol Biomarkers Prev 2009 18 2860 2868 19843676 PMC2783292
  15. [15]Franke AA Custer LJ Morimoto Y Nordt FJ Maskarinec G Analysis of urinary estrogens, their oxidized metabolites, and other endogenous steroids by benchtop orbitrap LCMS versus traditional quadrupole GCMS Anal Bioanal Chem 2011 401 1319 1330 21713421 PMC3249142
  16. [16]Maskarinec G Franke AA Williams AE Hebshi S Oshiro C Murphy SP Stanczyk FZ Effects of a 2-year randomized soy intervention on sex hormone levels in premenopausal women Cancer Epidemiol Biomarkers Prev 2004 13 1736 1744 15533901
  17. [17]Maskarinec G Morimoto Y Conroy SM Pagano IS Franke AA The volume of nipple aspirate fluid is not affected by 6 months of treatment with soy foods in premenopausal women J Nutr 2011 141 626 630 21325473 PMC3056579
  18. [18]Maskarinec G Ollberding NJ Conroy SM Morimoto Y Pagano IS Franke AA Gentzschein E Stanczyk FZ Estrogen levels in nipple aspirate fluid and serum during a randomized soy trial Cancer Epidemiol Biomarkers Prev 2011 20 1815 1821 21742946 PMC3169755
  19. [19]Maskarinec G Takata Y Franke AA Williams AE Murphy SP A 2-year soy intervention in premenopausal women does not change mammographic densities J Nutr 2004 134 3089 3094 15514280
  20. [20]Setchell KD Brown NM Lydeking-Olsen E The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones J Nutr 2002 132 3577 3584 12468591
  21. [21]Franke AA Lai JF Pagano I Morimoto Y Maskarinec G Equol production changes over time in pre-menopausal women Br J Nutr 2011 1 6 PMC3319310 21920062
  22. [22]Franke AA Lai JF Halm BM Pagano I Kono N Mack WJ Hodis HN Equol production changes over time in postmenopausal women J Nutr Biochem 2011 Epub ahead of print PMC3901250 21775122
  23. [24]Lampe JW Karr SC Hutchins AM Slavin JL Urinary equol excretion with a soy challenge: influence of habitual diet Proc Soc Exp Biol Med 1998 217 335 339 9492344
  24. [25]Fuhrman BJ Pfeiffer R Xu X Wu AH Korde L Gail MH Keefer LK Veenstra TD Hoover RN Ziegler RG Soy intake is associated with increased 2-hydroxylation and decreased 16alpha-hydroxylation of estrogens in Asian-American women Cancer Epidemiol Biomarkers Prev 2009 18 2751 2760 19789363 PMC2759852
  25. [26]Martini MC Dancisak BB Haggans CJ Thomas W Slavin JL Effects of soy intake on sex hormone metabolism in premenopausal women Nutr Cancer 1999 34 133 139 10578479
  26. [27]Maskarinec G Williams AE Stanczyk FZ Stanczyk FZ Franke AA A randomized isoflavone intervention among premenopausal women Cancer Epidemiol Biomarkers Prev 2002 11 195 201 11867507
  27. [28]Morimoto Y Conroy SM Pagano IS Isaki M Franke AA Nordt FJ Maskarinec G Urinary estrogen metabolites during a randomized soy trial Nutr Cancer 2012 64 307 314 22293063 PMC3279611
  28. [29]Messina MJ Loprinzi CL Soy for breast cancer survivors: a critical review of the literature J Nutr 2001 131 3095S 3108S 11694655
  29. [30]Nettleton JA Greany KA Thomas W Wangen KE Adlercreutz H Kurzer MS The effect of soy consumption on the urinary 2:16-hydroxyestrone ratio in postmenopausal women depends on equol production status but is not influenced by probiotic consumption J Nutr 2005 135 603 608 15735101
  30. [31]Atkinson C Skor HE Dawn FE Scholes D Chen C Wahala K Schwartz SM Lampe JW Urinary equol excretion in relation to 2-hydroxyestrone and 16alpha-hydroxyestrone concentrations: an observational study of young to middle-aged women J Steroid Biochem Mol Biol 2003 86 71 77 12943746
  31. [32]Brooks JD Ward WE Lewis JE Hilditch J Nickell L Wong E Thompson LU Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy Am J Clin Nutr 2004 79 318 325 14749240
  32. [33]Cassidy A Brown JE Hawdon A Faughnan MS King LJ Millward J Zimmer-Nechemias L Wolfe B Setchell KD Factors affecting the bioavailability of soy isoflavones in humans after ingestion of physiologically relevant levels from different soy foods J Nutr 2006 136 45 51 16365057

Cited by

Sorted by citations

Authors
Maskarinec, G., Morimoto, Y., Heak, S., Isaki, M., Steinbrecher, A., Custer, L., & Franke, A. A.
Affiliations
University of Hawaii Cancer Center (US)
Corresponding author
Maskarinec, G
ORCID
Venue
European Journal of Clinical Nutrition
Publisher
Springer Science and Business Media LLC
Published
2012-06-20
Volume
66
Issue
9
Pages
1044-1049
ISSN
  • 0954-3007 (ISSN-L)
  • 1476-5640
DOI
10.1038/ejcn.2012.71
PMC
PMC3437012
OpenAlex
W2033644242
Cited by
15
References
0
Citations by year
2025: 1 · 2024: 1 · 2021: 2 · 2019: 1 · 2017: 1 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 2
FWCI
1.09
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Clinical Nutrition (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (1s10rr020890-01)
  • National Cancer Institute (R01CA080843, P30CA071789)
  • National Center for Research Resources (S10-RR020890)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
Keywords
soy products, urinary estrogen metabolites, 4-hydroxyestrone, premenopausal women, breast cancer prevention
MeSH terms
Adult, Chromatography, Liquid, Diet, Estrogens, Female, Humans, Hydroxyestrones, Isoflavones, Regression Analysis, Mass Spectrometry, Premenopause, Cross-Over Studies, Soy Foods

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review