Clinical trial · Interventional

Effectiveness of DIM Supplements to Increase 2-OHE1/16 Ratio

Effectiveness of DIM Supplements to Increase 2-OHE1/16 Ratio in Premenopausal Mexican Women With Risk of Breast Cancer

NCT02525159CI-TRIAL-00018852EDIMI216OHE1completedPhase 3ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

Breast cancer is a public health problem in Mexico and its incidence rises when the woman is still premenopausal. Estrogen metabolism has been linked to breast cancer. Several studies reported that high concentrations of 2 hydroxyestrone (2OHE1) in urine have a protective effect for this neoplasia, whereas high concentrations of 16 alpha-hydroxyestrone (16αOHE1) in urine have the opposite effect, further has been reported that women with a ratio of estrogen metabolites 2OHE1:16αOHE1 in urine (REMU) less than 0.9, have ten times the risk of developing Breast Cancer than those women with an RMEU equal or more than 0.9. Other studies have showed that the active compounds of cruciferous vegetables, indole-3-carbinol (I3C) and its dimer, 3'3'diindolylmethane (DIM) induce benign pathway of metabolism of estrogens producing 2OHE1. Several studies, evaluate the pharmacokinetics and effect of I3C supplementation, finding that 300 to 600 mg of this compound are well tolerated and able to promote formation of 2OHE1 in women when supplemented for one month. In the case of DIM, only a pilot study has explored its effect in postmenopausal women with personal history of breast cancer in early stages, reporting an increase in the concentrations of 2OHE1. The purpose of this study was to evaluate the effectiveness of supplementation with DIM to increase urinary RMEU in premenopausal women at risk of Breast Cancer (RMEU less than 0.9). A clinical, randomized, double-blind study was performed with women attending on the urogynecology service of Institute National of Perinatology. Subjects were premenopausal women over 34 years who were healthy. The inclusion criteria's was had a RMEU less than 0.9 and were excluded for any medical condition, medication, or dietary or lifestyle habit that might interfere with estrogen metabolism. Patients were randomly assigned to one of two groups: one received orally at a daily dose of 75 mg of DIM for a period of 30 days and other group received orally at a daily placebo for a period of 30 days. All urine samples were collected from the women before DIM or placebo ingestion, after 30 days of DIM or placebo ingestion and finally after another 30 days once suspended supplementation. Analysis of the 2OHE1 and 16αOHE1 were determined using a commercially kit ESTRAMET™. The change in metabolites median concentrations and RMEU was assessed through the Wilcoxon test and these differences between groups through U Mann-Whitney test.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Breast Cancer	Malignant Breast Neoplasm	CURATED_EXACT	0.92

Interventions

Interventions (2)

Intervention	Type	Mapped drug	Match
DIM pills	Dietary Supplement	—	UNRESOLVED
Placebo Pill	Other	—	UNRESOLVED

Design

Arms and outcomes

Arms (2)

type
ACTIVE_COMPARATOR
label
DIM pills
description
75 mg of 3,3´-diindolylmethane (DIM) once a day for 30 days
interventionNames
1. Dietary Supplement: DIM pills
type
PLACEBO_COMPARATOR
label
Placebo pills
description
2 pills once a day for 30 days
interventionNames
1. Other: Placebo Pill

Primary outcomes (1)

measure
Change in ratio of estrogen metabolites 2OHE1:16αOHE1 in urine (REMU)
timeFrame
At day 0, at day 30 after the supplementation of DIM or placebo and 30 days after the end of the suplementation of DIM or placebo to evaluate the permanence of the response

Eligibility

Eligibility (as posted)

Sex: Female
Minimum age: 35 Years
Maximum age: 52 Years

Show eligibility criteria text

Inclusion Criteria:

* Postmenopausal woman
* Not pregnant or planning to become pregnant
* That are not nursing
* Nonsmokers
* No alcohol addiction
* Regular menstrual cycles
* 2-hydroxyestrone /16 urinary ratio less or equal to 0.9

Exclusion Criteria:

* Take drugs that interfere with estrogen metabolism like hormonal contraceptives , cimetidine , antidepressants, thyroxine , supplements of n-3 fatty acids or soy
* Endocrine or liver disease
* Pregnancy

References

Publications (5)

BACKGROUNDFalk RT, Rossi SC, Fears TR, Sepkovic DW, Migella A, Adlercreutz H, Donaldson J, Bradlow HL, Ziegler RG. A new ELISA kit for measuring urinary 2-hydroxyestrone, 16alpha-hydroxyestrone, and their ratio: reproducibility, validity, and assay performance after freeze-thaw cycling and preservation by boric acid. Cancer Epidemiol Biomarkers Prev. 2000 Jan;9(1):81-7. PMID 10667467
BACKGROUNDGodinez Martinez EY, Santillan Ballesteros R, Lemus Bravo AE, Samano R, Tolentino Dolores M, Rodriguez Ventura AL, Juarez Gonzalez AR. [Determination of 2-hydroxyestrone /16alpha-hydroxyestrone ratio in urine of Mexican women as a risk indicator for breast cancer and its relationship with other risk factors]. Nutr Hosp. 2014 Oct 25;31(2):835-40. doi: 10.3305/nh.2015.31.2.8172. Spanish. PMID 25617571
BACKGROUNDReed GA, Peterson KS, Smith HJ, Gray JC, Sullivan DK, Mayo MS, Crowell JA, Hurwitz A. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1953-60. doi: 10.1158/1055-9965.EPI-05-0121. PMID 16103443
BACKGROUNDDalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004;50(2):161-7. doi: 10.1207/s15327914nc5002_5. PMID 15623462
BACKGROUNDWong GY, Bradlow L, Sepkovic D, Mehl S, Mailman J, Osborne MP. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl. 1997;28-29:111-6. doi: 10.1002/(sici)1097-4644(1997)28/29+3.0.co;2-k. PMID 9589355