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

NCT02525159 | Completed Phase 3

• 1 other identifier: SDEI.PTID.05.3(CM)
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Breast Cancer

Keywords

3,3'-diindolylmethane; premenopause; 2-hydroxyestrone

Outcome Measures

Primary Outcomes (1)

• Change in ratio of estrogen metabolites 2OHE1:16αOHE1 in urine (REMU)

  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

Secondary Outcomes (2)

• Adherence

  Dialy, after the day 0 until the end of the supplementation of DIM or placebo (day 30)

• Presence of Side Effects

  At day 0 and 30 days after the supplementation of DIM or placebo

Other Outcomes (11)

• Prolonged use of hormonal contraceptives

  At day 0

• Late pregnancy or nulliparity

  At day 0

• Age

  At day 0

Study Arms (2)

DIM pills

ACTIVE COMPARATOR

75 mg of 3,3´-diindolylmethane (DIM) once a day for 30 days

Dietary Supplement: DIM pills

Placebo pills

PLACEBO COMPARATOR

2 pills once a day for 30 days

Other: Placebo Pill

Interventions

DIM pills DIETARY_SUPPLEMENT

Two pills of BioResponse DIM® 150 are equal to 75 mg of DIM pure

Also known as: BioResponse DIM® 150

DIM pills

Placebo Pill OTHER

Placebo pills, proportionate by the same provider, vials and pills were the same size, shape and material containing the DIM pills

Placebo pills

Eligibility Criteria

• Age: 35 Years - 52 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes: lead

Related Publications (5)

• Falk 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 BACKGROUND

• Godinez 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 BACKGROUND

• Reed 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 BACKGROUND

• Dalessandri 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 BACKGROUND

• Wong 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 BACKGROUND

Related Links

• Association of Market Research Agencies and Public Opinion 2005
• Inmune Care Corporation. USA.
• Studies with the ESTRAMET™ 2/16 kit

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Researcher in Medical Sciences B

Study Record Dates

• First Submitted: July 29, 2015
• First Posted: August 17, 2015
• Study Start: August 1, 2006
• Primary Completion: August 1, 2009
• Study Completion: February 1, 2010
• Last Updated: August 17, 2015

Record last verified: 2015-08