The Role of the Gut Microbiota in Estrogen Metabolism and Dietary Flax as a Potential Modulator.

The purpose of this pilot study is to determine if suppressing estrogen in premenopausal women results in changes in gut microbiota and if dietary flaxseed modulates these changes.

Study Overview

• Status: Active, not recruiting
• Conditions: Menopause
• Intervention / Treatment: Dietary supplement: Flaxseed

Detailed Description

This pilot study will begin to address whether gut microbiota change with estrogen suppression. Specifically, the investigators will test whether gut microbial diversity and abundance change in response to estrogen suppression and consumption of dietary flaxseed. To test this possibility the investigators will recruit premenopausal women (age 20-40 years old)and collect fecal samples before and after 1 month of estrogen suppression with GnRH agonist. The investigators will analyze the gut microbiota in response to estrogen loss and whether this differs with the consumption of flaxseed.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Fort Collins, Colorado, United States, 80523
      • Colorado State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• healthy premenopausal women (20-40 years)
• normal to overweight (22-29.9 kg/m2)
• normally menstruating (25-35 day cycles)
• not have used estrogen-based contraception for >6 months.
• sedentary to moderately active (exercise ≤120 min week-1)
• must not be taking phytoestrogenic dietary supplements, or lipid- or glucose- lowering medications.

Exclusion Criteria:

• smoking
• pregnancy or breastfeeding
• Hormonal contraceptive use (past 6 mo.)
• Women with contraindications to GnRHAG:
• History of fragility fracture
• Low BMD (i.e., proximal femur or lumbar spine z scores < -2.0)
• Abnormal vaginal bleeding
• History of breast cancer or other estrogen-dependent neoplasms
• History of venous thromboembolic events
• Hypersensitivity to leuprolide acetate or benzyl alcohol (the vehicle for injection of leuprolide acetate)
• Evidence for depressive symptoms (Score ≥ 18 on the Beck Depression Inventory, BDI)
• Moderate or severe renal impairment defined as a calculated creatinine clearance <50 mL/min based on the equation of Cockcroft and Gault91
• Chronic hepatobiliary disease, conservatively defined as liver function tests (AST, ALT, alkaline phosphatase, Total Bilirubin) >1.5 times the upper limit of normal (if such values are obtained on initial screening and thought to be transient in nature, repeated testing will be allowed)
• antibiotic or probiotic use within 2 months of sample collection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Estrogen suppression no flax; Control subjects will not consume flaxseed, but will receive GnRH suppression
Experimental: Estrogen suppression with flax; Flax subjects will consume flaxseed for 2 months in addition to GnRH suppression	Dietary supplement: Flaxseed; 2 months of dietary flaxseed supplementation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gut microbiota diversity	16s rRNA sequencing--Illumina MiSeq	At baseline (day 0) and 30 days after estrogen suppression, with and without dietary flaxseed 30 days before estrogen suppression and during the 30 days of estrogen suppression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estrogen metabolites	estrogen metabolites (parent:metabolite ratio) in urine and plasma	At baseline (day 0) and 30 days after estrogen suppression, with and without dietary flaxseed 30 days before estrogen suppression and during the 30 days of estrogen suppression

Collaborators and Investigators

• Sponsor: Colorado State University
• Investigators: Principal Investigator: Kimberly Cox-york, PhD, Colorado State University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): December 30, 2022
• Study Completion (Estimated): July 30, 2024

Study Registration Dates

• First Submitted: June 7, 2017
• First Submitted That Met QC Criteria: June 8, 2017
• First Posted (Actual): June 9, 2017

Study Record Updates

• Last Update Posted (Estimated): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 16-6978H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No