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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Menopause

Intervention / Treatment
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* Dietary Supplement: Flaxseed


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |