Targeting Pathways in Polycystic Ovary Syndrome (PCOS) Using Metformin (MET)

Study Overview
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Brief Summary
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The investigator's global hypothesis is that women with Polycystic Ovary Syndrome (PCOS) can be separated into subtypes based on their response to metformin. The investigators propose here to use both targeted and non-targeted metabolomic approach to identify pathways associated with metformin's effect on insulin sensitivity and endothelial function. This pilot project will be the foundation for developing tailored therapeutic approaches to Polycystic Ovary Syndrome and identifying novel drug targets.

Detailed Description
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The investigators propose to use both targeted and non-targeted metabolomic approaches to identify pathways associated with metformin's effect on insulin sensitivity, weight, androgens and endothelial function. This project will be the foundation for developing tailored therapeutic approaches to Polycystic Ovary Syndrome and identifying novel drug targets. This pilot project is intended to inform the development of hypothesis and specific aims for a future grant application to National Institutes of Health (NIH).

Official Title
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Targeting Pathophysiologic Pathways in Polycystic Ovary Syndrome Using a Response to Metformin Phenotype

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) greater than or equal to 25 Polycystic Ovary Syndrome criteria of both oligomenorrhea (<9 menses per year) and androgen excess [clinical hirsutism (Ferriman-Gallway score >8 or severe acne) or elevated testosterone]. Taking no medications for the treatment of insulin resistance. Exclusion Criteria: Diagnosis of Cushing's syndrome Untreated hypo/hyperthyroidism Elevated prolactin Congenital adrenal hyperplasia Renal insufficiency (creatinine > 1.5) Diabetes Medications that can significantly affect endothelial function Pregnancy Breast Feeding Taking oral contraceptives Currently smoking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>Metformin 500 mg. extended release (taken orally) one tablet with evening meal for one week, one tablet with morning and evening meal for one week, and one tablet at all three meals for the next three months. | Drug: Metformin<br>* Approximately 37 patients will start metformin therapy 3 months after their visit 2. All other patients will receive metformin therapy at their visit 2.<br>* Other names: Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet;|
| Other: Delayed Start Metformin<br>After baseline study visit, this arm will return after three months without metformin for a repeat of the baseline study visit prior to initiating metformin 500 mg. extended release (taken orally) one tablet with evening meal for one week, one tablet with morning and evening meal for one week, and one tablet at all three meals for the next three months. | Drug: Metformin<br>* Approximately 37 patients will start metformin therapy 3 months after their visit 2. All other patients will receive metformin therapy at their visit 2.<br>* Other names: Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insulin Sensitivity (SI) after 3 Months of Metformin Therapy | Insulin sensitivity will be calculated using an oral glucose minimal model. Insulin under the curve will be calculated geometrically with the trapezoidal rule. | Baseline, 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peripheral Flow-Mediated Vasodilatation after 3 Months of Metformin Therapy | The ratio of Peripheral Digital Arterial Tonometry (PAT) signal after cuff release compared with baseline is calculated through a computer algorithm normalizing for baseline measurements and indexing to measurements in the contra-lateral arm. The calculated ratio reflects the reactive hyperemia index (RHI). | baseline, 3 months |