Study of Brain Function in Women With Insulin Resistant Polycystic Ovary Syndrome

Not Applicable

Completed

Conditions: Polycystic Ovary Syndrome

Interventions: Drug: Metformin

Registration Number: NCT00670800

Lead Sponsor: University of Michigan

Brief Summary: The purpose of this study is to evaluate the effects of insulin resistance on brain function in women with Polycystic Ovary Syndrome (PCOS). PCOS affected women will be evaluated prior to and following 4-month treatment with Metformin. Additionally, brain function in women with PCOS will be compared to the brain activity in normal control subjects with regular menstrual cycles.

Detailed Description: The pathogenesis of Polycystic Ovary Syndrome (PCOS), a reproductive and metabolic disorder, is associated with insulin resistance. The effects of insulin resistance on cognition, mood, opioid system and reproductive function in PCOS affected women are investigated in the current study. The identification of reversible changes in brain function and reproductive measures in insulin resistant PCOS patients would likely significantly influence treatment protocols for these young women.

1. Evaluate the differences in opioid tone in women with insulin resistant PCOS compared to normal controls.

2. Evaluate whether an oral hypoglycemic agent is capable of altering opioid tone in women with insulin resistant PCOS.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 14

Inclusion Criteria

Insulin-resistant PCOS (Arm: PCOS Affected Women)
Irregular menstrual cycle (Arm: PCOS Affected Women)
Hyperandrogenism (Arm: PCOS Affected Women)
Regular menstrual cycles (Arm: Normal Controls)
Normal hormonal levels (Arm: Normal Controls)
Lack of hirsutism (Arm: Normal Controls)
Acne-free (Arm: Normal Controls)
Candidates are BMI-matched and screened for insulin resistance prior to inclusion. (Arm: Normal Controls)

Exclusion Criteria

Left handedness
Acute medical illness
Uncorrected thyroid disease
Diabetes renal
Cardiac or pulmonary insufficiency
Active liver disease
Neurological disease
Current psychiatric illness
Claustrophobia
Contraindications to MRI
Smoking
Use of hormones
Centrally acting or insulin sensitizing mediations
Allergy to any opioid medication
Substance abuse
Pregnancy
BMI >35.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PCOS Affected Women-Metformin Treatment	Metformin	Subjects with Polycystic Ovary Syndrome (PCOS) will be scheduled for 9 visits total: following the screening visit they will go through OGTT, neuro-psychological testing, fMRI and PET scan before and after 4 months of metformin use: 500mg tablets once daily with breakfast for 1 week, then increased to one tablet twice daily with breakfast \& lunch for 1 week, then increased to one tablet three times daily with breakfast, lunch \& dinner.

Primary Outcome Measures

Name	Time	Method
Mu-opioid Binding Potential Measured in Left Nucleus Accumbens	Baseline and after 4 months	Mu-opioid binding potential in left nucleus accumbens is measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.) Control group was measured at baseline only.
Mu-opioid Binding Potential Measured in Right Nucleus Accumbens	Baseline and after 4 months	Mu-opioid binding potential in right nucleus accumbens measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.) Control group was measured at baseline only.
Mu-opioid Binding Potential Measured in Left Amygdala	Baseline and after 4 months	Mu-opioid binding potential in left amygdala measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.)
Mu-opioid Binding Potential Measured in Right Amygdala	Baseline and 4 months	Mu-opioid binding potential in right amygdala measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.) Control group was measured at baseline only.