Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Nutritional and Metabolic Diseases

Syndrome

Polycystic Ovary Syndrome

Insulin Resistance

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Hypoglycemic Agents

All Drugs and Chemicals

Anti-Infective Agents

Central Nervous System Depressants

Micronutrients

Hematinics

Analgesics

Vitamins

Metformin

Ethanol

Insulin

Insulin, Globin Zinc

Folic Acid

Analgesics, Opioid

Vitamin B Complex

Vitamin B 12

Hydroxocobalamin

Folinic Acid

Methylcobalamin

Folate

Vitamin B9

Vitamin B12

Cobalamin

Cyanocobalamin

Control subjects will have 5 visits (screening, oral glucose tolerance test (OGTT), neuropsychological testing, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) as they will receive no treatment and will not have repeat studies. The baseline values obtained from the control subjects will be compared to the baseline values acquired from the PCOS affected subjects.

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.

Following the baseline studies, PCOS affected women will be initiated on metformin at a dose of 500 mg orally after breakfast and the dose will be increased the following week to 500 mg twice daily (BID), adding a dose after lunch. On the third week, the dose will be increased to 500 mg three times daily (TID), adding a 500 mg tablet after supper. All subjects will be monitored for possible side effects such as nausea, vomiting, diarrhea, anorexia, and abdominal discomfort. These side effects tend to be mild, dose-related and improve with continued use of metformin. Hypoglycemia is rare and tends to occur in the setting of alcohol abuse or prolonged starvation. Malabsorption of vitamin B12 and folate occurs with long-term treatment, although it usually does not lead to anemia.

Yolanda R Smith, MD, MS

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.

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.

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

Influence of Insulin Resistance on Cognitive, Emotional and Opioid System Functioning in Women With Polycystic Ovary Syndrome

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 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 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 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.

University of Michigan

Professor

Normal Controls

PCOS Affected Women on Metformin

Right handed women who don't smoke and who drink very little will be considered eligible. Women with the following conditions (exclusion criteria) may not participate: left handedness, acute medical illness, uncorrected thyroid disease, diabetes, neurological disease, current psychiatric illness, smoking within the last 6 months, use of hormones within the last 2 months, pregnancy within the last 6 months, current or past history of substance abuse, use of corticosteroids (such as cortisol and prednisone), history of lactic acidosis (condition caused by the buildup of lactic acid in the body), heart, lung and kidney problems, liver disease, use of intravenous dyes, current cimetidine (Tagamet) use, use of medications that affect the brain (for example, codeine, anti-depressants, anti-psychotics).

PCOS Affected Women - Metformin

Normal controls are matched for age and education and screened for insulin resistance. Controls will have HOMA2 IR of 80%S or greater, normal hormone levels, regular menstrual cycles, and lack hirsutism and acne. Exclusion criteria: Left handedness, acute medical illness, uncorrected thyroid disease, diabetes, neurological disease, current psychiatric illness, claustrophobia, contraindications to MRI (including pacemakers, pumps, surgical clips or metallic surgical devices), smoking within the last 6 months, use of hormones or insulin sensitizing mediation within the last 2 months, pregnancy within the last 6 months, current or past history of substance abuse, use of corticosteroids, cardiac or pulmonary insufficiency, active liver disease and transaminases elevations \>2.5 X normal values, renal insufficiency (plasma creatinine level ≥1.4 mg/dl), use of centrally acting medications, allergy to any opioid medication, 300 lbs maximum weight limit (which is the max

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Weight

lbs/inches squared (pounds over inches squared)

BMI (Body Mass Index)

Waist Circumference

Free testosterone measured in picograms over milliliters

Free Testosterone

Total Testosterone measured in nanograms over milliliters

Total Testosterone

Total cholesterol measured in milligrams over deciliter

Total Cholesterol

Dehydroepiandrosterone Sulfate (DHEAS)measured in micrograms/deciliter

DHEAS

High-density lipoprotein measured in milligrams/deciliter

Triglycerides measured in measured in milligrams/deciliter

Triglycerides

Fasting Insulin measured in microunits/milliliter

Fasting Insulin

Fasting Glucose measured in milligrams/deciliter

Fasting Glucose

Homeostatic model assessment sensitivity reported in percentage

Homeostatic Model Assessment (HOMA)

Homeostatic model assessment insulin resistance measured in milliunits per Liters

HOMA-IR

Two controls were excluded from data analysis as they were later found to be insulin resistant.

Yolanda Smith

PCOS will be defined as meeting the criteria of irregular menstrual cycles and hyperandrogenism (on physical exam or laboratory testing), with other causes ruled out. Subjects with insulin resistant PCOS must meet criteria for insulin resistance based on the 2 hr OGTT (Oral Glucose Tolerance Test). Insulin resistance will be defined as fasting HOMA2 IR of 60%S or less.

PCOS Affected Women Pre-Metformin (Baseline)

PCOS Affected Women Post-Metformin (After 4 Months)

Normal controls will have HOMA2 IR of 80%S or greater, normal hormone levels, regular menstrual cycles (range 24 - 34 days), and lack hirsutism and acne. Control subjects are matched for age and education with the PCOS affected women. Control data is measured once (at baseline time frame) for the entire study.

All 7 PCOS women completed the protocol and were included. 5 of 7 controls were included in this analysis. 2 controls were excluded from analysis because repeat baseline OGTT showed HOMA %S of \<80%.

Mu-opioid Binding Potential Measured in Left Nucleus Accumbens

Normal Control Women

All 7 PCOS women were included, 2 controls were excluded because repeat baseline HOMA2-IR %S was \<80%.

Mu-opioid Binding Potential Measured in Right Nucleus Accumbens

Mu-opioid Binding Potential Measured in Left Amygdala

Mu-opioid Binding Potential Measured in Right Amygdala

The Polycystic Ovary Syndrome (PCOS) affected group is comprised of subjects with insulin resistant PCOS, defined as having irregular menstrual cycles and hyperandrogenism with other causes ruled out. Insulin resistance will be identified as fasting homeostasis model assessment insulin resistance (HOMA2-IR) of 60%S or less.

Women Affected With PCOS - Metformin

Control group is comprised of subjects without PCOS. These women have normal menstrual cycles and no evidence of insulin resistance (fasting HOMA2 IR of 80%S or more).

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Exclusion criteria: left handedness, acute medical illness, uncorrected thyroid disease, diabetes, neurological disease, current psychiatric illness, smoking within the last 6 months, use of hormones within the last 2 months, pregnancy within the last 6 months, current or past history of substance abuse, use of corticosteroids (such as cortisol and prednisone), history of lactic acidosis (condition caused by the buildup of lactic acid in the body), heart, lung and kidney problems, liver disease, use of intravenous dyes, current cimetidine (Tagamet) use, use of medications that affect the brain (for example, codeine, anti-depressants, anti-psychotics).

Spots Global Cancer Trial Database for Study of Brain Function in Women With Insulin Resistant Polycystic Ovary Syndrome

Trial Identification

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Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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