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

Official Title: “Influence of Insulin Resistance on Cognitive, Emotional and Opioid System Functioning in Women With Polycystic Ovary Syndrome”

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.

AIM I. Determine whether identifiable differences can be observed in cognitive and emotional processing between women with insulin resistant PCOS compared to normal controls using validated fMRI tasks.

AIM II. Determine whether treatment with oral hypoglycemic agent will alter cognitive processing as measured with validated fMRI cognitive and emotional tasks.

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

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

Intervention(s) in this Clinical Trial

• Drug: Metformin
  • 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 BID adding a dose after lunch. On the third week, a 500 mg tablet will be added after supper for a final dose of 500 mg orally TID. 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.

Arms, Groups and Cohorts in this Clinical Trial

• No Intervention: 1: Control
  • Control subjects will have 5 visits (screening, OGTT, neuropsych, fMRI and 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.
• Experimental: 2: PCOS
  • Subjects with PCOS will be scheduled for 9 visits total: following the screening visit they will go through OGTT, neuropsychological testing, fMRI and PET scan before and after 4 months of metformin use.

Primary Measures

• PCOS affected women will be evaluated prior to and following 4-month metformin treatment utilizing the following measures: OGTT, neuropsychological testing battery, fMRI and PET scanning results.
  • Time Frame: Once
    Safety Issue?: No

Secondary Measures

• Hormonal studies
  • Time Frame: prior to and following 4-months metformin treatment
    Safety Issue?: No

Inclusion Criteria:

• Subjects with insulin resistant PCOS, irregular menstrual cycles and hyperandrogenism.
• Normal controls with regular menstrual cycles
• Normal hormonal levels, without hirsutism and acne are BMI matched and screened for insulin resistance prior to inclusion.

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.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: University of Michigan Other

Overall Clinical Trial Officials and Contacts

Yolanda R Smith, MD, MS Principal Investigator University of Michigan, Obstetrics and Gynecology  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00670800

Study ID Number: 2276

ClinicalTrials.gov Identifier: NCT00670800

Health Authority: United States: Institutional Review Board