Oral Contraceptives in the Metabolic Syndrome
Condition: Metabolic Syndrome X; Insulin Resistance; Obesity; Cardiovascular Diseases
MeSH terms: Cardiovascular Diseases; Microvascular Angina; Metabolic Syndrome; Insulin Resistance; Syndrome
Intervention: Ortho Tri Cyclen
Intervention description: Ortho Tri Cyclen, one tablet daily, for 6 cycles
Intervention MeSH terms: Moxifloxacin; Norgestimate, ethinyl estradiol drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Inflammatory markers, oral contraceptions, obesity, metabolic syndrome X

Summary:

      Oral contraceptives (OCs) are the most widely used method of reversible birth control.
      However, the long-term cardiovascular safety of the widely used low-dose OCs
      (ethinyl-estradiol < 50 mcg) is still debated. Although cardiovascular events are rare in
      young women whether they use OCs or not, the risks of myocardial infarction and ischemic
      stroke are increased among users of OCs who have conventional cardiovascular risk factors
      such as use of tobacco, diabetes or hypercholesterolemia. However, the risk of cardiovascular
      events in OC users with emerging cardiovascular risk factors (such as obesity and the
      metabolic syndrome) have not been investigated. Recently, the metabolic syndrome has been
      linked with the risk of cardiovascular disease. The syndrome is a clustering of risk factors
      in a single individual, and its underlying cause may be insulin resistance. Whether the
      metabolic syndrome predicts a higher cardiovascular risk in OC users has not been studied.
      This is a critical problem because the metabolic syndrome is prevalent in 24% of adults.
      Until the cardiovascular risks in users of OC are clearly defined, the appropriate use of OC
      with the least harm would not be possible.

      The investigator's long-term goal is to understand the best way to prevent and treat
      cardiovascular disease in women. The objective of this particular project is to obtain pilot
      data on the extent to which the metabolic syndrome and obesity affects glucose metabolism and
      cardiovascular risks in women taking OCs. The researchers hypothesize that women with
      metabolic syndrome and obese women will have worsened glucose metabolism and elevated
      cardiovascular risks associated with OC use, when compared to normal weight women without the
      metabolic syndrome. Results of this study will clarify the risk factors for cardiovascular
      events in women taking OCs, and will serve as pilot data for a National Institutes of Health
      (NIH) proposal. Once the cardiovascular risk factors of OC users are understood, clinicians
      can make better informed decisions about contraceptive choices for their patients.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Acceptable health based on interview, medical history, physical examination, and
             laboratory tests (comprehensive metabolic panel - SMA20, and complete blood count -
             CBC);

          2. Have not taken oral contraceptives (OCs) in the past 3 months;

          3. Ability to comply with the requirements of the study;

          4. Ability and willingness to provide signed, witnessed informed consent. In addition,
             women with the metabolic syndrome must meet the National Cholesterol Education Program
             (NCEP) defined criteria of the metabolic syndrome, that is, having at least 3 of the 5
             factors:

               1. increased waist circumference > 35 inches,

               2. hypertriglyceridemia ≥ 150 mg/dL,

               3. low high-density lipoprotein (HDL) cholesterol < 50 mg/dL in women,

               4. hypertension (≥ 130/≥ 85 mmHg),

               5. fasting glucose ≥ 100 mg/dL.

        Obese women with or without the metabolic syndrome should have a Body Mass Index (BMI) > 30
        kg/m2 and lean women should have a Body Mass Index BMI < 25 kg/m2.

        Exclusion Criteria:

          1. Diabetes mellitus by fasting glucose or a 2-hour oral glucose tolerance test (OGTT);

          2. Clinically significant pulmonary, cardiac (including but not limited to ischemic heart
             disease, stable/unstable angina, and congestive heart failure), renal, hepatic,
             cholestatic, neurologic, psychiatric, infectious, and malignant disease (other than
             melanoma skin cancer);

          3. History of thromboembolism, myocardial infarction, cerebrovascular accident, vascular
             disease, known coagulopathy, prolonged immobilization, or recent major surgery (within
             past 6 months);

          4. Systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than
             100 mmHg (mild hypertension is not an exclusion criterion);

          5. History of breast cancer, migraine headaches, or age ≥ 35 years and smoker of ≥ 20
             cigarettes/day;

          6. Use of metformin, thiazolidinediones, anti-hyperlipidemic drugs, anti-hypertensive
             drugs, glucocorticoids, or anti-androgens (spironolactone, flutamide, etc.) within 3
             months;

          7. Documented or suspected illicit drug abuse or alcoholism within one year;

          8. Ingestion of any investigational drugs within 3 months prior to the study onset; and

          9. Pregnancy or lactation (≤ 6 weeks postpartum);

         10. Hematocrit < 33g/dL. These exclusion criteria are based on study requirements and also
             go beyond guidelines for OC use published by the World Health Organization.