Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (PCOS) Women
Condition: Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Hyperandrogenism; Insulin Resistance; Syndrome
Intervention: Orlistat/Meal Replacement/Lifestyle Modification; Loestrin 1/20; Combination of treatments
Intervention description: Orlistat will be given at 60 mg three times per day (1 tablet 3 times a day) before meals, i.e., breakfast, lunch, and dinner.; Patients will be started on a low dose containing OCP for a continuous 4 month period.; Medications will be administered as described for the other 2 arms.
Intervention MeSH terms: Orlistat; Contraceptive Agents; Norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination; Contraceptives, Oral
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 217.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Polycystic Ovary Syndrome

Summary:

      The goal of this three-armed randomized controlled trial is to establish the relative roles
      of treatment of hyperandrogenism versus obesity (as the largest modifiable factor
      contributing to insulin resistance) in treating infertility and improving pregnancy outcomes
      among obese PCOS women. The investigators hypothesize that the key to restoring ovulation
      leading to live birth is to correct hyperandrogenism with oral contraceptive pills, but the
      key to avoiding later pregnancy complications is to improve insulin sensitivity with weight
      loss.
    

Eligibility criteria:

        Couples Inclusion Criteria:

          -  Partner with sperm concentration of >=14 million/mL in at least one ejaculate with
             motile sperm.

          -  Ability to have regular intercourse 2-3 times per week during the ovulation induction
             phase of study.

          -  At least one patent tube and normal uterine cavity as determined by sonohysterogram,
             hysterosalpingogram, or hysteroscopy/laparoscopy within the last 3 years, or
             confirmation of a intrauterine pregnancy within the past 2 years.

          -  No previous sterilization procedures(vasectomy, tubal ligation) that have been
             reversed.

          -  Wanting to seek pregnancy.

        Inclusion Criteria:

          -  Chronic anovulation or oligomenorrhea defined as intermenstrual periods of >= 45 days
             or a total of <=8 periods per year.

          -  Hyperandrogenism will be an elevated total testosterone >=50 ng/dL.

          -  Hirsutism determined by a modified Ferriman-Gallwey Score >8.

          -  PCO on ultrasound (12 or more follicles measuring 2-9 mm in diameter).

          -  BMI >=27 to <=42.

          -  Normal EKG to rule out any abnormalities with the heart.

        Exclusion Criteria:

          -  Current pregnancy.

          -  Patients on oral contraceptives, depo progestins, or hormonal implants.

          -  Patients with hyperprolactinemia defined as two prolactin levels at least one week
             apart >30 ng/mL.

          -  Patients with known 21-hydroxylase deficiency by a fasting 17-hydroxyprogesterone
             (17-OHP) level <2 ng/mL and ACTH stimulation test as needed, or other enzyme
             deficiency.

          -  Patients with menopausal FSH levels >20 mIU/mL.

          -  Patients with uncorrected thyroid disease (TSH <0.45 mIU/ML or >4.5 mIU/ML).

          -  Patients diagnosed with Type1 or Type II diabetes.

          -  Patients with liver disease defined as AST or ALT >2 times normal or total bilirubin
             >2.5 mg/dL.

          -  Patients with renal disease defined as BUN >30 mg/dL or serum creatinine >1.4 mg/dL.

          -  Patients with significant anemia (Hemoglobin <10 mg/dL).

          -  Patients with a history of deep venous thrombosis, pulmonary embolus, or
             cerebrovascular accident.

          -  Patients with known heart disease that is likely to be exacerbated by pregnancy.

          -  Patients with a history of , or suspected cervical carcinoma, endometrial carcinoma,
             or breast carcinoma. A normal PAP smear or reassuring colposcopy based on current ACOG
             guidelines will be required.

          -  Patient with current history of alcohol abuse.

          -  Patients enrolled simultaneously into other investigative studies.

          -  Patients taking other medications know to affect reproductive function or metabolism.

          -  Patients with a suspected adrenal or ovarian tumor secreting androgens.

          -  Patients with suspected Cushing's syndrome.

          -  Patients who have undergone a bariatric surgery procedure in the recent past (<12
             months).

          -  Patients with untreated poorly controlled hypertension defined as systolic blood
             pressure >=150 mm Hg or average diastolic >=100 mm Hg on three measurements obtained 5
             minutes apart. If treated, average systolic blood pressure >= 140 mm Hg or average
             diastolic >= 90 mm Hg.

          -  Patients with medical conditions that represent contraindications to orlistat, OCP,
             clomiphene, and/or pregnancy.

          -  Patients currently participating in lifestyle intervention program (Weight Watchers,
             Atkins Diet, Curves) or lost more than 5% body weight within the last 6 months.