Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (PCOS) Women

• Status: Completed
• Trial end date: 2014-03-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Milton S. Hershey Medical Center
• Collaborator: University of Pennsylvania
• Treatments: Contraceptive Agents; Contraceptives, Oral; Norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination; Norinyl; Orlistat

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.