Endometrial Effects of Metformin Action in Women With Polycystic Ovarian Syndrome (PCOS)

Endometrial assessments are proposed following three month and then nine month treatment with metformin; expression of specified markers at respective time points will be compared to baseline.

Visit 1: Screening

• Signed informed consent
• Comprehensive history intake
• Physical exam: Vital signs, height, weight, waist circumferences, waist : hip ratio
• Urine pregnancy test
• Subjects provided with a 10 day supply of vaginal progesterone and EMBx will be scheduled between days 6-8 of progesterone use.

Visit 2: Baseline

• Urine pregnancy test
• Endometrium thickness will be measured via transvaginal ultrasound
• EMBx: sample of endometrial tissue will be sent for histopathology to rule out endometrial hyperplasia or cancer
• 20cc blood
• Metformin prescription and dispensing will be as per clinical care.
• Women will be advised to use barrier method of contraception (ie; condoms, contraceptive jellies or foam, sponge, diaphragm, or cervical cap) for the duration of the study.

Visits 3 and 5 (Weeks 8-10 and 30-34, respectively)

• Urine pregnancy test
• A 10 day course of vaginal progesterone to allow scheduling of EMBx's time points specified under visit 1

Visits 4 and 6 (Weeks 12 ± 1 week and 36 ± 1 week respectively)

• The procedure specified for baseline (Visit 2) will be repeated.

Inclusion criteria

• Premenopausal between 18-42 years of age
• Diagnosed with PCOS as defined by chronic oligo- or amenorrhea (8 menstrual periods annually); biochemical hyperandrogenemia (elevated total or free testosterone) and /or clinical hyperandrogenism (excessive facial hair &/or acne); exclusion of common medical disorders (normal thyroid function tests and serum prolactin and exclusion of 21-hydroxylase deficiency by a fasting 17-hydroxyprogesterone <200 ng/dl).
• Acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (CBC, SMA20, urinalysis) performed within the past 6 months
• Able to provide signed informed consent
• Able to comply with study requirements
• Willing to delay the start of clinically prescribed metformin treatment

Exclusion criteria

• Known diabetics or those with clinically significant and known pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic and malignant disease (other than non-melanoma skin cancer)
• Current use of hormonal contraceptives
• Seeking pregnancy; use of fertility drugs within 6 months of study
• Current or recent (within 3 months) use of metformin
• Ingestion of any investigational drug within two months prior to study onset
• Evidence of endometrial hyperplasia or cancer upon baseline EMBx