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

Sponsor

Yale University (Other)

Overall Status

Completed

CT.gov ID

NCT01070160

Collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Enrollment

Location

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators aim is to conduct a prospective un-blinded pilot study of premenopausal women diagnosed with Polycystic Ovarian Syndrome (PCOS), defined using criteria developed at the 1990 NICHD conference on PCOS, undergoing treatment for ovulation induction with Metformin. We propose that improving insulin sensitivity with use of Metformin in women diagnosed with PCOS has facilitatory influences on the uterine endometrium.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovarian Syndrome	Drug: Endometrin (progesterone 100mg vaginal inserts) Drug: Metformin

Detailed Description

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.

Study Design

Study Type:

Observational

Actual Enrollment :

14 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
A Women with PCOS initiating Metformin and exposure to vaginal progesterone for 6-8 days prior ro Endometrium Biopsy	Drug: Endometrin (progesterone 100mg vaginal inserts) once a day, 6-8 days as specified (prior to each EMBx) Drug: Metformin per clinical care guidelines
B Women with PCOS not planning initiating Metformin and exposure to vaginal progesterone for 6-8 days prior to Endometrium Biopsy	Drug: Endometrin (progesterone 100mg vaginal inserts) once a day, 6-8 days as specified (prior to each EMBx)
Women with PCOS who previously initiated metformin Women with PCOS who initiated metformin at least 3 months prior to enrollment who have completed a 6-10 day course of progesterone

Arm

Intervention/Treatment

Women with PCOS initiating Metformin and exposure to vaginal progesterone for 6-8 days prior ro Endometrium Biopsy

Drug: Endometrin (progesterone 100mg vaginal inserts)

once a day, 6-8 days as specified (prior to each EMBx)

Drug: Metformin

per clinical care guidelines

Women with PCOS not planning initiating Metformin and exposure to vaginal progesterone for 6-8 days prior to Endometrium Biopsy

Drug: Endometrin (progesterone 100mg vaginal inserts)

once a day, 6-8 days as specified (prior to each EMBx)

Women with PCOS who previously initiated metformin

Women with PCOS who initiated metformin at least 3 months prior to enrollment who have completed a 6-10 day course of progesterone

Outcome Measures

Primary Outcome Measures

It is anticipated that endometrial expression of implantation markers will be upregulated by metformin treatment compared to baseline and improved parameters will be identified with longer duration of metformin exposure. endometrium biopsy [baseline]
It is anticipated that endometrial expression of implantation markers will be upregulated by metformin treatment compared to baseline and improved parameters will be identified with longer duration of metformin exposure. endometrium biopsy [3 months]
It is anticipated that endometrial expression of implantation markers will be upregulated by metformin treatment compared to baseline and improved parameters will be identified with longer duration of metformin exposure. endometrium biopsy [9 months]

Secondary Outcome Measures

blood draw (20mL) [on day of EMBx]
A combination of quantitative real time PCR, immunohistochemistry, and Western Blot techniques will be utilized for studying endometrial markers of receptivity in the endometrial tissue [9 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 42 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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