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

NCT ID: NCT01070160

Last Updated: 2020-03-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 14 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2013-07-31

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.

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.

Conditions

Polycystic Ovarian Syndrome

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

A

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

Endometrin (progesterone 100mg vaginal inserts)

Intervention Type: DRUG

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

Metformin

Intervention Type: DRUG

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

Endometrin (progesterone 100mg vaginal inserts)

Intervention Type: DRUG

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

No interventions assigned to this group

Interventions

Endometrin (progesterone 100mg vaginal inserts)

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

Intervention Type: DRUG

Metformin

per clinical care guidelines

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 42 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lubna Pal, MBBS MRCOG MSc

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale-New Haven Hospital Women's Center

New Haven, Connecticut, United States

Countries

United States

Related Links

http://www.nlm.nih.gov/medlineplus/ency/article/000369.htm

MedlinePlus related topics: Polycystic Ovary Disease

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a696005.html

Drug Information available for: Metformin

Other Identifiers

U54HD052668-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0905005203

Identifier Type: -

Identifier Source: org_study_id