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

Completed

• Conditions: Polycystic Ovarian Syndrome
• Interventions: Drug: Endometrin (progesterone 100mg vaginal inserts); Drug: Metformin

• Registration Number: NCT01070160
• Lead Sponsor: Yale University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2010-02-16
• Study First Submitted QC: 2010-02-16
• Study First Posted: 2010-02-17
• Primary Completion: 2013-07
• Study Completion: 2013-07
• Status Verified: 2014-06
• Last Update Submitted: 2020-03-27
• Last Update Posted: 2020-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 14

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
B	Endometrin (progesterone 100mg vaginal inserts)	Women with PCOS not planning initiating Metformin and exposure to vaginal progesterone for 6-8 days prior to Endometrium Biopsy
A	Endometrin (progesterone 100mg vaginal inserts)	Women with PCOS initiating Metformin and exposure to vaginal progesterone for 6-8 days prior ro Endometrium Biopsy
A	Metformin	Women with PCOS initiating Metformin and exposure to vaginal progesterone for 6-8 days prior ro Endometrium Biopsy

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Yale-New Haven Hospital Women's Center; 🇺🇸 New Haven, Connecticut, United States