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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01070160
Recruitment Status : Completed
First Posted : February 17, 2010
Last Update Posted : March 30, 2020
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Yale University

Study Description
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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
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
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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 : June 2009
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort 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


Outcome Measures
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Primary Outcome Measures :
  1. 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 [ Time Frame: baseline ]
  2. 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 [ Time Frame: 3 months ]
  3. 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 [ Time Frame: 9 months ]

Secondary Outcome Measures :
  1. blood draw (20mL) [ Time Frame: on day of EMBx ]
  2. 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 [ Time Frame: 9 months ]

Biospecimen Retention:   Samples With DNA
blood, endometrium tissue biopsy

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 42 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Women will be recruited from the multi-physician Yale Reproductive Endocrinology clinical practice and Yale Fertility Center. Metformin is a routinely employed therapeutic strategy utilized for managing PCOS by practitioners at YFC. Almost 1/3 of the patients with PCOS are not interested in pursuing fertility in the immediate future and it is these patients who will be offered participation in the trial.
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01070160


Locations
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United States, Connecticut
Yale-New Haven Hospital Women's Center
New Haven, Connecticut, United States, 06520-8063
Sponsors and Collaborators
Yale University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Principal Investigator: Lubna Pal, MBBS MRCOG MSc Yale University
More Information
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Additional Information:

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01070160    
Other Study ID Numbers: 0905005203
U54HD052668-02 ( U.S. NIH Grant/Contract )
First Posted: February 17, 2010    Key Record Dates
Last Update Posted: March 30, 2020
Last Verified: June 2014
Keywords provided by Yale University:
Polycystic Ovarian Syndrome (PCOS)
Metformin
Endometrin
Additional relevant MeSH terms:
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Polycystic Ovary Syndrome
Syndrome
Disease
Pathologic Processes
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
 Urogenital Diseases
Genital Diseases
Gonadal Disorders
Endocrine System Diseases
Metformin
Progesterone
Hypoglycemic Agents
Physiological Effects of Drugs
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists