Metformin Treatment in Polycystic Ovary Syndrome (PCOS)

Effects of Metformin on Mitochondrial Function in Polycystic Ovary Syndrome

PCOS occurs when a woman does not release an egg regularly each month, causing her periods to be irregular. Women with PCOS can also have increased hair growth on the face and body, acne, head balding, infertility, pre-diabetes, and diabetes. PCOS is commonly treated with oral contraceptive pills (also known as the birth control pills). Sometimes, a medication called metformin is also used to treat PCOS, especially if a woman has evidence of insulin resistance or if fertility is desired. Unfortunately, metformin works in only some women with PCOS. The mechanism through which metformin works in PCOS is not clear and it difficult to predict who will benefit from metformin treatment and who will not.

The investigators are doing this research study to look at how the medication metformin affects the cells in the body of patients with PCOS. Specifically, the investigators will look at how metformin affects the mitochondria. Mitochondria are the part of cells that produce fuel (energy) for other cells and play a role in metabolism. The investigators would like to see whether there is a relationship between mitochondrial activity and symptoms of polycystic ovary syndrome (PCOS) before and after treatment with metformin. They would also like to study whether genes affect the response to metformin in women with PCOS.

Study Overview

• Status: Unknown
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Metformin ER

Detailed Description

Women who are eligible to enroll in this study will be treated with the medication metformin for 12 weeks. Before and after treatment with metformin, the following will be assessed:

• Weight, blood pressure, waist circumference
• Lipids (cholesterol)
• Hormone levels (including testosterone and other androgens)
• IV glucose tolerance test (to assess for early evidence of insulin resistance)
• Effect of metformin on muscle mitochondria (this will involve one MRI scan and one muscle biopsy each before and after treatment with metformin)

Ovulation will be closely monitored at least twice a month with pelvic ultrasounds and blood tests for estrogen and progesterone levels.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Polycystic ovary syndrome
• No hormonal or antidiabetic medications for 1 month
• Good general health

Exclusion Criteria:

• Smoker
• Acute infection or chronic disease
• Diabetes
• Pregnant or trying to get pregnant over next half year
• Bleeding disorders
• Any metal or foreign implants (e.g., aneurysm clips, ear implants, heart pacemakers or defibrillators)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin; Metformin ER 1500 mg per day treatment for 12 weeks	Drug: Metformin ER; Treatment with metformin ER for 12 weeks; Other Names: Glucophage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle Metabolism/Mitochondrial Function	The change in mitochondrial activity before and after metformin treatment will be analyzed in relationship to the clinical response to 3 months of metformin treatment (i.e., clinical response to metformin = changes in glucose metabolism, hormone levels, and ovulation response)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic risk variants affecting mitochondrial function/metabolism	Blood will be analyzed for differences in genes between patients and its relationship to mitochondrial function.	3 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of Utah
• Investigators: Principal Investigator: Corrine Welt, M.D., Massachusetts General Hospital

Publications and helpful links

General Publications

• Pau CT, Keefe C, Duran J, Welt CK. Metformin improves glucose effectiveness, not insulin sensitivity: predicting treatment response in women with polycystic ovary syndrome in an open-label, interventional study. J Clin Endocrinol Metab. 2014 May;99(5):1870-8. doi: 10.1210/jc.2013-4021. Epub 2014 Feb 25.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: July 17, 2014
• First Submitted That Met QC Criteria: July 21, 2014
• First Posted (Estimate): July 23, 2014

Study Record Updates

• Last Update Posted (Actual): August 16, 2018
• Last Update Submitted That Met QC Criteria: August 14, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Infertility; PCOS; Acne; Polycystic Ovary Syndrome; Mitochondria; Metabolism; Irregular menses; Irregular period
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 2014P000911; R01HD065029 (U.S. NIH Grant/Contract)