Effects of Metformin and Oral Hormonal Contraceptive in Adolescents With Polycystic Ovary Syndrome

June 24, 2012 updated by: Margareth Chiharu Iwata, Federal University of São Paulo

Effect of Metformin Therapy on Insulin Resistance and Melatonin in Adolescents With Polycystic Ovary Syndrome.

The polycystic ovary syndrome is the most common endocrinopathy in reproductive age women. The pathophysiology of this syndrome remains unclear, but there are evidences that a decreased in insulin sensitivity may be related in this syndrome. There are studies that showed the action of factors on the sensitivity of the insulin receptor, such as melatonin. It is a hormone produced by the pineal gland, whose role is still uncertain in human reproduction, although many studies have found that it may relate sex hormone effect. Many patients with polycystic ovary syndrome (PCOS) may have hyperinsulinemia, and that pinealectomized rats determined hypoglycemia and hyperinsulinemia, with reduced release of insulin in response to glucose. Therefore, it is supposed that blood levels of melatonin might correlate with the blood insulin concentration in patients with the syndrome. Moreover, the insulin sensitizing agents have been used in the treatment of patients with insulin resistance and PCOS, based on its main pathophysiological substrate which is the hyperinsulinemia. In fact, the metformin is the most used in the literature. However, there are few studies on the use of metformin in adolescents. The evidences of this drugs in this group of patients have showed good therapeutic response with few side effects. The objective of the study is to evaluate the effects of metformin on insulin resistance and levels of melatonin in adolescents with PCOS. It will be performed a prospective, randomized, double-blind and placebo-controlled study with 90 adolescents with PCOS. It will be evaluated clinical and laboratory parameters (TSH, free T4, prolactin, FSH, LH, estradiol, total testosterone, androstenedione, DHEA-s, 17-OH progesterone, SHBG, free androgen index, index of HOMA-IR and QUICKI from fasting glucose and insulin, total cholesterol and fractions, triglycerides, creatinine, AST and ALT and creatinkinase, fibrinogen and PAI-1, and melatonin for 6 months of treatment.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Design: 90 patients will be selected to a prospective, randomized and double-blinded study. They will be assigned to two groups: A) 45 patients, treated with OC (oral contraceptive) and metformin 1500mg/ day. B) 45 patients, treated with OC and placebo. The length of treatment was six months.

Inclusion criteria: patients until 19 years-old, at least 2 years after menarche, with Polycystic Ovary Syndrome based on Rotterdan criterion. Exclusion criteria: patients with Diabetes Mellitus, hypertension, hyperprolactinemia, adrenal enzymatic deficiency, Cushing syndrome, thyroidopathy, renal or hepatic disfunction, use of OC or insulin-sensitising drugs in the last 90 days before, pregnancy, androgen tumors, hormonal-sensitive tumors in the past, contra-indication to the medications used in the study.

Clinical parameters included are weight and height (for BMI), waist to hip ratio, habits like smoking or drinking, drug addiction, blood pressure measurement, hirsutism and acne.

Laboratorial parameters included are TSH, free T4, prolactin, FSH, LH, estradiol, total testosterone, androstenedione, s-DHEA, 17-OH progesterone, SHBG, free androgen index, fasting glucose and insulin, total cholesterol and fractions, triglycerides, creatinin, TGO, TGP, CK, PAI-1, fibrinogen, melatonin.

Patients will be evaluated using these parameters in the beginning, 1, 3 and 6 months after use of the drugs.

Study Type

Interventional

Enrollment (Anticipated)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Sao Paulo, Brazil
        • Recruiting
        • Federal University of São Paulo
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

11 years to 19 years (ADULT, CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Patients until 19 years-old, at least 2 years after menarche
  • Patients with Polycystic Ovary Syndrome based on Rotterdan criteries

Exclusion Criteria:

  • Patients with Diabetes Mellitus, hypertension, hyperprolactinemia, adrenal enzymatic deficiency, Cushing syndrome, thyroidopathy, renal or hepatic disfunction
  • Use of OC or insulin-sensitising drugs in the last 90 days before
  • Pregnancy
  • Androgen tumors, hormonal-sensitive tumors in the past
  • Contra-indication to the medications used in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Metformin
Metformin 500mg three times a day for six months
Drug: Metformin
Metformin 500mg three times a day for six months
PLACEBO_COMPARATOR: Placebo
1 capsule three times a day for six months
Drug: Placebo
Capsule (without biologic action) administered three times a day for six months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
serum melatonin
Time Frame: 0 and 6 months
0 and 6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
hormonal and metabolic measurements, clinical assessment
Time Frame: 0, 3 and 6 months
0, 3 and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federal University of São Paulo

Investigators

  • Study Director: Jose Maria Soares Junior, Federal University os Sao Paulo
  • Study Chair: Alexandre Rossi, Federal University os Sao Paulo
  • Study Director: Eduardo Leme Alves da Motta, Federal University os Sao Paulo
  • Principal Investigator: Margareth Chiharu Iwata, Federal University of São Paulo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (ANTICIPATED)

October 1, 2013

Study Completion (ANTICIPATED)

December 1, 2013

Study Registration Dates

First Submitted

September 30, 2009

First Submitted That Met QC Criteria

September 30, 2009

First Posted (ESTIMATE)

October 1, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

June 26, 2012

Last Update Submitted That Met QC Criteria

June 24, 2012

Last Verified

October 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CEP 2102/08

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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