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

Sponsor

Federal University of São Paulo (Other)

Overall Status

Unknown status

CT.gov ID

NCT00988078

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome	Drug: Placebo Drug: Metformin	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2011

Anticipated Primary Completion Date :

Oct 1, 2013

Anticipated Study Completion Date :

Dec 1, 2013

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

serum melatonin [0 and 6 months]

Secondary Outcome Measures

hormonal and metabolic measurements, clinical assessment [0, 3 and 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

11 Years to 19 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Federal University of Sao Paulo	Sao Paulo		Brazil

Sponsors and Collaborators

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 Sao Paulo