Metformin and Lifestyle Intervention in Women With Polycystic Ovary Syndrome

Sponsor

Hospital Privado de Cordoba, Argentina (Other)

Overall Status

Completed

CT.gov ID

NCT00679679

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Polycystic ovary syndrome is a frequent cause of abnormal menses and infertility. It has also been related to cardiovascular disease.

The objective of this trial is to evaluate the clinical and metabolic efficacy of metformin plus life style modifications in women with polycystic ovary syndrome compared with life style modifications and placebo

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome	Drug: Metformin Drug: Placebo	Phase 4

Detailed Description

Polycystic ovary syndrome (PCOS) is a common and heterogeneous disorder of women in reproductive age. It is characterized by hyperandrogenism and chronic anovulation. Several studies in diverse populations estimate it's prevalence at 5-10%. Women present, in a high percentage of cases, with obesity, hirsutism, acne, menstrual irregularities and infertility. Although the exact physiopathology of PCOS remains unknown, several studies tend to point to insulinoresistance (IR) as the cause of the syndrome. IR is present in 60 to 70% of patients independently of obesity. Compensatory hyperinsulinism has a pivotal role in the physiopathogenesis of PCOS. In vitro, insulin stimulates androgen synthesis in thecal cells and decrease sex hormone-binding globulin synthesis in the liver, increasing free androgen availability.

Due to the high prevalence of IR, PCOS shares components of metabolic syndrome: abdominal obesity, impaired glucose tolerance, gestational and type 2 diabetes, abnormalities in lipid profile, blood hypertension, endothelial dysfunction and probably cardiovascular disease.

In the past, PCOS treatment was focus on ovulation induction for infertility, oral contraceptives for irregular bleeding, and androgens antagonists for hirsutism or acne. In later years insulin sensitizing agents have been used to reduce hyperinsulinemia, improve ovary function and associated metabolic abnormalities. Metformin (MTF), a biguanide, usually used in obese patients with type 2 diabetes,inhibits glucose hepatic production,decreases insulin secretion and increases peripheral insulin sensitivity.

Some studies have reported an improvement in insulin sensitivity associated with reduction of hyperandrogenism and improvements in reproductive abnormalities with MTF. On the other hand, other authors failed to observe those changes. However, an off label indication for it usage in PCOS for FDA and the lack of large controlled trials, MTF indication to treat PCOS has grown dramatically in later years.

In obese women with PCOS, weight loss effectively ameliorates hyperandrogenism and metabolic disorders by improving insulin resistance.

Some trials have suggested that those effects could be improved with insulin sensitizing agents without changes in body weigh.

The present study was designed to assess, in a randomized, double-blind, placebo-controlled way, the effects of MTF in addition to lifestyle modifications on endocrine and metabolic disturbances in women with PCOS.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Clinical Metabolic and Endocrine Parameters in Response to Metformin and Lifestyle Intervention in Women With Polycystic Ovary Syndrome: A Phase 4 Randomized, Double- Blind and Placebo Control Trial

Study Start Date :

Jan 1, 2003

Actual Primary Completion Date :

Sep 1, 2005

Actual Study Completion Date :

Dec 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metformin Every patient will be given diet and exercise counseling in both arms. Intervention arm will receive metformin	Drug: Metformin Metformin 750 mg BID for 4 months Other Names: D.B.I. 500 mg. 1 1/2 tables BID
Placebo Comparator: Placebo Every patient will be given diet and exercise counseling in both arms. Intervention arm will receive metformin	Drug: Placebo Diet counseling and exercise

Arm

Intervention/Treatment

Experimental: Metformin

Every patient will be given diet and exercise counseling in both arms. Intervention arm will receive metformin

Drug: Metformin

Metformin 750 mg BID for 4 months

Other Names:

D.B.I. 500 mg. 1 1/2 tables BID

Placebo Comparator: Placebo

Every patient will be given diet and exercise counseling in both arms. Intervention arm will receive metformin

Drug: Placebo

Diet counseling and exercise

Outcome Measures

Primary Outcome Measures

Body mass index,Normalization of menses,Pregnancy,Hirsutism,Waist to hip ratio, Testosterone, Androstenedione, DHEAS,Progesterone, FSH, LH,Glucose, OGTT,Insulinemia,Total HDL and LDL Cholesterol, Triglycerides,Uric acid, Prostate specific antigen [4 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women in reproductive age
With polycystic ovary syndrome defined by hyperandrogenism (elevated serum testosterone concentrations), and oligomenorrhea (cycles of 35 days or longer), or amenorrhea (no menses in the last 6 months) after negative screening pregnancy test

Exclusion Criteria:

Pregnancy
Cushing' s syndrome
Late onset congenital adrenal hyperplasia
Androgen-secreting tumors
Uncontrolled thyroid disease
Hyperprolactinemia
Diabetes any
Cardiovascular diseases (Ischaemic heart disease, uncontrolled hypertension, heart failure)
Acute or chronic infections at baseline
Renal disease
Liver disease
Had taken any medications for at least 3 months before enrolment in the study.