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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

Phase 4
18 Years
35 Years
Not Enrolling
Polycystic Ovary Syndrome

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Trial Information

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

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.

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

- Acute or chronic infections at baseline

- Renal disease

- Liver disease

- Had taken any medications for at least 3 months before enrolment in the study.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

4 months

Safety Issue:


Principal Investigator

Carolina Fux Otta, MD

Investigator Role:

Principal Investigator


Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Study ID:




Start Date:

January 2003

Completion Date:

December 2005

Related Keywords:

  • Polycystic Ovary Syndrome
  • Polycystic ovary syndrome
  • Treatment
  • Metformin
  • Polycystic Ovary Syndrome