Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00463112
Recruitment Status : Completed
First Posted : April 20, 2007
Last Update Posted : April 20, 2007
Information provided by:
Hippocration General Hospital

Brief Summary:

Studies on the effect of sibutramine, an anti-obesity drug, on hormonal and metabolic features of women with polycystic ovary syndrome (PCOS) are lacking.

The objective of this study is to examine the effect of sibutramine plus hypocaloric diet on body composition, hormonal and metabolic parameters and insulin resistance in obese patients with PCOS.

Overweight and obese women with PCOS were placed in a hypocaloric diet plus sibutramine (10 mg/day) for the first month and then on a hypocaloric diet plus sibutramine (10 mg/day) or hypocaloric diet only for the subsequent 6 months.

The main outcome measures are: Body composition, hormonal and metabolic features and insulin sensitivity (OGTT) at baseline, at 3 and 6 months of treatment.

Condition or disease Intervention/treatment Phase
Obesity Polycystic Ovary Syndrome Drug: Sibutramine Phase 4

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Detailed Description:

The Polycystic Ovary Syndrome (PCOS) is one of the most common hormonal disorders in women of reproductive age. As a syndrome it has multiple components, such as reproductive (chronic anovulation and infertility), metabolic and cardiovascular. Although lean women present PCOS, obesity is one of the main manifestations of the syndrome. Androgen excess and insulin resistance underline much of the clinical and metabolic features of the syndrome.

Recent evidence suggests that PCOS patients have a substantial risk for the development of metabolic and cardiovascular abnormalities similar to those presented in the metabolic syndrome. Obesity, particularly of the abdominal type, is presented in approximately half of the women with PCOS, although several studies have shown that percentage can vary from 30% to 75%. Several studies have demonstrated that obesity in women with PCOS enhances the clinical and metabolic abnormalities of the syndrome, since obese women with PCOS have more profound insulin resistance or type 2 DM,dyslipidemia and cardiovascular disease’s risk, and greater level of androgens due to low SHBG levels.

A modest weight loss (<5% or even 5-10% of initial body weight) has been shown to improve ovulation frequency and conception, to reduce miscarriage, hyperlipidemia, hypertension, hyperglycemia and insulin resistance in women with PCOS. There are only a few studies on the effect of anti-obesity drug administration in obese and overweight women with PCOS. To the authors’ best knowledge, the effect of sibutramine, a serotonin and noradrenaline reuptake inhibitor (SNRI) approved as antiobesity drug, has been studied in only one study with obese women with PCOS. Given this lack of information, the aim of the present study was to investigate any additional effect of sibutramine combined with a hypocaloric diet on body composition, hormonal and lipids parameters and insulin resistance in obese women with PCOS.

Study's design The study was prospective, open label, randomized, comparative trial. The study design included 3 periods; a screening period in order to confirm the diagnosis of PCOS, a lead-in period (4 weeks duration) that all patients were prescribed 10mg/day sibutramine plus a 600 kcal deficient diet, and a treatment period (for the subsequent 6 months) that subjects were randomized in a 2:1 ratio to the S group (10 mg/day of Sibutramine plus hypocaloric diet) and the D group (hypocaloric diet only). Diet was based on the individualized basal metabolic rate as defined by the Harris-Benedict’s equation adjusted for moderate physical activity. Before entering the lead-in period all subjects were prescribed an energy-restricted diet containing 50% as carbohydrate, 30% as fat (10% saturated), and 20% as protein. After randomization, subjects were advised not to modify their eating habits throughout the study period.

The randomization was performed using sealed envelopes prepared in advance of the study by a research associate not involved in the study. A randomisation table was created using blocks of 3 numbers with all possible combinations. A random number generator has been used to create balance between the treatment groups.

Clinical measures Body weight, waist circumference and fasting blood samples for total testosterone (T), Sex Hormone Binding Globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), androstenedione (Δ4Α), 17a-hydroxyprogesterone, follicle stimulating hormone (FSH), luteinising hormone (LH), thyroid stimulating hormone (TSH), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose, and insulin were taken at baseline as well as at 3 and 6 months of treatment. At the same period, an Oral Glucose Tolerance Test (OGGT) with 75-g glucose was performed.

Blood samples were collected between 08:30 and 09:00 a.m., after an overnight fast, and during the follicular phase of women’s menstrual cycle. Monthly, subjects’ body weight was measured, adverse events, heart rate, blood pressure, and study drug compliance were determined and a pregnancy urine test was performed. Body weight was always determined at morning hours with subjects in light clothes.

Study Type : Interventional  (Clinical Trial)
Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS: a Randomized, 24-Week Study
Study Start Date : March 2004
Actual Study Completion Date : September 2006

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Primary Outcome Measures :
  1. weight loss

Secondary Outcome Measures :
  1. FAI, insulin resistance and other metabolic parameters

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • overweight and obese women with PCOS

Exclusion Criteria:

  • Nonclassical 21-hydroxylase deficiency, hyperprolactinemia, adrenal or ovarian tumor and Cushing’s disease, hypertension, thyroid dysfunction, overt diabetes mellitus and concomitant treatment such as antihypertensive drugs, SSRI or other SNRI drug, oral contraceptive pills or any other antiandrogen treatment (cyproterone acetate, spirolactone, LHRH agonist) and insulin sensitizing agents (metformin, pioglitazone, roziglitazone) that may interact with insulin sensitivity and lipid profile.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00463112

Hippocratio General Hospital
Thessaloniki, Greece, 54642
Sponsors and Collaborators
Hippocration General Hospital
Principal Investigator: Dimos Florakis, MD Divison of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece Identifier: NCT00463112     History of Changes
Other Study ID Numbers: 511/8-1-04
First Posted: April 20, 2007    Key Record Dates
Last Update Posted: April 20, 2007
Last Verified: December 2003

Keywords provided by Hippocration General Hospital:
Polycystic Ovary Syndrome
weight loss

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Body Weight
Signs and Symptoms
Ovarian Cysts
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Antidepressive Agents
Psychotropic Drugs
Appetite Depressants
Anti-Obesity Agents