Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
Condition: Obesity; Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Overweight
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Sibutramine
Intervention type(s): Drug
Intervention MeSH terms: Sibutramine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Obesity; Polycystic Ovary Syndrome; weight loss; Hyperadrogonemia; Sibutramine