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