Effects of a Combined Treatment With Myo-inositol, D-chiro-inositol and Glucomannan in Women With PCOS

1. RATIONALE & BACKGROUND INFORMATION Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome and one of the most common female endocrine disorders, affecting 5-20% of women in reproductive age . Clinical expression is highly variable, but typically includes oligo-ovulation or anovulation, hyperandrogenism and polycystic ovaries . PCOS is associated with an increased risk of type 2 diabetes, cardiovascular events and endometrial cancer. Insulin Resistance (IR) plays a central role in approximately 70-80% of obese women and in 15-30% of lean women with PCOS, and represents the pathogenic link between metabolic and reproductive disorders in PCOS. According to recent guidelines, insulin-sensitizer drugs, like inositols, are the first-line therapy in women with metabolic abnormalities and irregular menstrual cycle with the purpose to improve fertility, whereas a lifestyle change with weight loss and physical activity is the first step in overweight and obese PCOS patients . Moreover, the association inositols-glucomannan may represent a good therapeutic strategy in the treatment of PCOS women with insulin resistance. Metabolomic approach is used to better define the pathophysiology of PCOS and to describe how different therapies can modify metabolic profiles. Although the association inositols-glucomannan may represent a good therapeutic strategy in the treatment of PCOS women with insulin resistance, the effect of inositols on the metabolomic profile of these women has not been described yet.
2. STUDY GOALDS AND OBJECTIVES The aim of this study is to analyze the metabolic profiles in women with PCOS before and after 3 months of therapy with a combination of myo-inositol, D-chiro-inositol and glucomannan, and compare these data with a group of healthy control women.
3. STUDY DESIGN The study is a prospective and observation. The inclusion criteria are: age between 18 and 35 years, overweight/obesity (BMI > 25 kg/m2), absence of any other acute intercurrent or chronic illness, a positive diagnosis of PCOS according to Rotterdam criteria. Exclusion criterion is using hormonal medications or drugs that affect insulin sensitivity (e.g., inositols or metformin) before enrollment.

The use of myo-inositol (1.75 g), D-chiro-inositol (0.25 g) and glucomannan (4.0 g)/die must precede the recruitment of no more than 30 days. The decision to start treatment must have already been made before and independently of the start of the study. The use of inositol and glucomannan must take place according to the technical data sheet. In particular, myo-inositol (1.75 g), D-chiro-inositol (0.25 g) and glucomannan (4.0 g) are expected to be subdivided into two doses before main meals. 4. METHODOLOGY 4.1 Admission visit (V0) Once the eligibility criteria have been checked, the investigator will inform the patient about the objectives of the study during the initial visit (V0) and obtain written informed consent form.

The compilation of a clinical card includes general information, anamnesis, BMI, the characteristics of the menstrual cycle, the amount of menstrual loss, the degree of hirsutism according to the Ferriman-Gallwey index and the degree of acne in agreement to the Global evaluation scale proposed in 2002 by FDA.

The investigator will collect from the clinical documentation available the baseline glycaemia, insulin, triglycerides, cholesterol values before the start of the treatment. Furthermore, information on the ultrasound picture will be collected in terms of ovary volumes and antral follicles.

A sample of 2-3 ml of basal blood will be collected for metabolomic evaluations, using a BD vacutainer (Becton Dickinson, Oxfordshire, UK) blood collection red tube (with no additives). After centrifugation, the sample will immediately freeze to -80 °C until the time of analysis.