Myo-inositol Versus D-chiro-inositol in the Treatment of Polycystic Ovary Syndrome and Insulin Resistance: Evaluation of Clinical, Metabolic, Endocrine and Ultrasound Parameters

Study Overview
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Brief Summary
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Insulin resistance has important implications in the pathogenesis of the polycystic ovary syndrome (PCOS) and insulin-sensitizing drugs are considered a useful therapeutic approach. Reduction of insulin levels with administration of insulin sensitizing agents has been found to be beneficial in lowering both hyperinsulinemia, hyperandrogenemia, and restoring ovulation. Metformin alone or in combination with oral contraceptives (OCs) has been widely used in the long term treatment of women with PCOS in whom it modifies the ovarian morphology, improves intraovarian androgen levels, and enhances systemic and local insulin resistance. Despite to these beneficial effects, several side effects have been reported due to the long term administration of this drug. In the recent years, inositol has found more and more space in the reproductive clinical practice. Indeed, inositol have been classified as insulin sensitizing agent and it is mainly used as a chronic treatment for PCOS. Inositol exists in 9 different isomers and in particular several studies on Myo-inositol and D-chiro-inositol were reported. In this study myo-inositol versus D-chiro-inositol treatments were compared to placebo in women with PCOS and with or without insulin resistance.

Conditions
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PCOS

Intervention / Treatment
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* Dietary Supplement: Myo-inositol + Folic acid
* Dietary Supplement: Myo-inositol + Folic acid
* Dietary Supplement: D-chiro-inositol, manganese, folic acid, vit B12
* Dietary Supplement: D-chiro-inositol, manganese, folic acid, vit B12
* Drug: Folic acid, vit B12
* Drug: Folic acid, vit B12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women fulfilled two out of three diagnostic criteria for PCOS Exclusion Criteria: Women with pre-existing secondary endocrine disorders Women with personal history of hypertension, diabetes mellitus or cardiovascular disorders Women who received treatment with other drugs for the previous 6 months before entering the study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Insulin resistant patients<br> | Dietary Supplement: Myo-inositol + Folic acid<br>* Myo-inositol (2g) Folic acid (200mcg) (2 per day)<br>Dietary Supplement: D-chiro-inositol, manganese, folic acid, vit B12<br>* D-Chiro-inositol (500 mg), manganese (1 mg), folic acid (200 mcg), vit B12 (1.25 mcg) (2 per day)<br>Drug: Folic acid, vit B12<br>* Folic acid (200 mcg), vit B12 (1.25 mcg) (2 per day)<br>|
| Other: Non-insulin resistant patients<br> | Dietary Supplement: Myo-inositol + Folic acid<br>* Myo-inositol (2g) Folic acid (200mcg) (2 per day)<br>Dietary Supplement: D-chiro-inositol, manganese, folic acid, vit B12<br>* D-chiro-inositol (500 mg), manganese (1 mg), folic acid (200 mcg), vit B12 (1.25 mcg) (2 per day)<br>Drug: Folic acid, vit B12<br>* Folic acid (200 mcg), vit B12 (1.25 mcg) (2 per day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index (BMI) |  |  | 
| Menstrual cycle |  |  | 
| Score acne (acne grading system by Cremoncini et al) |  |  | 
| Score hirsutism (Ferriman-Gallwey score) |  |  | 
| Alopecia |  |  | 
| Oral Glucose Tolerance Test (OGTT) |  |  | 
| Glucagon levels |  |  | 
| C-peptide test |  |  | 
| Myo-inositol serum concentration |  |  | 
| D-chiro-inositol serum concentration |  |  | 
| Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and Estradiol (E2) levels test |  |  | 
| Prolactin (PRL) levels test |  |  | 
| Thyroid-stimulating hormone (TSH), free thyroid hormone (fT3 and fT4), and alpha-1 antitrypsin (AAT) test |  |  | 
| Total and free testosterone levels |  |  | 
| Sex hormone binding globulin (SHBG) test |  |  | 
| 17-Hydroxyprogesterone (17-OHP) levels |  |  | 
| Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) levels |  |  | 
| delta 4-androstenedione levels |  |  | 
| progesterone levels |  |  | 
| Adrenocorticotropic Hormone (ACTH) stimulation test |  |  | 
| Ovarian size and morphology | Ovarian ultrasound scan for the assessment of size and morphology |  | 
| Antral follicle counts |  |  | 
| Stromal/Cortical ratio in the ovary |  |  | 
| Endometrial thickness | Transvaginal ultrasound measurement of endometrial thickness performed between day 3 and 5 of the menstrual cycle. |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, Insulin resistance, Myo-inositol, D-chiro-inositol