Effects of Myo-inositol in Women With Polycystic Ovary Syndrome

Study Overview
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Brief Summary
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The study will be carried out at the hospital of the medical school of sao paulo (HC-FMUSP) and the goal is to compare the effects of the administration of myo-inositol in relation to the effects of metformin in women with Polycystic Ovary Syndrome and insulin resistance or glucose intolerance. Menstrual cycle, hyperandrogenism, chronic inflammatory process, carbohydrate metabolism, hepatic steatosis will be evaluated. In total, 60 women in the reproductive period, with a variable age between 18 and 36 years old will be recruited and randomized in two groups: intervention- myo-inositol for 6 months, control group will use metformin also for 6 months.

Detailed Description
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The study will involve 60 women in the reproductive period, with a variable between 18 and 36 years old and diagnosed with polycystic ovary syndrome (PCOS), according to Rotterdam- European Society of Human Reproduction and Embryology (ESHRE) / American Society for Reproductive Medicine (ASRM) criteria defined in 2003 and by the entity The Androgen Excess and Polycystic Ovary Syndrome Society (AE-PCOS) 2018, and insulin resistance (presence acanthosis nigricans) or glucose intolerance (fasting glycemia, glycated hemoglobin or 75g glycemic overload and blood glucose assessment after 2 hours). It is a comparative and non-inferiority study of myo-inositol in relation to metformin. They will be divided into two groups of 30 patients: Group I (control) - they will receive metformin, orally, three times a day; Group II (experiment) - they will receive myo-inositol 2g, orally, twice a day.

Official Title
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Effects of Myo-inositol on the Menstrual Cycle, Hyperandrogenism, Chronic Inflammatory Process and Carbohydrate Metabolism in Women With Polycystic Ovary Syndrome

Conditions
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Polycystic Ovary Syndrome, Resistance, Insulin, Glucose Intolerance

Intervention / Treatment
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* Drug: Myo-inositol
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18 to 36 with diagnosis of PCOS and insulin resistance or glucose intolerance. Exclusion Criteria: Previous use of any hormonal treatment in the past three months; Other causes of anovulation; Gynecological or other associated conditions (endometriosis, adenomyosis or diabetes mellitus); FSH (Follicle Stimulating Hormone) > 15 Ul / L (2nd to 5th day of the cycle); Beta-hcG (human chorionic gonadotropin) positive (pregnancy).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 36 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Comparative and non-inferiority study of myo-inositol in relation to metformin. They will be divided into two groups of 30 patients: Group I (control) - they will receive metformin, orally, three times a day; Group II (experiment) - they will receive myo-inositol 2g, orally, twice a day.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Myo-inositol<br>30 women with resistance insulin or glucose intolerance will receive myo-inositol 2g, orally, twice a day for 6 months. | Drug: Myo-inositol<br>* 30 women with polycystic ovary syndrome and insulin resistance or glucose intolerance will used myo-inositol 2g twice daily for 6 months, having a re-evaluation every 3 months. Evaluation will be made by transvaginal ultrasound, abdominal ultrasound, inflammatory tests, hormonal tests, glycemic curve with insulin curve, lipid profile, body mass index, evaluation of abdominal and hip circumference.<br>|
| Active Comparator: Metformin<br>30 women with resistance insulin or glucose intolerance will receive metformin, orally, three times a day for 6 months | Drug: Metformin<br>* 30 women with polycystic ovary syndrome and insulin resistance or glucose intolerance will used metformin three times a day for 6 months, having a re-evaluation every 3 months. Evaluation will be made by transvaginal ultrasound, abdominal ultrasound, inflammatory tests, hormonal tests, glycemic curve with insulin curve, lipid profile, body mass index, evaluation of abdominal and hip circumference.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Menstrual cycle | Analysis of period calendar. | 6 months | 
| Change in glucose metabolism | Glucose tolerance curve with insulin curve will be performed every 3 months. | Every 3 months for up to 6 months | 
| Change in glycated hemoglobin | Glycated hemoglobin will be performed every 3 months. | Every 3 months for up to 6 months | 
| Change in ultrasound of the ovaries | Transvaginal ultrasound to assess ovarian volume (measured in cubic centimeters) will be done before and after treatment. | 6 months | 
| Change in antral follicle count | Ultrasound of the ovaries will be done before and after treatment for antral follicle count (all follicles from 2 to 9 mm will be measured) | 6 months | 
| Change in body mass index | Body mass index (kg/m2) will be assessed every 3 months. | Every 3 months for up to 6 months | 
| Change in Abdominal Circumference and Hip Circumference | Abdominal circumference and hip circumference (measured in centimeters) will be assessed every 3 months. | Every 3 months for up to 6 months | 
| Change in body weight in kilograms | Patients will be weighed every 3 months (measured in kilograms). | Every 3 months for up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess adherence to treatment. | Medication use diary will be delivered and will be reviewed every 3 months to assess adherence to treatment (good adherence will be considered use of more than 80% of the medication provided). | Every 3 months for up to 6 months | 
| Side effects | Questionnaire will be carried out every 3 months for patient to describe the 3 main side effects and how much they have hindered the treatment or not. | Every 3 months for up to 6 months | 
| Hepatic steatosis | Initial liver ultrasound will be done and repeated after 6 months of treatment to assess the presence or absence of hepatic steatosis and classify it as mild (grade 1), moderate (grade 2) and severe (grade 3). | 6 months | 
| Liver enzymes | Liver enzymes (aspartate aminotransferase, alanine aminotransferase,alkaline phosphatase) will be collected before and after treatment | 6 months | 
| Chronic inflammatory process | Chronic inflammatory markers will be accessed by analyzing RNA messenger from cervical-vaginal cytology before and after treatment. | 6 months | 
| C-reactive protein | Chronic inflammatory process will be also evaluated by serum measurement of c-reactive protein before and after treatment. | 6 months | 
| Homocysteine | Serum homocysteine dosage will be done before and after treatment to help assess a chronic inflammatory process. | 6 months | 
| Change in Lipid Profile | Serum dosage of the lipid profile (high density lipoprotein - HDL, low density lipoprotein - LDL , very low density lipoprotein - VLDL, triglycerides, total cholesterol) will be done every 3 months | Every 3 months for up to 6 months | 
| Modified Ferriman-Gallwey Score | Modified Ferriman-Gallwey Score will be performed before and after treatment and patients with a score above 7 will be considered hirsute. | 6 months | 
| Hormonal dosage (FSH, LH, progesterone, estradiol) | Hormonal dosage (FSH - Follicle-stimulating hormone, LH - luteinizing hormone, progesterone, estradiol) will be preformed before and after treatment. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metformin, myo-inositol, polycystic ovary syndrome, resistance insulin, glucose intolerance