Clinical, Metabolic and Endocrine Effects of the Treatment With Drospirenone and Ethinyl Estradiol Alone or in Combination With Myo-inositol in Young Women With Polycystic Ovary Syndrome (PCOS) and Insulin Resistance

Study Overview
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Brief Summary
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Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome with a variety of metabolic and endocrine abnormalities and clinical symptoms. The primary defect in PCOS consists of an abnormal androgen synthesis and secretion, particularly by ovarian theca cells. Insulin resistance and obesity may act as triggers, explaining the frequent association of PCOS with these metabolic conditions. Hyperinsulinaemia, which results from insulin resistance, stimulates both ovarian and adrenal androgen secretion and suppresses sex hormone-binding globulin synthesis from the liver. It results in an increase in free, biologically active androgens which are related to clinical signs such as hirsutism, acne, seborrhea, and alopecia. Combined oral contraceptive (COC) therapy is a common treatment for PCOS and it was widely used in this group of patients providing clinical improvement in the areas of excessive hair growth, unpredictable menses, acne, and weight gain. More recent studies outlined a deficiency in myo-inositol in women with PCOS and insulin-resistance. Myo-inositol is a precursor for many inositol-containing compounds and it plays critical and diverse roles in signal transduction, membrane biogenesis, vesicle trafficking, and chromatin remodeling. It is a precursor in the synthesis of phosphatidylinositol polyphosphates (PIPs) that are a source of several second messengers. It has been reported that the administration of myo-inositol reduces serum insulin, decreases serum testosterone and enhances ovulation. Due to the different beneficial actions, the aim of the present study is to evaluate the clinical, metabolic and endocrine effects of treatment with COC (drospirenone and ethinyl estradiol)alone or in combination with myo-inositol, in young women with PCOS and insulin resistance.

Conditions
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PCOS, Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Drospirenone Ethinyl estradiol
* Drug: Drospirenone Ethinyl estradiol Myo-inositol
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women fulfilled two out of three diagnostic criteria for PCOS, according to the 2003 Rotterdam Consensus conference Women with PCOS, insulin resistance, acne, hirsutism and seborrhea Exclusion Criteria: Women with pre-existing secondary endocrine disorders Women wishing to conceive during the next 12 months Women with contradictions to oral contraceptive use Women with personal history of hypertension, diabetes mellitus or cardiovascular disorders Women who received treatment with oral contraceptives, or other drugs for the previous 6 months before entering the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Drospirenone + Ethinyl estradiol<br> | Drug: Drospirenone Ethinyl estradiol<br>* Drospirenone 3mg/die Ethinyl estradiol 30 mg/die (21 days/month for 6 months)<br>|
| Experimental: Drospirenone + Ethinyl estradiol + Myo-inositol<br> | Drug: Drospirenone Ethinyl estradiol Myo-inositol<br>* Drospirenone 3mg/die Ethinyl estradiol 30 mg/die (21 days/months for 6 months) + Myo-inositol 6g /die for 6 months<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score acne (acne grading system by Cook et al) |  |  | 
| Score hirsutism (Ferriman-Gallwey classification) |  |  | 
| Measurement of sex hormones in serum |  |  | 
| Oral glucose tolerance test (OGTT) |  |  | 
| Measurement of blood glucose and insulin levels |  |  | 
| BMI |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse effects |  |  | 

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