Effects of Cyproterone Compound-spironolactone, Metformin and Pioglitazone on Inflammatory Markers in PCOS

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effects of three-month course of treatment modalities (Cyproterone compound-Spironolactone, Metformin and Pioglitazone) in patients with polycystic ovary syndrome (PCOS) on markers of inflammation [serum complement, homocysteine and high sensitive C-reactive protein (hs-CRP)] levels.

Detailed Description
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Polycystic ovary syndrome (PCOS) is estimated to affect up to10% of women of reproductive age, making it one of the most common endocrine disorders in this population. PCOS is associated with a broad range of adverse sequel, including hypertension, dyslipidemia, insulin resistance, hyperandrogenaemia, gestational and type 2 diabetes,which ultimately increase the cardiovascular morbidity in these patients. Also PCOS is increasingly recognized as a component of the metabolic syndrome. Management depends on symptoms or the source of androgen excess. Several treatment options are available, which allows for an individualized approach. Spironolactone is the safest potent available antiandrogen. It is effective in lowering the hirsutism score by approximately one third, although considerable individual variations exist. Other antiandrogens used to treat hirsutism and hirsutism equivalents include cyproterone acetate that has weak antiglucocorticoid effects. Metformin and thiazolidinediones, are promising adjuncts for treating PCOS. Although both of them increase insulin sensitivity, but their mechanism of action differ. Serum complement, homocysteine and C-reactive protein (CRP) levels have been reported to be linked with insulin resistance. The investigators want to measure serum complement, homocysteine and hs-CRP levels in patients with PCOS before and after three-month course of treatment with Cyproterone compound-Spironolactone (CC-S), metformin (M) and pioglitazone (P).

Official Title
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Effects of Treatment With Cyproterone Compound-spironolactone, Metformin and Pioglitazone on Serum Inflammatory Markers in Patients With Polycystic Ovary Syndrome (PCOS)

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Cyproterone compound + Spironolactone
* Drug: Metformin
* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-35 years Diagnosis of Polycystic Ovary Syndrome (PCOS) according to Rotterdam criteria 2003 (two out of three required): Oligomenorrhea or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic ovaries (by ultrasound) Exclusion Criteria: Smoking Pregnancy Diabetes mellitus Renal failure (serum creatinine >1.5) Congenital adrenal hyperplasia Hyper or hypothyroidism Sex hormone therapy or antiandrogen therapy during the last three months Unexplained serum alanin aminotransferase (ALT) elevation more than 2.5 times above normal range Any systemic or febrile illnesses Use of glucocorticoid or anti-inflammatory drugs during the last three months Androgen secreting tumor Malignancy

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

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cyproterone compound + Spironolactone<br>Cyproterone compound (Cyproterone acetate 2mg+Ethinyl estradiol 35 mcg) once daily + Spironolactone 50 mg twice daily | Drug: Cyproterone compound + Spironolactone<br>* Cyproterone compound (Cyproterone Acetate 2mg-Ethinyl estradiol 35mcg) 1 tablet daily + Spironolactone 50 mg twice daily<br>* Other names: CC-S;|
| Active Comparator: Metformin<br>Metformin 1500 mg daily | Drug: Metformin<br>* Metformin 500mg three times daily<br>|
| Active Comparator: Pioglitazone<br>Pioglitazone 30 mg daily | Drug: Pioglitazone<br>* Pioglitazone 30mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum C3 level | Serum concentration of a component of complement cascade: C3 | 3 months | 
| Serum C4 level | Serum concentration of a component of complement cascade: C4 | 3 months | 
| Serum high-sensitive CRP (C-reactive protein) | Serum concentration of high-sensitive C-reactive protein (hs-CRP) | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum total Testosterone level | Serum concentration of total Testosterone | 3 months | 
| Serum free Testosterone level | Serum concentration of free Testosterone | 3 months | 
| Serum Dehydroepiandrosterone sulfate (DHEAS) level | Serum concentration of Dehydroepiandrosterone sulfate | 3 months | 
| Serum follicle stimulating hormone (FSH) level | Serum concentration of follicle stimulating hormone | 3 months | 
| Serum luteinizing hormone (LH) level | Serum concentration of luteinizing hormone | 3 months | 
| Fasting Blood Sugar (FBS) | Fasting Blood Sugar | 3 months | 
| Fasting Serum Insulin level | Serum concentration of insulin | 3 months | 
| Serum homocysteine level | Serum concentration of homocysteine | 3 months | 
| Number of patients with adverse events | Number of patients with adverse events | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammation, Complement system proteins, Homocysteine, C-Reactive Protein, Cyproterone, Ethinyl Estradiol, Androgen Antagonists, Metformin, Thiazolidinediones, Pioglitazone