Evaluation of the Effects of Diosmin/Hespiridin Combination on the Clinical Outcomes in Patients With Polycystic Ovary Syndrome

Study Overview
=================
Brief Summary
-----------------
Polycystic ovary syndrome (PCOS) is one of the most prevalent disorders worldwide. Insulin resistance, inflammation and disturbance in sex hormone levels are the main contributing factors of this disease.The majority of studies addressing the status of chronic low-grade inflammation in PCOS have focused on the measurement of C-reactive protein (CRP) followed by stimulation of interleukin 6 (IL-6) and tumor necrosis factor (TNF-alpha). Daflon 500 mg tablets (containing 90% of diosmin and 10% of hesperidin) is used in patients to treat varicose veins, venous ulcers, hemorrhoids and lymphatic insufficiency. It has anti-diabetic, anti-inflammatory, microcirculatory, and antioxidant effects. So the aim of the work is to investigate the effect of Diosmin/Hesperidin in the management of PCOS through evaluation of Oxidative stress and inflammation, improvement of signs and symptoms through patients' follow-up, improvement of PCOS status by sonography and hormonal levels, measuring of anti-diabetic effect by measuring, fasting insulin, HOMA-IR and measuring the improvement of patient's quality of life by using the women health questionnaire (WHQ).

Official Title
-----------------
Effect of Diosmin/Hespiridin Combination on the Clinical Outcomes in Patients With Polycystic Ovary Syndrome

Conditions
-----------------
Poly Cystic Ovary Syndrome

Intervention / Treatment
-----------------
* Drug: Daflon
* Drug: Combined oral contraceptive
* Drug: Metformin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with confirmed diagnosis of PCOS aged in the range from18-40 (premenopausal adults) diagnosed with PCOS according to Rotterdam criteria by an expert gynecologist; (1) oligo-ovulation and/or anovulation (2) Clinical and biochemical hyperandrogenism and (3) polycystic ovaries on ultrasonography Exclusion Criteria: 1-Pregnant and nursing women 2-Menopause women 3-Diabetic patients 4-Adrenal hyperplasia 5-Adrenal Tumor 6-Thyroid dysfunction 7-Women on confounding medications which affect ovarian function

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin + Combined oral contraceptive<br>Metformin (Glucophage ® 500 tablets twice daily)+ Combined oral contraceptive (standard therapy) (Yassmin ® film-coated tablets 3 mg of drospirenone and 0.03 mg of ethinyl estradiol once daily daily) | Drug: Combined oral contraceptive<br>* Yassmin ® film-coated tablets 3 mg of drospirenone and 0.03 mg of ethinyl estradiol once daily daily<br>Drug: Metformin<br>* Glucophage ® 500 tablets twice daily<br>|
| Experimental: Diosmin /Hesperidin + Combined oral contraceptive<br>Diosmin /Hesperidin (Daflon two tablets 500 mg daily)+ Combined oral contraceptive((Yassmin ® film-coated tablets 3 mg of drospirenone and 0.03 mg of ethinyl estradiol once daily daily) | Drug: Daflon<br>* Daflon; two film coated tablets 500 mg daily<br>Drug: Combined oral contraceptive<br>* Yassmin ® film-coated tablets 3 mg of drospirenone and 0.03 mg of ethinyl estradiol once daily daily<br>|
| Active Comparator: Diosmin /Hesperidin +Metformin + Combined oral contraceptive combination<br>Diosmin /Hesperidin (Daflon two tablets 500 mg daily) +Metformin (Glucophage ® 500 tablets twice daily) + Combined oral contraceptive combination (Yassmin ® film-coated tablets 3 mg of drospirenone and 0.03 mg of ethinyl estradiol once daily daily | Drug: Daflon<br>* Daflon; two film coated tablets 500 mg daily<br>Drug: Combined oral contraceptive<br>* Yassmin ® film-coated tablets 3 mg of drospirenone and 0.03 mg of ethinyl estradiol once daily daily<br>Drug: Metformin<br>* Glucophage ® 500 tablets twice daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of the inflammation | Improvement of PCOS status by improvement of the inflammatory markers (IL-6) | 4 months | 
| Improvement of glycemic index | Improvement of glycemic index by measuring fasting Insulin, HOMA-IR | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of PCOS status levels | Improvement of PCOS status by improvement of signs and symptoms, hormone levels | 4 months | 
| Improvement of patient's quality of life | Improvement of patient's quality of life by using the women health questionnaire (WHQ) | 4 months |