Hemocoagulation and Lipoperoxidation in Women Using Combined Oral Contraceptives, Correction by Antioxidants

Study Overview
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Brief Summary
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We investigate parameters of hemocoagulation and lipoperoxidation in women using combined oral contraceptives with antiandrogenic activity (containing drospirenone with 20 or 30 mcg ethinylestradiol; or cyproterone acetate); correction of these changes by antioxidants

Detailed Description
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It is well known that hormonal contraceptives using increase risk of thrombosis. We conduct parameters of hemostasis in women that use combined oral contraceptives with antiandrogenic activity for contraception and treatment. Considering relationship between lipoperoxidation in platelets and hemostasis we expect that limitation of lipoperoxidation by antioxidants can restrict hypercoagulation and decrease risk of thrombosis. The purpose of this study is decrease of thrombosis risk in women that use combined oral contraceptives containing 20 mcg ethinylestradiol/3 mg drospirenone, 30 mcg ethinylestradiol/3 mg drospirenone, 35 mcg ethinylestradiol/2mg cyproterone acetate. Half of the women of each arm (group) receive only combined oral contraceptives (COC), other women receive combined oral contraceptives and antioxidant complex Selmevit. The blood tests conduct on 19-21 days of the menstrual cycle before COC use (control group) or on 19-21 days of COC use after 1, 3, 6 and 12 cycles. Also we investigate subjective tolerability, therapeutic effects, menstrual cycle control and adverse effects of COCs in women that have or have no antioxidant complex Selmevit

Official Title
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The Changes of Hemocoagulation and Lipoperoxidation in Women Using Combined Oral Contraceptives With Antiandrogenic Activity, Correction by Antioxidants

Conditions
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Polycystic Ovarian Syndrome, Hyperandrogenism, Menstrual Irregularities

Intervention / Treatment
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* Drug: 20 mcg ethinylestradiol /3 mg drospirenone
* Drug: 20 mcg ethinylestradiol/3 mg drospirenone and Selmevit
* Drug: 30 mcg ethinylestradiol/3 mg drospirenone
* Drug: 30 mcg ethinylestradiol/3 mg drospirenone and Selmevit
* Drug: 35 mcg ethinylestradiol/2 mg cyproterone
* Drug: 35 mcg ethinylestradiol/2 mg cyproterone and Selmevit


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18-35 years Absence of contraindications for COC use Informed voluntary consent for examination Exclusion Criteria: Age younger than 18 and older than 35 years Refusal or failure to comply with the study protocol Drug or alcohol dependence Psychiatric diseases Severe somatic and allergic diseases Pregnancy Malignancies Taking drugs that affect haemostasis, including hormonal contraceptives during 6 months before study beginning Cases of thrombosis among first-line relatives in family history Contraindications to the COC use under Eligibility Criteria of hormonal contraception (WHO, 2012)

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br>Healthy women that no use combined oral contraceptives | |
| Experimental: 20 mcg EE/3 mg drospirenone<br>Women that use combined oral contraceptives containing 20 mcg ethinylestradiol/3 mg drospirenone (Yaz) | Drug: 20 mcg ethinylestradiol /3 mg drospirenone<br>* One contraceptive pill in each day of 28 day cycle. Number of Cycles: 12<br>* Other names: Yaz;|
| Experimental: 20 mcg EE/3 mg drospirenone and Selmevit<br>Women that use combined oral contraceptives containing 20 mcg ethinylestradiol/3 mg drospirenone (Yaz) and antioxidant complex Selmevit | Drug: 20 mcg ethinylestradiol/3 mg drospirenone and Selmevit<br>* One contraceptive pill in each day of 28 day cycle. Number of Cycles: 12. Two pills of Selmevit in each day during 30 days, repeat of the course every 3 months.<br>* Other names: Selmevit;|
| Experimental: 30 mcg EE/3 mg drospirenone<br>Women that use combined oral contraceptives containing 30 mcg ethinylestradiol/3 mg drospirenone (Yasmin) | Drug: 30 mcg ethinylestradiol/3 mg drospirenone<br>* One contraceptive pill in each of 21 days, than 7 days break. Number of Cycles: 12<br>* Other names: Yasmin;|
| Experimental: 30 mcg EE/3 mg drospirenone and Selmevit<br>Women that use combined oral contraceptives containing 30 mcg ethinylestradiol/3 mg drospirenone (Yasmin) and antioxidant complex Selmevit | Drug: 30 mcg ethinylestradiol/3 mg drospirenone and Selmevit<br>* One contraceptive pill in each of 21 days, than 7 days break. Number of Cycles: 12 Two pills of Selmevit in each day during 30 days, repeat of the course every 3 months.<br>* Other names: Selmevit;|
| Experimental: 35 mcg EE/2mg cyproterone<br>Women that use combined oral contraceptives containing 35 mcg ethinylestradiol/2 mg cyproterone | Drug: 35 mcg ethinylestradiol/2 mg cyproterone<br>* 1 contraceptive pill in each day of 28 day cycle. Number of Cycles: 12<br>* Other names: Chloe;|
| Experimental: 35 mcg EE/2 mg cyproterone and Selmevit<br>Women that use combined oral contraceptives containing 20 mcg ethinylestradiol/2 mg cyproterone and Selmevit | Drug: 35 mcg ethinylestradiol/2 mg cyproterone and Selmevit<br>* One contraceptive pill in each day of 28 day cycle. Number of Cycles: 12. Two pills of Selmevit in each day during 30 days, repeat of the course every 3 months.<br>* Other names: Selmevit;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Activated recalcification time |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Activated partial thromboplastin time |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Prothrombin time |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in International normalized ratio |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in D-dimer concentration |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Fibrinogen concentration |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Soluble fibrin-monomer complexes concentration |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Platelet aggregation |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Antithrombin III activity |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Reserve plasminogen index |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Erythrocyte Lipoperoxidation products, extractable in heptane and isopropanol |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Malondialdehyde Concentration in Erythrocytes |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Glutathion-S-transferase Activity in Erythrocytes |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Change from Baseline in Superoxide dismutase Activity in Erythrocytes |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 
| Vitamin A and E plasma concentration |  | Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse effects |  | 12 cycles of 4 weeks | 
| Subjective tolerability of contraceptives |  | 12 cycles of 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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combined oral contraceptives, drospirenone, cyproterone, hemostasis, antioxidants