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

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

• 20 mcg ethinylestradiol /3 mg drospirenone (Drug), also known as Yaz: One contraceptive pill in each day of 28 day cycle. Number of Cycles: 12
• 20 mcg ethinylestradiol/3 mg drospirenone and Selmevit (Drug), also known as Yaz, Selmevit: 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.
• 30 mcg ethinylestradiol/3 mg drospirenone (Drug), also known as Yasmin: One contraceptive pill in each of 21 days, than 7 days break. Number of Cycles: 12
• 30 mcg ethinylestradiol/3 mg drospirenone and Selmevit (Drug), also known as Yasmin, Selmevit: 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.
• 35 mcg ethinylestradiol/2 mg cyproterone (Drug), also known as Diane-35, Chloe: 1 contraceptive pill in each day of 28 day cycle. Number of Cycles: 12
• 35 mcg ethinylestradiol/2 mg cyproterone and Selmevit (Drug), also known as Diane-35, Chloe, Selmevit: 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.

Primary outcomes

• 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 outcomes

• Frequency of adverse effects [12 cycles of 4 weeks]
• Subjective tolerability of contraceptives [12 cycles of 4 weeks]

Sex: Female, ages: 18 Years to 35 Years, accepts healthy volunteers

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)