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

Phase 4

• Conditions: Menstrual Irregularities; Hyperandrogenism; Polycystic Ovarian Syndrome
• Interventions: Drug: 35 mcg ethinylestradiol/2 mg cyproterone; Drug: 30 mcg ethinylestradiol/3 mg drospirenone; Drug: 30 mcg ethinylestradiol/3 mg drospirenone and Selmevit; Drug: 20 mcg ethinylestradiol /3 mg drospirenone; Drug: 20 mcg ethinylestradiol/3 mg drospirenone and Selmevit; Drug: 35 mcg ethinylestradiol/2 mg cyproterone and Selmevit

• Registration Number: NCT02027337
• Lead Sponsor: Tyumen State Medical Academy

Brief Summary

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

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

Study Timeline

• Study Start: 2013-12
• Study First Submitted: 2013-12-26
• Status Verified: 2014-01
• Study First Submitted QC: 2014-01-02
• Study First Posted: 2014-01-06
• Last Update Submitted: 2014-11-20
• Last Update Posted: 2014-11-21
• Primary Completion: 2015-03
• Study Completion: 2015-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 200

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
35 mcg EE/2mg cyproterone	35 mcg ethinylestradiol/2 mg cyproterone	Women that use combined oral contraceptives containing 35 mcg ethinylestradiol/2 mg cyproterone
30 mcg EE/3 mg drospirenone	30 mcg ethinylestradiol/3 mg drospirenone	Women that use combined oral contraceptives containing 30 mcg ethinylestradiol/3 mg drospirenone (Yasmin)
30 mcg EE/3 mg drospirenone and Selmevit	30 mcg ethinylestradiol/3 mg drospirenone and Selmevit	Women that use combined oral contraceptives containing 30 mcg ethinylestradiol/3 mg drospirenone (Yasmin) and antioxidant complex Selmevit
20 mcg EE/3 mg drospirenone	20 mcg ethinylestradiol /3 mg drospirenone	Women that use combined oral contraceptives containing 20 mcg ethinylestradiol/3 mg drospirenone (Yaz)
20 mcg EE/3 mg drospirenone and Selmevit	20 mcg ethinylestradiol/3 mg drospirenone and Selmevit	Women that use combined oral contraceptives containing 20 mcg ethinylestradiol/3 mg drospirenone (Yaz) and antioxidant complex Selmevit
35 mcg EE/2 mg cyproterone and Selmevit	35 mcg ethinylestradiol/2 mg cyproterone and Selmevit	Women that use combined oral contraceptives containing 20 mcg ethinylestradiol/2 mg cyproterone and Selmevit

Primary Outcome Measures

Name	Time	Method
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 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 Platelet aggregation	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 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 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 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 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 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

Name	Time	Method
Subjective tolerability of contraceptives	12 cycles of 4 weeks
Frequency of adverse effects	12 cycles of 4 weeks

Trial Locations

Locations (1)

Tyumen State Medical Academy; 🇷🇺 Tyumen, Russian Federation