Synthetic vs Natural Estrogen in Combined Oral Contraception

Phase 4

Completed

Interventions: Drug: Estradiol valerate / dienogest
Drug: Ethinyl estradiol / dienogest
Drug: Dienogest

Brief Summary: The main objective of the study is to compare the metabolic effects of natural estradiol and synthetic ethinylestradiol used in combined oral contraception in healthy women. A progestin-only preparation will be used in comparison. The main goal is to study the effects on glucose metabolism, coagulation and a markers of chronic inflammation (such as hs-CRP). Our hypothesis is that the natural estradiol preparation will influence blood glucose levels, markers of coagulation and chronic inflammation less than the ethinylestradiol preparation. The progestin-only preparation will not effect these parameters.

Recruitment & Eligibility

Inclusion Criteria

BMI 19-24.9, regular menstrual cycles (21-35 days), a minimum of 2 months without any hormonal contraceptives, no contraindications for use of hormonal contraception

Exclusion Criteria

Polycystic ovaries, hypertension, smoking, alcohol abuse, pregnancy, lactation, abnormal result in pre-screening 2h oral glucose tolerance test, regular medications

Arm && Interventions

Group	Intervention	Description
Natural estrogen + progestin	Estradiol valerate / dienogest	Estradiol valerate / dienogest
Synthetic estrogen + progestin	Ethinyl estradiol / dienogest	Ethinyl estradiol / dienogest
Progestin-Only	Dienogest	Dienogest

Primary Outcome Measures

Name	Time	Method
Matsuda Index- Whole Body Insulin Sensitivity Index	We calculated the change in Matsuda index from baseline to 9 weeks.	Matsuda index is calculated from the standard 2h Oral Glucose Tolerance Test and corresponding insulin values. Matsuda index = 10,000/square root of \[fasting glucose x fasting insulin\] x \[mean glucose x mean insulin during OGTT\]) The Matsuda index is correlated (r = 0.73) with the rate of whole-body glucose disposal during the euglycemic insulin clamp. Matsuda index \<2.5 is considered insulin resistant, higher values indicate less insulin resistance. A decrease in matsuda index over the study period would indicate decreased insulin sensitivity.

Secondary Outcome Measures

Name	Time	Method
Low-Density Lipoprotein (LDL)	baseline and 9 weeks	Change in concentration of Low-Density Lipoprotein LDL from baseline to nine weeks
Triglyceride	baseline and 9 weeks	Change in triglyceride concentrations from baseline to nine weeks
F1+2	baseline and 9 weeks	Change in plasma concentrations of F1+2 a marker of coagulation activation
High-sensitivity C Reactive Protein	baseline and 9 weeks	Change in plasma concentrations of acute phase protein 'C reactive protein' (CRP), a marker of chronic inflammation.
Total Cholesterol	baseline and 9 weeks	Change in concentrations of total cholesterol from baseline to nine weeks
D-dimer	baseline and 9 weeks	Markers of coagulation activation
Thrombin Generation, ETP Endogenous Thrombin Potential	baseline and 9 weeks	Change from baseline in thrombin generation, measured by thrombin generation assay-Calibrated automated thrombogram
High-Density Lipoprotein (HDL)	baseline and 9 weeks	Change in concentration of High-Density Lipoprotein HDL from baseline to nine weeks
Fasting Insulin	baseline and 9 weeks	Mean change in fasting serum insulin from baseline to nine weeks

Locations (2): Helsinki University Central Hospital, Kätilöopisto Maternity Hospital
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Helsinki, Finland
Oulu University Hospital, Department of Gynecology and Obstetrics
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Oulu, Finland