Synthetic vs Natural Estrogen in Combined Oral Contraception

Study Overview
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Brief Summary
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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.

Official Title
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Synthetic vs Natural Estrogen in Combined Oral Contraception- Effect on Insulin Sensitivity, Coagulation, Inflammation and Endometrium - a Comparison With a Progestin-only Preparation.

Conditions
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Contraception

Intervention / Treatment
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* Drug: Ethinyl estradiol / dienogest
* Drug: Estradiol valerate / dienogest
* Drug: Dienogest


Participation Criteria
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Eligibility Criteria
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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

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synthetic estrogen + progestin<br>Ethinyl estradiol / dienogest | Drug: Ethinyl estradiol / dienogest<br>* One tablet orally for 9 weeks, continuous use<br>* Other names: Valette, ATC code G03AA;|
| Experimental: Natural estrogen + progestin<br>Estradiol valerate / dienogest | Drug: Estradiol valerate / dienogest<br>* One tablet orally for 9 weeks, continuous use<br>* Other names: Qlaira, ATC code G03AB08;|
| Active Comparator: Progestin-Only<br>Dienogest | Drug: Dienogest<br>* One tablet orally for 9 weeks, continuous use<br>* Other names: Visanne, ATC code G03D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Matsuda Index- Whole Body Insulin Sensitivity Index | 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. | We calculated the change in Matsuda index from baseline to 9 weeks. | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Contraception, oral, Ethinyl Estradiol, Estradiol Valerate, Dienogest, Insulin resistance, Chronic inflammation, Coagulation