Synthetic vs Natural Estrogen in Combined Oral Contraception (SYLVI)

May 23, 2023 updated by: Annina Haverinen, Helsinki University Central Hospital

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

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Helsinki, Finland
        • Helsinki University Central Hospital, Kätilöopisto Maternity Hospital
      • Oulu, Finland
        • Oulu University Hospital, Department of Gynecology and Obstetrics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 33 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Matsuda Index- Whole Body Insulin Sensitivity Index
Time Frame: 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.

We calculated the change in Matsuda index from baseline to 9 weeks.

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti Mullerian Hormone (AMH)
Time Frame: baseline and 9 weeks
Change in Serum concentrations of anti-mullerian hormone reflecting ovarian reserve from baseline to nine weeks
baseline and 9 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Study Chair: Oskari Heikinheimo, Prof., PhD., MD., Helsinki University Central Hospital, Department of Gynecology and Obstetrics. Helsinki Univeristy, Medical Faculty
  • Study Chair: Juha Tapanainen, Prof., PhD, MD., Helsinki University Central Hospital, Department of Gynecology and Obstetrics. Helsinki Univeristy, Medical Faculty
  • Principal Investigator: Terhi Piltonen, PhD, MD, Oulu University Hospital, Department of Gynecology and Obstetrics
  • Principal Investigator: Annina Haverinen, MD, PhD student, Helsinki University Central Hospital, Department of Gynecology and Obstetrics. Helsinki University, Faculty of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2015

Primary Completion (Actual)

December 30, 2018

Study Completion (Actual)

December 30, 2018

Study Registration Dates

First Submitted

January 20, 2015

First Submitted That Met QC Criteria

January 27, 2015

First Posted (Estimated)

February 2, 2015

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

May 23, 2023

Last Verified

May 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Contraception

Clinical Trials on Ethinyl estradiol / dienogest

3
Subscribe