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ContraceptionPhase 4SYLVINCT02352090

Synthetic vs Natural Estrogen in Combined Oral Contraception

A Phase 4 study testing Ethinyl estradiol / dienogest, Estradiol valerate / dienogest and Dienogest in people with Contraception, run by Helsinki University Central Hospital at 2 sites in Finland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 35 years, women onlyHealthy volunteers can take part
Conditions the study is for
Contraception
What is being tested?
Ethinyl estradiol / dienogest, Estradiol valerate / dienogest and Dienogest
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
2 sitesFinland
Study dates
1 Apr 2015to 30 Dec 2018
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

2 sites in 1 country.

Finland2 sites

  • Helsinki University Central Hospital, Kätilöopisto Maternity Hospital

    Helsinki

  • Oulu University Hospital, Department of Gynecology and Obstetrics

    Oulu

Other trials in Finland

About this study

Official title: 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.

Conditions
Contraception
Being tested
Ethinyl estradiol / dienogest, Estradiol valerate / dienogest, Dienogest
Keywords
Contraception, oral, Ethinyl Estradiol, Estradiol Valerate, Dienogest, Insulin resistance, Chronic inflammation, Coagulation
Medical subject headings
Insulin Resistance, Thrombosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ethinyl estradiol / dienogestDrug

    Also called Valette, ATC code G03AA

    One tablet orally for 9 weeks, continuous use

  • Estradiol valerate / dienogestDrug

    Also called Qlaira, ATC code G03AB08

    One tablet orally for 9 weeks, continuous use

  • DienogestDrug

    Also called Visanne, ATC code G03D

    One tablet orally for 9 weeks, continuous use

Study groups in NCT02352090
Study groupRoleWhat they receive
Synthetic estrogen + progestinExperimentalEthinyl estradiol / dienogest
Receives: Drug: Ethinyl estradiol / dienogest
Natural estrogen + progestinExperimentalEstradiol valerate / dienogest
Receives: Drug: Estradiol valerate / dienogest
Progestin-OnlyActive comparatorDienogest
Receives: Drug: Dienogest

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

Secondary outcomes (9)

  1. Fasting Insulin

    Mean change in fasting serum insulin from baseline to nine weeks

    Measured: baseline and 9 weeks

  2. High-sensitivity C Reactive Protein

    Change in plasma concentrations of acute phase protein 'C reactive protein' (CRP), a marker of chronic inflammation.

    Measured: baseline and 9 weeks

  3. Total Cholesterol

    Change in concentrations of total cholesterol from baseline to nine weeks

    Measured: baseline and 9 weeks

  4. Low-Density Lipoprotein (LDL)

    Change in concentration of Low-Density Lipoprotein LDL from baseline to nine weeks

    Measured: baseline and 9 weeks

  5. High-Density Lipoprotein (HDL)

    Change in concentration of High-Density Lipoprotein HDL from baseline to nine weeks

    Measured: baseline and 9 weeks

  6. Triglyceride

    Change in triglyceride concentrations from baseline to nine weeks

    Measured: baseline and 9 weeks

  7. D-dimer

    Markers of coagulation activation

    Measured: baseline and 9 weeks

  8. F1+2

    Change in plasma concentrations of F1+2 a marker of coagulation activation

    Measured: baseline and 9 weeks

  9. Thrombin Generation, ETP Endogenous Thrombin Potential

    Change from baseline in thrombin generation, measured by thrombin generation assay-Calibrated automated thrombogram

    Measured: baseline and 9 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2015 (estimated)
  2. Study start1 Apr 2015
  3. Primary completion30 Dec 2018
  4. Study completion30 Dec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02352090
Sponsor's protocol ID
SYLVI030785
Acronym
SYLVI
Status last verified
May 2023
First submitted
20 Jan 2015
Last updated
22 Jun 2023
Data monitoring committee
Yes

Publications

  • Kangasniemi MH, Arffman RK, Joenvaara S, Haverinen A, Luiro K, Tohmola T, Renkonen R, Heikinheimo O, Tapanainen JS, Piltonen TT. Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial. Hum Reprod. 2023 Jan 5;38(1):89-102. doi: 10.1093/humrep/deac250.

    PubMed 36416543

  • Kangasniemi MH, Arffman RK, Haverinen A, Luiro K, Hustad S, Heikinheimo O, Tapanainen JS, Piltonen TT. Effects of estradiol- and ethinylestradiol-based contraceptives on adrenal steroids: A randomized trial. Contraception. 2022 Dec;116:59-65. doi: 10.1016/j.contraception.2022.08.009. Epub 2022 Sep 7.

    PubMed 36084710

  • Haverinen AH, Luiro KM, Szanto T, Kangasniemi MH, Hiltunen L, Sainio S, Piltonen TT, Lassila R, Tapanainen JS, Heikinheimo O. Combined oral contraceptives containing estradiol valerate vs ethinylestradiol on coagulation: A randomized clinical trial. Acta Obstet Gynecol Scand. 2022 Oct;101(10):1102-1111. doi: 10.1111/aogs.14428. Epub 2022 Jul 31.

    PubMed 35909329

  • Kangasniemi MH, Haverinen A, Luiro K, Hiltunen JK, Komsi EK, Arffman RK, Heikinheimo O, Tapanainen JS, Piltonen TT. Estradiol Valerate in COC Has More Favorable Inflammatory Profile Than Synthetic Ethinyl Estradiol: A Randomized Trial. J Clin Endocrinol Metab. 2020 Jul 1;105(7):dgaa186. doi: 10.1210/clinem/dgaa186.

    PubMed 32303765

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ethinyl estradiol / dienogest, Estradiol valerate / dienogest and Dienogest in people with Contraception, run by Helsinki University Central Hospital at 2 sites in Finland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Matsuda Index- Whole Body Insulin Sensitivity Index (time frame: We calculated the change in Matsuda index from baseline to 9 weeks.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02352090, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.

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