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| Name | Class |
|---|---|
| Oulu University Hospital | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Synthetic estrogen + progestin | Experimental | Ethinyl estradiol / dienogest |
|
| Natural estrogen + progestin | Experimental | Estradiol valerate / dienogest |
|
| Progestin-Only | Active Comparator | Dienogest |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ethinyl estradiol / dienogest | Drug | One tablet orally for 9 weeks, continuous use |
|
| 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. |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Anti Mullerian Hormone (AMH) | Change in Serum concentrations of anti-mullerian hormone reflecting ovarian reserve from baseline to nine weeks | baseline and 9 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 | Study Chair |
| 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 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Helsinki University Central Hospital, Kätilöopisto Maternity Hospital | Helsinki | Finland | ||||
| Oulu University Hospital, Department of Gynecology and Obstetrics |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36416543 | Derived | 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. | |
| 36084710 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Synthetic Estrogen + Progestin | Ethinyl estradiol / dienogest Ethinyl estradiol / dienogest: One tablet orally for 9 weeks, continuous use |
| FG001 | Natural Estrogen + Progestin | Estradiol valerate / dienogest Estradiol valerate / dienogest: One tablet orally for 9 weeks, continuous use |
| FG002 | Progestin-Only | Dienogest Dienogest: One tablet orally for 9 weeks, continuous use |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Synthetic Estrogen + Progestin | Ethinyl estradiol / dienogest Ethinyl estradiol / dienogest: One tablet orally for 9 weeks, continuous use |
| BG001 | Natural Estrogen + Progestin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | 95% Confidence Interval | units on a scale | We calculated the change in Matsuda index from baseline to 9 weeks. |
|
9 weeks. During the study period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Synthetic Estrogen + Progestin | Ethinyl estradiol / dienogest Ethinyl estradiol / dienogest: One tablet orally for 9 weeks, continuous use |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Oskari Heikinheimo | Helsinki University Central Hospital | +358 50 4271533 | oskari.heikinheimo@helsinki.fi |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 21, 2014 | Jun 4, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 21, 2014 | Jun 4, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D013927 | Thrombosis |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D004997 | Ethinyl Estradiol |
| C023635 | dienogest |
| C454300 | estradiol valerate-dienogest |
| ID | Term |
|---|---|
| D009651 | Norpregnatrienes |
| D009650 | Norpregnanes |
| D009654 | Norsteroids |
| D013256 | Steroids |
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| Estradiol valerate / dienogest | Drug | One tablet orally for 9 weeks, continuous use |
|
|
| Dienogest | Drug | One tablet orally for 9 weeks, continuous use |
|
|
| 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 |
| Oulu |
| Finland |
| 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. |
| 35909329 | Derived | 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. |
| 32303765 | Derived | 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. |
Estradiol valerate / dienogest
Estradiol valerate / dienogest: One tablet orally for 9 weeks, continuous use
| BG002 | Progestin-Only | Dienogest Dienogest: One tablet orally for 9 weeks, continuous use |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| OG001 | Natural Estrogen + Progestin | Estradiol valerate / dienogest Estradiol valerate / dienogest: One tablet orally for 9 weeks, continuous use |
| OG002 | Progestin-Only | Dienogest Dienogest: One tablet orally for 9 weeks, continuous use |
|
|
|
| Secondary | Fasting Insulin | Mean change in fasting serum insulin from baseline to nine weeks | Posted | Mean | 95% Confidence Interval | mU/l | baseline and 9 weeks |
|
|
|
| Secondary | High-sensitivity C Reactive Protein | Change in plasma concentrations of acute phase protein 'C reactive protein' (CRP), a marker of chronic inflammation. | Posted | Mean | 95% Confidence Interval | mg/L | baseline and 9 weeks |
|
|
|
| Secondary | Total Cholesterol | Change in concentrations of total cholesterol from baseline to nine weeks | Posted | Mean | 95% Confidence Interval | mmol/L | baseline and 9 weeks |
|
|
|
| Secondary | Low-Density Lipoprotein (LDL) | Change in concentration of Low-Density Lipoprotein LDL from baseline to nine weeks | Posted | Mean | 95% Confidence Interval | mmol/L | baseline and 9 weeks |
|
|
|
| Secondary | High-Density Lipoprotein (HDL) | Change in concentration of High-Density Lipoprotein HDL from baseline to nine weeks | Posted | Mean | 95% Confidence Interval | mmol/L | baseline and 9 weeks |
|
|
|
| Secondary | Triglyceride | Change in triglyceride concentrations from baseline to nine weeks | Posted | Mean | 95% Confidence Interval | mmol/L | baseline and 9 weeks |
|
|
|
| Secondary | D-dimer | Markers of coagulation activation | Posted | Mean | 95% Confidence Interval | percentage change from baseline | baseline and 9 weeks |
|
|
|
| Secondary | F1+2 | Change in plasma concentrations of F1+2 a marker of coagulation activation | Posted | Mean | 95% Confidence Interval | percentage change from baseline | baseline and 9 weeks |
|
|
|
| Secondary | Thrombin Generation, ETP Endogenous Thrombin Potential | Change from baseline in thrombin generation, measured by thrombin generation assay-Calibrated automated thrombogram | Posted | Mean | 95% Confidence Interval | percentage change from baseline | baseline and 9 weeks |
|
|
|
| Other Pre-specified | Anti Mullerian Hormone (AMH) | Change in Serum concentrations of anti-mullerian hormone reflecting ovarian reserve from baseline to nine weeks | Posted | Mean | 95% Confidence Interval | ng/mL | baseline and 9 weeks |
|
|
|
| 0 |
| 19 |
| 0 |
| 19 |
| 0 |
| 19 |
| EG001 | Natural Estrogen + Progestin | Estradiol valerate / dienogest Estradiol valerate / dienogest: One tablet orally for 9 weeks, continuous use | 0 | 20 | 0 | 20 | 0 | 20 |
| EG002 | Progestin-Only | Dienogest Dienogest: One tablet orally for 9 weeks, continuous use | 0 | 17 | 0 | 17 | 0 | 17 |
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| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D042782 | Estrogenic Steroids, Alkylated |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |