Synthetic vs Natural Estrogen in Combined Oral Contraception

NCT02352090 | Completed Phase 4 Results DMC

• 1 other identifier: SYLVI030785
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 2

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.

Conditions

Contraception

Keywords

Contraception, oral; Ethinyl Estradiol; Estradiol Valerate; Dienogest; Insulin resistance; Chronic inflammation; Coagulation

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (9)

• Fasting Insulin

  baseline and 9 weeks

• High-sensitivity C Reactive Protein

  baseline and 9 weeks

• Total Cholesterol

  baseline and 9 weeks

• Low-Density Lipoprotein (LDL)

  baseline and 9 weeks

• High-Density Lipoprotein (HDL)

  baseline and 9 weeks

Other Outcomes (1)

• Anti Mullerian Hormone (AMH)

  baseline and 9 weeks

Study Arms (3)

Synthetic estrogen + progestin

EXPERIMENTAL

Ethinyl estradiol / dienogest

Drug: Ethinyl estradiol / dienogest

Natural estrogen + progestin

EXPERIMENTAL

Estradiol valerate / dienogest

Drug: Estradiol valerate / dienogest

Progestin-Only

ACTIVE COMPARATOR

Dienogest

Drug: Dienogest

Interventions

Ethinyl estradiol / dienogest DRUG

One tablet orally for 9 weeks, continuous use

Also known as: Valette, ATC code G03AA

Synthetic estrogen + progestin

Estradiol valerate / dienogest DRUG

One tablet orally for 9 weeks, continuous use

Also known as: Qlaira, ATC code G03AB08

Natural estrogen + progestin

Dienogest DRUG

One tablet orally for 9 weeks, continuous use

Also known as: Visanne, ATC code G03D

Progestin-Only

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Helsinki University Central Hospital: lead
• Oulu University Hospital: collaborator

Study Sites (2)

Helsinki University Central Hospital, Kätilöopisto Maternity Hospital

Helsinki, Finland

Location

Oulu University Hospital, Department of Gynecology and Obstetrics

Oulu, Finland

Location

Related Publications (4)

• 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.

  PMID: 36416543 DERIVED

• 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.

  PMID: 36084710 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.

  PMID: 35909329 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.

  PMID: 32303765 DERIVED

MeSH Terms

Conditions

Insulin Resistance; Thrombosis

Interventions

Ethinyl Estradiol; dienogest; estradiol valerate-dienogest

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Oskari Heikinheimo
• Organization: Helsinki University Central Hospital

oskari.heikinheimo@helsinki.fi

+358 50 4271533

Study Officials

• 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

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 20, 2015
• First Posted: February 2, 2015
• Study Start: April 1, 2015
• Primary Completion: December 30, 2018
• Study Completion: December 30, 2018
• Last Updated: June 22, 2023
• Results First Posted: June 29, 2021

Record last verified: 2023-05

Locations

FI (2)