Clinical trial NCT02352090: Synthetic vs Natural Estrogen in Combined Oral Contraception
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Contraception
Keywords: Contraception, oral
Ethinyl Estradiol
Estradiol Valerate
Dienogest
Insulin resistance
Chronic inflammation
Coagulation
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: Oulu University Hospital
First posted: 2015-02-02
Enrollment: 59
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Matsuda Index- Whole Body Insulin Sensitivity Index
timeFrame: We calculated the change in Matsuda index from baseline to 9 weeks.
Secondary outcomes:
measure: Fasting Insulin
timeFrame: baseline and 9 weeks
measure: High-sensitivity C Reactive Protein
timeFrame: baseline and 9 weeks
measure: Total Cholesterol
timeFrame: baseline and 9 weeks
measure: Low-Density Lipoprotein (LDL)
timeFrame: baseline and 9 weeks
measure: High-Density Lipoprotein (HDL)
timeFrame: baseline and 9 weeks
measure: Triglyceride
timeFrame: baseline and 9 weeks
measure: D-dimer
timeFrame: baseline and 9 weeks
measure: F1+2
timeFrame: baseline and 9 weeks
measure: Thrombin Generation, ETP Endogenous Thrombin Potential
timeFrame: baseline and 9 weeks
Other outcomes:
measure: Anti Mullerian Hormone (AMH)
timeFrame: baseline and 9 weeks
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital, Kätilöopisto Maternity Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital, Department of Gynecology and Obstetrics
Study officials:
affiliation: Helsinki University Central Hospital, Department of Gynecology and Obstetrics. Helsinki Univeristy, Medical Faculty
name: Oskari Heikinheimo, Prof., PhD., MD.
role: STUDY_CHAIR
affiliation: Helsinki University Central Hospital, Department of Gynecology and Obstetrics. Helsinki Univeristy, Medical Faculty
name: Juha Tapanainen, Prof., PhD, MD.
role: STUDY_CHAIR
affiliation: Oulu University Hospital, Department of Gynecology and Obstetrics
name: Terhi Piltonen, PhD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Helsinki University Central Hospital, Department of Gynecology and Obstetrics. Helsinki University, Faculty of Medicine
name: Annina Haverinen, MD, PhD student
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.