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Cited by 17Reproductive Health and ContraceptionOvarian function and disordersDiabetes, Cardiovascular Risks, and Lipoproteins

Ethinyl estradiol vs estradiol valerate in combined oral contraceptives—effect on glucose tolerance: a randomized, controlled clinical trial

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Haverinen, Annina, Kangasniemi, Marika, Luiro, Kaisu, Piltonen, Terhi, Heikinheimo, Oskari, Tapanainen, Juha S.·2021·Contraception
DOI 10.1016/j.contraception.2020.10.014
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Abstract

Objective To compare the effects of two formulations of combined oral contraceptives (COCs), estradiol valerate (EV) and ethinyl estradiol (EE) combined with dienogest (DNG), and DNG-only, on glucose tolerance.Study design We performed a randomized, controlled 9-week clinical trial. Inclusion criteria were: age 18-35 years, regular menstrual cycle (28 ± 7 days), no polycystic ovaries, non-smoking, no contraindications for COC use and a 2-month wash-out from hormonal contraceptive use. The women were randomized to EV + DNG (n = 20), EE + DNG (n = 20), and DNG-only (n = 19), and evaluated at baseline, at 4-5 weeks and 8-9 weeks of treatment. Study medications were used continuously for 63 days. Primary outcome measure was change in the whole-body insulin sensitivity index (Matsuda index) derived from the oral glucose tolerance test (OGTT) over the treatment period. Secondary outcome measures were area under curves (AUC) of glucose and insulin, homeostatic model assessment - insulin resistance (HOMA-IR) and Insulin Sensitivity Index (ISI).Results Fifty-nine women enrolled, and 56 women completed the study. The Matsuda index changed from baseline as follows (mean percentage change, mean change [95%CI]): DNG-only -12%, -1.45 [95%CI -3.22-0.325] P = 0.10; EV + DNG + 2.7%, -0.10 [-1.34 to 1.14] P = 0.86; EE + DNG -5.5%, -1.02 [-2.51 to 0.46] P = 0.16, comparing the groups P = 0.27. There were no clinically significant differences in glucose tolerance between the COC groups, but the DNG-only group showed an improvement in the 2-h glucose levels (5.5 [95%CI 5.0-6.0] to 4.7 mmol/l [4.2-5.2], P = 0.001).Conclusion We found no clinically significant differences between EV and EE combined with DNG and DNG-only on glucose tolerance in healthy, young, normal-weight women, indicating that these preparations appear close to neutral regarding glucose metabolism when used continuously for nine weeks.Implications Combinations of both ethinyl estradiol and natural estradiol (estradiol valerate) with dienogest (DNG), as well as DNG-only, seem metabolically safe in young and healthy women in short-term continuous use.

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Authors
Haverinen, A., Kangasniemi, M., Luiro, K., Piltonen, T., Heikinheimo, O., & Tapanainen, J. S.
Affiliations
  • University of Helsinki (FI)
  • Oulu University Hospital (FI)
Corresponding author
Tapanainen, Juha S.
ORCID
Venue
Contraception
Publisher
Elsevier BV
Published
2021-01
Volume
103
Issue
1
Pages
53-59
ISSN
0010-7824 (ISSN-L)
DOI
10.1016/j.contraception.2020.10.014
OpenAlex
W3094022776
Cited by
17
References
39
Citations by year
2025: 4 · 2023: 2 · 2022: 9 · 2021: 2
FWCI
2.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Contraception (acceptedVersion)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • Sigrid Juséliuksen Säätiö
  • Finska Läkaresällskapet
  • Suomalainen Lääkäriseura Duodecim
  • Japan Science and Technology Agency
  • Helsingin ja Uudenmaan Sairaanhoitopiiri
  • Academy of Finland
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
ethinyl estradiol, estradiol valerate, dienogest, combined oral contraceptives, glucose tolerance, insulin sensitivity, insulin resistance, Matsuda index, HOMA-IR, insulin sensitivity index, oral glucose tolerance test, young women, menstrual cycle regulation, polycystic ovary syndrome
MeSH terms
Adolescent, Adult, Contraceptives, Oral, Combined, Estradiol, Ethinyl Estradiol, Female, Glucose, Glucose Tolerance Test, Humans, Nandrolone, Young Adult

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