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Cited by 22Reproductive Health and ContraceptionInflammatory mediators and NSAID effectsEstrogen and related hormone effects

Estradiol valerate in COC has more favorable inflammatory profile than synthetic ethinyl estradiol: a randomized trial

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Kangasniemi, Marika H, Haverinen, Annina, Luiro, Kaisu, Hiltunen, J Kalervo, Komsi, Elina K, Arffman, Riikka K, Heikinheimo, Oskari, Tapanainen, Juha S +1 more·2020·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/clinem/dgaa186
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Abstract

CONTEXT: Combined oral contraceptives (COCs) alter inflammatory status and lipid metabolism. Whether different estrogens have different effects is poorly understood. OBJECTIVE: We compared the effects of COCs containing ethinyl estradiol (EE) or estradiol valerate (EV) and dienogest (DNG) with those containing DNG only on inflammation and lipid metabolism. DESIGN: Randomized, controlled, open-label clinical trial. SETTING: Two-center study in Helsinki and Oulu University Hospitals. PARTICIPANTS: Fifty-nine healthy, young, nonsmoking women with regular menstrual cycles. Age, body mass index, and waist-to-hip ratio were comparable in all study groups at the beginning. Fifty-six women completed the study (EV + DNG, n = 20; EE + DNG, n = 19; DNG only, n = 17). INTERVENTIONS: Nine-week continuous use of COCs containing either EV + DNG or EE + DNG, or DNG only as control. MAIN OUTCOME MEASURES: Parameters of chronic inflammation (high-sensitivity C-reactive protein [hs-CRP], and pentraxin 3 [PTX-3]) and lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol). RESULTS: Serum hs-CRP increased after 9-week use of EE + DNG (mean change ± standard deviation 1.10 ± 2.11 mg/L) compared with EV + DNG (-0.06 ± 0.97 mg/L, P = 0.001) or DNG only (0.13 ± 0.68 mg/L, P = 0.021). Also, PTX-3 increased in the EE + DNG group compared with EV + DNG and DNG-only groups (P = 0.017 and P = 0.003, respectively). In the EE + DNG group, HDL and triglycerides increased compared with other groups (HDL: EE + DNG 0.20 ± 0.24 mmol/L vs EV + DNG 0.02 ± 0.20 mmol/L [P = 0.002] vs DNG 0.02 ± 0.18 mmol/L [P = 0.002]; triglycerides: EE + DNG 0.45 ± 0.21 mmol/L vs EV + DNG 0.18 ± 0.36 mmol/L [P = 0.003] vs DNG 0.06 ± 0.18 mmol/L [P < 0.001]). CONCLUSIONS: EV + DNG and DNG only had a neutral effect on inflammation and lipids, while EE + DNG increased both hs-CRP and PTX-3 levels as well as triglycerides and HDL. TRIAL REGISTRATION: ClinicalTrials.gov NCT02352090.

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Authors
Kangasniemi, M. H., Haverinen, A., Luiro, K., Hiltunen, J. K., Komsi, E. K., Arffman, R. K., Heikinheimo, O., Tapanainen, J. S., & Piltonen, T. T.
Affiliations
  • Oulu University Hospital (FI)
  • University of Helsinki (FI)
  • University of Oulu (FI)
Corresponding author
Piltonen, Terhi T
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2020-04-18
Volume
105
Issue
7
Pages
e2483-e2490
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/clinem/dgaa186
OpenAlex
W3016297837
Cited by
22
References
20
Citations by year
2026: 2 · 2025: 4 · 2024: 1 · 2023: 7 · 2022: 5 · 2021: 2 · 2020: 1
FWCI
2.81
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • Research Foundation of the University of Helsinki
  • Hospital District of Helsinki and Uusimaa
  • University of Oulu Graduate School
  • Sigrid Juselius Foundation
  • Academy of Finland (315921, 321763)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
estradiol valerate, ethinyl estradiol, dienogest, combined oral contraceptives, chronic inflammation, C-reactive protein, pentraxin 3, lipid profile, HDL cholesterol, triglycerides, estrogen-progestin combination, young women, menstrual cycle regulation, dysmenorrhea, dysmenorrhea severity
MeSH terms
Pentraxins, Adult, Serum Amyloid P-Component, C-Reactive Protein, Cholesterol, Contraceptives, Oral, Combined, Estradiol, Ethinyl Estradiol, Female, Humans, Inflammation, Lipoproteins, LDL, Nandrolone, Triglycerides, Lipid Metabolism, Young Adult

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