University of Oulu

Marika H Kangasniemi, Annina Haverinen, Kaisu Luiro, J Kalervo Hiltunen, Elina K Komsi, Riikka K Arffman, Oskari Heikinheimo, Juha S Tapanainen, Terhi T Piltonen, Estradiol Valerate in COC Has More Favorable Inflammatory Profile Than Synthetic Ethinyl Estradiol: A Randomized Trial, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 7, July 2020, Pages e2483–e2490,

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

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Author: Kangasniemi, Marika H.1; Haverinen, Annina2; Luiro, Kaisu2;
Organizations: 1Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
2Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
3Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
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Language: English
Published: Endocrine society, 2020
Publish Date: 2021-11-30


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.

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Series: Journal of clinical endocrinology & metabolism
ISSN: 0021-972X
ISSN-E: 1945-7197
ISSN-L: 0021-972X
Volume: 105
Issue: 7
Pages: e2483 - e2490
DOI: 10.1210/clinem/dgaa186
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: Funding was obtained from Research Foundation of the University of Helsinki research funds, Hospital District of Helsinki and Uusimaa, University of Oulu Graduate School, Sigrid Juselius Foundation, The Finnish Medical Foundation, the Academy of Finland (grant numbers 315921 and 321763), Medical Society of Finland, Emil Aaltonen Foundation, and North Ostrobothnia Regional Fund.
Academy of Finland Grant Number: 315921
Detailed Information: 315921 (Academy of Finland Funding decision)
321763 (Academy of Finland Funding decision)
Copyright information: © Endocrine Society 2020. The final authenticated version is available online at