University of Oulu

Annina Haverinen, Kaisu Luiro, Marika H Kangasniemi, Terhi T Piltonen, Steinar Hustad, Oskari Heikinheimo, Juha S Tapanainen, Estradiol Valerate vs Ethinylestradiol in Combined Oral Contraceptives: Effects on the Pituitary-Ovarian Axis, The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 7, July 2022, Pages e3008–e3017, https://doi.org/10.1210/clinem/dgac150

Estradiol valerate vs ethinylestradiol in combined oral contraceptives : effects on the pituitary-ovarian axis

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Author: Haverinen, Annina1; Luiro, Kaisu1; Kangasniemi, Marika H2;
Organizations: 1Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 140, 00029 Helsinki, Finland
2Department of Obstetrics and Gynecology, University of Oulu, Oulu University Hospital and Medical Research Centre PEDEGO Research Unit, PO Box 5000, 90014 Oulu, Finland
3Department of Clinical Science and Core Facility for Metabolomics, University of Bergen, NO-5020 Bergen, Norway
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2022093060626
Language: English
Published: Endocrine society, 2022
Publish Date: 2023-03-13
Description:

Abstract

Context: Limited studies have compared the effects of combined oral contraceptives (COCs) containing natural estrogens and synthetic ethinylestradiol (EE) on reproductive hormones.

Objective: To compare estradiol valerate (EV) + dienogest (DNG), EE + DNG, and DNG alone (active control) on levels of follicle stimulating hormone (FSH), luteinizing hormone, anti-Müllerian hormone (AMH), ovarian steroids, sex hormone binding globulin (SHBG), and the free androgen index (FAI).

Methods: This spin-off study from a randomized trial enrolled 59 healthy, 18 to 35-year-old ovulatory women, outpatients at Helsinki and Oulu University Hospitals, Finland, who were randomized to EV 2 mg + DNG 2‐3 mg (n = 20); EE 0.03 mg + DNG 2 mg (n = 20); and DNG 2 mg (n = 19) for 9 weeks. Blood samples were drawn at baseline, and at 5 and 9 weeks. Age and BMI were comparable between groups; 3 women discontinued.

Results: EV + DNG suppressed FSH by −27% (−51% to −3%) (median [95% CI]) vs EE + DNG, −64% (−78 to −51), P = 0.04, but AMH levels decreased similarly by −9% (−18 to −0.1) vs −13% (−28 to 0.2), P = 0.38, respectively. EV + DNG increased SHBG levels by 56% (30% to 82%) and EE + DNG by 385% (313% to 423%), P < 0.001. Total testosterone decreased by 16% (−27% to −5%) in the EV + DNG group but it did not decrease in the EE + DNG group, whereas the FAI decreased by −39% (−54% to −25%) vs −72% (−78% to −67%), P < 0.001. DNG alone did not induce changes in any of these parameters.

Conclusions: Compared with EE + DNG, treatment with EV + DNG resulted in milder pituitary downregulation and reduced induction of hepatic SHBG synthesis—potentially carrying more beneficial health effects.

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Series: Journal of clinical endocrinology & metabolism
ISSN: 0021-972X
ISSN-E: 1945-7197
ISSN-L: 0021-972X
Volume: 107
Issue: 7
Pages: e3008 - e3017
DOI: 10.1210/clinem/dgac150
OADOI: https://oadoi.org/10.1210/clinem/dgac150
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3123 Gynaecology and paediatrics
Subjects:
Funding: This work was supported by The Swedish Cultural Foundation in Finland (A.H.); Helsinki University Hospital research funds (J.S.T., O.H., A.H., K.L.); The Sigrid Jusélius Foundation (J.S.T., T.P.); The Finnish Medical Association (A.H., T.P., M.H.K.); The Academy of Finland (J.S.T., T.P.); University of Oulu Graduate School (M.H.K.) and The Emil Aaltonen Foundation (M.H.K.).
Copyright information: © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Clinical Endocrinology & Metabolism following peer review. The version of record Annina Haverinen, Kaisu Luiro, Marika H Kangasniemi, Terhi T Piltonen, Steinar Hustad, Oskari Heikinheimo, Juha S Tapanainen, Estradiol Valerate vs Ethinylestradiol in Combined Oral Contraceptives: Effects on the Pituitary-Ovarian Axis, The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 7, July 2022, Pages e3008–e3017 is available online at: https://doi.org/10.1210/clinem/dgac150.