Effects of estradiol- and ethinylestradiol-based contraceptives on adrenal steroids : a randomized trial
Kangasniemi, Marika H; Arffman, Riikka K; Haverinen, Annina; Luiro, Kaisu; Hustad, Steinar; Heikinheimo, Oskari; Tapanainen, Juha S; Piltonen, Terhi T (2022-09-07)
Marika H Kangasniemi, Riikka K Arffman, Annina Haverinen, Kaisu Luiro, Steinar Hustad, Oskari Heikinheimo, Juha S Tapanainen, Terhi T Piltonen, Effects of estradiol- and ethinylestradiol-based contraceptives on adrenal steroids: A randomized trial, Contraception, Volume 116, 2022, Pages 59-65, ISSN 0010-7824, https://doi.org/10.1016/j.contraception.2022.08.009
© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe2022100360816
Tiivistelmä
Abstract
Objectives: Ethinylestradiol (EE)-based combined oral contraceptives (COC) affect adrenal function by altering steroid and corticosteroid-binding globulin (CBG) synthesis that may contribute to adverse effects related to these drugs. The effects of COCs containing natural estrogens remain unclear. We compared the effects of COCs containing estradiol valerate (EV) and EE on cortisol and other adrenal steroid hormones.
Study design: A spin-off study of a randomized, open-label trial. Fifty-nine healthy women were allocated to groups that engaged in the continuous use of EV+dienogest (DNG), EE+DNG, or DNG only for 9 weeks. We measured changes in adrenal steroids, CBG, and the free cortisol index (FCI).
Results: Treatment with EE+DNG increased total cortisol (mean increment 668 nmol/L, p < 0.001) and cortisone (10 nmol/L, p= 0.001) levels, whereas the change from the baseline was insignificant for the EV+DNG and DNG-only groups. Dehydroepiandrosterone sulfate decreased by 24% in the EE+DNG group but remained unchanged in the EV+DNG and DNG-only groups. Aldosterone and 17-hydroxyprogesterone levels did not differ between the groups. All preparations increased CBG, but the increase in the EE+DNG group (median increment 42 µg/mL, p < 0.001) was 9- and 49-fold higher than that in the EV+DNG and DNG-only groups, respectively. The FCI remained unchanged in all study groups, indicating that cortisol and CBG mainly increased in parallel, although some individuals demonstrated larger alterations in the cortisol–CBG balance.
Conclusions: In COCs, EV had a milder effect on circulating CBG and adrenal steroid levels than EE; however, further research is necessary to determine the long-term effects.
Trial Registration: ClinicalTrials.gov NCT02352090
Implications: EV-based COC had reduced effects on circulating CBG and adrenal steroids compared to EE, probably due to a lower hepatic impact. Whether the sensitization of the adrenals to ACTH varies according to COC contents and whether it relates to experienced side effects needs to be investigated. These results encourage further research and development of contraceptives containing natural estrogens.
Kokoelmat
- Avoin saatavuus [31657]