Characteristics of uterine bleeding associated with an oral contraceptive containing drospirenone in combination with estetrol: A multicenter observational study

Cover Page

Cite item

Full Text

Abstract

Background. An unfavorable bleeding pattern is a common reason for refusing to continue hormonal contraception.

Aim. To evaluate the characteristics of uterine bleeding when using a new combined oral contraceptive (COC) containing estetrol and drospirenone (Esteretta®).

Materials and methods. A multicenter observational study included 1402 females aged 18–49 who received Esteretta® for 6 cycles. The frequency, duration, and severity of withdrawal bleeding, as well as the frequency of unpredictable bleeding, were assessed.

Results. The rate of regular withdrawal bleeding was 100%. The proportion of women with heavy menstruation/withdrawal bleeding decreased from 29.6 to 10.07% (p<0.0001). The duration of regular withdrawal bleeding was significantly reduced (p=0.008). The incidence of unpredictable bleeding during COC use decreased from 4.57 to 3.29% (p=0.05). Satisfactory cycle control was observed in 87.43% of women. 2.5% of participants refused to continue using COCs.

Conclusion. Esteretta® provides a high rate of regular withdrawal bleeding and a low rate of unpredictable bleeding. Given the optimal safety profile, this drug may be the first choice for contraception in sexually active women who are not planning a pregnancy.

About the authors

Irina V. Kuznetsova

Vitbiomed+ LLC

Author for correspondence.
Email: ms.smith.ivk@gmail.com
ORCID iD: 0000-0001-5541-3767

D. Sci. (Med.), Prof., Vitbiomed+ LLC

Russian Federation, Moscow

Liudmila V. Evsyukova

Pavlov Ryazan State Medical University

Email: ms.smith.ivk@gmail.com

Cand. Sci. (Med.), Assoc. Prof.

Russian Federation, Ryazan

References

  1. Bastianelli C, Farris M, Bruni V, et al. Effects of progestin-only contraceptives on the endometrium. Expert Rev Clin Pharmacol. 2020;13(10):1103-23. doi: 10.1080/17512433.2020.1821649
  2. Abou-Ismail MY, Citla Sridhar D, Nayak L. Estrogen and thrombosis: A bench to bedside review. Thromb Res. 2020;92:40-51. doi: 10.1016/j.thromres.2020.05.008
  3. Skeith L, Le Gal G, Rodger MA. Oral contraceptives and hormone replacement therapy: How strong a risk factor for venous thromboembolism? Thromb Res. 2021;202:134-8. doi: 10.1016/j.thromres.2021.03.012
  4. Weill A, Dalichampt M, Raguideau F, et al. Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study. BMJ. 2016;353:i2002. doi: 10.1136/bmj.i2002
  5. Allen RH. Combined estrogen-progestin oral contraceptives: Patient selection, counseling and use. Waltham (MA): UpToDate, 2023.
  6. Rott H. Birth Control Pills and Thrombotic Risks: Differences of Contraception Methods with and without Estrogen. Hamostaseologie. 2019;39(1):42-8. doi: 10.1055/s-0039-1677806
  7. Stocco B, Fumagalli HF, Franceschini SA, et al. Comparative study of the effects of combined oral contraceptives in hemostatic variables: an observational preliminary study. Medicine (Baltimore). 2015;94(4):e385. doi: 10.1097/MD.0000000000000385
  8. Dinger J, Do Minh T, Heinemann K. Impact of estrogen type on cardiovascular safety of combined oral contraceptives. Contraception. 2016;94(4):328-39. doi: 10.1016/j.contraception.2016.06.010
  9. Stanczyk FZ, Winer SA, Foidart JM, Archer DF. Comparison of estrogenic components used for hormonal contraception. Contraception. 2024;130:110310. doi: 10.1016/j.contraception.2023.110310
  10. Douxfils J, Klipping C, Duijkers I, et al. Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters. Contraception. 2020;102(6):396-402. doi: 10.1016/j.contraception.2020.08.015
  11. Gérard C, Foidart JM. Estetrol: From Preclinical to Clinical Pharmacology and Advances in the Understanding of the Molecular Mechanism of Action. Drugs R D. 2023;23(2):77-92. doi: 10.1007/s40268-023-00419-5
  12. Morimont L, Haguet H, Dogné JM, et al. Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk. Front Endocrinol (Lausanne). 2021;12:769187. doi: 10.3389/fendo.2021.769187
  13. Morimont L, Jost M, Gaspard U, et al. Low Thrombin Generation in Users of a Contraceptive Containing Estetrol and Drospirenone. J Clin Endocrinol Metab. 2022;108(1):135-43. doi: 10.1210/clinem/dgac511
  14. Polis CB, Hussain R, Berry A. There might be blood: a scoping review on women’s responses to contraceptive-induced menstrual bleeding changes. Reprod Health. 2018;15(1):114. doi: 10.1186/s12978-018-0561-0
  15. Mawet M, Nollevaux F, Nizet D, et al. Impact of a new levonorgestrel intrauterine system, Levosert(®), on heavy menstrual bleeding: results of a one-year randomised controlled trial. Eur J Contracept Reprod Health Care. 2014;19(3):169-79. doi: 10.3109/13625187.2014.894184
  16. Rowe P, Farley T, Peregoudov A, et al. Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: a 7-year randomized comparative study with the TCu380A. Contraception. 2016;93(6):498-506. doi: 10.1016/j.contraception.2016.02.024
  17. Archer DF, Mansour D, Foidart JM. Bleeding Patterns of Oral Contraceptives with a Cyclic Dosing Regimen: An Overview. J Clin Med. 2022;11(15):4634. doi: 10.3390/jcm11154634
  18. Critchley HOD, Maybin JA, Armstrong GM, Williams ARW. Physiology of the Endometrium and Regulation of Menstruation. Physiol Rev. 2020;100(3):1149-79. doi: 10.1152/physrev.00031.2019
  19. Kuan KKW, Saunders PTK. Female Reproductive Systems: Hormone Dependence and Receptor Expression. Adv Exp Med Biol. 2022;1390:21-39. doi: 10.1007/978-3-031-11836-4_2
  20. Burris TP, de Vera IMS, Cote I, et al. International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023. Pharmacol Rev. 2023;75(6):1233-318. doi: 10.1124/pharmrev.121.000436
  21. Hirota Y. Progesterone governs endometrial proliferation-differentiation switching and blastocyst implantation. Endocr J. 2019;66(3):199-206. doi: 10.1507/endocrj.EJ18-0431
  22. Patel B, Elguero S, Thakore S, et al. Role of nuclear progesterone receptor isoforms in uterine pathophysiology. Hum Reprod Update. 2015;21(2):155-73. doi: 10.1093/humupd/dmu056
  23. Dinh A, Sriprasert I, Williams AR, Archer DF. A review of the endometrial histologic effects of progestins and progesterone receptor modulators in reproductive age women. Contraception. 2015;91(5):360-7. doi: 10.1016/j.contraception.2015.01.008
  24. Gérard C, Arnal JF, Jost M, et al. Profile of estetrol, a promising native estrogen for oral contraception and the relief of climacteric symptoms of menopause. Expert Rev Clin Pharmacol. 2022;15(2):121-37. doi: 10.1080/17512433.2022.2054413
  25. Klipping C, Duijkers I, Mawet M, et al. Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone. Contraception. 2021;103(4):213-21. doi: 10.1016/j.contraception.2021.01.001
  26. Inoue K, Barratt A, Richters J. Does research into contraceptive method discontinuation address women’s own reasons? A critical review. J Fam Plann Reprod Health Care. 2015;41(4):292-9. doi: 10.1136/jfprhc-2014-100976
  27. Abot A, Fontaine C, Buscato M, et al. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014;6(10):1328-46. doi: 10.15252/emmm.201404112
  28. Gaspard U, Taziaux M, Mawet M, et al. A multicenter, randomized study to select the minimum effective dose of estetrol (E4) in postmenopausal women (E4Relief): part 1. Vasomotor symptoms and overall safety. Menopause. 2020;27(8):848-57. doi: 10.1097/GME.0000000000001561
  29. Creinin MD, Westhoff CL, Bouchard C, et al. Estetrol-drospirenone combination oral contraceptive: North American phase 3 efficacy and safety results. Contraception. 2021;104(3):222-8. doi: 10.1016/j.contraception.2021.05.002
  30. Gemzell-Danielsson K, Apter D, Zatik J, et al. Estetrol-Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia. BJOG. 2022;129(1):63-71. doi: 10.1111/1471-0528.16840
  31. Kaunitz AM, Achilles SL, Zatik J, et al. Pooled analysis of two phase 3 trials evaluating the effects of a novel combined oral contraceptive containing estetrol/drospirenone on bleeding patterns in healthy women. Contraception. 2022;116:29-36. doi: 10.1016/j.contraception.2022.07.010
  32. Hoffman BL, Schorge JO, Bradshaw KD, et al. Williams Gynecology. 3rd Ed. New York: McGraw-Hill Professional, 2016.
  33. Villavicencio J, Allen RH. Unscheduled bleeding and contraceptive choice: increasing satisfaction and continuation rates. Open Access J Contracept. 2016;7:43-52.
  34. Foidart JM, Gemzell-Danielsson K, Kubba A, et al. The benefits of estetrol addition to drospirenone for contraception. AJOG Glob Rep. 2023;3(4):100266. doi: 10.1016/j.xagr.2023.100266
  35. Seif MW, Diamond K, Nickkho-Amiry M. Obesity and menstrual disorders. Best Pract Res Clin Obstet Gynaecol. 2015;29(4):516-27. doi: 10.1016/j.bpobgyn.2014.10.010

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).