Progestins and combined oral contraceptives in the hormonal treatment of endometriosis – a review
DOI:
https://doi.org/10.15584/ejcem.2023.2.21Keywords:
combined oral contraceptives, endometriosis, health-related quality of life, infertility, pelvic pain, progestinsAbstract
Introduction and aim. Endometriosis is a common inflammatory disease affecting 6-10% of women of reproductive age. It is defined as the growth of endometrial-like tissue outside the uterine cavity. Dysmenorrhea, pelvic pain, dyspareunia and infertility are the main symptoms of endometriosis patients. Endometriosis treatment methods can be broadly divided into surgical and pharmacological. Currently, hormonal drugs are often used for women with endometriosis to relieve bothersome symptoms. The aim of this article is to review new publications presenting the effectiveness as well as side effects of the use of progestins and combined oral contraceptives in the hormonal treatment of endometriosis.
Material and methods. A review of the literature regarding progestins and combined oral contraceptives in the treatment of endometriosis was performed using the PubMed database. In the end, 67 articles were included in this review.
Analysis of the literature. Progestins and combined oral contraceptives significantly reduce dysmenorrhea, dyspareunia and pelvic pain in women with endometriosis. However, there is a risk of potential side effects, which should be taken into account when choosing a therapy for each patient individually.
Conclusion. Endometriosis is a chronic disease that has a significant impact on the health-related quality of life of patients. When choosing a treatment, many aspects should be considered, primarily the patient’s preferences, drug tolerance and safety. Further drug research is needed to determine the most effective treatment for endometriosis.
Downloads
References
Saunders PTK, Horne AW. Endometriosis: Etiology, pathobiology, and therapeutic prospects. Cell. 2021;184(11):2807-2824. doi: 10.1016/j.cell.2021.04.041
Lai ZZ, Yang HL, Ha SY, et al. Cyclooxygenase-2 in endometriosis. Int J Biol Sci. 2019;15(13):2783-2797. doi: 10.7150/ijbs.35128
Horne AW, Saunders PTK. SnapShot: Endometriosis. Cell. 2019;179(7):1677-1677.e1. doi: 10.1016/j.cell.2019.11.033
Tanbo T, Fedorcsak P. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. Acta Obstet Gynecol Scand. 2017;96(6):659-667. doi: 10.1111/aogs.13082
Vannuccini S, Clemenza S, Rossi M, Petraglia F. Hormonal treatments for endometriosis: The endocrine background. Rev Endocr Metab Disord. 2022;23(3):333-355. doi: 10.1007/s11154-021-09666-w
Koninckx PR, Fernandes R, Ussia A, et al. Pathogenesis Based Diagnosis and Treatment of Endometriosis. Front Endocrinol (Lausanne). 2021;12:1-13. doi: 10.3389/fendo.2021.745548
Ezzati M, Carr BR. Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain. Women’s Heal. 2015;11(1):19-28. doi: 10.2217/whe.14.68
Kalaitzopoulos DR, Samartzis N, Kolovos GN, et al. Treatment of endometriosis: a review with comparison of 8 guidelines. BMC Womens Health. 2021;21(1):1-9. doi: 10.1186/s12905-021-01545-5
Api M. Surgery for endometriosis-related pain. Women’s Heal. 2015;11(5):665-669. doi: 10.2217/whe.15.52
Bafort C, Beebeejaun Y, Tomassetti C, Bosteels J, Duffy JM. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev. 2020;10(10):CD011031. doi: 10.1002/14651858.CD011031.pub3
Gezer A, Oral E. Progestin therapy in endometriosis. Women’s Heal. 2015;11(5):643-652. doi: 10.2217/whe.15.42
Reis FM, Coutinho LM, Vannuccini S, Batteux F, Chapron C, Petraglia F. Progesterone receptor ligands for the treatment of endometriosis: The mechanisms behind therapeutic success and failure. Hum Reprod Update. 2020;26(4):565-585. doi: 10.1093/humupd/dmaa009
Becker CM, Bokor A, Heikinheimo O, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022(2):hoac009. doi: 10.1093/hropen/hoac009
Mitchell JB, Chetty S, Kathrada F. Progestins in the symptomatic management of endometriosis: a meta-analysis on their effectiveness and safety. BMC Womens Health. 2022;22(1):526. doi: 10.1186/s12905-022-02122-0
Sachedina A, Todd N. Dysmenorrhea, endometriosis and chronic pelvic pain in adolescents. JCRPE J Clin Res Pediatr Endocrinol. 2020;12(1):7-17. doi: 10.4274/jcrpe.galenos.2019.2019.S0217
Quaas AM, Weedin EA, Hansen KR. On-label and off-label drug use in the treatment of endometriosis. Fertil Steril. 2015;103(3):612-625. doi: 10.1016/j.fertnstert.2015.01.006
Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862. doi: 10.26355/eurrev_202207_29210
Murji A, Biberoğlu K, Leng J, et al. Use of dienogest in endometriosis: a narrative literature review and expert commentary. Curr Med Res Opin. 2020;36(5):895-907. doi: 10.1080/03007995.2020.1744120
Laganà AS, Vitale SG, Granese R, et al. Clinical dynamics of Dienogest for the treatment of endometriosis: from bench to bedside. Expert Opin Drug Metab Toxicol. 2017;13(6):593-596. doi: 10.1080/17425255.2017.1297421
Techatraisak K, Hestiantoro A, Ruey S, et al. Effectiveness of dienogest in improving quality of life in Asian women with endometriosis (ENVISIOeN): Interim results from a prospective cohort study under real-life clinical practice. BMC Womens Health. 2019;19(1):1-12. doi: 10.1186/s12905-019-0758-6
Harada T, Momoeda M, Taketani Y, et al. Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis-a randomized, double-blind, multicenter, controlled trial. Fertil Steril. 2009;91(3):675-681. doi: 10.1016/j.fertnstert.2007.12.080
Strowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: A 24-week, randomized, multicentre, open-label trial. Hum Reprod. 2010;25(3):633-641. doi: 10.1093/humrep/dep469
Bedaiwy MA, Allaire C, Alfaraj S. Long-term medical management of endometriosis with dienogest and with a gonadotropin-releasing hormone agonist and add-back hormone therapy. Fertil Steril. 2017;107(3):537-548. doi: 10.1016/j.fertnstert.2016.12.024
Caruso S, Iraci M, Cianci S, Vitale SG, Fava V, Cianci A. Effects of long-term treatment with dienogest on the quality of life and sexual function of women affected by endometriosis-associated pelvic pain. J Pain Res. 2019;12:2371-2378. doi: 10.2147/JPR.S207599
Wiegratz I, Mittmann K, Dietrich H, Zimmermann T, Kuhl H. Fertility after discontinuation of treatment with an oral contraceptive containing 30 μg of ethinyl estradiol and 2 mg of dienogest. Fertil Steril. 2006;85(6):1812-1819. doi: 10.1016/j.fertnstert.2005.11.052
Liu Y, Gong H, Gou J, Liu X, Li Z. Dienogest as a Maintenance Treatment for Endometriosis Following Surgery: A Systematic Review and Meta-Analysis. Front Med. 2021;8:1-9. doi: 10.3389/fmed.2021.652505
Strowitzki T, Faustmann T, Gerlinger C, Schumacher U, Ahlers C, Seitz C. Safety and tolerability of dienogest in endometriosis: Pooled analysis from the European clinical study program. Int J Womens Health. 2015;7:391-401. doi: 10.2147/IJWH.S77202
Park SY, Kim SH, Chae HD, Kim CH, Kang BM. Efficacy and safety of dienogest in patients with endometriosis: A single-center observational study over 12 months. Clin Exp Reprod Med. 2016;43(4):215-220. doi: 10.5653/cerm.2016.43.4.215
Griesinger G, Tournaye H, Macklon N, et al. Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction. Reprod Biomed Online. 2019;38(2):249-259. doi: 10.1016/j.rbmo.2018.11.017
Peng C, Huang Y, Zhou Y. Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis. Arch Gynecol Obstet. 2021;304(1):231-252. doi: 10.1007/s00404-020-05900-z
Sukhikh GT, Adamyan L V, Dubrovina SO, et al. Prolonged cyclical and continuous regimens of dydrogesterone are effective for reducing chronic pelvic pain in women with endometriosis: results of the ORCHIDEA study. Fertil Steril. 2021;116(6):1568-1577. doi: 10.1016/j.fertnstert.2021.07.1194
Kitawaki J, Koga K, Kanzo T, Momoeda M. An assessment of the efficacy and safety of dydrogesterone in women with ovarian endometrioma: An open-label multicenter clinical study. Reprod Med Biol. 2021;20(3):345-351. doi: 10.1002/rmb2.12391
Muneyyirci-Delale O, Anopa J, Charles C, et al. Medical management of recurrent endometrioma with long-term norethindrone acetate. Int J Womens Health. 2012;4(1):149-154. doi: 10.2147/ijwh.s27819
Vercellini P, Buggio L, Berlanda N, Barbara G, Somigliana E, Bosari S. Estrogen-progestins and progestins for the management of endometriosis. Fertil Steril. 2016;106(7):1552-1571.e2. doi: 10.1016/j.fertnstert.2016.10.022
Vercellini P, Bracco B, Mosconi P, et al. Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: A before and after study. Fertil Steril. 2016;105(3):734-743.e3. doi: 10.1016/j.fertnstert.2015.11.016
Bender RA. Medroxyprogesterone Acetate for Abnormal Uterine Bleeding Due to Ovulatory Dysfunction: The Effect of 2 Different-Duration Regimens. Med Sci Monit. 2022;28:1-6. doi: 10.12659/MSM.936727
Cheewadhanaraks S, Choksuchat C, Dhanaworavibul K, Liabsuetrakul T. Postoperative depot medroxyprogesterone acetate versus continuous oral contraceptive pills in the treatment of endometriosis-associated pain: A randomized comparative trial. Gynecol Obstet Invest. 2012;74(2):151-156. doi: 10.1159/000337713
Schlaff WD, Carson SA, Luciano A, Ross D, Bergqvist A. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Fertil Steril. 2006;85(2):314-325. doi: 10.1016/j.fertnstert.2005.07.1315
Halpern V, Brache V, Taylor D, et al. Clinical trial to evaluate pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after subcutaneous administration of Depo-Provera. Fertil Steril. 2021;115(4):1035-1043. doi: 10.1016/j.fertnstert.2020.11.002
Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev. 2020;9(9):CD012658. doi: 10.1002/14651858.CD012658.pub2
Lethaby A, Wise MR, Weterings MA, Bofill Rodriguez M, Brown J. Combined hormonal contraceptives for heavy menstrual bleeding. Cochrane Database Syst Rev. 2019;2(2):CD000154. doi: 10.1002/14651858.CD000154.pub3
Costanzi F, De Marco MP, Colombrino C, et al. The treatment with Levonorgestrel Releasing Intrauterine System (LNG-IUS) in patients affected by menometrorrhagia, dysmenorrhea and adenomimyois: Clinical and ultrasonographic reports. Eur Rev Med Pharmacol Sci. 2021;25(9):3432-3439. doi: 10.26355/eurrev_202105_25823
Bofill Rodriguez M, Lethaby A, Jordan V. Progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2020;6(6):CD002126. doi: 10.1002/14651858.CD002126.pub4
Romero SA, Young K, Hickey M, Su HI. Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen. Cochrane Database Syst Rev. 2020;12(12):CD007245. doi: 10.1002/14651858.CD007245.pub4
Moreira IF de A, Bianchini MP, Moreira GRC, Almeida AM, Rezende BA. Sexual function and metabolic/hormonal changes in women using long-term hormonal and non-hormonal contraceptives: a pilot study. BMC Womens Health. 2020;20(1):1-11. doi: 10.1186/s12905-020-01107-1
Carvalho N, Margatho D, Cursino K, Benetti-Pinto CL, Bahamondes L. Control of endometriosis-associated pain with etonogestrel-releasing contraceptive implant and 52-mg levonorgestrel-releasing intrauterine system: randomized clinical trial. Fertil Steril. 2018;110(6):1129-1136. doi: 10.1016/j.fertnstert.2018.07.003
Tokushige N, Markham R, Russell P, Fraser IS. Effect of progestogens and combined oral contraceptives on nerve fibers in peritoneal endometriosis. Fertil Steril. 2009;92(4):1234-1239. doi: 10.1016/j.fertnstert.2008.07.1774
Vercellini P, Frontino G, De Giorgi O, Pietropaolo G, Pasin R, Crosignani PG. Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill regimen. Fertil Steril. 2003;80(3):560-563. doi: 10.1016/S0015-0282(03)00794-5
Harada T, Momoeda M, Taketani Y, Hoshiai H, Terakawa N. Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. Fertil Steril. 2008;90(5):1583-1588. doi: 10.1016/j.fertnstert.2007.08.051
Harada T, Kosaka S, Elliesen J, Yasuda M, Ito M, Momoeda M. Ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial. Fertil Steril. 2017;108(5):798-805. doi: 10.1016/j.fertnstert.2017.07.1165
Caruso S, Cianci A, Iraci Sareri M, Panella M, Caruso G, Cianci S. Randomized study on the effectiveness of nomegestrol acetate plus 17β-estradiol oral contraceptive versus dienogest oral pill in women with suspected endometriosis‑associated chronic pelvic pain. BMC Womens Health. 2022;22(1):1-9. doi: 10.1186/s12905-022-01737-7
Jensen JT, Schlaff W, Gordon K. Use of combined hormonal contraceptives for the treatment of endometriosis-related pain: a systematic review of the evidence. Fertil Steril. 2018;110(1):137-152.e1. doi: 10.1016/j.fertnstert.2018.03.012
AlSheef M, Abuzied Y, Alzahrani GR, et al. Combined Oral Contraceptives and Vascular Thrombosis: A Single-Center Experience. Cureus. 2022;14(6):e25865. doi: 10.7759/cureus.25865
Klipping C, Duijkers I, Parke S, Mellinger U, Serrani M, Junge W. Hemostatic effects of a novel estradiol-based oral contraceptive: An open-label, randomized, crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel. Drugs R D. 2011;11(2):159-170. doi: 10.2165/11591200-000000000-00000
Shi J, Leng J. Effect and safety of drospirenone and ethinylestradiol tablets (II) for dysmenorrhea: A systematic review and meta-analysis. Front Med. 2022;9:1-12. doi: 10.3389/fmed.2022.938606
Momoeda M, Akiyama S, Tanaka K, Suzukamo Y. Quality of life in japanese patients with dysmenorrhea treated with ethinylestradiol 20 μg/drospirenone 3 mg in a real-world setting: An observational study. Int J Womens Health. 2020;12:327-338. doi: 10.2147/IJWH.S238460
Yoshino O, Suzukamo Y, Yoshihara K, Takahashi N. Quality of Life in Japanese Patients with Dysmenorrhea or Endometriosis-Associated Pelvic Pain Treated with Extended Regimen Ethinylestradiol/Drospirenone in a Real-World Setting: A Prospective Observational Study. Adv Ther. 2022;39(11):5087-5104. doi: 10.1007/s12325-022-02301-3
Momoeda M, Kondo M, Elliesen J, Yasuda M, Yamamoto S, Harada T. Efficacy and safety of a flexible extended regimen of ethinylestradiol/drospirenone for the treatment of dysmenorrhea: A multicenter, randomized, open-label, active-controlled study. Int J Womens Health. 2017;9:295-305. doi: 10.2147/IJWH.S134576
Simu S, Marcovici I, Dobrescu A, et al. Insights into the behavior of triple-negative mda-mb-231 breast carcinoma cells following the treatment with 17β-ethinylestradiol and levonorgestrel. Molecules. 2021;26(9):1-15. doi: 10.3390/molecules26092776
Harada T, Momoeda M. Efficacy of cyclic and extended regimens of ethinylestradiol 0.02 mg -levonorgestrel 0.09 mg for dysmenorrhea: A placebo-controlled, double-blind, randomized trial. Reprod Med Biol. 2021;20(2):215-223. doi: 10.1002/rmb2.12373
Dragoman MV, Tepper NK, Fu R, Curtis KM, Chou R, Gaffield ME. A systematic review and meta-analysis of venous thrombosis risk among users of combined oral contraception. Int J Gynecol Obstet. 2018;141(3):287-294. doi: 10.1002/ijgo.12455
Waiyaput W, Wattanakamolchai K, Tingthanatikul Y, et al. Effect of combined contraceptive pill on immune cell of ovarian endometriotic tissue. J Ovarian Res. 2021;14(1):1-8. doi: 10.1186/s13048-021-00819-8
Vercellini P, De Giorgi O, Mosconi P, Stellato G, Vicentini S, Crosignani PG. Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis. Fertil Steril. 2002;77(1):52-61. doi: 10.1016/s0015-0282(01)02951-x
Sophonsritsuk A, Tantanavipas S, Tingthanatikul Y, Lertvikool S, Dittharot K, Waiyaput W. Effects of Ethinyl Estradiol in Combined Oral Contraceptives on Cell Proliferation and Apoptosis in Ectopic Endometrial Tissue: A Randomized Controlled Study. J Fam Reprod Heal. 2021;15(1):45-52. doi: 10.18502/jfrh.v15i1.6077
Yamamoto N, Wada-Hiraike O, Hirano M, et al. Ovarian reserve may influence the outcome of bone mineral density in patients with long-term use of dienogest. SAGE Open Med. 2021;9:205031212110059. doi: 10.1177/20503121211005992
Hadji P, Colli E, Regidor PA. Bone health in estrogen-free contraception. Osteoporos Int. 2019;30(12):2391-2400. doi: 10.1007/s00198-019-05103-6
Gallo MF, Nanda K, Grimes DA, Lopez LM, Schulz KF. 20 µg versus >20 µg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev. 2013;2013(8):CD003989. doi: 10.1002/14651858.CD003989.pub5
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 European Journal of Clinical and Experimental Medicine
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our open access policy is in accordance with the Budapest Open Access Initiative (BOAI) definition: this means that articles have free availability on the public Internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from having access to the Internet itself.
All articles are published with free open access under the CC-BY Creative Commons attribution license (the current version is CC-BY, version 4.0). If you submit your paper for publication by the Eur J Clin Exp Med, you agree to have the CC-BY license applied to your work. Under this Open Access license, you, as the author, agree that anyone may download and read the paper for free. In addition, the article may be reused and quoted provided that the original published version is cited. This facilitates freedom in re-use and also ensures that Eur J Clin Exp Med content can be mined without barriers for the research needs.
