Kosin Med J.  2021 Dec;36(2):116-124. /10.7180/kmj.2021.36.2.116.

Observational Study for Adverse Effects and Discontinuation with Long-Term Post-Operative Hormonal Treatment for Endometriosis in Real-World Practice

• Kim IH
• Yoon H
• Lee HJ
• Noh HK
• Joo JK
• Kim KH

• KMID: 2524644
• DOI: http://doi.org//10.7180/kmj.2021.36.2.116

Abstract

Objectives
To evaluate the side effects and causes of discontinuation of either combined oral contraceptives or dienogest (DNG) used to prevent recurrence in patients with surgically confirmed endometriosis.
Methods
We retrospectively analyzed the medical records of 213 women with endometriosis who had been treated with combined oral contraceptives (ethinyl estradiol 0.02 mg/drospirenone 3 mg [EE/DRSP]) or DNG 2 mg for 12 months or more. The side effects reported by the patients, laboratory parameters, causes of discontinuation of medication, and recurrence rates were evaluated one, two, three, four, and five years after starting medication (Y1, Y2, Y3, Y4, and Y5).
Results
EE/DRSP were administered to 59 patients, while DNG was administered to 154 patients. The mean durations of postoperative use of EE/DRSP and DNG were 44.5 ± 22.6 months and 23.6 ± 13.5 months, respectively. The prevalence of side effects was 27.1%, 19.0%, 10.0%, 10.5%, and 7.4% in the EE/DRSP group and 29.2%, 15.7%, 14.0%, 23.1%, and 0.0% in the DNG group at Y1, Y2, Y3, Y4, and Y5, respectively. The discontinuation rates were 1.7%, 1.7%, 4.0%, 0.0%, and 7.4% at Y1, Y2, Y3, Y4, and Y5, respectively, in the EE/DRSP group and 10.4%, 3.3%, 4.0%, 3.8%, and 0.0% at the same times in the DNG group. The recurrence rates were less than 4% in both the groups.
Conclusions
The side effects of commonly prescribed postoperative hormone treatments were relatively mild, and the occurrence of side effects decreased with continuous administration. Further, the long-term use of postoperative hormone treatments is likely to prevent recurrence of endometriosis after surgery.

Keyword

Adverse effects; Dienogest; Endometriosis; Oral contraceptives; Recurrences

Reference

1. Agarwal SK, Foster WG, Groessl EJ. Rethinking endometriosis care: applying the chronic care model via a multidisciplinary program for the care of women with endometriosis. Int J Womens Health. 2019; 11:405–10.

2. Dunselman G, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014; 29:400–12.

3. Cheong Y, Tay P, Luk F, Gan HC, Li TC, Cooke I. Laparoscopic surgery for endometriosis: How often do we need to re-operate? J Obstet Gynaecol. 2008; 28:82–5.

4. Guo SW. Recurrence of endometriosis and its control. Hum Reprod Update. 2009; 15:441–61.

5. Taniguchi F, Enatsu A, Ota I, Toda T, Arata K, Harada T. Effects of low dose oral contraceptive pill containing drospirenone/ethinylestradiol in patients with endometrioma. Eur J Obstet Gynecol Reprod Biol. 2015; 191:116–20.

6. 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 and Steril. 2017; 107:537–48.

7. Godin R, Marcoux V. Vaginally administered danazol: an overlooked option in the treatment of rectovaginal endometriosis? J Obstet Gynaecol Can. 2015; 37:1098–103.

8. Cosson M, Querleu D, Donnez J, Madelenat P, Konincks P, Audebert A, et al. Dienogest is as effective as triptorelin in the treatment of endometriosis after laparoscopic surgery: results of a prospective, multicenter, randomized study. Fertil and Steril. 2002; 77:684–92.

9. Harada T, Momoeda M, Taketani Y, Aso T, Fukunaga M, Hagino H, 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 and Steril. 2009; 91:675–81.

10. Köhler G, Faustmann TA, Gerlinger C, Seitz C, Mueck AO. A dose-ranging study to determine the efficacy and safety of 1, 2, and 4mg of dienogest daily for endometriosis. Int J Gynaecol Obstet. 2010; 108:21–5.

11. Strowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C. Detailed analysis of a randomized, multicenter, comparative trial of dienogest versus leuprolide acetate in endometriosis. Int J Gynaecol Obstet. 2012; 117:228–33.

12. Davis L, Kennedy SS, Moore J, Prentice A. Oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev. 2007; 3:Cd001019.

13. 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 and Steril. 2003; 80:560–3.

14. Vercellini P, Somigliana E, Viganò P, De Matteis S, Barbara G, Fedele L. Post-operative endometriosis recurrence: a plea for prevention based on pathogenetic, epidemiological and clinical evidence. Reprod Biomed Online. 2010; 21:259–65.

15. Vercellini P, Trespidi L, Colombo A, Vendola N, Marchini M, Crosignani PG. A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Fertil and Steril. 1993; 60:75–9.

16. Rokitansky Cv. Ueber Uterusdrusen-neubildung in Uterus and Ovariul Sarcomen. Z Gesellschaft Aerzte Wien. 1860; 16:577.

17. 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; 43:215–20.

18. Kim HG, Song YJ, Na YJ. Long-term dienogest treatment for prevention of recurrent symptoms and lesions after surgery for endometriosis: a study evaluating adverse events and tolerability in Korean women. J Reprod Med. 2020; 65:195–200.

19. Kitawaki J, Kusuki I, Yamanaka K, Suganuma I. Maintenance therapy with dienogest following gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain. Eur J Obstet Gynecol Reprod Biol. 2011; 157:212–6.

20. Yanase T, Tsuneki I, Tamura M, Kurabayashi T. Relief of uterine bleeding by cyclic administration of dienogest for endometriosis. Gynecol Endocrinol. 2014; 30:804–7.