Efficacy and safety of dienogest in the treatment of endometriosis: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LI Rui ¹ , LIU Xuan ² , LI Xiaoyan ³ , XIAO Feiyi ¹ , WANG Yaoling ¹ , ZHANG Yuzheng ¹ , ZHAO Kun ¹ ,  GUO Wudong ¹ ,  LI Xue ¹

1. China National Health Development Research Center, Beijing 100044, P. R. China;
2. School of Business Administration, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China;
3. Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, National Clinical Research Center for Obstetric and Gynecologic Diseases, Beijing 100730, P. R. China;

Corresponding author：

GUO Wudong, Email: guowudong@hotmail.com; LI Xue, Email: lx0204@126.com

Keywords：

Dienogest; Endometriosis; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.202401009

Video：

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Objective To systematically review the efficacy and safety of dienogest in the treatment of endometriosis. Methods The PubMed, Embase, Cochrane Library, CBM, WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) of dienogest for the treatment of endometriosis from inception to February 2024. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4 software. Results A total of 20 RCTs, involving 2 826 patients were included. Meta-analysis showed that compared with gonadotropin-releasing hormone agonist (GnRH-a), dienogest had similar efficacy. Compared with placebo, dienogest was more effective in reducing endometriosis-related pelvic pain. Compared with oral contraceptives, dienogest performed better in relieving endometriosis-related pelvic pain and improving recurrence and pregnancy rates. Compared with other drugs (such as non-steroidal anti-inflammatory drugs, dydrogesterone, etc.), dienogest could gradually reduce the pain. In terms of safety, dienogest could reduce bone density damage and hot flashes in patients with endometriosis compared with the control group. Conclusion Current evidence shows that dienogest is effective and safely tolerated in the treatment of endometriosis. Due to the limitations of the quantity and quality of included studies, the above conclusion needs to be verified by more high-quality studies.

1.	中国医师协会妇产科医师分会. 子宫内膜异位症的诊治指南. 中华妇产科杂志, 2015, 56(12): 812-824.
2.	Dunselman GA, Vermeulen N, Becker C, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod, 2014, 29(3): 400-412.
3.	Johnson NP, Hummelshoj L,. Consensus on current management of endometriosis. Hum Reprod, 2013, 28(6): 1552-1568.
4.	中国医师协会妇产科医师分会子宫内膜异位症专业委员会, 中华医学会妇产科学分会子宫内膜异位症协作组. 子宫内膜异位症长期管理中国专家共识. 中华妇产科杂志, 2018, 53(12): 836-841.
5.	Köhler G, Faustmann TA, Gerlinger C, et al. 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(1): 21-25.
6.	Petraglia F, Hornung D, Seitz C, et al. Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment. Arch Gynecol Obstet, 2012, 285(1): 167-173.
7.	Strowitzki T, Faustmann T, Gerlinger C, et al. Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program. Int J Womens Health, 2015, 7: 393-401.
8.	Cosson M, Querleu D, Donnez J, et al. Dienogest is as effective as triptorelin in the treatment of endometriosis after laparoscopic surgery: results of a prospective, multicenter, randomized study. Fertil Steril, 2002, 77(4): 684-692.
9.	Harada T, Momoeda M, Taketani Y, et a1. 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.
10.	Strowitzki T, Faustmann T, Gerlinger C, et al. Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol, 2010, 151(2): 193-198.
11.	Strowitzki T, Marr J, Gerlinger C, et al. 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.
12.	Caruso S, Iraci M, Cianci S, et al. Quality of life and sexual function of women affected by endometriosis-associated pelvic pain when treated with dienogest. J Endocrinol Invest, 2015, 38(11): 1211-1218.
13.	Takaesu Y, Nishi H, Kojima J, et al. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. J Obstet Gynaecol Res, 2016, 42(9): 1152-1158.
14.	Abdou AM, Ammar IMM, Alnemr AAA, et al. Dienogest versus leuprolide acetate for recurrent pelvic pain following laparoscopic treatment of endometriosis. J Obstet Gynaecol India, 2018, 68(4): 306-313.
15.	Lang J, Yu Q, Zhang S, et a1. Dienogest for treatment of endometriosis in Chinese women: a placebo-controlled, randomized, double-blind phase 3 study. J Womens Health, 2018, 2018: 148‐155.
16.	el Taha L, Abu Musa A, Khalifeh D, et a1. Efficacy of dienogest vs combined oral contraceptive on pain associated with endometriosis: Randomized clinical trial. Eur J Obstet Gynecol Reprod Biol, 2021, 267: 205-212.
17.	P. JP, Yusuf E, Heriyadi M, et al. Effectiveness, safety and obedience of dienogest and leuprolide acetatein postlaparoscopic endometriosis patients. Indones J Obstet Gynecol, 2020, 2020: 44-51.
18.	Yu Q, Zhang S, Li H, et al. Dienogest for treatment of endometriosis in women: a 28-week, open-label, extension study. J Womens Health (Larchmt), 2019, 28(2): 170-177.
19.	朱奕融, 方淑芬, 彭淑华. 地诺孕素治疗复发型卵巢子宫内膜异位症的临床效果. 中国当代医药, 2021, 28(20): 118-121.
20.	Ceccaroni M, Clarizia R, Liverani S, et a1. Dienogest vs GnRH agonists as postoperative therapy after laparoscopic eradication of deep infiltrating endometriosis with bowel and parametrial surgery: a randomized controlled trial. Gynecol Endocrinol, 2021, 37(10): 930-933.
21.	Niakan G, Rokhgireh S, Ebrahimpour M, et al. Comparing the effect of dienogest and ocps on pain and quality of life in women with endometriosis: a randomized, double-blind, placebo-controlled trial. Arch Iran Med, 2021, 24(9): 670-677.
22.	王久兰, 何伟, 周夏伶, 等. 地诺孕素、亮丙瑞林辅助治疗卵巢子宫内膜异位囊肿的临床效果比较. 中国妇产科临床杂志, 2022, 23(3): 275-277.
23.	梁海莹, 周雪勤, 胡明淼, 等. 地诺孕素与促性腺激素释放激素激动剂类药物治疗对子宫内膜异位症手术患者血清糖类抗原125、骨密度、雌二醇和肿块大小的影响. 中国性科学, 2023, 32(3): 54-58.
24.	伍志虹, 陈圆虹, 廖小梅. 地诺孕素治疗子宫内膜异位症的临床效果分析. 中外医疗, 2023, 42(3): 113-116,121.
25.	Tang M, Yang W, Zhang H. Comparison of the efficacy of dienogest and GnRH-a after endometriosis surgery. BMC Womens Health, 2023, 23(1): 85.
26.	马振军, 仵淑娟. 促性腺激素释放激素激动剂、地诺孕素、孕三烯酮在卵巢型子宫内膜异位症手术后的应用效果对比. 当代医药论丛, 2023, 21(14): 29-33.
27.	尹小超, 陈若兰, 刘青. 地诺孕素与米非司酮在EMs保守术后长期维持治疗中的应用. 海南医学, 2023, 34(23): 3411-3414.
28.	Morotti M, Vincent K, Becker CM. Mechanisms of pain in endometriosis. Eur J Obstet Gynecol Reprod Biol, 2017, 209: 8-13.
29.	Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am, 2012, 39(4): 535-549.
30.	Guo SW, Zilberberg MD, Hummelshoj L. Endometriosis and ovarian cancer. Lancet Oncol, 2012, 13(5): e189-e190.
31.	Sasagawa S, Shimizu Y, Kami H, et al. Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids, 2008, 73(2): 222-231.
32.	Oettel M, Zentel HJ, Nickisch K. A progestin isn't a progestin: dienogest for endometriosis as a blueprint for future research - Review as a contribution for discussion. Horm Mol Biol Clin Investig, 2020, 42(2): 133-142.
33.	Chandra A, Rho AM, Jeong K, et al. Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma. Obstet Gynecol Sci, 2018, 61(1): 111-117.
34.	Ota Y, Andou M, Yanai S, et al. Long-term administration of dienogest reduces recurrence after excision of endometrioma. J Endomet Pelvic Pain Disord, 2015, 7(2): 63-67.

1. 中国医师协会妇产科医师分会. 子宫内膜异位症的诊治指南. 中华妇产科杂志, 2015, 56(12): 812-824.
2. Dunselman GA, Vermeulen N, Becker C, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod, 2014, 29(3): 400-412.
3. Johnson NP, Hummelshoj L,. Consensus on current management of endometriosis. Hum Reprod, 2013, 28(6): 1552-1568.
4. 中国医师协会妇产科医师分会子宫内膜异位症专业委员会, 中华医学会妇产科学分会子宫内膜异位症协作组. 子宫内膜异位症长期管理中国专家共识. 中华妇产科杂志, 2018, 53(12): 836-841.
5. Köhler G, Faustmann TA, Gerlinger C, et al. 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(1): 21-25.
6. Petraglia F, Hornung D, Seitz C, et al. Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment. Arch Gynecol Obstet, 2012, 285(1): 167-173.
7. Strowitzki T, Faustmann T, Gerlinger C, et al. Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program. Int J Womens Health, 2015, 7: 393-401.
8. Cosson M, Querleu D, Donnez J, et al. Dienogest is as effective as triptorelin in the treatment of endometriosis after laparoscopic surgery: results of a prospective, multicenter, randomized study. Fertil Steril, 2002, 77(4): 684-692.
9. Harada T, Momoeda M, Taketani Y, et a1. 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.
10. Strowitzki T, Faustmann T, Gerlinger C, et al. Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol, 2010, 151(2): 193-198.
11. Strowitzki T, Marr J, Gerlinger C, et al. 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.
12. Caruso S, Iraci M, Cianci S, et al. Quality of life and sexual function of women affected by endometriosis-associated pelvic pain when treated with dienogest. J Endocrinol Invest, 2015, 38(11): 1211-1218.
13. Takaesu Y, Nishi H, Kojima J, et al. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. J Obstet Gynaecol Res, 2016, 42(9): 1152-1158.
14. Abdou AM, Ammar IMM, Alnemr AAA, et al. Dienogest versus leuprolide acetate for recurrent pelvic pain following laparoscopic treatment of endometriosis. J Obstet Gynaecol India, 2018, 68(4): 306-313.
15. Lang J, Yu Q, Zhang S, et a1. Dienogest for treatment of endometriosis in Chinese women: a placebo-controlled, randomized, double-blind phase 3 study. J Womens Health, 2018, 2018: 148‐155.
16. el Taha L, Abu Musa A, Khalifeh D, et a1. Efficacy of dienogest vs combined oral contraceptive on pain associated with endometriosis: Randomized clinical trial. Eur J Obstet Gynecol Reprod Biol, 2021, 267: 205-212.
17. P. JP, Yusuf E, Heriyadi M, et al. Effectiveness, safety and obedience of dienogest and leuprolide acetatein postlaparoscopic endometriosis patients. Indones J Obstet Gynecol, 2020, 2020: 44-51.
18. Yu Q, Zhang S, Li H, et al. Dienogest for treatment of endometriosis in women: a 28-week, open-label, extension study. J Womens Health (Larchmt), 2019, 28(2): 170-177.
19. 朱奕融, 方淑芬, 彭淑华. 地诺孕素治疗复发型卵巢子宫内膜异位症的临床效果. 中国当代医药, 2021, 28(20): 118-121.
20. Ceccaroni M, Clarizia R, Liverani S, et a1. Dienogest vs GnRH agonists as postoperative therapy after laparoscopic eradication of deep infiltrating endometriosis with bowel and parametrial surgery: a randomized controlled trial. Gynecol Endocrinol, 2021, 37(10): 930-933.
21. Niakan G, Rokhgireh S, Ebrahimpour M, et al. Comparing the effect of dienogest and ocps on pain and quality of life in women with endometriosis: a randomized, double-blind, placebo-controlled trial. Arch Iran Med, 2021, 24(9): 670-677.
22. 王久兰, 何伟, 周夏伶, 等. 地诺孕素、亮丙瑞林辅助治疗卵巢子宫内膜异位囊肿的临床效果比较. 中国妇产科临床杂志, 2022, 23(3): 275-277.
23. 梁海莹, 周雪勤, 胡明淼, 等. 地诺孕素与促性腺激素释放激素激动剂类药物治疗对子宫内膜异位症手术患者血清糖类抗原125、骨密度、雌二醇和肿块大小的影响. 中国性科学, 2023, 32(3): 54-58.
24. 伍志虹, 陈圆虹, 廖小梅. 地诺孕素治疗子宫内膜异位症的临床效果分析. 中外医疗, 2023, 42(3): 113-116,121.
25. Tang M, Yang W, Zhang H. Comparison of the efficacy of dienogest and GnRH-a after endometriosis surgery. BMC Womens Health, 2023, 23(1): 85.
26. 马振军, 仵淑娟. 促性腺激素释放激素激动剂、地诺孕素、孕三烯酮在卵巢型子宫内膜异位症手术后的应用效果对比. 当代医药论丛, 2023, 21(14): 29-33.
27. 尹小超, 陈若兰, 刘青. 地诺孕素与米非司酮在EMs保守术后长期维持治疗中的应用. 海南医学, 2023, 34(23): 3411-3414.
28. Morotti M, Vincent K, Becker CM. Mechanisms of pain in endometriosis. Eur J Obstet Gynecol Reprod Biol, 2017, 209: 8-13.
29. Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am, 2012, 39(4): 535-549.
30. Guo SW, Zilberberg MD, Hummelshoj L. Endometriosis and ovarian cancer. Lancet Oncol, 2012, 13(5): e189-e190.
31. Sasagawa S, Shimizu Y, Kami H, et al. Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids, 2008, 73(2): 222-231.
32. Oettel M, Zentel HJ, Nickisch K. A progestin isn't a progestin: dienogest for endometriosis as a blueprint for future research - Review as a contribution for discussion. Horm Mol Biol Clin Investig, 2020, 42(2): 133-142.
33. Chandra A, Rho AM, Jeong K, et al. Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma. Obstet Gynecol Sci, 2018, 61(1): 111-117.
34. Ota Y, Andou M, Yanai S, et al. Long-term administration of dienogest reduces recurrence after excision of endometrioma. J Endomet Pelvic Pain Disord, 2015, 7(2): 63-67.

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