Dienogest versus gonadotropin-releasing hormone analogues for the clinical treatment of endometriosis: an updated meta-analysis

Kanwal Majeed; Zainab Muhammad Hanif; Muzna Murtaza; Hassam Ali; Atiya Batool; Hina Syed

doi:10.18203/issn.2454-2156.IntJSciRep20243494

Authors

Kanwal Majeed Department of Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan
Zainab Muhammad Hanif Department of Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan
Muzna Murtaza Department of Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan
Hassam Ali Department of Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan
Atiya Batool Department of Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan
Hina Syed Department of Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan

DOI:

https://doi.org/10.18203/issn.2454-2156.IntJSciRep20243494

Keywords:

Dienogest, GnRH analogue, GnRH agonist and endometriosis

Abstract

Endometriosis is a chronic gynecological condition where endometrial-like tissue grows outside the uterus, leading to persistent pelvic pain, dysmenorrhea, dyspareunia, and infertility. The objective of the systematic review was to examine the efficacy and safety of Dienogest, which is a synthetic, orally active 19-nortestosterone derivative, in the treatment of women with endometriosis compared to GnRH-a, which is commonly used to treat conditions like endometriosis. We conducted a search of PubMed, Google Scholar, and Cochrane Library databases from inception until August 2024 for clinical studies, using the following keywords: ("Dienogest") and ("gonadotropin-releasing hormone analogue" or GnRH Analogues OR GnRH agonist) and (Endometriosis). Relevant randomized control trials were identified. Pooled effect estimates were calculated using a random effect model. This meta-analysis included eight randomized controlled trials (RCTs) with 1,219 patients, 602 in the dienogest group and 617 in the GnRH analogue group. Both treatments were equally effective in controlling pain, dysmenorrhea, and dyspareunia, but dienogest offered advantages. Dienogest significantly reduced the recurrence rate (RR: 0.37, 95% CI [0.15, 0.91]; p=0.03) and hot flushes (RR: 0.24, 95% CI [0.10, 0.59]; p=0.002) and protected against bone mineral density (BMD) loss. However, it increased the risk of irregular vaginal bleeding (RR: 3.61, 95% CI [1.09, 11.97]; p=0.04). Other side effects, such as headache, vaginal dryness, spotting, and alopecia, were not statistically significant. It concluded that Dienogest has comparatively fewer side effects than GnRH analogue, making it a considerably safer option for treating endometriosis.

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References

Kennedy S, Bergqvist A, Chapron C, Thomas D, Gerard D, Robert G, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005;20(10):2698-704. DOI: https://doi.org/10.1093/humrep/dei135

Lee J, Park HJ, Yi KW. Dienogest in endometriosis treatment: A narrative literature review. Clin Exp Reprod Med. 2023;50(4):223. DOI: https://doi.org/10.5653/cerm.2023.06128

Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet. 2010;27(8):441. DOI: https://doi.org/10.1007/s10815-010-9436-1

Andres M de P, Lopes LA, Baracat EC, Podgaec S. Dienogest in the treatment of endometriosis: systematic review. Arch Gynecol Obstet. 2015;292(3):523-9. DOI: https://doi.org/10.1007/s00404-015-3681-6

Granese R, Perino A, Calagna G, Salvatore S, Pasquale DF, Nicola C, et al. Gonadotrophin-releasing hormone analogue or dienogest plus estradiol valerate to prevent pain recurrence after laparoscopic surgery for endometriosis: a multi-center randomized trial. Acta Obstet Gynecol Scand. 2015;94(6):637-45. DOI: https://doi.org/10.1111/aogs.12633

Veth VB, van de Kar MMA, Duffy JMN, van Wely M, Mijatovic V, Maas JWM. Gonadotropin-releasing hormone analogues for endometriosis. Cochrane Database Syst Rev. 2023;6(6). DOI: https://doi.org/10.1002/14651858.CD014788.pub2

New EP, Mikhail E. A narrative review of using GnRH analogues to reduce endometriosis recurrence after surgery: a double-edged sword. Gynecol Pelvic Med. 2021;4(0):8-8. DOI: https://doi.org/10.21037/gpm-2020-mtet-03

Malik R, Mann MK. Role of Dienogest in Endometriosis in Young Women. J Obstet Gynaecol India. 2021;71(5):522. DOI: https://doi.org/10.1007/s13224-021-01483-0

Oliveira SA de, Melo BS, Pereira MF. Dienogest versus gonadotropin-releasing hormone analogue for the clinical treatment of endometriosis: a systematic review and meta-analysis. Int J Reprod Contracept Obstet Gynecol. 2017;6(9):3712-20. DOI: https://doi.org/10.18203/2320-1770.ijrcog20174013

Liberati A, Altman DG, Tetzlaff J, Cynthia M, Peter CG, John PAI, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1-e34. DOI: https://doi.org/10.1016/j.jclinepi.2009.06.006

Sterne JAC, Savović J, Page MJ, Roy GE, Natalie SB, Isabelle B, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. DOI: https://doi.org/10.1136/bmj.l4898

Harada T, Momoeda M, Taketani Yl. 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):675-81. DOI: https://doi.org/10.1016/j.fertnstert.2007.12.080

Cosson M, Querleu D, Donnez J. 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):684-92. DOI: https://doi.org/10.1016/S0015-0282(01)03270-8

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(3):228-33. DOI: https://doi.org/10.1016/j.ijgo.2012.01.009

Takaesu Y, Nishi H, Kojima J, Toru S, Yuzo N, Rina K, et al. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. J Obstet Gynaecol Res. 2016;42(9):1152-8. DOI: https://doi.org/10.1111/jog.13023

Tang M, Yang W, Zhang H. Comparison of the efficacy of dienogest and GnRH-a after endometriosis surgery. BMC Womens Health. 2023;23(1):1-6.

Ceccaroni M, Clarizia R, Liverani S, Agnese D, Matteo C, Maria M, et al. 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):930-3. DOI: https://doi.org/10.1080/09513590.2021.1929151

Purwanto JP, Effendi Y, Manan H, Theodorus. Effectiveness, Safety and Obedience of Dienogest and Leuprolide Acetate in Postlaparoscopic Endometriosis Patients: Indon J Obstetr Gynecol. 2020;8(1):44-51. DOI: https://doi.org/10.32771/inajog.v8i1.1110

Abdou AM, Ammar IMM, Alnemr AAA, Abdelrhman AA. Dienogest Versus Leuprolide Acetate for Recurrent Pelvic Pain Following Laparoscopic Treatment of Endometriosis. J Obstet Gynaecol India. 2018;68(4):306. DOI: https://doi.org/10.1007/s13224-018-1119-3

Bloski T, Pierson R. Endometriosis and Chronic Pelvic Pain: Unraveling the Mystery Behind this Complex Condition. Nurs Womens Health. 2008;12(5):382. DOI: https://doi.org/10.1111/j.1751-486X.2008.00362.x

Dueholm M. Minimally invasive treatment of adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2018;51:119-137. DOI: https://doi.org/10.1016/j.bpobgyn.2018.01.016

Schindler AE. Dienogest in long-term treatment of endometriosis. Int J Womens Health. 2011;3(1):175. DOI: https://doi.org/10.2147/IJWH.S5633

Vincent K, Stagg CJ, Warnaby CE, Moore J, Kennedy S, Tracey I. “Luteal Analgesia”: Progesterone Dissociates Pain Intensity and Unpleasantness by Influencing Emotion Regulation Networks. Front Endocrinol (Lausanne). 2018;9(JUL):413. DOI: https://doi.org/10.3389/fendo.2018.00413

Dubrovina SO, Berlim YD, Bezhenar VF, Gimbut VS, Baranov II. Pharmacological Management of Endometriosis-related Pain: The Expert Opinion. J S Asian Federation Obstetr Gynaecol. 2021;12(6):415-420. DOI: https://doi.org/10.5005/jp-journals-10006-1838

McCormack PL. Dienogest: a review of its use in the treatment of endometriosis. Drugs. 2010;70(16):2073-88. DOI: https://doi.org/10.2165/11206320-000000000-00000

Resta C, Moustogiannis A, Chatzinikita E. Gonadotropin-Releasing Hormone (GnRH)/GnRH Receptors and Their Role in the Treatment of Endometriosis. Cureus. 2023;15(4):10. DOI: https://doi.org/10.7759/cureus.38136

Fan Y, Zhu S, Liang X. Conservative surgical and drug therapies for adenomyosis Medicine. Reprod Biol. 2022;22(3):100664. DOI: https://doi.org/10.1016/j.repbio.2022.100664

Jimenez JCV, Romero LL, Garcia IB, Sanchez ML, Fernandez RO. Endometriosis and dyspareunia: Solving the enigma. Eur J Obstet Gynecol Reprod Biol X. 2023;19:100224. DOI: https://doi.org/10.1016/j.eurox.2023.100224

Barcena De Arellano ML, Arnold J, Vercellino GF, Vito C, Andreas DE, Achim S, et al. Influence of Nerve Growth Factor in Endometriosis-Associated Symptoms. Reprod Sci. 2011;18(12):1202-10. DOI: https://doi.org/10.1177/1933719111410711

Liang Y, Yao S. Potential role of estrogen in maintaining the imbalanced sympathetic and sensory innervation in endometriosis. Mol Cell Endocrinol. 2016;424:42-9. DOI: https://doi.org/10.1016/j.mce.2016.01.012

Zupi E, Marconi D, Sbracia M, Fulvio Z, Bonaventura DV, Caterina E, et al. Add-back therapy in the treatment of endometriosis-associated pain. Fertil Steril. 2004;82(5):1303-8. DOI: https://doi.org/10.1016/j.fertnstert.2004.03.062

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):537-48. DOI: https://doi.org/10.1016/j.fertnstert.2016.12.024

Tang M, Yang W, Zhang H. Comparison of the efficacy of dienogest and GnRH-a after endometriosis surgery. BMC Womens Health. 2023;23(1):1. DOI: https://doi.org/10.1186/s12905-022-02118-w

Zhang Z, Divittorio JR, Joseph AM, Correa SM. The Effects of Estrogens on Neural Circuits That Control Temperature. Endocrinology. 2021;162(8):20. DOI: https://doi.org/10.1210/endocr/bqab087

Tang H, Jia Q, Dong Z. Add-Back and Combined Regulation in GnRH-a Treatment of Endometriosis. Clin Exp Obstet Gynecol. 2023;50(10):224. DOI: https://doi.org/10.31083/j.ceog5010224

Raffaelli B, Do TP, Chaudhry BA, Ashina M, Amin FM, Ashina H. Menstrual migraine is caused by estrogen withdrawal: revisiting the evidence. Journal of Headache and Pain. 2023;24(1):1-10. DOI: https://doi.org/10.1186/s10194-023-01664-4

Krause M, Wheeler TL, Snyder TE, Richter HE. Local Effects of Vaginally Administered Estrogen Therapy: A Review. J Pelvic Med Surg. 2009;15(3):105. DOI: https://doi.org/10.1097/SPV.0b013e3181ab4804

Brough KR, Torgerson RR. Hormonal therapy in female pattern hair loss. Int J Womens Dermatol. 2017;3(1):53. DOI: https://doi.org/10.1016/j.ijwd.2017.01.001

Väänänen HK, Härkönen PL. Estrogen and bone metabolism. Maturitas. 1996;23(1):10. DOI: https://doi.org/10.1016/0378-5122(96)01015-8

Farmer JE, Prentice A, Breeze A. Gonadotrophin‐releasing hormone analogues for endometriosis: bone mineral density. Cochrane Database Syst Rev. 2003;2003(4). DOI: https://doi.org/10.1002/14651858.CD001297

Surrey ES. GnRH agonists in the treatment of symptomatic endometriosis: a review. F S Rep. 2023;4(2):40-5. DOI: https://doi.org/10.1016/j.xfre.2022.11.009

Takagi H, Takakura M, Sasagawa T. Risk factors of heavy uterine bleeding in patients with endometriosis and adenomyosis treated with dienogest. Taiwan J Obstet Gynecol. 2023;62(6):852-7. DOI: https://doi.org/10.1016/j.tjog.2023.08.003

Maybin JA, Critchley HO. Medical management of heavy menstrual bleeding. Women’s Health. 2016;12(1):27. DOI: https://doi.org/10.2217/whe.15.100