Dienogest versus gonadotropin-releasing hormone analogue for the clinical treatment of endometriosis: a systematic review and meta-analysis

Sofia Andrade, Bárbara Souza Melo, Marina Fernandes Pereira
In: International Journal of Reproduction, Contraception, Obstetrics and Gynecology · 2017 · vol. 6(9) , pp. 3712 · doi:10.18203/2320-1770.ijrcog20174013 · W2745747978
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⚙ AI-generated summary by claude@2026-06, 2026-06-10 ⓘ

This meta-analysis found dienogest and GnRH analogues showed no difference in treating pelvic pain, dyspareunia, or pouch of Douglas induration, but dienogest had fewer headaches and less BMD loss.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 · read from full text ⓘ

This systematic review and meta-analysis compared dienogest with gonadotropin-releasing hormone (GnRH) analogues for clinical treatment of endometriosis, using four eligible studies selected from 31 articles. Across evaluations of maintenance of lower abdominal/pelvic pain, dyspareunia, induration of the Pouch of Douglas after treatment, and side effects (including hot flushes, headache, and bone mineral density loss), the review found no difference between the groups for pain, dyspareunia, induration, or hot flushes. However, the dienogest group had a lower incidence of headache and less bone mineral density loss. The main caveat is that only four studies met inclusion criteria, limiting the breadth of evidence contributing to the pooled comparisons. This paper is centrally about endometriosis — it directly meta-analyzes dienogest versus GnRH analogues for symptom control and side-effect outcomes in endometriosis.

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Abstract

Endometriosis is a chronic inflammatory disease, defined by the presence of endometrial tissue outside the uterine cavity. It causes symptoms such as dysmenorrhea, chronic pelvic pain, dyspareunia, infertility, with great loss of quality of life for the patient. The objective of the study was to compare, through a meta-analysis, GnRH analogues, which are considered clinical first line treatment for endometriosis, versus dienogest, a selective oral progestin in the treatment of endometriosis. A systematic review was conducted to select the studies. In total, 31 articles were found. Four studies met criteria, the following variables were analyzed: pelvic pain, dyspareunia and induration of the Pouch of Douglas after treatment and it was evaluated the presence of side effects during treatment: hot flushes, headache and BMD loss. There was no difference between the dienogest group and GnRH analogue group when it was evaluated maintenance of lower abdominal pain, dyspareunia, induration of the Pouch of Douglas after treatment and hot flushes during treatment. Besides those results, the dienogest group had a lower incidence of headache and less BMD loss. The treatment of endometriosis continues to be a challenge, even with new treatment options such as new drugs (dienogest) and surgical procedures. This meta-analysis provides evidence of the absence of dienogest inferiority compared with GnRH analogues with less BMD loss and less headache incidence.
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Dienogest versus gonadotropin-releasing hormone analogue for the clinical treatment of endometriosis: a systematic review and meta-analysis DOI: https://doi.org/10.18203/2320-1770.ijrcog20174013Keywords: Clinical treatment, Dienogest, Endometriosis, Gonadotropin-releasing hormoneAbstract Endometriosis is a chronic inflammatory disease, defined by the presence of endometrial tissue outside the uterine cavity. It causes symptoms such as dysmenorrhea, chronic pelvic pain, dyspareunia, infertility, with great loss of quality of life for the patient. The objective of the study was to compare, through a meta-analysis, GnRH analogues, which are considered clinical first line treatment for endometriosis, versus dienogest, a selective oral progestin in the treatment of endometriosis. A systematic review was conducted to select the studies. In total, 31 articles were found. Four studies met criteria, the following variables were analyzed: pelvic pain, dyspareunia and induration of the Pouch of Douglas after treatment and it was evaluated the presence of side effects during treatment: hot flushes, headache and BMD loss. There was no difference between the dienogest group and GnRH analogue group when it was evaluated maintenance of lower abdominal pain, dyspareunia, induration of the Pouch of Douglas after treatment and hot flushes during treatment. Besides those results, the dienogest group had a lower incidence of headache and less BMD loss. The treatment of endometriosis continues to be a challenge, even with new treatment options such as new drugs (dienogest) and surgical procedures. This meta-analysis provides evidence of the absence of dienogest inferiority compared with GnRH analogues with less BMD loss and less headache incidence. Metrics References Andres MP, Lopes LA, Baracat EC, Podgaec S. Dienogest in the treatment of endometriosis: Systematic review. Arch Gynecol Obstet. 2015;292:523-9. 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. Granese R, Perino A, Calagna G, Saitta S, De Franciscis P, Colacurci N 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. Takenaka, M. Exploratory study of pre-surgical medications with Dienogest or Leuprorelin in laparoscopic cystectomy of endometrial cysts. J Obstet Gynaecol Res. 2015:41(8);1234-9. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:332-9. Methley AM, Campbell S, Chew-Graham C, McNally R, Cheraghi-Sohi S. PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res. 2014;14:579. Howick J. Oxford Centre for Evidence-based Medicine - Levels of Evidence; 2009. Available in: http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. Available in: www.cochrane-handbook.org. Higgins JPT, Thompson SG, Deeks JJ, Altman DJ. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-60. Harada T, Momoeda M, Taketani Y, Aso T, Fukunaga S, 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 Steril. 2009;91(3):675-81. Cosson M, Querleu D, Donnez J, Madelenat J, Koninckx 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 Steril. 2002;77(4):684-92. 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 Gynecol Obstet. 2012;117:228-33. Takaesu Y, Nishi H, Kojima J, Sasaki T, Nagamitsu Y, Kato R, et al. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis J Obstet Gynaecol Res. 2016;42(9):1152-8. Borenstein M, Hedges LV, Higgins J, Rothstein HR. Introduction to Meta-Analysis, 1st Edition. Chichester, UK: John Wiley and Sons; 2009:391-403. Der Simonian R, Laird N. Meta-analysis in clinical trials. Controlled Clinical Trials. 1986:7(3);177-88. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Statistics in Medic. 2002:21(11);1539-58. Sutton AJ, Abrams KR, Jones DR, Jones DR, Sheldon TA, Song F. Methods for meta-analysis in medical research. 1st Edition. Leicester, UK: John Wiley and Sons; 2000:37-56. Katsuki Y, Takano Y, Futamura Y, Shibutani Y, Aoki D, Udagawa Y, et al. Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. Eur J Endocrinol. 1998;138:216-26. Petraglia F, Hornung D, Seitz D, Faustmann T, Gerlinger C, Luisi S, et al. Reduced pelvic pain in women with endometriosis: efficacy of long-term Dienogest treatment. Arch Gynecol Obstet. 2012;285(1):167-73. Biberoglu KO, Behrman SJ. Dosage aspects of danazol therapy in endometriosis: short term and long term effectiveness. Am J Obstet Gynecol. 1981;139:645.

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