Gonadotropin-releasing hormone agonist with add–back treatment is as effective and tolerable as dienogest in preventing pain recurrence after laparoscopic surgery for endometriosis

Purpose This study was performed to compare the efficacy and tolerability of GnRH agonist with add–back therapy versus dienogest treatment for preventing pelvic pain recurrence after laparoscopic surgery for endometriosis.

Sixty-four reproductive-aged women who underwent laparoscopic surgery for endometriosis received post-operative medical treatment with either GnRH agonist plus 17β-estradiol and norethisterone acetate (n = 28) or dienogest (n = 36) for 6 months. The pre- to post-treatment changes in pain were assessed using a visual analogue scale, and changes in quality-of-life and menopausal symptoms were measured by questionnaire.

Visual analogue scale pain score decreased significantly for both treatments with no significant differences between groups. Neither physical, psychological, social, and environmental components of quality-of-life nor menopausal rating scale score were significantly different between the two groups. Bone mineral density at the lumbar spine declined significantly in both treatment groups (−2.5 % for GnRH agonist plus add–back and −2.3 % for dienogest), with no significant difference between the two groups.

GnRH agonist and add–back therapy using 17β-estradiol and norethisterone acetate are as effective and tolerable as dienogest for the prevention of pelvic pain recurrence after laparoscopic surgery for endometriosis. Similar content being viewed by others

Jacobson TZ, Duffy JM, Barlow D, Koninckx PR, Garry R (2009) Laparoscopic surgery for pelvic pain associated with endometriosis. Cochrane Database Syst Rev 4:CD001300 Guo SW (2009) Recurrence of endometriosis and its control. Hum Reprod Update 15:441–461 Vercellini P, Crosignani PG, Abbiati A, Somigliana E, Viganò P, Fedele L (2009) The effect of surgery for symptomatic endometriosis: the other side of the story. Hum Reprod Update 15:177–188 Brown J, Pan A, Hart RJ (2010) Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev 12:CD008475 Hornstein MD, Surrey ES, Weisberg GW, Casino LA (1998) Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Lupron Add-Back Study Group. Obstet Gynecol 91:16–24 Franke HR, van de Weijer PH, Pennings TM, van der Mooren MJ (2000) Gonadotropin-releasing hormone agonist plus “add-back” hormone replacement therapy for treatment of endometriosis: a prospective, randomized, placebo-controlled, double-blind trial. Fertil Steril 74:534–539 Sagsveen M, Farmer JE, Prentice A, Breeze A (2003) Gonadotrophin-releasing hormone analogues for endometriosis: bone mineral density. Cochrane Database Syst Rev 4:CD001297 Wu D, Hu M, Hong L et al (2014) Clinical efficacy of add-back therapy in treatment of endometriosis: a meta-analysis. Arch Gynecol Obstet 290:513–523 Andres Mde P, Lopes LA, Baracat EC, Podgaec S (2015) Dienogest in the treatment of endometriosis: systematic review. Arch Gynecol Obstet 292:523–529 Koga K, Takamura M, Fujii T, Osuga Y (2015) Prevention of the recurrence of symptom and lesions after conservative surgery for endometriosis. Fertil Steril 104:793–801 Strowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C (2012) Detailed analysis of a randomized, multicenter, comparative trial of dienogest versus leuprolide acetate in endometriosis. Int J Gynaecol Obstet 117:228–233 Barbieri RL (1992) Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obstet Gynecol 166:740–745 Schindler AE (2011) Dienogest in long-term treatment of endometriosis. Int J Womens Health 3:175–184 Strowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C (2010) Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Hum Reprod 25:633–641 Cosson M, Querleu D, Donnez J et al (2002) Dienogest is as effective as triptorelin in the treatment of endometriosis after laparoscopic surgery: results of a prospective, multicenter, randomized study. Fertil Steril 77:684–692 Harada T, Momoeda M, Taketani Y et al (2009) 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 91:675–681 Heinemann LA, Potthoff P, Schneider HP (2003) International versions of the Menopause Rating Scale (MRS). Health Qual Life Outcomes 1:28 Dunselman GA, Vermeulen N, Becker C et al (2014) ESHRE guideline: management of women with endometriosis. Hum Reprod 29:400–412 DiVasta AD, Feldman HA, Sadler Gallagher J et al (2015) Hormonal add-back therapy for females treated with gonadotropin-releasing hormone agonist for endometriosis: a randomized controlled trial. Obstet Gynecol 126:617–627 Momoeda M, Harada T, Terakawa N et al (2009) Long-term use of dienogest for the treatment of endometriosis. J Obstet Gynaecol Res 35:1069 Klipping C, Duijkers I, Remmers A et al (2012) Ovulation-inhibiting effects of dienogest in a randomized, dose-controlled pharmacodynamic trial of healthy women. J Clin Pharmacol 52:1704–1713 Strowitzki T, Faustmann T, Gerlinger C, Schumacher U, Ahlers C, Seitz C (2015) Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program. Int J Womens Health 7:393–401 Surrey ES, Judd HL (1992) Reduction of vasomotor symptoms and bone mineral density loss with combined norethindrone and long-acting gonadotropin-releasing hormone agonist therapy of symptomatic endometriosis: a prospective randomized trial. J Clin Endocrinol Metab 75:558–563 Matsuo H (2004) Prediction of the change in bone mineral density induced by gonadotropin-releasing hormone agonist treatment for endometriosis. Fertil Steril 81:149–153 Surrey ES, Hornstein MD (2002) Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up. Obstet Gynecol 99:709–719 Fernandez H, Lucas C, Hédon B, Meyer JL, Mayenga JM, Roux C (2004) One year comparison between two add-back therapies in patients treated with a GnRH agonist for symptomatic endometriosis: a randomized double-blind trial. Hum Reprod 19:1465–1471 Chu I, Arnaout A, Loiseau S et al (2007) Formation of ethinyl estradiol in women during treatment with norethindrone acetate. J Clin Endocrinol Metab 92:2205–2207 Onobrakpeya OA, Fall PM, Willard A, Chakravarthi P, Hansen A, Raisz LG (2001) Effect of norethindrone acetate on hormone levels and markers of bone turnover in estrogen-treated postmenopausal women. Endocr Res 27:473–480 Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest DYL declares that he has no conflict of interest. JYL declares that she has no conflict of interest. JWS declares that he has no conflict of interest. BKY declares that he has no conflict of interest. DC declares that he has no conflict of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in this study. Additional information D.-Y. Lee and J.-Y. Lee contributed equally to this work. Rights and permissions About this article Cite this article Lee, DY., Lee, JY., Seo, JW. et al. Gonadotropin-releasing hormone agonist with add–back treatment is as effective and tolerable as dienogest in preventing pain recurrence after laparoscopic surgery for endometriosis. Arch Gynecol Obstet 294, 1257–1263 (2016). https://doi.org/10.1007/s00404-016-4184-9 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-016-4184-9