Pelvic Pain and Quality of Life of Women With Endometriosis During Quadriphasic Estradiol Valerate/Dienogest Oral Contraceptive: A Patient-Preference Prospective 24-Week Pilot Study

Objective The progestin dienogest (DNG) given alone effectively reduces pelvic pain of women with endometriosis. It is not clear whether the same occurs when DNG is associated with estradiol (E2). Design Patient preference prospective observational study. Setting Outpatient centre of university hospital. Patients 40 patients with endometriosis and menstrual pain. Interventions 24-week treatment with a quadriphasic association of E2 valerate (E2V) and DNG or a nonsteroidal anti-inflammatory drug (NSAID) to be used only in case of pain (ketoprofene 200-mg tablets). Main Outcome Measures Menstrual pain and, when present, intermenstrual pain, and dyspareunia were investigated by means of a 10-cm visual analogue scale (VAS). Quality of life was investigated by the short form 36 (SF-36) of the health-related quality of life questionnaire.

Final study group consists of 34 patients, 19 in the E2V/DNG group and 15 in the NSAID group. After 24 weeks, no significant modification of menstrual pain, intermenstrual pain, dyspareunia, or SF-36 score was observed in the NSAID group. Treatment with E2V/DNG reduced the VAS score of menstrual pain by 61% (P < .0001). In the subgroups of women with intermenstrual pain or dyspareunia, E2V/DNG reduced these complaints by 65% (P = .013) and 52% (P = .016), respectively. The reduction in menstrual (P = .0001) and intermenstrual pain (p = 0.03) was significantly greater during E2V/DNG than NSAID. Quality of life improved during E2V/DNG (P = .0002), both in physical (P = .0003) and mental domains (P = .0065). Only a few minor adverse effects were described during E2V/DNG, and none caused withdrawal from treatment.

In patients with endometriosis and pelvic pain, the 24-week administration of the quadriphasic association of E2V/DNG decreases pelvic pain and improves quality of life. Similar content being viewed by others

Sinaii N, Cleary SD, Younes N, Ballweg ML, Stratton P. Treatment utilization for endometriosis symptoms: a cross-sectional survey study of lifetime experience. Fertil Steril. 2007;87(6): 1277–1286. Viganò P, Parazzini F, Somigliana E, Vercellini P. Endometriosis: epidemiology and aetiological factors. Best Pract Res Clin Obstet Gynecol. 2004;18(2):177–200. Nnoaham KE, Hummelshoj L, Webster P, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011;96(2):366–373. Vercellini P, Crosignani P, Somigliana E, Viganò P, Frattaruolo MP, Fedele L. ‘Waiting for Godot’: a commonsense approach to the medical treatment of endometriosis. Hum Reprod. 2011; 26(1):3–13. Practice Committee of American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis. Fertil Steril. 2008;90(5 suppl):S260–S269. Johnson NP, Hummelshoj L; World Endometriosis Society Montpellier Consortium. Consensus on current management of endometriosis. Hum Reprod. 2013;28(6): 1552–1568. Harada T, Momoeda M, Taketani Y, Hoshiai H, Terakawa N. Low-oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. Fertil Steril. 2008;90(5):1583–1588. Strowitzki T, Faustmann T, Gerlinger C, Seitz C. 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. Strowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, open-label trial. Hum Reprod. 2010;25(3):633–641. Harada T, Momoeda M, Taketani Y, 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):675–681. 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. 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(3):228–233. Shimizu Y, Takeuchi T, Mita S, et al. Dienogest, a synthetic progestin, inhibits the proliferation of immortalized human endometrial epithelial cells with suppression of cyclin D1 gene expression. Mol Hum Reprod. 2009;15(10):693–701. Yamanaka K, Xu B, Suganuma I, et al. Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E2 production in human endometriotic stromal cells in spheroid culture. Fertil Steril. 2012;97(2):477–482. Katayama H, Katayama T, Uematsu K, et al. Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model. Hum Reprod. 2010;25(11): 2851–2858. Momoeda M, Harada T, Terakawa N, et al. Long-term use of dienogest for the treatment of endometriosis. J Obstet Gynecol Res. 2009;35(6):1069–1076. World Health Organization (WHO). Medical Eligibility Criteria for Contraceptive Use. Fourth Edition. Geneva, Switzerland: WHO; 2009. Streuli I, de Ziegler D, Santulli P, et al. An update on the pharmacological management of endometriosis. Expert Opin Pharmacother. 2013;14(3):291–305. Grandi G, Xholli A, Ferrari S, Cannoletta M, Volpe A, Cagnacci A. Intermenstrual pelvic pain, quality of life and mood. Gynecol Obstet Invest. 2013;75(2):97–100. Ware JE Jr, Sherbourne CD, The MOS 36-item short-form health survey (SF-36). Conceptual framework and item selection. Med Care. 1992;30(6):473–483. Allen C, Hopewell S, Prentice A, Gregory D. Nonsteroidal antiinflammatory drugs for pain in women with endometriosis. Cochrane Database Syst Rev. 2009;15:CD004753. Vercellini P, Barbara G, Somigliana E, Bainchi S, Abbiati A, Fedele L. Comparison of contraceptive ring and patch for the treatment of symptomatic endometriosis. Fertil Steril. 2010; 93(7):2150–2161. Seracchioli R, Mabrouk M, Frascà C, Manuzzi L, Savelli L, Venturoli S. Long-term oral contraceptive pills and postoperative pain management after laparoscopic excision of ovarian endometrioma: a randomized controlled trial. Fertil Steril. 2010;94(2): 464–471. Vercellini P, Pietropaolo G, De Giorgi O, Pasin R, Chiodini A, Crosignani PG. Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate. Fertil Steril. 2005;84(5):1375–1387. Mabrouk M, Frascà C, Geraci E, et al. Combined oral contraceptive therapy in women with posterior deep infiltrating endometriosis. J Minim Invasiv Gynecol. 2011;18(4):470–474 Vercellini P, Trespidi L, Colombo A, Vendola N, Marchini M, Crosignani PG. A gonadotrophin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Fertil Steril. 1993;60(1):75–79. Leone Roberti Maggiore U, Remorgida V, Scala C, Tafi E, Venturini PL, Ferrero S. Desogestrel-only contraceptive pill versus sequential contraceptive vaginal ring in the treatment of rectovaginal endometriosis infiltrating the rectum: a prospective open-label comparative study. Acta Obstet Gynecol Scand. 2013;93(3): 239–247. Mabrouk M, Solfrini S, Frascà C, et al. A new oral contraceptive regimen for endometriosis management: preliminary experience with 24/4-day drospirenone/ethinylestradiol 3 mg/20 mcg. Gynecol Endocrinol. 2012;28(6):451–455. Razzi S, Luisi S, Ferretti C, et al. Use of a progestogen only preparation containing desogestrel in the treatment of recurrent pelvic pain after conservative surgery for endometriosis. Eur J Obstet Gynecol Reprod Biol. 2007;135(2):188–190. Guzick DS, Huang LS, Broadman BA, Nealon M, Hornstein MD. Randomized trial of leuprolide versus continuous oral contraceptives in the treatment of endometriosis-associated pelvic pain. Fertil Steril. 2011;95(5):1568–1573. Morelli M, Sacchinelli A, Venturella R, Mocciaro R, Zullo F. Postoperative administration of dienogest plus estradiol valerate versus levonorgestrel-releasing intrauterine device for prevention of pain relapse and disease recurrence in endometriosis patients. J Obstet Gynecol Res. 2013;39(5):985–990. Endrikat J, Parke S, Trummer D, Serrani M, Duijkers I, Klipping C. Pituitary, ovarian and additional contraceptive benefits of an estradiol-based combined oral contraceptive: results of a randomized, open-label, study. Contraception. 2013;87(2): 227–234. Macìas G, Merki-Feld GS, Parke S, Mellinger U, Serrani M. Effects of a combined oral contraceptive containing oestradiol valerate/dienogest on hormone withdrawal-associated symptoms: results from the multicentre, randomized, double-blind, activecontrolled HARMONY II study. J Obstet Gynecol. 2013;33(6): 591–596. Caruso S, Agnello C, Romano M. Preliminary study on the effect of four-phasic estradiol valerate and dienogest (E2V/DNG) oral contraceptive on the quality of sexual life. J Sex Med. 2011; 8(10):2841–2850. Grandi G, Piacenti I, Volpe A, Cagnacci A. Modification of body composition and metabolism during oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl-estradiol. Gynecol Endocrinol. 2014;30(9):676–680. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Grandi, G., Xholli, A., Napolitano, A. et al. Pelvic Pain and Quality of Life of Women With Endometriosis During Quadriphasic Estradiol Valerate/Dienogest Oral Contraceptive: A Patient-Preference Prospective 24-Week Pilot Study. Reprod. Sci. 22, 626–632 (2015). https://doi.org/10.1177/1933719114556488 Published: Issue date: DOI: https://doi.org/10.1177/1933719114556488