Medikamentöse Therapie der Endometriose

Zusammenfassung Die medikamentöse Therapie der Endometriose verfolgt einen symptomatischen Ansatz, ist nicht kausal und kann die natürliche Fertilität nicht beeinflussen. Die Durchführung einer hormonellen medikamentösen Therapie verhindert das gleichzeitige Erfüllen eines Kinderwunsches. Bei einer Therapiedauer von 6 Monaten sind die hormonellen Therapieoptionen bezüglich der Schmerzreduktion gleichwertig. Die Auswahl der Behandlungsform und der Dauer sollten symptomorientiert erfolgen, nicht in Abhängigkeit von der Ausdehnung der Erkrankung. Aufgrund des Nebenwirkungsprofils ist als First-line-Therapie orale Kontrazeptiva (OC)oder Gestagenen zu empfehlen, GnrH-Analoga in der Second-line-Therapie. Bei fehlendem Kinderwunsch kann mit C und Gestagenen ggf. auch eine Dauertherapie unter Beachtung des Nebenwirkungsprofils erfolgen. Am besten sollten OC und Gestagene im Langzyklus eingesetzt werden. Dabei kann eine gute Wirkung insbesondere auf die Dysmenorrhö, allerdings nur eine mäßige Wirkung auf andere typische Beschwerden erwartet werden. GnRH-Analoga sollten im Add-back-Verfahren eingesetzt werden und sind eine sinnvolle Alternative nach histologischer Sicherung der Erkrankung und bei fehlender Wirksamkeit von OC und Gestagenen. Ist eine assistierte Reproduktion geplant, sollte ggf. das Ultralangprotokoll mit GnRH-Analoga-Stimulation erwogen werden. Andere Substanzklassen sind spezifischen Indikationen vorbehalten und haben keinen Stellenwert in der Routinetherapie. Abstract Medical treatment of endometriosis is strictly symptomatic and not etiological. Natural fertility is not influenced by it. Simultaneous hormonal medical treatment and reproduction are not possible. Over a 6-month treatment period, the different hormonal treatment options are equally effective in reducing pain. The choice of a medical treatment option and its duration should be made on the basis of symptom control and not on the extent of the disease. Because of its advantageous side effect profile, oral contraceptives (OC) or progestogens should be used as first-line therapy. Gonadotropin-releasing hormone (GnRH) analogs are a second-line therapeutic option. If there is no wish for pregnancy, OC and progestogens can be used as permanent therapy depending on their side effects. OC and progestogens should be used as long cycle therapy. Dysmenorrhea is reduced very effectively, whereas other typical complaints are not equally reduced. GnRH analogs should be used with add-back regimens. They constitute a sensible choice after histological proof of endometriosis and in case OC and progestogens have been ineffective. If assisted reproduction is planned, an ultralong GnRH analog protocol can be considered. Other substances are reserved for special indications and are not an integral part of routine treatment. Literatur Vercellini P, Fedele L, Aimi G et al (2006) Reproductive performance, pain recurrence and disease relapse after conservative surgical treatment for endometriosis: the predictive value of the current system. Hum Reprod 21:2679–2685 Sallam HN, Garcia-Velasco JA, Dias S et al (2006) Long-term pituitary down regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev 1:CD004635 Vercellini P, Cortesi I, Crosigniani PG (1997) Progestins for symptomatic endometriosis: a critical analysis of the evidence. Fertil Steril 68:393–401 Allen C, Hopewell S, Prentice A (2005) Non-steroidal anti-inflammatory drugs for pain in women with endometriosis. Cochrane Database Syst Rev 19(4):CD004753 Vercellini P, Somigliana E, Viganò P et al (2008) Endometriosis: current and future medical therapies. Best Pract Res Clin Obstet Gynecol 22:275–306 Davis L, Kennedy S, Moore J et al (2007) Modern combined oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev 3:CD001019 Prentice A, Deary A, Goldbeck-Wood S et al (2007) Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev 3:CD000346 Selak V, Farquhar C, Prentice A et al (2001) Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev 4:CD000068 Rotondi M, Labriola D, Rotondi M et al (2002) Depot leuprorelin acetate versus danazol in the treatment of infertile women with symptomatic endometriosis. Eur J Gynecol Oncol 23:523–526 Cobellis L, Razzi S, Fava A et al (2004) A danazol-loaded intrauterine device decreases dysmenorrheal, pelvic pain, and dyspareunia associated with endometriosis. Fertil Steril 82:239–240 Waller KG, Shaw RW (1993) Gonadotropin-releasing hormone analogues for the treatment of endometriosis: long-term follow-up. Fertil Steril 59:511–515 Bedaiwy M, Casper R (2006) Treatment with leuprolide acetate and hormonal add-back for up to 10 years in stage IV endometriosis patients with chronic pelvic pain. Fertil Steril 86:220–222 Crosigniani P, Olive D, Bergqvist A et al (2006) Advances in the management of endometriosis: an update for clinicians. Hum Reprod Update 12:179–189 Bedaiwy M, Casper R (2006) Treatment with leuprolide acetate and hormonal add-back for up to 10 years in stage IV endometriosis patients with chronic pelvic pain. Fertil Steril 86:220–222 Barbieri RL (1992) Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obstet Gynecol 166:740–745 Hornstein MD, Yuzpe AA, Burry KA et al (1995) Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain. Fertil Steril 63(5):955–962 Vercellini P, Somigliana E, Viganò P et al (2009) Endometriosis: current therapies and new pharmacological developments. Drugs 69(6):649–675 Harada T, Momoeda M, Taketani Y et al (2008) Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind randomized trial. Fertil Steril 90:1583–1588 Seracchioli R, Mabrouk M, Frascà C et al (2010) Long-term oral contraceptive pills and postoperative pain management after laparoscopic excision of ovarian endometrioma: a randomized controlled trial. Fertil Steril 94(2):464–471 Bergqvist A, Theorell T (2001) Changes in quality of life after hormonal treatment of endometriosis. Acta Obstet Gynecol Scand 80:628–637 Strowitzki T, Marr J, Gerlinger C et al (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(3):633–641 Köhler G, Faustmann TA, Gerlinger C et al (2010) A dose ranging study to determine the efficacy and safety of 1, 2 and 4 mg of dienogest daily for endometriosis. Int J Gynaecol Obstet 108(1):21–25 Schindler AE, Henkel A, Moore C et al (2009) Effect and safety of high dose dienogest (20 mg/day) in the treatment of women with endometriosis. Arch Gynecol Obstet Muneyyirci-Delale O, Karacan M (1998) Effect of norethindrone acetate in the treatment of symptomatic endometriosis. Int J Fertil Womens Med 43:24–27 Riis BJ, Lehmann HJ, Christiansen C (2002) Norethisterone acetate in combination with estrogen: effects on the skeleton and other organs: a review. Am J Obstet Gynecol 187:1101–1106 Vercellini (2002) Fertil Steril Lockhat FB, Emembolu JO, Konje JC (2004) The evaluation oft he effectiveness of an intrauterine-administered progestogen (levonorgestrel) in the symptomatic treatment of endometriosis and in the staging of the disease. Hum Reprod 19:179–184 Petta CA, ferriani RA, Abrao MS et al (2005) Randomized clinical trial of a levonorgestrel releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod 20:1993–1998 Lockhat FB, Emembolu JO, Konje JC (2005) The efficacy, side-effects and continuation rates in women with symptomatic endometriosis undergoing treatment with an intrauterine administered progestogen (levonorgestrel): a 3 year follow-up. Hum Reprod 20:789–793 Vercellini P, Viganò P, Somigliana E (2005) The role of the levonorgestrel-releasing intrauterine device in the management of symptomatic endometriosis. Curr Opin Obstet Gynecol 17:359–365 Crosigniani P, Luciano A, Ray A et al (2006) Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Hum Reprod 21:248–256 Fedele L, Bianchi S, Raffaeli R et al (1999) Comparison of transdermal estradiol and tibolone for the treatment of oophorectomized women with deep residual endometriosis. Maturitas 32:189–193 Lindsay PC, Shaw RW, Bennink HJ et al (1996) The effect of add-back treatment with tibolone (Livial) on patients treated with the gonadotropin-releasing hormone agonist triptorelin (Decapeptyl). Fertil Steril 65:342–348 Kupker W, Felberbaum RE, Krapp M et al (2002) Use of GnRH antagonists in the treatment of endometriosis. Reprod Biomed Online 5:12–16 Seli E, Berkkanoglu M, Arici A (2003) Pathogenesis of endometriosis. Obstet Gynecol Clin N Am 30:41–61 Ailawadi RK, Jobanputra S, Kataria M et al (2004) Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril 81:290–296 Amsterdam LL, Gentry W, Jobanputra S et al (2005) Anastrozole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril 84:300–304 Soysal S, Soysal ME, Ozer S et al (2004) The effects of postsurgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod 19:160–167 Matsuzaki S, Canis M, Pouly JL et al (2004) Cyclooxygenase-2 expression in deep endometriosis and matched eutopic endometrium. Fertil Steril 82:1309–1315 Barrier BF, Bates GW, Leland MM et al (2004) Efficacy of anti-tumor necrosis factor therapy in the treatment of spontaneous endometriosis in baboons. Fertil Steril 81 (suppl 1):775–779 Koninckx PR, Craessaerts M, Timmerman D et al (2008) Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod 23:2017–2023 Donnez J, Smoes P, Gillerot S et al (1998) Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod 13:1686–1690 Becker CM, Sampson DA, Rupnick MA et al (2005) Endostatin inhibits the growth of endometriotic lesions but does not affect fertility. Fertil Steril 84 (suppl 2):1144–1155 Chwalisz K, Perez MC, Demanno D et al (2005) Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev 26:423–438 Chwalisz K, Mattia-Goldberg C, Lee M et al (2004) Treatment of endometriosis with the novel selective progesterone receptor modulator (SPRM) Asoprisnil. Fertil Steril 82:S83–S84 Vercellini P, Somigliana E, Daguati R et al (2008) Postoperative oral contraceptive exposure and risk of endometrioma recurrence. Am J Obstet Gynecol 198:504e1–e5 Viganò P, Somigliana E, Parazzini F et al (2007) Bias versus causality: interpreting recent evidence of association between endometriosis and ovarian cancer. Fertil Steril 88:588–593 Modugno F, Ness RB, Allen GO et al (2004) Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis. Am J Obstet Gynecol 191:733–740 Vercellini P, Pietropaolo G, De Giorgio O et al (2005) Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate. Fertil Steril 84:1375–1387 Audebert A, Descamps P, Marret H et al (1998) Pre- or post-operative medical treatment with nafarelin in stage III-IV endometriosis: a French multicenter study. Eur J Obstet Gynecol Reprod Biol 79(2):145–148 Yap C, Furness S, Farquhar C (2004) Pre and postoperative medical therapy for endometriosis surgery. Cochrane Database Syst Rev 3:CD003678 Soliman NF, Evans AJ (2004) Malignancy arising in residual endometriosis following hysterectomy and hormone replacement therapy. J Br Menopause Soc 10:123–124 Somigliana E, Viganò P, Parazzini F et al (2006) Association between endometriosis and cancer: a comprehensive review and a critical analysis of clinical and epidemiological evidence. Gynecol Oncol 101:331–341 Oxholm D, Knudsen UB, Kryger-Baggesen N et al (2007) Postmenopausal endometriosis. Acta Obstet Gynecol Scand 4:1–7 Einhaltung ethischer Richtlinien Interessenkonflikt. Keine Angaben Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Schäfer, S. Medikamentöse Therapie der Endometriose. Gynäkologe 46, 739–750 (2013). https://doi.org/10.1007/s00129-013-3218-7 Published: Issue date: DOI: https://doi.org/10.1007/s00129-013-3218-7