{"paper_id":"3c1c866a-944a-4520-988b-68ab0b482878","body_text":"Abstract\nEndometriosis is a chronic inflammatory condition that is responsive to management with steroids. The establishment of a steady hormonal environment and inhibition of ovulation can temporarily suppress ectopic implants and reduce inflammation as well as associated pain symptoms. In terms of pharmacological management, the currently available agents are not curative, and treatment often needs to be continued for years or until pregnancy is desired. Similar efficacy has been observed from the various therapies that have been investigated for endometriosis. Accordingly, combined oral contraceptives and progestins, based on their favourable safety profile, tolerability and cost, should be considered as first-line options, as an alternative to surgery and for post-operative adjuvant use. In situations where progestins and oral contraceptives prove ineffective, are poorly tolerated or are contraindicated, gonadotrophin-releasing hormone analogues, danazol or gestrinone may be used. Future therapeutic options for managing endometriosis must compare favourably against existing agents before they can be considered for inclusion into current practice. Finally, as reproductive prognosis is not ameliorated by medical treatment, it is not indicated for women seeking conception.\nSimilar content being viewed by others\nReferences\nVercellini P, Fedele L, Aimi G, et al. Reproductive performance, pain recurrence and disease relapse after conservative surgical treatment for endometriosis: the predictive value of the current system. Hum Reprod 2006; 21: 2679–85\nVercellini P, Fedele L, Pietropaolo G, et al. Progestogens for endometriosis: forward to the past. Hum Reprod Up 2003; 9: 387–96\nThe American College of Obstetricians and Gynecologists. Medical management of endometriosis: number 11, December 1999. Int J Gynaecol Obstet 2000; 71: 183–96\nPractice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility. Fertil Steril 2006; 86: S156–60\nKennedy S, Bergqvist A, Chapron C, et al. ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Development Group. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005; 20: 2698–704\nTelimaa S, Puolakka J, Ronnberg L, et al. Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery. Gynecol Endocrinol 1987; 1: 13–23\nDlugi AM, Miller JD, Knittle J. Lupron depot (leuprolide acetate) for depot suspension in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Fertil Steril 1990; 54: 419–27\nFedele L, Bianche S, Bocciolone L, et al. Buserelin acetate in the treatment of pelvic pain associated with minimal and mild endometriosis: a controlled study. Fertil Steril 1993; 59: 516–21\nBergqvist A, Bergh T, Hogstöm L, et al. Effects of triptorelin versus placebo on the symptoms of endometriosis. Fertil Steril 1998; 69: 702–8\nVercellini P, Somigliana E, Viganò P, et al. Endometriosis: current and future medical therapies. Best Pract Res Clin Obstet Gynaecol 2008; 22: 275–306\nPrentice A. Endometriosis. BMJ 2001; 323: 93–5\nVercellini P, Cortesi I, Crosignani PG. Progestins for symptomatic endometriosis: a critical analysis of the evidence. Fertil Steril 1997; 68: 393–401\nVercellini P, Trespidi L, Colombo A, et al. A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Fertil Steril 1993; 60: 75–9\nParazzini F, Di Cintio E, Chatenoud L, et al. Estroprogestin vs. gonadotropin agonists plus estroprogestin in the treatment of endometriosis-related pelvic pain: a randomized trial. Eur J Obstet Gynecol Reprod Biol 2000; 88: 11–4\nHarada T, Momoeda M, Taketani Y, et al. Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. Fertil Steril 2008; 90: 1583–8\nSulak PJ, Cressman BE, Waldrop E, et al. Extending the duration of active oral contraceptive pills to manage hormone withdrawal symptoms. Obstet Gynecol 1997; 89: 179–83\nSulak P, Thomas J, Ortiz M, et al. Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms. Am J Obstet Gynecol 2002; 186: 1142–9\nCoffee AL, Sulak PJ, Kuehl TJ. Long-term assessment of symptomatology and satisfaction of an extended oral contraceptive regimen. Contraception 2007; 75: 444–9\nDuleba AJ, Keltz MD, Olive DL. Evaluation and management of chronic pelvic pain. J Am Assoc Gynecl Laparosc 1996; 3: 205–27\nVercellini P, Frontino G, De Giorgi O, et al. Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhoea that does not respond to a cyclic pill regimen. Fertil Steril 2003; 80: 560–3\nMuneyyirci-Delale O, Karacan M. Effect of norethindrone acetate in the treatment of symptomatic endometriosis. Int J Fertil Womens Med 1998; 43: 24–7\nMoore C, Kohler G, Muller A. The treatment of endometriosis with dienogest. Drugs Today 1999; 35 Suppl. C: 41–52\nRiis BJ, Lehmann HJ, Christiansen C. Norethisterone acetate in combination with estrogen: effects on the skeleton and other organs: a review. Am J Obstet Gynecol 2002; 187: 1101–6\nChu MC, Zhang X, Gentzschein E, et al. Formation of ethinyl estradiol in women during treatment with norethindrone acetate. J Clin Endocrinol Metab 2007; 92: 2205–7\nBeksinska ME, Kleinschmidt I, Smit JA, et al. Bone mineral density in adolescents using norethisterone enanthate, depot-medroxyprogesterone acetate or combined oral contraceptives for contraception. Contraception 2007; 75: 438–43\nBeksinska ME, Smit JA, Kleinschmidt I, et al. Bone mineral density in women aged 40–49 years using depot-medroxyprogesterone acetate, norethisterone enanthate or combined oral contraceptives for contraception. Contraception 2005; 71: 170–5\nFedele L, Arcaini L, Bianchi S, et al. Comparison of cyproterone acetate and danazol in the treatment of pelvic pain associated with endometriosis. Obstet Gynecol 1989; 73: 1000–4\nMoran C, Alcivia JC, Garcia-Hernandez E, et al. Treatment of endometriosis with cyproterone acetate: preliminary report. Arch Med Res 1996; 27: 535–8\nVercellini P, De Giorgi O, Mosconi P, et al. Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis. Fertil Steril 2002; 77: 52–61\nHarrison RF, Barry-Kinsella C. Efficacy of medroxyprogesterone treatment in infertile women with endometriosis: a prospective, randomized, placebo-controlled study. Fertil Steril 2000; 74: 24–30\nThe American Fertility Society. Revised American Fertility Society classification of endometriosis: 1985. Fertil Steril 1985; 43: 351–2\nBergqvist A, Theorell T. Changes in quality of life after hormonal treatment of endometriosis. Acta Obstet Gynecol Scand 2001; 80: 628–37\nKaunitz AM. Long-acting injectable contraception with depot medroxyprogesterone acetate. Am J Obstet Gynecol 1994; 170: 1543–9\nSkegg DCG, Noonan EA, Paul C, et al. Depot medroxyprogesterone acetate and breast cancer: a pooled analysis of the World Health Organization and New Zealand Studies. JAMA 1995; 273: 799–804\nCundy T, Evans M, Roberts H, et al. Bone density in women receiving depot medroxyprogesterone acetate for contraception. BMJ 1991; 303: 13–6\nScholes D, LaCroix AZ, Ichikawa LE, et al. Injectable hormone contraception and bone density: results from a prospective study. Epidemiology 2002; 13: 581–7\nClark MK, Sowers MR, Nichols S, et al. Bone mineral density changes over two years in first-time users of depot medroxyprogesterone acetate. Fertil Steril 2004; 82: 1580–6\nShaarawy M, El-Mallah SY, Seoudi S, et al. Effect of long-term use of depot medroxyprogesterone acetate as hormonal contraceptive on bone mineral density and biochemical markers of bone remodeling. Contraception 2006; 74: 297–302\nCundy T, Cornish J, Roberts H, et al. Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception. Am J Obstet Gynecol 2002; 186: 978–83\nCundy T, Cornish J, Evans MC, et al. Recovery of bone density in women who stop using medroxyprogesterone acetate. BMJ 1994; 308: 247–8\nOrr-Walker BJ, Evans MC, Ames RW, et al. The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post-menopausal women. Clin Endocrinol (Oxf) 1998; 49: 615–8\nCrosignani PG, Luciano A, Ray A, et al. Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Hum Reprod 2006; 21: 248–56\nVercellini P, De Giorgi O, Oldani S, et al. Depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol for long-term treatment of pelvic pain associated with endometriosis. Am J Obstet Gynecol 1996; 175: 396–401\nSchlaff WD, Carson SA, Luciano A, et al. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosisassociated pain. Fertil Steril 2006; 85: 314–25\nSalmi A, Pakarinen P, Peltola AM, et al. The effect of intrauterine levonorgestrel use on the expression of C-Jun, oestrogen receptors, progesterone receptors and Ki-67 in human endometrium. Mol Hum Reprod 1998; 4: 1110–5\nLockhat FB, Emembolu JO, Konje JC. The evaluation of the effectiveness of an intrauterine-administered progestogen (levonorgestrel) in the symptomatic treatment of endometriosis and in the staging of the disease. Hum Reprod 2004; 19: 179–84\nHigham JM, O’Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol 1990; 97: 734–9\nLockhat FB, Emembolu JO, Konje JC. The efficacy, side-effects and continuation rates in women with symptomatic endometriosis undergoing treatment with an intra-uterine administered progestogen (levonorgestrel): a 3 year follow-up. Hum Reprod 2005; 20: 789–93\nPetta CA, Ferriani RA, Abrao MS, et al. 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 2005; 20: 1993–8\nVercellini P, Aimi G, Panazza S, et al. A levonorgestrelreleasing intrauterine system for the treatment of dysmenorrhea associated with endometriosis: a pilot study. Fertil Steril 1999; 72: 505–8\nVercellini P, Frontino G, De Giorgi O, et al. Comparison of a levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study. Fertil Steril 2003; 80: 305–9\nShulman LP, Nelson AL, Darney PD. Recent developments in hormone delivery system. Am J Obstet Gynecol 2004; 190: S39–48\nJain S, Dalton ME. Chocolate cysts from ovarian follicles. Fertil Steril 1999; 72: 852–6\nVercellini P, Vigano P, Somigliana E. The role of the levonorgestrel-releasing intrauterine device in the management of symptomatic endometriosis. Curr Opin Obstet Gynecol 2005; 17: 359–65\nEwies AAA. Mirena: the other side of the story. BJOG 2007; 114: 1307–8\nFedele L, Bianchi S, Zanconato G, et al. Long-term follow-up after conservative surgery for rectovaginal endometriosis. Am J Obstet Gynecol 2004; 190: 1020–4\nFord J, English J, Miles WA, et al. Pain, quality of life and complications following the radical resection of rectovaginal endometriosis. BJOG 2004; 111: 353–6\nVercellini P, Frontino G, Pietropaolo G, et al. Deep endometriosis: definition, pathogenesis, and clinical management. J Am Assoc Gynecol Laparosc 2004; 11: 127–36\nFedele L, Bianchi S, Zanconato G, et al. Use of a levonorgestrel-releasing intrauterine device in the treatment of rectovaginal endometriosis. Fertil Steril 2001; 75: 485–8\nVercellini P, Pietropaolo G, De Giorgi O, et al. Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate. Fertil Steril 2005; 84: 1375–87\nRemorgida V, Abbamonte HL. Letrozole and norethisterone acetate in rectovaginal endometriosis. Fertil Steril 2007; 88: 724–6\nKikuchi I, Takeuchi H, Shimanuki H, et al. Recurrence rate of endometriomas following laparoscopic cystectomy. Acta Obstet Gynecol Scand 2006; 85: 1120–4\nKoga K, Takemura Y, Osuga Y, et al. Recurrence of ovarian endometrioma after laparoscopic excision. Hum Reprod 2006; 21: 2171–4\nLiu X, Yuan L, Shen F, et al. Patterns of and risk factors for recurrence in women with ovarian endometriomas. Am J Obstet Gynecol 2007; 109: 1411–20\nBusacca M, Chiaffarino F, Candiani M, et al. Determinants of long term clinically detected recurrence rates of deep, ovarian, and pelvic endometriosis. Am J Obstet Gynecol 2006; 195: 426–32\nVercellini P, Somigliana E, Daguati R, et al. Postoperative oral contraceptive exposure and risk of endometrioma recurrence. Am J Obstet Gynecol 2008; 198: 504e1-5\nMissmer SA, Hankinson SE, Spiegelman D, et al. Reproductive history and endometriosis among premenopausal women. Obstet Gynecol 2004; 104: 965–74\nNess RB. Endometriosis and ovarian cancer: thoughts on shared pathophysiology. Am J Obstet Gynecol 2003; 189: 280–94\nVigano P, Somigliana E, Chiodo I, et al. Molecular mechanisms and biological plausibility underlying the malignant transformation of endometriosis: a critical analysis. Hum Reprod Update 2006; 12: 77–89\nSomigliana E, Vigano P, Parazzini F, et al. Association between endometriosis and cancer: a comprehensive review and a critical analysis of clinical and epidemiological evidence. Gynecol Oncol 2006; 101: 331–41\nVigano P, Somigliana E, Parazzini F, et al. Bias versus causality: interpreting recent evidence of association between endometriosis and ovarian cancer. Fertil Steril 2007; 88: 588–93\nModugno F, Ness RB, Allen GO, et al. Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis. Am J Obstet Gynecol 2004; 191: 733–40\nSoliman NF, Hillard TC. Hormone replacement therapy in women with past history of endometriosis. Climacteric 2006; 9: 325–35\nReimnitz C, Brand E, Nieberg RK, et al. Malignancy arising in endometriosis associated with unopposed estrogen replacement. Obstet Gynecol 1988; 71: 444–7\nLavery S, Gillmer M. Malignant transformation of residual endometriosis in women on unopposed oestrogen hormone replacement therapy. BJOG 2001; 108: 1106–7\nSoliman NF, Evans AJ. Malignancy arising in residual endometriosis following hysterectomy and hormone replacement therapy. J Br Menopause Soc 2004; 10: 123–4\nGücer F, Pieber D, Arikan MG. Malignancy arising in extraovarian endometriosis during estrogen stimulation. Eur J Gynaecol Oncol 1998; 19: 39–41\nZanetta GM, Webb MJ, Li H, et al. Hyperestrogenism: a relevant risk factor for the development of cancer from endometriosis. Gynecol Oncol 2000; 79: 18–22\nJones KD, Owen E, Berresford A, et al. Endometrial adenocarcinoma arising from endometriosis of the rectosigmoid colon. Gynecol Oncol 2002; 86: 220–2\nOxholm D, Knudsen UB, Kryger-Baggesen N, et al. Postmenopausal endometriosis. Acta Obstet Gynecol Scand 2007; 4: 1–7\nHaney AF, Wild RA. Options for hormone therapy in women who have had a hysterectomy. Menopause 2007; 14: 592–7\nFedele L, Bianchi S, Raffaelli R, et al. Comparison of transdermal estradiol and tibolone for the treatment of oophorectomized women with deep residual endometriosis. Maturitas 1999; 32: 189–93\nLindsay PC, Shaw RW, Bennink HJ, et al. The effect of add-back treatment with tibolone (Livial) on patients treated with the gonadotropin-releasing hormone agonist triptorelin (Decapeptyl). Fertil Steril 1996; 65: 342–8\nJanssens RM, Brus L, Cahill DJ, et al. Direct ovarian effects and safety aspects of GnRH agonists and antagonists. Hum Reprod Update 2000; 6: 505–18\nGuillemin R. Hypothalamic hormones a.k.a. hypothalamic releasing factors. J Endocrinol 2005; 184: 11–28\nHuirne JA, Lambalk CB. Gonadotropin-releasinghormone-receptor antagonists. Lancet 2001; 358:1793–803\nOlive D. Optimizing gonadotropin-releasing hormone agonist therapy in women with endometriosis. Treat Endocrinol 2004; 3: 83–9\nBatzer FR. GnRH analogs: options for endometriosisassociated pain treatment. J Minim Invasive Gynecol 2006; 13: 539–45\nDavis L, Kennedy S, Moore J, et al. Modern combined oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev 2007; 3: CD001019\nPrentice A, Deary A, Goldbeck-Wood S, et al. Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev 2007; 3: CD000346\nPickersgill A. GnRH agonists and add-back therapy: is there a perfect combination? Br J Obstet Gynaecol 1998; 105: 475–85\nBedaiwy M, Casper R. Treatment with leuprolide acetate and hormonal add-back for up to 10 years in stage IV endometriosis patients with chronic pelvic pain. Fertil Steril 2006; 86: 220–2\nWaller KG, Shaw RW. Gonadotropin-releasing hormone analogues for the treatment of endometriosis: long-term follow-up. Fertil Steril 1993; 59: 511–5\nBarbieri RL. Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obstet Gynecol 1992; 166: 740–5\nCasper R. Estrogen with interrupted progestin HRT: a review of experimental and clinical studies. Maturitas 2000; 34: 97–108\nMitwally MF, Gotlieb L, Casper R. Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premestrual syndrome. Menopause 2002; 9: 236–41\nSurrey E, Hornstein M. Prolonged GnRH agonist and addback therapy for symptomatic endometriosis: long-term follow-up. Obstet Gynecol 2002; 99: 709–19\nZupi E, Marconi D, Sbracia M, et al. Add-back therapy in the treatment of endometriosis-associated pain. Fertil Steril 2004; 82: 1303–8\nSchindler AE. Gonadotropin-releasing hormone agonists for prevention of postoperative adhesions: an overview. Gynecol Endocrinol 2004; 19: 51–5\nVercellini P, Frontino G, De Giorgi O, et al. Endometriosis: preoperative and postoperative medical treatment. Obstet Gynecol Clin North Am 2003; 30: 163–80\nYap C, Furness S, Farquhar C. Pre and post operative medical therapy for endometriosis surgery. Cochrane Database Syst Rev 2004; 3: CD003678\nParazzini F, Fedele L, Busacca M, et al. Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial. Am J Obstet Gynecol 1994; 171: 1205–7\nHornstein R, Hemmings AA, Yuzpe H. Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis. Fertil Steril 1997; 68: 860–4\nVercellini P, Crosignani PG, Fadini R, et al. A gonadotrophin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis. Br J Obstet Gynecol 1999; 106: 672–7\nBusacca M, Somigliana E, Bianchi S, et al. Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III/IV: a randomized controlled trial. Hum Reprod 2001; 16: 2399–402\nCosson M, Querleu D, Donnez J, 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: 684–92\nLoverro G, Carriero C, Rossi AC, et al. A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III-IV endometriosis. Eur J Obstet Gynecol Reprod Biol 2008 Feb; 136(2): 194–8\nDicker D, Goldman GA, Ashkenazi J, et al. The value of pre-treatment with gonadotrophin releasing hormone (GnRH) analogue in IVF-ET therapy of severe endometriosis. Hum Reprod 1990; 5: 418–20\nSallam HN, Garcia-Velasco JA, Dias S, et al. Long-term pituitary down regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev 2006; 1: CD004635\nDicker D, Goldman JA, Levy T, et al. The impact of long-term gonadotropin-releasing hormone analogue treatment on preclinical abortions in patients with severe endometriosis undergoing in vitro fertilization-embryo transfer. Fertil Steril 1992; 57: 597–600\nRickes D, Nickel I, Kropf S, et al. Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis. Fertil Steril 2002; 78: 757–62\nSurrey ES, Silverberg KM, Surrey MW, et al. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertil Steril 2002; 78: 699–704\nSomigliana E, Vercellini P, Vigano P, et al. Should endometriomas be treated before IVF-ICSI cycles? Hum Reprod Update 2006; 12: 57–64\nReissmann T, Schally AV, Bouchard P, et al. The LHRH antagonist cetrorelix: a review. Hum Reprod Update 2000; 6: 322–31\nAlbano C, Platteau P, Devroey P. Gonadotropin-releasing hormone antagonist: how good is the new hope? Curr Opin Obstet Gynecol 2001; 13: 257–62\nFelberbaum RE, Kupker W, Diedrich K. Will GnRH antagonists assist in the treatment of benign gynaecological diseases? Reprod Biomed Online 2002; 5 Suppl. 1: 68–72\nArmer RE, Smelt KH. Non-peptidic GnRH receptor antagonists. Curr Med Chem 2004; 11: 3017–28\nSchultze-Mosgau A, Griesinger G, Altgassen C, et al. New developments in the use of peptide gonadotropinreleasing hormone antagonists versus agonists. Expert Opin Investig Drugs 2005; 14: 1085–97\nFinas D, Hornung D, Diedrich K, et al. Cetrorelix in the treatment of female infertility and endometriosis. Expert Opin Pharmacother 2006; 7: 2155–68\nKupker W, Felberbaum RE, Krapp M, et al. Use of GnRH antagonists in the treatment of endometriosis. Reprod Biomed Online 2002; 5: 12–6\nPabuccu R, Onalan G, Kaya C. GnRH agonist and antagonist protocols for stage I-II endometriosis and endometrioma in in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil Steril 2007; 88: 832–9\nStruthers RS, Xie Q, Sullivan SK, et al. Pharmacological characterization of a novel nonpeptide antagonist of the human gonadotropin-releasing hormone receptor, NBI-42902. Endocrinology 2007; 148: 857–67\nCrosignani P, Olive D, Bergqvist A, et al. Advances in the management of endometriosis: an update for clinicians. Hum Reprod Update 2006; 12: 179–89\nHenzl MR, Corson SL, Moghissi K, et al. Administration of nasal nafarelin as compared with oral danazol for endometriosis: a multicenter double-blind comparative clinical trial. N Engl J Med 1988; 318: 485–9\nFraser IS, Shearman RP, Jansen RP, et al. A comparative treatment trial of endometriosis using the gonadotrophinreleasing hormone agonist, nafarelin, and the synthetic steroid, danazol. Aust N Z J Obstet Gynaecol 1991; 31: 158–63\nRotondi M, Labriola D, Rotondi M, et al. Depot leuprorelin acetate versus danazol in the treatment of infertile women with symptomatic endometriosis. Eur J Gynaecol Oncol 2002; 23: 523–6\nSelak V, Farquhar C, Prentice A, et al. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev 2001; 4: CD000068\nBianchi S, Busacca M, Agnoli B, et al. Effects of 3 month therapy with danazol after laparoscopic surgery for stage III/IV endometriosis: a randomized study. Hum Reprod 1999; 14: 1335–7\nCobellis L, Razzi S, Fava A, et al. A danazol-loaded intrauterine device decreases dysmenorrhea, pelvic pain, and dispareunia associated with endometriosis. Fertil Steril 2004; 82: 239–40\nRazzi S, Luisi S, Calonaci F, et al. Efficacy of vaginal danazol treatment in women with recurrent deeply infiltrating endometriosis. Fertil Steril 2007; 88: 789–94\nSurrey ES. The role of progestins in treating the pain of endometriosis. J Minim Invasive Gynecol 2006; 13: 528–34\nFedele L, Bianchi S, Viezzoli T, et al. Gestrinone versus danazol in the treatment of endometriosis. Fertil Steril 1989; 51: 781–5\nGestrinone Italian Study Group. Gestrinone versus a gonadotropin-releasing hormone agonist for the treatment of pelvic pain associated with endometriosis: a multicenter, randomized, double-blind study. Fertil Steril 1996; 66: 911–9\nSeli E, Berkkanoglu M, Arici A. Pathogenesis of endometriosis. Obstet Gynecol Clin N Am 2003; 30: 41–61\nLake DE, Hudis C. Aromatase inhibitors in breast cancer: an update. Cancer Control 2002; 9: 490–8\nBulun SE, Zeitoun KM, Takayama K, et al. Aromatase expression in endometriosis: biology and clinical perspectives. In: Lemay A, Maheux R, editors. Understanding and managing endometriosis: advances in research and practice. Quebec City (QC): Parthenon Publishing, 1998: 139–48\nBulun SE, Zeitoun KM, Takayama K, et al. Molecular basis for treating endometriosis with aromatase inhibitors. Hum Reprod Update 2000; 6: 413–8\nMiller WR, Anderson TJ, Dixon JM. Anti-tumor effects of letrozole. Cancer Invest 2002; 20: 15–21\nViganò P, Mangioni S, Odorizzi MP, et al. Use of estrogen antagonists and aromatase inhibitors in endometriosis. Curr Opin Investig Drugs 2003 Oct; 4(10): 1209–12\nVignali M, Infantino M, Matrone R, et al. Endometriosis: novel etiopathogenetic concepts and clinical perspectives. Fertil Steril 2002; 78: 665–78\nAilawadi RK, Jobanputra S, Kataria M, et al. Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril 2004; 81: 290–6\nAmsterdam LL, Gentry W, Jobanputra S, et al. Anastrazole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril 2005; 84: 300–4\nSoysal S, Soysal ME, Ozer S, et al. The effects of postsurgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod 2004; 19: 160–7\nHo HN, Wu MY, Yang YS. Peritoneal cell immunity and endometriosis. Am J Reprod Immunol 1997; 38: 400–12\nSharpe-Timms KL. Basic research in endometriosis. Obstet Gynecol Clin Nor Am 1997; 24: 269–90\nKupker W, Schultze-Mosgau A, Diedrich K. Paracrine changes in the peritoneal environment of women with endometriosis. Hum Reprod Update 1998; 4: 719–23\nLebovic DI, Mueller M, Taylor RN. Immunobiology of endometriosis. Fertil Steril 2001; 75: 1–10\nBiron CA. Role of early cytokines, including alpha and beta interferons (IFN-alpha/beta), in innate and adaptive immune responses to viral infections. Semin Immunol 1998; 10: 383–90\nGoodman MG, Reitz AB, Chen R, et al. Selective modulation of elements of the immune system by low molecular weight nucleosides. J Pharmacol Exp Ther 1995; 274: 1552–7\nHolcombe RF, Milovanovic T, Stewart RM, et al. Investigating the role of immunomodulation for colon cancer prevention: results of an in vivo dose escalation trial of levamisole with immunologic endpoints. Cancer Detect Prev 2001;25: 183–91\nNamazi MR. Levamisole: a safe and economical weapon against pediculosis. Int J Dermatol 2001; 40: 292–3\nIngelmo JM, Quereda F, Acien P. Intraperitoneal and subcutaneous treatment of experimental endometriosis with recombinant human interferon-alpha-2b in a murine model. Fertil Steril 1999; 71: 907–11\nKeenan JA, Williams-Boyce PK, Massey PJ, et al. Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole. Fertil Steril 1999; 72: 135–41\nSomigliana E, Vigano P, Rossi G, et al. Endometrial ability to implant in ectopic sites can be prevented by interleukin12 in a murine model of endometriosis. Hum Reprod 1999; 14: 2944–50\nBadawy SZ, Etman A, Cuenca V, et al. Effect of interferon alpha-2b on endometrioma cells in vitro. Obstet Gynecol 2001; 98: 417–20\nNothnick WB. Treating endometriosis as an autoimmune disease. Fertil Steril 2001; 76: 223–31\nChishima F, Hayakawa S, Sugita K, et al. Increased expression of cyclooxygenase-2 in local lesions of endometriosis patients. Am J Reprod Immunol 2002; 48: 50–6\nMatsuzaki S, Canis M, Pouly JL, et al. Cyclooxygenase-2 expression in deep endometriosis and matched eutopic endometrium. Fertil Steril 2004; 82: 1309–15\nLev-Ari S, Lichtenberg D, Arber N. Compositions for treatment of cancer and inflammation. Recent Pat Anticancer Drug Discov 2008 Jan; 3(1): 55–62\nEfstathiou JA, Sampson DA, Levine Z, et al. Nonsteroidal antiinflammatory drugs differentially suppress endometriosis in a murine model. Fertil Steril 2005 Jan; 83(1): 171–81\nHull ML, Prentice A, Wang DY, et al. Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis. Hum Reprod 2005 Feb; 20(2): 350–8\nCobellis L, Razzi S, De Simone S, et al. The treatment with a COX-2 specific inhibitor is effective in the management of pain related to endometriosis. Eur J Obstet Gynecol Reprod Biol 2004; 116: 100–2\nBarrier BF, Bates GW, Leland MM, et al. Efficacy of antitumor necrosis factor therapy in the treatment of spontaneous endometriosis in baboons. Fertil Steril 2004; 81 Suppl. 1: 775–9\nKoninckx PR, Craessaerts M, Timmerman D, et al. Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod 2008; 23: 2017–23\nHealy DL, Rogers PA, Hii L, et al. Angiogenesis: a new theory for endometriosis. Hum Reprod Update 1998; 4: 736–40\nMcLaren J. Vascular endothelial growth factor and endometriotic angiogenesis. Hum Reprod Update 2000; 6: 45–55\nDonnez J, Smoes P, Gillerot S, et al. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod 1998; 13: 1686–90\nMcLaren J, Prentice A, Charnock-Jones DS, et al. Vascular endothelial growth factor (VEGF) concentrations are elevated in peritoneal fluid of women with endometriosis. Hum Reprod 1996; 11: 220–3\nTan XJ, Lang JH, Liu DY, et al. Expression of vascular endothelial growth factor and thrombospondin-1 mRNA in patients with endometriosis. Fertil Steril 2002; 78: 148–53\nBecker CM, Sampson DA, Rupnick MA, et al. Endostatin inhibits the growth of endometriotic lesions but does not affect fertility. Fertil Steril 2005 Oct; 84 Suppl. 2: 1144–55\nChabbert-Buffet N, Meduri G, Bouchard P, et al. Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum Reprod Update 2005; 11: 293–307\nChwalisz K, Perez MC, Demanno D, et al. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev 2005; 26: 423–38\nOlive DL, Lindheim SR, Pritts EA. New medical treatments for endometriosis. Best Pract Res Clin Obstet Gynaecol 2004; 18: 319–28\nFerrero S, Abbamonte LH, Anserini P, et al. Future perspectives in the medical treatment of endometriosis. Obstet Gynecol Surv 2005; 60: 817–26\nChwalisz K, Mattia-Goldberg C, Lee M, et al. Treatment of endometriosis with the novel selective progesterone receptor modulator (SPRM) Asoprisnil. Fertil Steril 2004; 82: S83–4\nRoyal College of Obstetricians and Gynaecologists. The investigation and management of endometriosis: guideline no. 24. London: RCOG Press, 2006 Jun\nAcknowledgements\nThis review was supported in part by the University of Milan School of Medicine Research Grant FIRST no. 12-01-5068118-00067 and by the Center for Research in Obstetrics and Gynecology, Milan, Italy. The authors declare that they have no conflicts of interest that are directly relevant to the contents of this review.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nRights and permissions\nAbout this article\nCite this article\nVercellini, P., Somigliana, E., Viganò, P. et al. Endometriosis. Drugs 69, 649–675 (2009). https://doi.org/10.2165/00003495-200969060-00002\nPublished:\nIssue date:\nDOI: https://doi.org/10.2165/00003495-200969060-00002","source_license":"CC0","license_restricted":false}