Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-76fb5796d-22dnz Total loading time: 0 Render date: 2024-04-26T08:34:17.230Z Has data issue: false hasContentIssue false

33 - Medical Management of Endometriosis

from PART II - INFERTILITY EVALUATION AND TREATMENT

Published online by Cambridge University Press:  04 August 2010

By
Botros R. M. B. Rizk ,
Mary George Nawar ,
Christine B. Rizk  and
David B. Rizk
Edited by
Botros R. M. B. Rizk ,
Juan A. Garcia-Velasco ,
Hassan N. Sallam  and
Antonis Makrigiannakis
Botros R. M. B. Rizk
Affiliation:
University of South Alabama
Juan A. Garcia-Velasco
Affiliation:
Rey Juan Carlos University School of Medicine,
Hassan N. Sallam
Affiliation:
University of Alexandria School of Medicine
Antonis Makrigiannakis
Affiliation:
University of Crete
Get access

Summary

The successful treatment of endometriosis-associated symptoms typically requires surgical as well as medical intervention. Although medical therapies are not curative per se, the medical management of endometriosis remains to be the cornerstone of the treatment of endometriosis-associated pelvic pain (1). However, medical treatment has no place in the management of infertility associated with endometriosis, with the exception of downregulation prior to in vitro fertilization in advanced disease. Historically, the treatment for endometriosis has been high-dose androgens and progestins. These options have been discontinued because of their significant side effects. The modern era for hormonal therapy began with Danazol in 1971. This has been replaced by GnRH agonists two decades ago (2); more recently, the treatment of endometriosis shifted to decreasing the local estrogen production by aromatase inhibitors. Clinical trials are awaited with interest for selective progesterone modulators, angiostatic agents, and matrix metalloproteinase inhibitors (Table 33.1).

Successful treatment of endometriosis depends on the understanding of the effect of hormones and therapeutics on the in situ endometrium. However, there is a significant difference between the in situ endometrium and the ectopic endometrium “endometriosis.” Significant aberrant gene expression has been demonstrated in the endometriotic tissue (3). These changes explain excessive local production and decrease inactivation of estrogen in the endometriotic tissue. These include inactivation of 17β-hydroxysteroid dehydrogenase (4), progesterone receptor isoform B (5), and HOXA10 (6) to the upregulation of matrix metalloproteinases (7) and P450 aromatase (8) and to massive gene expression aberration uncovered by the microarray technology (9–12).

Keywords

add-back therapyantiangiogenesis therapyaromatase inhibitorsendometriosisnonsteroidal inflammatory drugsprogestogensselective progesterone receptor modulatorsgonadotrophin-releasing hormone agonist
Type
Chapter
Information
Infertility and Assisted Reproduction , pp. 309 - 317
Publisher: Cambridge University Press
Print publication year: 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Rizk, B, Abdalla, H. (2003). Medical treatment of endometriosis. In: Rizk, B, Abdalla, H (Eds.). Endometriosis, Oxford, England; Health Press, Chapter 4, pp. 55–70.Google Scholar
Lemay, A, Maheux, R, Faure, N, et al. (1984). Reversible hypogonadism induced by a luteinizing hormone-releasing hormone (LHRH) agonist (Buserelin) as a new therapeutic approach for endometriosis. Fertil Steril 41:863–71.CrossRefGoogle ScholarPubMed
Wu, Y, Strawn, E, Basir, Z, Halverson, G, Guo, S-W. (2007). Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Fertil Steril 87:24–32.CrossRefGoogle ScholarPubMed
Zeitoun, K, Takayama, K, Sasano, H, Suzuki, T, Moghrabi, N, Andersson, S, et al. (1998). Deficient 17beta-hydroxysteriod dehydrogenase type 2 expression in endometriosis: failure to metabolize 17 beta-estradiol. J Clin Endocrinol Metab 83:4474–80.Google Scholar
Attia, GR, Zeitoun, K, Edwards, D, Johns, A, Carr, BR, Bulun, SE. (2000). Progesterone receptor isoform A but not B is expressed in endometriosis. J Clin Endocrinol Metab 85:2897–902.Google Scholar
Taylor, HS, Bagot, C, Kardana, A, Olive, D, Arici, A. (1999). HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod 14:1328–31.CrossRefGoogle ScholarPubMed
Osteen, KG, Yeaman, GR, Bruner-Tran, KL. (2003). Matrix metalloproteinases and endometriosis. Semin Reprod Med 21:155–64.Google ScholarPubMed
Noble, LS, Simpson, ER, Johns, A, Bulun, SE. (1996). Aromatase expression in endometriosis. J Clin Endocrinol Metab 81:174–9.Google ScholarPubMed
Kao, LC, Germeyer, A, Tulax, S, Lobo, S, Yang, JP, Taylor, RN, et al. (2003). Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility: Endocrinology 144:2870–81.CrossRefGoogle ScholarPubMed
Matsuzaki, S, Canis, M, Vaurs-Barriere, C, Bosespflug-Tanguy, O, Penault-Llorca, F, et al. (2004). DNA microarray analysis of gene expression profiles in deep endometriosis using laser capture microdissection: Mol Hum Reprod 10:719–28.CrossRefGoogle ScholarPubMed
Matsuzaki, S, Canis, M, Vaurs-Barriere, C, Boespflug-Tanguy, O, Dastugue, B, Mage, G. (2005). DNA microarray analysis of gene expression in eutopic endometrium from patients with deep endometriosis using laser capture microdissection: Fertil Steril 84(Suppl. 2):1180–90.CrossRefGoogle ScholarPubMed
Wu, K, Kajdacsy-Balla, A, Strawn, E, Basir, Z, Halverson, G, Jailwala, P, et al. (2006). Transcriptional characterizations of differences between eutopic and ectopic endometrium. Endocrinology 147:232–46.CrossRefGoogle ScholarPubMed
Kistner, RW. (1958). The use of progestins in the treatment of endometriosis. Am J Obstet Gynecol 75:264–78.CrossRefGoogle ScholarPubMed
Telimaa, S, Ronnberg, L, Kauppila, A. (1987). Placebo-controlled comparison of Danazol and high dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery. Gynecol Endocrinol 1:363–71.CrossRefGoogle ScholarPubMed
Overton, CE, Lindsay, PC, Johal, B. (1994). A randomized, double blind, placebo controlled study of luteal phase dydrogesterone (Duphasone) in women with minimal to mild endometriosis. Fertil Steril 62:701–7.CrossRefGoogle Scholar
Vercellini, P, Giorgi, O, Oldani, S, Cortesti, I, Panazza, S, Crosignnani, PG. (1996). 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 175:396–401.CrossRefGoogle ScholarPubMed
Metzger, D, Luciano, A. (1989). Hormonal therapy of endometriosis. Obstet Gynecol Clin (N.A.) 16:105–22.Google ScholarPubMed
Ota, H, Igarashi, S, Hayakawa, M, et al. (1996). Effect of danazol on the immunocompetent cell in the eutopic endometrium in patients with endometriosis: a multicenter cooperative study. Fertil Steril 65:545–51.CrossRefGoogle ScholarPubMed
Dmowski, W, Kapetanakis, E, Scommegna, A. (1982). Variable effects of danazol on endometriosis at 4 low-dose levels. Obstet Gynecol 59:408–15.Google ScholarPubMed
Selak, V, Farquhar, C, Prentice, A, Singla, A. (2001). Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev (4):CD000068.CrossRefGoogle ScholarPubMed
Fedele, L, Bianchi, S, Viezzoli, T, Arcaini, L, Candiani, GB. (1989). Gestrinone versus danazol in the treatment of endometriosis. Fertil Steril 51:781–5.CrossRefGoogle ScholarPubMed
Bromham, DR, Booker, MW, Rose, GL, Wardle, PG, Newton, JR. (1995). A multicentre comparative study of gestrinone and danazol in the treatment of endometriosis. Am J Obstet Gynecol 15:188–94.CrossRefGoogle Scholar
The Gestrinone Italian Study Group. (1996). Gestrinone versus gonadotropin releasing hormone agonist for the treatment of pelvic pain associated with endometriosis: a multicenter, randomized, double-blind study. Fertil Steril 66:911–19.
Hornstein, MD, Glaeson, RE, Barbieri, RI. (1990). A randomized, double-blind prospective trial of two doses of gestrinone in the treatment of endometriosis. Fertil Steril 53:237–41.CrossRefGoogle ScholarPubMed
Kettel, LM, Murphy, AA, Morales, AJ, et al. (1996). Treatment of endometriosis with the antiprogesterone mifepristone (RU486). Fertil Steril 65:23.CrossRefGoogle Scholar
Kettel, LM, Murphy, AA, Mortola, JF, et al. (1991). Endocrine responses to long-term administration of the antiprogesterone RU486 in patients with pelvic endometriosis. Fertil Steril 56:402.CrossRefGoogle ScholarPubMed
Prentice, A, Deary, AJ, Bland, E. (2000). Progestogens and anti-progestogens for pain associated with endometriosis. Cochrane Database Syst Rev(2):CD002122.Google Scholar
Henzl, MR, Corson, SL, Moghissi, K, et al. (1988). Administration of nasal nafarelin as compared multicenter double-blind comparative clinical trial with oral danazol for endometriosis. N Engl J Med 318:485–9.CrossRefGoogle ScholarPubMed
Dlugi, AM, Miller, JD, Knittle, J. (1990). Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group. Fertil Steril 54:419–27.CrossRefGoogle ScholarPubMed
Bergqvist, A. (1998). Effects of triptorelin versus placebo on the symptoms of endometriosis. Fertil Steril 69:702–8.CrossRefGoogle ScholarPubMed
Barbieri, RL. (1992). Hormone treatment of endometriosis: the oestrogen threshold hypothesis. Am J Obstet Gynecol 166:740–5.CrossRefGoogle ScholarPubMed
Moghissi, KS. (1996). Add-back therapy in the treatment of endometriosis: the North American experience. Br J Obstet Gynecol 103:14.Google ScholarPubMed
Edmonds, DK. (1996). Add-back therapy in the treatment of endometriosis: the European experience. Br J Obstet Gynecol 103:10–13.Google ScholarPubMed
Barbieri, RL. (2004). Gonadotropin releasing hormone agonist and antagonist for endometriosis. In: Tulandi, T, Redwine, D, (Eds.) Endometriosis: Advances and Controversies. New York: Marcel Dekker, Chapter 13, pp. 219–43.Google Scholar
Hull, ME, Barbieri, RL. (1994). Nafarelin in the treatment of endometriosis: dose management. Gynecol Obstet Invest 37:263–4.CrossRefGoogle ScholarPubMed
Tahara, M, Matsouka, T, Yodoi, T, Tasaka, K, Kurachi, H, Murata, Y. (2000). Treatment of endometriosis with a decreasing dosage of a gonadotropin releasing hormone agonist (nafarelin): a pilot study with low-dose agonist therapy. Fertil Steril 73:799–804.CrossRefGoogle ScholarPubMed
Uemura, T, Shirasu, K, Datagiri, N, Asukai, K, Suzuki, T, Suzuki, N. (1999). Low-dose GnRH agonist therapy for the management of endometriosis. J Obstet Gynecol Res 25:295–301.CrossRefGoogle ScholarPubMed
Tse, CY, Chow, AM, Chan, SC. (2000). Effects of extended-interval dosing regimen of triptorelin depot on the hormonal profile of patients with endometriosis: prospective observational study. Hong Kong Med J 6:260–4.Google ScholarPubMed
Prentice A, Deary AJ, Goldbeck-Wood S, Farquhar C, Smith SK. Gonadotropin releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev CD00346.
Kupker, W, Felberbaum, RE, Krapp, M, et al. (2002). Use of GnRH antagonists in the treatment of endometriosis. Reprod BioMed Online 5:12–16.CrossRefGoogle ScholarPubMed
Martha, P, Gray, M, Campion, M, Kuca, B, Garnick, M. (1999). Prolonged suppression of circulating estrogen levels without an initial hormonal flare using abarelix-depot, a pure GnRH antagonist, in women with endometriosis. Fertil Steril 72:S210–11.Google Scholar
Chwalisz, K, Garg, R, Brenner, RM, Schubert, G, Elger, W. (2002). Selective progesterone receptor modulators (SPRMs)—a novel therapeutic concept in endometriosis. Ann N Y Acad Sci 955: 373–88.CrossRefGoogle ScholarPubMed
Chwalisz, K, Brenner, RM, Fuhrmann, U, Hess-Stumpp, Elger W. (2000). Antiproliferative effects of progesterone antagonists and progesterone receptor modulators on the endometrium. Steroids 65:741–51.CrossRefGoogle ScholarPubMed
Elger, W, Bartley, J. Schneider, B, Kaufmann, G, Schubert, G, Chwalisz, K. (2000). Endocrine pharmacological characterization of progesterone antagonists and progesterone receptor modulators (PRMs) with respect to PR-agonistic and antagonistic activity. Steroids 65:713–23CrossRefGoogle ScholarPubMed
Fanning, P, Kuehl, T, Lee, R, Pearson, S, et al. (1997). Video mapping to assess efficacy of an antiestrogen (raloxifene) on spontaneous endometriosis in the rhesus monkey. Fertil Steril 68:S38–9.CrossRefGoogle Scholar
Noble, LS, Takayama, K, Zeitoun, KM, et al. (1997). Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab 82:600–6.Google ScholarPubMed
Bulun, SE, Gurates, B, Fang, Z, et al. (2004). Treatment with aromatase inhibitors. In: Tulandi, T, Redwine, D, (Eds.) Endometriosis: Advances and Controversies. New York: Marcel Dekker, Chapter 11, pp. 189–202.Google Scholar
Takayama, K, Zeitoun, K, Gunby, RT, et al. (1998). Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril 69:709–713.CrossRefGoogle ScholarPubMed
Scarpellini, F, Sbracia, M, Lecchini, S, Scarpellini, L. (2002). Anti-angiogenesis treatment with thalidomide in endometriosis: a pilot study. Fertil Steril 78:S87.CrossRefGoogle Scholar
Vignali, M, Infantino, M, Matrone, R, et al. (2002). Endometriosis: novel etiopathogenetic concepts and clinical perspectives. Fertil Steril 78:665–78.CrossRefGoogle ScholarPubMed
Badawy, S, Etman, A, Cuenca, V, et al. (2001). Effect of interferon α-2b on endometrial cells in vitro. Obstet Gynecol 98:417–20.Google Scholar
D'Hooghe, T, Cuneo, S, Nugent, N, et al. (2001). Recombinant human TNF binding protein-1 (r-hTBP-1) inhibits the development of endometriosis in baboons: a prospective, randomized, placebo- and drug controlled study. Fertil Steril 76:S1.CrossRefGoogle Scholar
Keenan, J, Williams-Boyle, P, Massey, P, Chen, T, et al. (1999). Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole. Fertil Steril 721:135–41.CrossRefGoogle Scholar
Tindle, HA, Davis, RB, Phillips, RS, Eisenberg, DM. (2005). Trends in use of complementary and alternative medicine by US adults: 1997-2002. Altern Ther Health Med 11:42–9.Google ScholarPubMed
Weiser, F, Cohen, M, Gaeddert, A, et al. (2007). Evolution of medical treatment for endometriosis: back to the roots?Hum Reprod Update 13(5):487–99.Google Scholar
Hughes, EG, Fedorkow, DM, Collins, JA. (1993). A quantitative overview of controlled trials in endometriosis-associated infertility. Fertil Steril 59:963–70.CrossRefGoogle ScholarPubMed
Adamson, GD, Pasta, D. (1994). Surgical treatment of endometriosis-associated infertility: meta-analysis compared with survival analysis. Am J Obstet Gynecol 171:1488–505.CrossRefGoogle ScholarPubMed
Surrey, ES. (2004). Medical therapy for endometriosis: an overview. In: Tulandi, T, Redwine, D, (Eds.) Endometriosis: Advances and Controversies. New York: Marcel Dekker, Chapter 10, pp. 167–88.Google Scholar
Surrey, ES, Silverberg, K, Surrey, MW, Schoolcraft, WB. (2002). The effect of prolonged GnRH agonist therapy on in vitro fertilization-embryo transfer cycle outcome in endometriosis patients: a multicenter randomized trial. Fert Steril 78:699–704.CrossRefGoogle Scholar
Dicker, D, Goldman, GA, Ashkenazi, J, Feldbert, D, et al. (1990). The value of pretreatment with long-term gonadotropin-releasing hormone (GnRH) analogue in IVF-ET therapy of severe endometriosis. Hum Reprod 5:418–20.CrossRefGoogle Scholar
Marcus, SF, Edwards, RG. (1994). High rates of pregnancy after long-term downregulation of women with severe endometriosis. Am J Obstet Gynecol 171:812–17.CrossRefGoogle ScholarPubMed
Nakamura, K, Oosawa, M, Kondou, I, Inagaki, S, et al. (1992). Menotropin stimulation after prolonged gonadotropin releasing hormone agonist pretreatment of in vitro fertilization in patients with endometriosis. J Assist Reprod Genet 9:113–17.CrossRefGoogle ScholarPubMed
Curtis, P, Jackson, A, Bernard, A, Shaw, RW. (1993). Pretreatment with gonadotrophin releasing hormone (GnRH) analogue prior to in vitro fertilization for patients with endometriosis. Eur J Obstet Gynecol Reprod Biol 52:211–16.CrossRefGoogle ScholarPubMed
Rizk, B, Abdalla, H. (2003). Treatment of infertility associated with endometriosis. In: Rizk, B, Abdalla, H, (Eds.) Endometriosis. Oxford: United Kingdom, Health press, Chapter 6, pp. 85–6.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×