Progestogens and Endometriosis

In: Progestogens in Obstetrics and Gynecology · 2015 · pp. 129–147 · doi:10.1007/978-3-319-14385-9_9 · W2183311682
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Progestogens effectively treat endometriosis pain and recurrence, likely by modulating the inflammatory response, despite progesterone resistance in the endometriotic tissue.

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This paper reviews how progestogens relate to endometriosis pathophysiology and treatment, describing endometriosis as having progesterone-resistant endometrial-like tissue and an immunologically compromised peritoneal microenvironment. It reports that progestogens are effective for controlling endometriosis pain and recurrence, with the likely mechanism being modulation of inflammatory reactions around endometriotic deposits rather than direct correction of progesterone resistance. A key caveat emphasized is that the exact mode of action on target tissue remains uncertain, and it notes limited comparative data between different progestogens, with no effect on endometriosis-related infertility; it also contrasts progestogen therapy’s relatively low side-effect profile with broader side-effect variability for other medical options. This paper is centrally about endometriosis — it focuses specifically on progestogens as a therapy for endometriosis-associated pain and recurrence and discusses the unresolved mechanisms given progesterone resistance.

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Abstract

In endometriosis endometrial-like tissue is found most commonly in the peritoneal cavity, ovaries and rectovaginal septum. Endometriosis is characterised by a progesterone resistant endometrium and an immunologically compromised peritoneal microenvironment. The sequelae are infertility, dysmenorrhea, dyspareunia and chronic pelvic pain. Chronic pelvic pain causes disability and distress with a very high economic impact. The main treatment modality is surgery. Progestogens are effective in controlling the pain, and for treating recurrences. However, the mode of action on the target tissue is still uncertain, due to the progesterone resistance. The most likely mechanism of effect is on the inflammatory reaction surrounding endometriotic deposits. Other therapies include:- debulking by surgery, estrogen reduction by GnRH analogues and Danazol, inducing endomerial atrophy with the levonorgestrel releasing intra-uterine contraceptive, and gestrinone. Surgery is associated with a relatively high recurrence rate, The other medical treatments apart from progestogens are associated with a wide range of side effects. Progestogens are indicated for pain relief, bleeding and other symptoms of endometriosis when long-term medication or repeated courses of treatment are indicated. The main advantage of progestogen therapy is the relative lack of side effects. However, there is little data comparing different progestogens and progestogens have no effect on endometriosis related infertility, Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

References

Cornillie FJ, Oosterlynck D, Lauweryns JM, et al. Deeply infiltrating pelvic endometriosis: histology and clinical significance. Fertil Steril. 1990;53(6):978–83. Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24:235–58. Meuleman C, Tomassetti C, D’Hoore A, Van Cleynenbreugel B, Penninckx F, Vergote I, D’Hooghe T. Surgical treatment of deeply infiltrating endometriosis with colorectal involvement. Hum Reprod Update. 2011;17:311–26. Leibovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001;75:1–10. Sharpe-Timms KL, Piva M, Ricke EA, Surewicz K, Zhang YL, Zimmer RL. Endometriosis synthesizes and secretes a haptoglobin-like protein. Biol Reprod. 1998;58:988–94. Piva M, Horowitz GM, Sharpe-Timms KL. Interleukin-6 differentially stimulates haptoglobin production by peritoneal and endometriotic cells in vitro: a model for endometrium-peritoneum interaction in endometriosis. J Clin Endocrinol Metab. 2001;86:2553–61. Oosterlynck DJ, Cornillie FJ, Waer M, Vandeputte M, Koninckx PR. Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium. Fertil Steril. 1991;56:45–51. Taylor RN, Lebovic DI, Meuller MD. Angiogenic factors in endometriosis. Ann N Y Acad Sci. 2001;955:89–100. Santanam N, Murphy AA, Parthasarathy S. Macrophages, oxidation, and endometriosis. Ann N Y Acad Sci. 2001;955:183–200. Van Langendonckt A, Casanas-Roux F, Donnez J. Oxidative stress and peritoneal endometriosis. Fertil Steril. 2002;77:861–70. Eisenberg VH, Zolti M, Soriano D. Is there an association between autoimmunity and endometriosis? Autoimmun Rev. 2012;11(11):806–14. Nothnick WB. Treating endometriosis as an autoimmune disease. Fertil Steril. 2001;76:223–40. Gleicher N, El-Roeiy A, Confino E, Friberg J. Is endometriosis an autoimmune disease? Obstet Gynecol. 1987;70:115–22. Grossinkinsky CM, Halme J. Endometriosis: the host response. Baillieres Clin Obstet Gynaecol. 1993;7:701–13. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17:2715–24. Poppe K, Glinoer D, Van Steirteghem A, Tournaye H, Devroey P, Schiettecatte J, et al. Thyroid dysfunction and autoimmunity in infertile women. Thyroid. 2002;12:997–1001. Osteen KG, Keller NR, Feltus FA, Melner MH. Paracrine regulation of matrix metalloproteinase expression in the normal endometrium. Gynecol Obstet Invest. 1999;48 suppl 1:2–13. Garcia-Velasco JA, Arici A. Apoptosis and the pathogenesis of endometriosis. Semin Reprod Med. 2003;21:165–72. Guo SW. Nuclear factor-kappab (NF-kappaB): an unsuspected major culprit in the pathogenesis of endometriosis that is still at large? Gynecol Obstet Invest. 2007;63:71–97. Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol. 2007;8:49–62. Gonzalez-Ramos R, Donnez J, Defrere S, et al. Nuclear factor-kappa B is constitutively activated in peritoneal endometriosis. Mol Hum Reprod. 2007;13:503–9. Gonzalez-Ramos R, Rocco J, Rojas C, et al. Physiologic activation of nuclear factor kappa-B in the endometrium during the menstrual cycle is altered in endometriosis patients. Fertil Steril. 2012;97:645–51. Kitawaki J, Kado N, Ishihara H, Koshiba H, Kitaoka Y, Honjo H. Endometriosis: the pathophysiology as an estrogen-dependent disease. J Steroid Biochem Mol Biol. 2002;83:149–55. Zeitoun K, Takayama K, Sasano H, Suzuki T, Moghrabi N, Andersson S, et al. Deficient 17beta-hydroxysteroid dehydrogenase type 2 expression in endometriosis: failure to metabolize 17beta-estradiol. J Clin Endocrinol Metab. 1998;83:4474–80. Noble LS, Takayama K, Zeitoun KM, Putman JM, Johns DA, Hinshelwood MM, et al. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab. 1997;82:600–6. Bulun SE, Cheng YH, Yin P, Imir G, Utsunomiya H, Attar E, et al. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol. 2006;248:94–103. Attia GR, Zeitoun K, Edwards D, Johns A, Carr BR, Bulun SE. Progesterone receptor isoform A but not B is expressed in endometriosis. J Clin Endocrinol Metab. 2000;85:2897–902. Lee II, Kim JJ. Influence of AKT on progesterone action in endometrial diseases. Biol Reprod. 2014;91:63. pii: biolreprod.114.119255. [Epub ahead of print]. Cakmak H, Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Hum Reprod Update. 2011;17(2):242–53. Reis FM, Petraglia F, Taylor RN. Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update. 2013;4:406–18. Tokushige N, Markham R, Russell P, Fraser IS. High density of small nerve fibres in the functional layer of the endometrium in women with endometriosis. Hum Reprod. 2006;21:782–7. Tokushige N, Markham R, Russell P, Fraser IS. Nerve fibres in peritoneal endometriosis. Hum Reprod. 2006;21:3001–7. Bokor A, Kyama CM, Vercruysse L, Fassbender A, Gevaert O, Vodolazkaia A, De Moor B, Fülöp V, D’Hooghe T. Density of small diameter sensory nerve fibres in endometrium: a semi–invasive diagnostic test for minimal to mild endometriosis. Hum Reprod. 2009;24:3025–32. McKinnon B, Bersinger NA, Wotzkow C, Mueller MD. Endometriosis-associated nerve fibers, peritoneal fluid cytokine concentrations, and pain in endometriotic lesions from different locations. Fertil Steril. 2012;97:373–80. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011;17:327–46. Somigliana E, Vigano P, Gaffuri B, Guarneri D, Busacca M, Vignali M. Human endometrial stromal cells as a source of soluble intercellular adhesion molecule (ICAM)-1 molecules. Hum Reprod. 1996;11:1190–4. Jacobson TZ, Duffy JM, Barlow D, Koninckx PR, Garry R. Laparoscopic surgery for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2009;4:CD001300. Johnson NP, Hummelshoj L. Consensus on current management of endometriosis. Hum Reprod. 2013;28(6):1552–68. Vercellini P, Somigliana E, Viganò P, De Matteis S, Barbara G, Fedele L. The effect of second-line surgery on reproductive performance of women with recurrent endometriosis: a systematic review. Acta Obstet Gynecol Scand. 2009;88:1074–82. Guo SW. Recurrence of endometriosis and its control. Hum Reprod Update. 2009;15:441–61. Shakiba K, Bena JF, McGill KM, Minger J, Falcone T. Surgical treatment of endometriosis: a 7-year follow-up on the requirement for further surgery. Obstet Gynecol. 2008;111:1285–92. Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R. Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil Steril. 2004;82:878–84. Vercellini P, Pietropaolo G, De Giorgi O, Daguati R, Pasin R, Crosignani PG. Reproductive performance in infertile women with rectovaginal endometriosis: is surgery worthwhile? Am J Obstet Gynecol. 2006;195:1303–10. Koninckx PR, Timmermans B, Meuleman C, Penninckx F. Complications of CO2-laser endoscopic excision of deep endometriosis. Hum Reprod. 1996;11:2263–8. Ford J, English J, Miles WA, Giannopolous T. Pain, quality of life and complications following the radical resection of rectovaginal endometriosis. Br J Obstet Gynaecol. 2004;111:353–6. Fagervold B, Jenssen M, Hummelshoj L, Moen MH. Life after a diagnosis with endometriosis—a 15 years follow-up study. Acta Obstet Gynecol Scand. 2009;88:914–9. Kauppila A, Rönnberg L, Viehko R. Steroidrezeptoren in endometrischem Gewebe. Endometriose. 1986;4:56–9. Vierikko P, Kauppila A, Rönnberg L, Viehko R. Steroidal regulation of endometriosis tissue. Fertil Steril. 1985;43:218–23. Horie S, Harada T, Mitsunari M, Taniguchi F, Iwabe T, Terakawa N. Progesterone and progestational compounds attenuate tumor necrosis factor alpha-induced interleukin-8 production via nuclear kappa B inactivation in endometriotic stromal cells. Fertil Steril. 2005;83:1530–5. Alimohamadi S, Javadian P, Gharedaghi MH, Javadian N, Alinia H, Khazardoust S, Borna S, Hantoushzadeh S. Progesterone and threatened abortion: a randomized clinical trial on endocervical cytokine concentrations. J Reprod Immunol. 2013;98(1–2):52–60. Aisemberg J, Vercelli CA, Bariani MV, Billi SC, Wolfson ML, Franchi AM. Progesterone is essential for protecting against LPS-induced pregnancy loss. LIF as a potential mediator of the anti-inflammatory effect of progesterone. PLoS One. 2013;8(2):e56161. Ragupathy R, Al Mutawa E, Makhseed M, Azizieh F, Szekeres-Bartho J. Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriage. BJOG. 2005;112:1096–101. Simoncini T, Caruso A, Giretti MS, Scorticati C, Fu XD, Garibaldi S, et al. Effects of dydrogesterone and of its stable metabolite, 20-alpha-dihydrodydrogesterone, on nitric oxide synthesis inhumanendothelial cells. Fertil Steril. 2006;86 Suppl 4:1235–42. King RJ, Whitehead MI. Assessment of the potency of orally administered progestins in women. Fertil Steril. 1986;46(6):1062–6. Schweppe KW. The place of dydrogesterone in the treatment of endometriosis and adenomyosis. Maturitas. 2009;65S:S23–7. Brown J, Kives S, Akhtar M. Progestagens and anti-progestagens for pain associated with endometriosis. Cochrane Database Syst Rev. 2012;3:CD002122. doi:10.1002/14651858.CD002122.pub2. Overton CE, Lindsay PC, Johal B, Collins SA, Siddle NC, Shaw RW, Barlow DH. A randomized, double-blind, placebo-controlled study of luteal phase dydrogesterone (Duphaston) in women with minimal to mild endometriosis. Fertil Steril. 1994;62(4):701–7. Strowitzki T, Faustmann T, Gerlinger C, et al. 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;151:193–8. Klipping C, Duijkers I, Remmers A, et al. Ovulation-inhibiting effects of dienogest in a randomized, dose-controlled pharmacodynamic trial of healthy women. J Clin Pharmacol. 2011;52:1704–13. Strowitzki T, Marr J, Gerlinger C, et al. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Hum Reprod. 2010;25:633–41. Kuhl H. Comparative pharmacology of newer progestogens. Drugs. 1996;51:188–215. Zimmermann H, Duvauchelle T, Gualano V, Kaufmann G, Bervoas-Martin S, Breitbarth H. Pharmacokinetics of dienogest as a single drug or in combination with estradiol valerate or ethinylestradiol. Drugs Today. 1999;35(Suppl C):27–39. Bergqvist A, Theorell T. Changes in quality of life after hormonal treatment of endometriosis. Acta Obstet Gynecol Scand. 2001;80:628–37. Telimaa S, Puolakka J, Ronnberg L, et al. Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis. Gynecol Endocrinol. 1987;1:13–23. Harrison 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. Vercellini P, De Giorgi O, Oldani S, Cortesi I, Panazza S, Crosignani PG. 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. Brown. Sclaff W, Carson S, Luciano A, Ross D, Bergvist A. Subcutaneous injection of depot medoxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis associated pain. Fertil Steril. 2006;85(2):314–25. Vercellini P, De Giorgi O, Mosconi P, Stellato G, Vicentini S, Crosignani PG. 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(1):52–61. Luukkainen T, Lahteenmaki P, Toivonen J. Levonorgestrel-releasing intrauterine device. Ann Med. 1990;22:85–90. Streuli I, de Ziegler D, Santulli P, Marcellin L, Borghese B, Batteux F, Chapron C. An update on the pharmacological management of endometriosis. Expert Opin Pharmacother. 2013;14(3):291–305. Engemise SL, Willets JM, Taylor AH, Emembolu JO, Konje JC. Changes in glandular and stromal estrogen and progesterone receptor isoform expression in eutopic and ectopic endometrium following treatment with the levonorgestrel-releasing intrauterine system. Eur J Obstet Gynecol Reprod Biol. 2011;157:101–6. Lockhat 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. Vercellini 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. Fedele 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. Serachioli 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;94:464–71. Tanmahasamut P, Rattanachaiyanont M, Angsuwathana S, et al. Postoperative levonorgestrel-releasing intrauterine system for pelvic endometriosis-related pain: a randomized controlled trial. Obstet Gynecol. 2012;119:519–26. Wong AY, Tang LC, Chin RK. Levonorgestrel-releasing intrauterine system (Mirena) and Depot medroxyprogesterone acetate (Depoprovera) as long-term maintenance therapy for patients with moderate and severe endometriosis: a randomised controlled trial. Aust N Z J Obstet Gynaecol. 2010;50:273–9. Bayoglu Tekin Y, Dilbaz B, Altinbas SK, et al. Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue. Fertil Steril. 2011;95:492–6. Muneyyirci-Delale O, Karacan M. Effect of norethindrone acetate in the treatment of symptomatic endometriosis. Int J Fertil Womens Med. 1998;43:24–7. Muneyyirci-Delale O, Anopa J, Charles C, Mathur D, Parris R, Cutler JB, Salame G, Abulafia O. Medical management of recurrent endometrioma with long-term norethindrone acetate. Int J Womens Health. 2012;4:149–54. Riis 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;187:1101–16. Ferrero S, Camerini G, Ragni N, Venturini PL, Biscaldi E, Seracchioli R, Remorgida V. Letrozole and norethisterone acetate in colorectal endometriosis. Eur J Obstet Gynecol Reprod Biol. 2010;150:199–202. Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM, Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database Syst Rev. 2007;3:CD000155. Review. 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):1568–73. Modugno F, Ness RB, Allen GO, Schildkraut JM, Davis FG, Goodman MT. Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis. Am J Obstet Gynecol. 2004;191(3):733–40. Gestrinone 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. Bromham DR, Booker MW, Rose GL, Wardle PG, Newton JR. A multicentre comparative study of gestrinone and danazol in the treatment of endometriosis. J Obstet Gynaecol. 1995;15:188–94. Fedele L, Arcaini L, Bianchi S, Viezzoli T, Arcaini L, Candiani GB. Gestrinone versus danazol in the treatment of endometriosis. Fertil Steril. 1989;51(5):781–5. Surrey ES. Gonadotropin-releasing hormone agonist and add-back therapy: what do the data show? Curr Opin Obstet Gynecol. 2010;22:283–8. Brown J, Pan A, Hart RJ. Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev 2010;CD008475. Selak V, Farquhar C, Prentice A, et al. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2007;CD000068. Johnson NP, Hummelshoj L; Consensus on current management of endometriosis. World Endometriosis Society Montpellier Consortium. Hum Reprod. 2013;28:1552–68. Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2015 Springer International Publishing Switzerland About this chapter Cite this chapter Carp, H.J.A., Soriano, D., Zolti, M. (2015). Progestogens and Endometriosis. In: Carp, H. (eds) Progestogens in Obstetrics and Gynecology. Springer, Cham. https://doi.org/10.1007/978-3-319-14385-9_9 Download citation DOI: https://doi.org/10.1007/978-3-319-14385-9_9 Publisher Name: Springer, Cham Print ISBN: 978-3-319-14384-2 Online ISBN: 978-3-319-14385-9 eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

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