Gestagens in the treatment of endometriosis

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Endometriosis occurs in 10% of females of reproductive age and ranks third among gynecological diseases, being one of the causes of infertility. The success of endometriosis treatment depends on individually selected therapy based on molecular-genetic characterization of the patient endometrial tissue. The review addresses the mechanisms of endometriosis development and the role of gestagens in the pathogenesis of this disease. We describe the genetic and epigenetic mechanisms of endometriosis development, which lead to resistance to endogenous progesterone, a key link in the pathogenesis of endometriosis. Because gestagen monotherapy is considered as first-line treatment, we analyze the gestagen properties that underlie the indications for their use in endometriosis. In particular, gestagen should have high gestagenic activity and an antiproliferative effect on target cells. An original domestic drug, an oral gestagen Gestobutanoil based on 17a-acetoxy-3b-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (AMP-17), is promising for clinical use. The gestagenic activity of AMP-17 in the Clauberg-McPhail test is 102-fold higher than that of progesterone. AMP-17 has a pronounced antiproliferative effect on estrogen-dependent targets, such as breast cancer cells, cervical cancer cells, etc.

Keywords:

endometriosis; progesterone; polymorphism; progesterone receptors; estradiol receptors; resistance

Authors:

Fedotcheva T.A.

Pirogov Russian National Research Medical University, Moscow, Russia

Shimanovsky N.L.

Pirogov Russian National Research Medical University, Moscow, Russia

List of references:

Igenbaeva EV, Uzlova TV, Kurenkov EL. Endometrioz — voprosy prezhnie... Sovremennye problemy nauki i obrazovanija. 2016;(6):58-67. (In Russ.)
Denisova VM, Yarmolinskaya MI, Poliakova VO, et al. Osobennosti ekspressii receptorov steroidnykh gormonov pri naruzhnom genitalnom endometrioze. Molekularnaya meditsina. 2014;(5):29-32. (In Russ.)
Schindler AE. Non-contraceptive benefits of oral hormonal contraceptives. Int J Endocrinol Metab. 2013;11(1):41-47. doi:10.5812/ijem.4158
Jordania KI, Pajanidi UG, Sonova MN, et al. Endometrioz i rak jaichnikov. Onkoginekologija. 2015;(2):16-24. (In Russ.)
Endometrioz: diagnostika, lechenie i reabilitaciya. Federal’nye klinicheskie recomendatsii po vedeniya bol’nych. M. 2013. (In Russ.)
Brusnitsina VYu. Geneticheskij polimorfism i endometrioz. Vestnik Uralskoi meditsinskoj akademitcheskoj nauki. 2009;(4):7-9. (In Russ.)
Hu X, Zhou Y, Feng Q, et al. Association of endometriosis risk and genetic polymorphisms involving biosynthesis of sex steroids and their receptors: an updating meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2012;164(1):1-9. doi:10.1016/j.ejogrb.2012.05.008
Hsieh YY, Chang CC, Tsai FJ, et al. Association of an A allele for interleukin-10 -627 gene promoter polymorphism with higher susceptibility to endometriosis. J Reprod Med. 2003;48(9):735-738.
Hsieh YY, Chang CC, Tsai FJ, et al. Interleukin-2 receptor beta (IL-2R beta)-627*C homozygote but not IL-12R beta 1 codon 378 or IL-18 105 polymorphism is associated with higher susceptibility to endometriosis. Fertil Steril. 2005;84(2):510-512. doi:10.1016/j.fertnstert.2005.02.025
Hsieh YY, Chang CC, Tsai FJ, et al. Polymorphism for transforming growth factor beta 1-509 (TGF-B1-509): association with endometriosis. Biochem Genet. 2005;43(5-6):203-210.
Kim SH, Choi YM, Choung SH. Vascular endothelial growth factor gene +405 C/G polymorphism is associated with susceptibility to advanced stage endometriosis. Hum Reprod. 2005;20(10):2904-2908. doi:10.1093/humrep/dei146
Arosh JA, Lee J, Balasubbramanian D, et al. Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis. Proc Natl Acad Sci USA. 2015;112(31):9716-9721. doi:10.1073/pnas.1507931112
Xu X, Zheng Q, Zhang Z, et al. Periostin enhances migration, invasion, and adhesion of human endometrial stromal cells throughIntegrin-linked kinase 1/Akt signaling pathway. Reprod Sci. 2015;22(9):1098-1106. doi:10.1177/1933719115572481
Zheng QM, Lu JJ, Zhao J, et al. Periostin facilitates the epithelial-mesenchymal transition of endometrial epithelial cells through ILK-Akt signaling pathway. Biomed Res Int. 2016;2016:9842619. doi:10.1155/2016/9842619
Pan H, Zhang P, Li JR, et al. c-Fos-Regulated matrix metalloproteinase-9 expression is involved in 17β-estradiol-promoted invasion of human endometrial stromal cell. Curr Mol Med. 2016;16(3):266-275.
Descamps P, Andreeva E, Leng J, et al. The place of gonadotropin-releasing hormone agonists in the management of endometriosis. J Endometr Pelvic Pain Disord. 2014;6(1):1-11. doi:10.5301/je.5000174
Nazarenko TA, Durinjan ER, Revishvili NA, et al. Sovremennye podkhody k primeneniju progestinov u zhenshchin reproduktivnogo vozrasta. Vestnik reproductivnogo zdorovja. 2010;(3-4):6-8. (In Russ.)
Orlova SA, Balan VE, Levkovich EA. Sovremennye tendentsii medikamentoznogo lechenija endometrioza. Meditsinskij sovet. 2015;(20):28-33. (In Russ.)
Andreeva EN, Gavrilova EF. Genitalnij endometrioz: puti reshenija v XXI veke. Vestnik reproduktivnogo zdorovja. 2011;(2):3-10. (In Russ.)
Johnson NP, Hummelshoj L. Konsensus po vedeniju endometrioza. Reproduktivnaja endokrinologija. 2013;(12):66-88. (In Russ.)
Li X, Bao Y, Fang P, et al. Effect of mifepristone on COX-2 both in eutopic and ectopic endometrium in mouse endometriotic model. Arch Gynecol Obstet. 2012;286(4):939-946. doi:10.1007/s00404-012-2379-2
Leconte M, Santulli P, Chouzenoux S, et al. Inhibition of MAPK and VEGFR by Sorafenib Controls the Progression of Endometriosis. Reprod Sci. 2015;22(9):1171-1180. doi:10.1177/1933719115592708
Carr B, Giudice L, Dmowski WP, et al. Elagolix, an oral GnRH antagonist for endometriosis-associated pain: a randomized controlled study. J Endometr Pelvic Pain Disorders. 2013;5(3):105-115. doi:10.5301/je.5000157
Torshin IYu, Gromova OA, Sukhikh GT, et al. Molekularnye mekhanizmy didrogesterona (DYuFASTON). Polnogenomnoe issledovanie transkriptsionnykh faktorov progesterona, androgenov i estrogenov. Ginekologija. 2009;11(5):9-15. (In Russ.)
Sergeev PV, Shimanovskij NL. Farmakologicheskie svojstva gestagenov. Farmateka. 2003;71(8):33-41. (In Russ.)
Schindler AE. Dienogest in long-term treatment of endometriosis. Int J Womens Health. 2011;(3):175-184. doi:10.2147/IJWH.S5633
Moore C, Kohler G, Muller A. The treatment of endometriosis with dienogest. Drugs of Today. 1999;35(C):41-52.
Щелкунова Т.А., Морозов И.А. Молекулярные основы и тканевая специфичность действия прогестинов. // Молекулярная биология. — 2015. — Т. 49. — №5. — С. 649—667. [Shchelkunova TA, Morozov IA. Molecular basis and tissue specificity of the progestins action. Mol Biol (Mosk). 2015;49(5):728-748. doi:10.7868/S0026898415050158
Savilova AM, Yushina MN, Rudimova YV, et al. Characteristics of multipotent mesenchymal stromal cells isolated from human endometrium and endometriosis lesions. Bull Exp Biol Med. 2016;161(4):610-615. doi:10.1007/s10517-016-3469-0
Han SJ, O’Malley BW. The dynamics of nuclear receptors and nuclear receptor coregulators in the pathogenesis of endometriosis. Hum Reprod Update. 2014;20(4):467-484. doi:10.1093/humupd/dmu002
Senol S, Sayar I, Ceyran AB, et al. Stromal clues in endometrial carcinoma: loss of expression of β-catenin, epithelial-mesenchymal transition regulators, and estrogen-progesterone receptor. Int J Gynecol Pathol. 2016;35(3):238-248. doi:10.1097/PGP.0000000000000233
Kim JJ, Kurita T, Bulun SE. Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev. 2013;34(1):130-162. doi:10.1210/er.2012-1043
Kareva EN, Solomatina AA, Bekhbudova LH. Molekularnye mekhanizmy deistvija progesterone v ebdometrii. Molekularnaja meditsina. 2016;14(3):9-16. (In Russ.)
Valentijn AJ, Saretzki G, Tempest N, et al. Human endometrial epithelial telomerase is important for epithelial proliferation and glandular formation with potential implications in endometriosis. Hum Reprod. 2015;30(12):2816-2828. doi:10.1093/humrep/dev267
Deviatova EA, Tsaturova KA, Esmurzieva ZI, et al. Endometrioz. Akusherstvo i ginekologija: novosti, mnenija, obuchenije.2015;(3):91-100. (In Russ.)
Schindler AE. Dienogest in long-term treatment of endometriosis. Int J Womens Health. 2011;3:175-184. doi:10.2147/IJWH.S5633
Tetelutina FK, Markova SS, Fazleeva ER. Osobennosti psikhoemotsionalnoj adaptatsii bolnykh genitalnym endometriozom pri ispolzovanii dienogesta v kompleksnom lechenii endometrioza. Problemy reproduktsii. 2015;21(5):80-83. (In Russ.)
Suknovalova MV, Bekhbudova LKh, Klimenko MP, et al. Relative binding activity of dydrogesterone with blood mononuclear cells progesterone receptors of women included in the IVF program. Eksp Klin Farmakol. 2013;76(7):24-26. (In Russ.)
Patent RUS №2238095/20.10.2004. Byul. №34. Rzheznikov VM, Golubovskaya LE, Minailova ON, et al. Sostav, obladajushchij kontratseptivnoj aktivnostiu. (In Russ.) http://bd.patent.su/2238000-2238999/pat/servl/servleted4d.html
Fedotcheva TA, Odintsova EV, Shimanovskiĭ NL. Molecular mechanisms of cytostatic and chemosensitizing action of gestagens. Vestn Ross Akad Med Nauk. 2010;(9):42-50. (In Russ.)
Schindler AE, Campagnoli C, Druckmann R, et al. Classification and pharmacology of progestins. Maturitas. 2008;61(1-2):171-180.
Sergeev PV, Fedotcheva TA, Rzheznikov VM, et al. A new Russian gestagen with anticancer activity. Vestn Ross Akad Med Nauk. 2007;(5):27-32. (In Russ.)

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