Adenomyozis Etiyolojisi
Synopsis
Adenomyozis, endometrial dokunun miyometriuma invaze olmasıyla karakterize, ağrılı adetler, anormal kanama ve infertilite gibi sorunlara yol açabilen yaygın ve kronik bir jinekolojik hastalıktır. Etiyolojisi tam olarak anlaşılamamış olsa da, mevcut literatür çeşitli potansiyel mekanizmaları ortaya koymaktadır.
Endometriumun doğrudan invazyonu, travma sonrası mikrotravmalar, de novo metaplazi, dış endometrial implantların invazyonu, hormonal dengesizlikler, genetik ve epigenetik yatkınlıklar, hipofiz hormonlarındaki düzensizlikler, kimyasal maruziyet ve immün sistem disfonksiyonu gibi faktörlerin adenomyozis gelişiminde rol oynayabileceği düşünülmektedir.
Bu karmaşık etiyolojik faktörlerin daha iyi anlaşılması, adenomyozisli hastaların tanı ve tedavisinde daha hedefli ve etkili yaklaşımlar geliştirmemize olanak sağlayacaktır.
Adenomyosis, characterized by the invasion of endometrial tissue into the myometrium, is a common and chronic gynecological condition that can lead to painful periods, abnormal bleeding, and infertility. Although its etiology remains incompletely understood, current literature suggests several potential mechanisms.
Factors such as direct invasion of the endometrium, microtrauma following trauma, de novo metaplasia, invasion of external endometrial implants, hormonal imbalances, genetic and epigenetic predispositions, pituitary hormone dysregulation, chemical exposure, and immune system dysfunction are thought to play a role in the development of adenomyosis.
A better understanding of these complex etiological factors will enable us to develop more targeted and effective approaches for the diagnosis and treatment of patients with adenomyosis.
References
Orazov MR, Nosenko EN, Radzinsky VE, Khamoshina MB, Lebedeva MG, Sounov MA. Proangiogenic features in chronic pelvic pain caused by adenomyosis. Gynecol Endocrinol. 2016 Oct;32(sup2):7-10. doi: 10.1080/09513590.2016.1232902. PMID: 27759451.
Rotkitansky K. Ueber uterusdruesen-neubildung. Z Gesellschaft Aerzte Wien 1860;16:577–581
Frankl O. Adenomyosis uteri. Am J Obstet Gynecol 1925;10:680–684.
Bird CC, McElin TW, Manalo-Estrella P. The elusive adenomyosis of the uterus--revisited. Am J Obstet Gynecol. 1972 Mar;112(5):583-93. doi: 10.1016/0002-9378(72)90781-8. PMID: 5059589.
Antero MF, Ayhan A, Segars J, Shih IM. Pathology and Pathogenesis of Adenomyosis. Semin Reprod Med. 2020 May;38(2-03):108-118. doi: 10.1055/s-0040-1718922. Epub 2020 Oct 20. PMID: 33080632; PMCID: PMC7987203.
Ertan B, Akdöner A, Yavuz O, et al. Adenomyozis; tanı, klinik bulgular ve tedavinin güncel yaklaşımları. Turkish Journal of Reproductive Medicine and Surgery. 2022;6(1):135-41. doi: 10.24074/tjrms.2021-87530
Stratopoulou CA, Donnez J, Dolmans MM. Origin and Pathogenic Mechanisms of Uterine Adenomyosis: What Is Known So Far. Reprod Sci. 2021 Aug;28(8):2087-2097. doi: 10.1007/s43032-020-00361-w. Epub 2020 Oct 22. PMID: 33090375.
García-Solares J, Donnez J, Donnez O, Dolmans MM. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018 Mar;109(3):371-379. doi: 10.1016/j.fertnstert.2017.12.030. PMID: 29566849.
Bergeron C, Amant F, Ferenczy A. Pathology and physiopathology of adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2006 Aug;20(4):511-21. doi: 10.1016/j.bpobgyn.2006.01.016. Epub 2006 Mar 24. PMID: 16563870.
Maier V., Höll M., Dietze R., Mecha E., Omwandho C.O., Tinneberg H.-R., Meinhold-Heerlein I., Konrad L. Adenomyotic glands are highly related to endometrial glands. Reprod. Biomed. Online. 2019;40:769–778. doi: 10.1016/j.rbmo.2019.11.007.
Ibrahim MG, Chiantera V, Frangini S, Younes S, Köhler C, Taube ET, Plendl J, Mechsner S. Ultramicro-trauma in the endometrial-myometrial junctional zone and pale cell migration in adenomyosis. Fertil Steril. 2015 Dec;104(6):1475-83.e1-3. doi: 10.1016/j.fertnstert.2015.09.002. Epub 2015 Oct 9. PMID: 26439760.
Curtis KM, Hillis SD, Marchbanks PA, Peterson HB. Disruption of the endometrial-myometrial border during pregnancy as a risk factor for adenomyosis. Am J Obstet Gynecol 2002; 187 ( 03 ): 543–544. https://doi.org/10.1067/mob.2002.124285
García-Solares J, Donnez J, Donnez O, Dolmans MM. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018 Mar;109(3):371-379. doi: 10.1016/j.fertnstert.2017.12.030. PMID: 29566849.
Batt RE, Yeh J. Müllerianosis: four developmental (embryonic) mullerian diseases. Reprod Sci. 2013 Sep;20(9):1030-7. doi: 10.1177/1933719112472736. Epub 2013 Jan 11. PMID: 23314961.
Ferenczy A. Pathophysiology of adenomyosis. Hum Reprod Update. 1998 Jul-Aug;4(4):312-22. doi: 10.1093/humupd/4.4.312. PMID: 9825847.
Chun S, Kim YM, Ji YI. Uterine adenomyosis which developed from hypoplastic uterus in postmenopausal woman with mayer-rokitansky-kuster-hauser syndrome: a case report. J Menopausal Med. 2013 Dec;19(3):135-8. doi: 10.6118/jmm.2013.19.3.135. Epub 2013 Dec 27. PMID: 25371879; PMCID: PMC4217560.
Hoo PS, Norhaslinda AR, Reza JN. Rare Case of Leiomyoma and Adenomyosis in Mayer-Rokitansky-Kuster-Hauser Syndrome. Case Rep Obstet Gynecol. 2016;2016:3725043. doi: 10.1155/2016/3725043. Epub 2016 Oct 23. PMID: 27843659; PMCID: PMC5097798.
Zhai J, Vannuccini S, Petraglia F, Giudice LC. Adenomyosis: Mechanisms and Pathogenesis. Semin Reprod Med. 2020 May;38(2-03):129-143. doi: 10.1055/s-0040-1716687. Epub 2020 Oct 8. PMID: 33032339; PMCID: PMC7932680.
Chapron C, Tosti C, Marcellin L, Bourdon M, Lafay-Pillet MC, Millischer AE, Streuli I, Borghese B, Petraglia F, Santulli P. Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes. Hum Reprod. 2017 Jul 1;32(7):1393-1401. doi: 10.1093/humrep/dex088. PMID: 28510724.
García-Solares J, Donnez J, Donnez O, Dolmans MM. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018 Mar;109(3):371-379. doi: 10.1016/j.fertnstert.2017.12.030. PMID: 29566849.
Wang Y.-Y., Duan H., Wang S., Quan Y.-J., Huang J.-H., Guo Z.-C. Upregulated Talin1 synergistically boosts β-estradiol-induced proliferation and pro-angiogenesis of eutopic and ectopic endometrial stromal cells in adenomyosis. Reprod. Biol. Endocrinol. 2021;19:70. doi: 10.1186/s12958-021-00756-7.
Li J.-J., Duan H., Wang S., Sun F.-Q., Gan L., Tang Y.-Q., Xu Q., Li T.C. Expression Pattern of G-Protein-Coupled Estrogen Receptor in Myometrium of Uteri with and without Adenomyosis. BioMed Res. Int. 2017;2017:5974693. doi: 10.1155/2017/5974693.
Brosens I, Gordts S, Habiba M, Benagiano G. Uterine Cystic Adenomyosis: A Disease of Younger Women. J Pediatr Adolesc Gynecol. 2015 Dec;28(6):420-6. doi: 10.1016/j.jpag.2014.05.008. Epub 2014 May 28. PMID: 26049940.
Zannoni L, Del Forno S, Raimondo D, Arena A, Giaquinto I, Paradisi R, Casadio P, Meriggiola MC, Seracchioli R. Adenomyosis and endometriosis in adolescents and young women with pelvic pain: prevalence and risk factors. Minerva Pediatr (Torino). 2024 Feb;76(1):57-63. doi: 10.23736/S2724-5276.20.05842-9. Epub 2020 Jun 16. PMID: 32549030.
Inoue S, Hirota Y, Ueno T, Fukui Y, Yoshida E, Hayashi T, Kojima S, Takeyama R, Hashimoto T, Kiyono T, Ikemura M, Taguchi A, Tanaka T, Tanaka Y, Sakata S, Takeuchi K, Muraoka A, Osuka S, Saito T, Oda K, Osuga Y, Terao Y, Kawazu M, Mano H. Uterine adenomyosis is an oligoclonal disorder associated with KRAS mutations. Nat Commun. 2019 Dec 19;10(1):5785. doi: 10.1038/s41467-019-13708-y. PMID: 31857578; PMCID: PMC6923389.
Ye H, He Y, Wang J, Song T, Lan Z, Zhao Y, Xi M. Effect of matrix metalloproteinase promoter polymorphisms on endometriosis and adenomyosis risk: evidence from a meta-analysis. J Genet. 2016 Sep;95(3):611-9. doi: 10.1007/s12041-016-0675-5. PMID: 27659332.
Kang S, Li SZ, Wang N, Zhou RM, Wang T, Wang DJ, Li XF, Bui J, Li Y. Association between genetic polymorphisms in fibroblast growth factor (FGF)1 and FGF2 and risk of endometriosis and adenomyosis in Chinese women. Hum Reprod. 2010 Jul;25(7):1806-11. doi: 10.1093/humrep/deq128. Epub 2010 May 26. PMID: 20504870.
Kang S, Zhao J, Liu Q, Zhou R, Wang N, Li Y. Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosis. Environ Mol Mutagen. 2009 Jun;50(5):361-6. doi: 10.1002/em.20455. PMID: 19197986.
Zhai J, Li S, Sen S, Opoku-Anane J, Du Y, Chen ZJ, Giudice LC. m6A RNA Methylation Regulators Contribute to Eutopic Endometrium and Myometrium Dysfunction in Adenomyosis. Front Genet. 2020 Jul 3;11:716. doi: 10.3389/fgene.2020.00716. PMID: 32719721; PMCID: PMC7350935.
Singtripop T, Mori T, Park MK, Sakamoto S, Kawashima S. Development of uterine adenomyosis after treatment with dopamine antagonists in mice. Life Sci. 1991;49(3):201-6. doi: 10.1016/0024-3205(91)90004-u. PMID: 2062175.
Guo SW, Mao X, Ma Q, Liu X. Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis. Fertil Steril. 2013 Jan;99(1):231-240. doi: 10.1016/j.fertnstert.2012.08.038. Epub 2012 Sep 19. PMID: 22999795.
Bruner-Tran KL, Gnecco J, Ding T, Glore DR, Pensabene V, Osteen KG. Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models. Reprod Toxicol. 2017 Mar;68:59-71. doi: 10.1016/j.reprotox.2016.07.007. Epub 2016 Jul 14. PMID: 27423904; PMCID: PMC5237424.
Ota H, Igarashi S, Hatazawa J, Tanaka T. Is adenomyosis an immune disease? Hum Reprod Update. 1998 Jul-Aug;4(4):360-7. doi: 10.1093/humupd/4.4.360. PMID: 9825851.
Xiang Y, Sun Y, Yang B, Yang Y, Zhang Y, Yu T, Huang H, Zhang J, Xu H. Transcriptome sequencing of adenomyosis eutopic endometrium: A new insight into its pathophysiology. J Cell Mol Med. 2019 Dec;23(12):8381-8391. doi: 10.1111/jcmm.14718. Epub 2019 Oct 1. PMID: 31576674; PMCID: PMC6850960.
Yang JH, Chen MJ, Chen HF, Lee TH, Ho HN, Yang YS. Decreased expression of killer cell inhibitory receptors on natural killer cells in eutopic endometrium in women with adenomyosis. Hum Reprod. 2004 Sep;19(9):1974-8. doi: 10.1093/humrep/deh372. Epub 2004 Jun 24. PMID: 15217996.
Rotkitansky K. Ueber uterusdruesen-neubildung. Z Gesellschaft Aerzte Wien 1860;16:577–581
Frankl O. Adenomyosis uteri. Am J Obstet Gynecol 1925;10:680–684.
Bird CC, McElin TW, Manalo-Estrella P. The elusive adenomyosis of the uterus--revisited. Am J Obstet Gynecol. 1972 Mar;112(5):583-93. doi: 10.1016/0002-9378(72)90781-8. PMID: 5059589.
Antero MF, Ayhan A, Segars J, Shih IM. Pathology and Pathogenesis of Adenomyosis. Semin Reprod Med. 2020 May;38(2-03):108-118. doi: 10.1055/s-0040-1718922. Epub 2020 Oct 20. PMID: 33080632; PMCID: PMC7987203.
Ertan B, Akdöner A, Yavuz O, et al. Adenomyozis; tanı, klinik bulgular ve tedavinin güncel yaklaşımları. Turkish Journal of Reproductive Medicine and Surgery. 2022;6(1):135-41. doi: 10.24074/tjrms.2021-87530
Stratopoulou CA, Donnez J, Dolmans MM. Origin and Pathogenic Mechanisms of Uterine Adenomyosis: What Is Known So Far. Reprod Sci. 2021 Aug;28(8):2087-2097. doi: 10.1007/s43032-020-00361-w. Epub 2020 Oct 22. PMID: 33090375.
García-Solares J, Donnez J, Donnez O, Dolmans MM. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018 Mar;109(3):371-379. doi: 10.1016/j.fertnstert.2017.12.030. PMID: 29566849.
Bergeron C, Amant F, Ferenczy A. Pathology and physiopathology of adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2006 Aug;20(4):511-21. doi: 10.1016/j.bpobgyn.2006.01.016. Epub 2006 Mar 24. PMID: 16563870.
Maier V., Höll M., Dietze R., Mecha E., Omwandho C.O., Tinneberg H.-R., Meinhold-Heerlein I., Konrad L. Adenomyotic glands are highly related to endometrial glands. Reprod. Biomed. Online. 2019;40:769–778. doi: 10.1016/j.rbmo.2019.11.007.
Ibrahim MG, Chiantera V, Frangini S, Younes S, Köhler C, Taube ET, Plendl J, Mechsner S. Ultramicro-trauma in the endometrial-myometrial junctional zone and pale cell migration in adenomyosis. Fertil Steril. 2015 Dec;104(6):1475-83.e1-3. doi: 10.1016/j.fertnstert.2015.09.002. Epub 2015 Oct 9. PMID: 26439760.
Curtis KM, Hillis SD, Marchbanks PA, Peterson HB. Disruption of the endometrial-myometrial border during pregnancy as a risk factor for adenomyosis. Am J Obstet Gynecol 2002; 187 ( 03 ): 543–544. https://doi.org/10.1067/mob.2002.124285
García-Solares J, Donnez J, Donnez O, Dolmans MM. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018 Mar;109(3):371-379. doi: 10.1016/j.fertnstert.2017.12.030. PMID: 29566849.
Batt RE, Yeh J. Müllerianosis: four developmental (embryonic) mullerian diseases. Reprod Sci. 2013 Sep;20(9):1030-7. doi: 10.1177/1933719112472736. Epub 2013 Jan 11. PMID: 23314961.
Ferenczy A. Pathophysiology of adenomyosis. Hum Reprod Update. 1998 Jul-Aug;4(4):312-22. doi: 10.1093/humupd/4.4.312. PMID: 9825847.
Chun S, Kim YM, Ji YI. Uterine adenomyosis which developed from hypoplastic uterus in postmenopausal woman with mayer-rokitansky-kuster-hauser syndrome: a case report. J Menopausal Med. 2013 Dec;19(3):135-8. doi: 10.6118/jmm.2013.19.3.135. Epub 2013 Dec 27. PMID: 25371879; PMCID: PMC4217560.
Hoo PS, Norhaslinda AR, Reza JN. Rare Case of Leiomyoma and Adenomyosis in Mayer-Rokitansky-Kuster-Hauser Syndrome. Case Rep Obstet Gynecol. 2016;2016:3725043. doi: 10.1155/2016/3725043. Epub 2016 Oct 23. PMID: 27843659; PMCID: PMC5097798.
Zhai J, Vannuccini S, Petraglia F, Giudice LC. Adenomyosis: Mechanisms and Pathogenesis. Semin Reprod Med. 2020 May;38(2-03):129-143. doi: 10.1055/s-0040-1716687. Epub 2020 Oct 8. PMID: 33032339; PMCID: PMC7932680.
Chapron C, Tosti C, Marcellin L, Bourdon M, Lafay-Pillet MC, Millischer AE, Streuli I, Borghese B, Petraglia F, Santulli P. Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes. Hum Reprod. 2017 Jul 1;32(7):1393-1401. doi: 10.1093/humrep/dex088. PMID: 28510724.
García-Solares J, Donnez J, Donnez O, Dolmans MM. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018 Mar;109(3):371-379. doi: 10.1016/j.fertnstert.2017.12.030. PMID: 29566849.
Wang Y.-Y., Duan H., Wang S., Quan Y.-J., Huang J.-H., Guo Z.-C. Upregulated Talin1 synergistically boosts β-estradiol-induced proliferation and pro-angiogenesis of eutopic and ectopic endometrial stromal cells in adenomyosis. Reprod. Biol. Endocrinol. 2021;19:70. doi: 10.1186/s12958-021-00756-7.
Li J.-J., Duan H., Wang S., Sun F.-Q., Gan L., Tang Y.-Q., Xu Q., Li T.C. Expression Pattern of G-Protein-Coupled Estrogen Receptor in Myometrium of Uteri with and without Adenomyosis. BioMed Res. Int. 2017;2017:5974693. doi: 10.1155/2017/5974693.
Brosens I, Gordts S, Habiba M, Benagiano G. Uterine Cystic Adenomyosis: A Disease of Younger Women. J Pediatr Adolesc Gynecol. 2015 Dec;28(6):420-6. doi: 10.1016/j.jpag.2014.05.008. Epub 2014 May 28. PMID: 26049940.
Zannoni L, Del Forno S, Raimondo D, Arena A, Giaquinto I, Paradisi R, Casadio P, Meriggiola MC, Seracchioli R. Adenomyosis and endometriosis in adolescents and young women with pelvic pain: prevalence and risk factors. Minerva Pediatr (Torino). 2024 Feb;76(1):57-63. doi: 10.23736/S2724-5276.20.05842-9. Epub 2020 Jun 16. PMID: 32549030.
Inoue S, Hirota Y, Ueno T, Fukui Y, Yoshida E, Hayashi T, Kojima S, Takeyama R, Hashimoto T, Kiyono T, Ikemura M, Taguchi A, Tanaka T, Tanaka Y, Sakata S, Takeuchi K, Muraoka A, Osuka S, Saito T, Oda K, Osuga Y, Terao Y, Kawazu M, Mano H. Uterine adenomyosis is an oligoclonal disorder associated with KRAS mutations. Nat Commun. 2019 Dec 19;10(1):5785. doi: 10.1038/s41467-019-13708-y. PMID: 31857578; PMCID: PMC6923389.
Ye H, He Y, Wang J, Song T, Lan Z, Zhao Y, Xi M. Effect of matrix metalloproteinase promoter polymorphisms on endometriosis and adenomyosis risk: evidence from a meta-analysis. J Genet. 2016 Sep;95(3):611-9. doi: 10.1007/s12041-016-0675-5. PMID: 27659332.
Kang S, Li SZ, Wang N, Zhou RM, Wang T, Wang DJ, Li XF, Bui J, Li Y. Association between genetic polymorphisms in fibroblast growth factor (FGF)1 and FGF2 and risk of endometriosis and adenomyosis in Chinese women. Hum Reprod. 2010 Jul;25(7):1806-11. doi: 10.1093/humrep/deq128. Epub 2010 May 26. PMID: 20504870.
Kang S, Zhao J, Liu Q, Zhou R, Wang N, Li Y. Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosis. Environ Mol Mutagen. 2009 Jun;50(5):361-6. doi: 10.1002/em.20455. PMID: 19197986.
Zhai J, Li S, Sen S, Opoku-Anane J, Du Y, Chen ZJ, Giudice LC. m6A RNA Methylation Regulators Contribute to Eutopic Endometrium and Myometrium Dysfunction in Adenomyosis. Front Genet. 2020 Jul 3;11:716. doi: 10.3389/fgene.2020.00716. PMID: 32719721; PMCID: PMC7350935.
Singtripop T, Mori T, Park MK, Sakamoto S, Kawashima S. Development of uterine adenomyosis after treatment with dopamine antagonists in mice. Life Sci. 1991;49(3):201-6. doi: 10.1016/0024-3205(91)90004-u. PMID: 2062175.
Guo SW, Mao X, Ma Q, Liu X. Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis. Fertil Steril. 2013 Jan;99(1):231-240. doi: 10.1016/j.fertnstert.2012.08.038. Epub 2012 Sep 19. PMID: 22999795.
Bruner-Tran KL, Gnecco J, Ding T, Glore DR, Pensabene V, Osteen KG. Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models. Reprod Toxicol. 2017 Mar;68:59-71. doi: 10.1016/j.reprotox.2016.07.007. Epub 2016 Jul 14. PMID: 27423904; PMCID: PMC5237424.
Ota H, Igarashi S, Hatazawa J, Tanaka T. Is adenomyosis an immune disease? Hum Reprod Update. 1998 Jul-Aug;4(4):360-7. doi: 10.1093/humupd/4.4.360. PMID: 9825851.
Xiang Y, Sun Y, Yang B, Yang Y, Zhang Y, Yu T, Huang H, Zhang J, Xu H. Transcriptome sequencing of adenomyosis eutopic endometrium: A new insight into its pathophysiology. J Cell Mol Med. 2019 Dec;23(12):8381-8391. doi: 10.1111/jcmm.14718. Epub 2019 Oct 1. PMID: 31576674; PMCID: PMC6850960.
Yang JH, Chen MJ, Chen HF, Lee TH, Ho HN, Yang YS. Decreased expression of killer cell inhibitory receptors on natural killer cells in eutopic endometrium in women with adenomyosis. Hum Reprod. 2004 Sep;19(9):1974-8. doi: 10.1093/humrep/deh372. Epub 2004 Jun 24. PMID: 15217996.
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January 21, 2025
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