多囊卵巢综合征致子宫内膜病变相关影响因素研究进展

doi:10.12280/gjszjk.20210137

摘要/Abstract

摘要：

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是一种多病因引起的生殖内分泌代谢性疾病,临床多表现为多毛、痤疮、排卵障碍、月经稀发甚至闭经,其远期并发症有代谢综合征、心血管疾病和子宫内膜癌（endometrial carcinoma,EC）等。子宫内膜病变是指各种原因所致内分泌失调引起妇女不规则阴道出血、经期延长和经量增多等,包括子宫内膜增生（endometrial hyperplasia,EH）和EC。PCOS患者因内分泌代谢紊乱（包括各种原因所致雌激素、雄激素分泌失调,胰岛素抵抗及高胰岛素血症）、炎症反应、微卫星不稳定性、微小RNA（miRNA）表达失调及其远期合并症（肥胖、糖尿病等）致子宫内膜病变风险增加,发生EH甚至EC从而影响妇女身心健康。就PCOS致子宫内膜病变影响因素的研究进展进行了综述。

关键词: 多囊卵巢综合征, 子宫疾病, 雌激素类, 雄激素类, 微卫星不稳定性

Abstract:

Polycystic ovary syndrome (PCOS) is a reproductive endocrine and metabolic disease caused by multiple etiologies. It is clinically manifested as hirsutism, acne, ovulation disorders, oligomenorrhea and amenorrhea. The long-term complications of PCOS include metabolism syndrome, cardiovascular disease, endometrial carcinoma (EC), etc. Endometrial disease refers to the irregular vaginal bleeding, prolonged menstrual period and increased menstrual flow caused by endocrine disorders. Endometrial disease includes endometrial hyperplasia (EH) and EC. The risk of endometrial disease in PCOS patients is increased due to their endocrine and metabolic disorders (including the disorder of estrogen and androgen secretion, insulin resistance and hyperinsulinemia), inflammation, microsatellite instability, miRNA expression disorders and their long-term comorbidities ( such as obesity, diabetes, etc.). The EH and EC in PCOS patients affect their physical and mental health. This article summarizes the research progress of PCOS-related endometrial disease and influencing factors.

Key words: Polycystic ovary syndrome, Uterine diseases, Estrogens, Androgens, Microsatellite instability

曹婧, 苏芮, 王晓慧. 多囊卵巢综合征致子宫内膜病变相关影响因素研究进展[J]. 国际生殖健康/计划生育, 2021, 40(5): 415-419.

CAO Jing, SU Rui, WANG Xiao-hui. Influencing Factors Related to Endometrial Disease Caused by Polycystic Ovary Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(5): 415-419.

参考文献 31

[1]	Jia X, Yang L, Xu P, et al. Endometrial cancer combined with polycystic ovary syndrome in 9 women under 40-years old: A case report[J]. Biomed Rep, 2020, 13(5):50. doi: 10.3892/br.2020.1357. doi: 10.3892/br.2020.1357
[2]	Meczekalski B, Pérez-Roncero GR, López-Baena MT, et al. The polycystic ovary syndrome and gynecological cancer risk[J]. Gynecol Endocrinol, 2020, 36(4):289-293. doi: 10.1080/09513590.2020.1730794. doi: 10.1080/09513590.2020.1730794 pmid: 32103691
[3]	Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients[J]. Cancer, 1985, 56(2):403-412. doi: 10.1002/1097-0142(19850715)56:2<403::aid-cncr2820560233>3.0.co;2-x. doi: 10.1002/1097-0142(19850715)56:2<403::aid-cncr2820560233>3.0.co;2-x pmid: 4005805
[4]	王立群, 周月希, 张娟. 多囊卵巢综合征大鼠子宫内膜细胞凋亡及VEGF-A的表达[J]. 暨南大学学报(自然科学与医学版), 2019, 40(2):143-149. doi: 10.11778/j.jdxb.2019.02.007. doi: 10.11778/j.jdxb.2019.02.007
[5]	Jumaah AS, Al-Haddad HS, Mahdi LH, et al. Increased PTEN gene expression in patients with endometrial carcinoma from areas of high risk depleted uranium exposure[J]. BMC Res Notes, 2019, 12(1):708. doi: 10.1186/s13104-019-4756-4. doi: 10.1186/s13104-019-4756-4 pmid: 31665075
[6]	Liu J, Ding J, Qu B, et al. CircPSMC3 alleviates the symptoms of PCOS by sponging miR-296-3p and regulating PTEN expression[J]. J Cell Mol Med, 2020, 24(18):11001-11011. doi: 10.1111/jcmm.15747. doi: 10.1111/jcmm.15747 URL
[7]	Bian X, Gao J, Luo F, et al. PTEN deficiency sensitizes endometrioid endometrial cancer to compound PARP-PI3K inhibition but not PARP inhibition as monotherapy[J]. Oncogene, 2018, 37(3):341-351. doi: 10.1038/onc.2017.326. doi: 10.1038/onc.2017.326 pmid: 28945226
[8]	李小芳, 李秀莹, 林辉瑞, 等. 多囊卵巢综合征相关子宫内膜增生病变的研究进展[J]. 中华妇幼临床医学杂志(电子版), 2018, 14(4):470-476. doi: 10.3877/cma.j.issn.1673-5250.2018.04.016. doi: 10.3877/cma.j.issn.1673-5250.2018.04.016
[9]	Gao X, Qin T, Mao J, et al. PTENP1/miR-20a/PTEN axis contributes to breast cancer progression by regulating PTEN via PI3K/AKT pathway[J]. J Exp Clin Cancer Res, 2019, 38(1):256. doi: 10.1186/s13046-019-1260-6. doi: 10.1186/s13046-019-1260-6 URL
[10]	李可君, 张慧英, 张艳芳, 等. PTEN蛋白在多囊卵巢综合征患者子宫内膜中的表达与临床意义[J]. 中国计划生育学杂志, 2013, 21(9):607-610. doi: 10.3969/j.issn.1004-8189.2013.09. doi: 10.3969/j.issn.1004-8189.2013.09
[11]	Sahoo SS, Tanwar PS. VEGF-mTOR signaling links obesity and endometrial cancer[J]. Oncoscience, 2018, 5(5/6):150-151. doi: 10.18632/oncoscience.430. doi: 10.18632/oncoscience.430 URL
[12]	MacLaughlan SD, Palomino WA, Mo B, et al. Endometrial expression of Cyr61: a marker of estrogenic activity in normal and abnormal endometrium[J]. Obstet Gynecol, 2007, 110(1):146-154. doi: 10.1097/01.AOG.0000269047.46078.28. doi: 10.1097/01.AOG.0000269047.46078.28 pmid: 17601910
[13]	Wang C, Tran DA, Fu MZ, et al. Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Markers in Endometrial Cancer[J]. J Cancer, 2020, 11(7):1693-1701. doi: 10.7150/jca.41943. doi: 10.7150/jca.41943 URL
[14]	Zeng X, Xie YJ, Liu YT, et al. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity[J]. Clin Chim Acta, 2020, 502:214-221. doi: 10.1016/j.cca.2019.11.003. doi: S0009-8981(19)32118-7 pmid: 31733195
[15]	He FF, Li YM. Role of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome: a review[J]. J Ovarian Res, 2020, 13(1):73. doi: 10.1186/s13048-020-00670-3. doi: 10.1186/s13048-020-00670-3 URL
[16]	Anagnostis P, Tarlatzis BC, Kauffman RP. Polycystic ovarian syndrome (PCOS): Long-term metabolic consequences[J]. Metabolism, 2018, 86:33-43. doi: 10.1016/j.metabol.2017.09.016. doi: 10.1016/j.metabol.2017.09.016 URL
[17]	罗国群, 邓伟芬, 柳倩茹, 等. PCOS患者子宫内膜病变和胰岛素受体表达的临床研究[J]. 中国计划生育学杂志, 2013, 21(1):32-35. doi: 10.3969/j.issn.1004-8189.2012.11. doi: 10.3969/j.issn.1004-8189.2012.11
[18]	Sidorkiewicz I, Józwik M, Niemira M, et al. Insulin Resistance and Endometrial Cancer: Emerging Role for microRNA[J]. Cancers (Basel), 2020, 12(9):2559. doi: 10.3390/cancers12092559. doi: 10.3390/cancers12092559 URL
[19]	Ma Z, Lou S, Jiang Z. PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway[J]. Aging (Albany NY), 2020, 12(9):7985-8000. doi: 10.18632/aging.103117. doi: 10.18632/aging.103117
[20]	Xie BY, Lv QY, Ning CC, et al. TET1-GPER-PI3K/AKT pathway is involved in insulin-driven endometrial cancer cell proliferation[J]. Biochem Biophys Res Commun, 2017, 482(4):857-862. doi: 10.1016/j.bbrc.2016.11.124. doi: 10.1016/j.bbrc.2016.11.124 URL
[21]	Jiang Y, Chen X, Wei Y, et al. Metformin sensitizes endometrial cancer cells to progestin by targeting TET1 to downregulate glyoxalase I expression[J]. Biomed Pharmacother, 2019, 113:108712. doi: 10.1016/j.biopha.2019.108712. doi: 10.1016/j.biopha.2019.108712 URL
[22]	Zheng XR, Pan X, Zhang J, et al. Hyperinsulinemia-induced PAX6 expression promotes endometrial epithelial cell proliferation via negatively modulating p27 signaling[J]. Biomed Pharmacother, 2018, 97:802-808. doi: 10.1016/j.biopha.2017.10.156. doi: 10.1016/j.biopha.2017.10.156 URL
[23]	Bracho GS, Altamirano GA, Kass L, et al. Hyperandrogenism Induces Histo-Architectural Changes in the Rat Uterus[J]. Reprod Sci, 2019, 26(5):657-668. doi: 10.1177/1933719118783881. doi: 10.1177/1933719118783881 URL
[24]	Levental KR, Yu H, Kass L, et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling[J]. Cell, 2009, 139(5):891-906. doi: 10.1016/j.cell.2009.10.027. doi: 10.1016/j.cell.2009.10.027 pmid: 19931152
[25]	Kubyshkin AV, Aliev LL, Fomochkina II, et al. Endometrial hyperplasia-related inflammation: its role in the development and progression of endometrial hyperplasia[J]. Inflamm Res, 2016, 65(10):785-794. doi: 10.1007/s00011-016-0960-z. doi: 10.1007/s00011-016-0960-z pmid: 27312112
[26]	Hashmi AA, Mudassir G, Hashmi RN, et al. Microsatellite Instability in Endometrial Carcinoma by Immunohistochemistry, Association with Clinical and Histopathologic Parameters[J]. Asian Pac J Cancer Prev, 2019, 20(9):2601-2606. doi: 10.31557/APJCP.2019.20.9.2601. doi: 10.31557/APJCP.2019.20.9.2601 URL
[27]	于文亮, 潘长清, 郑茜文. 子宫内膜癌组织中错配修复蛋白的表达情况及与患者免疫功能和微卫星不稳定的关系[J]. 癌症进展, 2020, 18(12):1248-1252. doi: 10.11877/j.issn.1672-1535.2020.18.12.15. doi: 10.11877/j.issn.1672-1535.2020.18.12.15
[28]	Correia de Sousa M, Gjorgjieva M, Dolicka D, et al. Deciphering miRNAs′ Action through miRNA Editing[J]. Int J Mol Sci, 2019, 20(24):6249. doi: 10.3390/ijms20246249. doi: 10.3390/ijms20246249 URL
[29]	Rodriguez AM, Polychronopoulou E, Hsu E, et al. Factors associated with endometrial cancer and hyperplasia among middle-aged and older Hispanics[J]. Gynecol Oncol, 2021, 160(1):16-23. doi: 10.1016/j.ygyno.2020.10.033. doi: 10.1016/j.ygyno.2020.10.033 pmid: 33221024
[30]	Njoku K, Abiola J, Russell J, et al. Endometrial cancer prevention in high-risk women[J]. Best Pract Res Clin Obstet Gynaecol, 2020, 65:66-78. doi: 10.1016/j.bpobgyn.2019.12.005. doi: 10.1016/j.bpobgyn.2019.12.005 URL
[31]	李延钦, 万洁, 刘国红. 糖尿病在子宫内膜癌中的作用探讨[J]. 医学食疗与健康, 2020, 18(2):192. doi: CNKI:SUN:YXSL.0.2020-02-150. doi: CNKI:SUN:YXSL.0.2020-02-150