Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2019, Vol. 10 Issue (1) : 190-196     DOI: 10.14336/AD.2018.0224
Review |
Relationship between Hypothyroidism and Endometrial Cancer
Yiqin Wang, Rong Zhou*, Jianliu Wang*
Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, China
Download: PDF(317 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Thyroid dysfunction is involved in several types of carcinoma. Hypothyroidism is one of the most common medical morbidities among patients with endometrial cancer; however, the related mechanism is unclear. Among the risk factors related to endometrial cancer, hypothyroidism interacts with metabolic syndrome, polycystic ovarian syndrome and infertility or directly acts on the endometrium itself, which may influence the development and progression of endometrial cancer. We summarize recent studies on the relationship between hypothyroidism and endometrial cancer and its risk factors to provide references for basic research as well as for clinical treatment and prognostic evaluation.

Keywords Hypothyroidism      Endometrial cancer      Sex hormone      Metabolic syndrome      Fertility     
Corresponding Authors: Zhou Rong,Wang Jianliu   
About author:

These authors contributed equally.

Issue Date: 20 July 2017
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Wang Yiqin
Zhou Rong
Wang Jianliu
Cite this article:   
Wang Yiqin,Zhou Rong,Wang Jianliu. Relationship between Hypothyroidism and Endometrial Cancer[J]. Aging and disease, 2019, 10(1): 190-196.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2018.0224     OR     http://www.aginganddisease.org/EN/Y2019/V10/I1/190
ParameterMS
PCOSInfertilityLeptin
DyslipidemiaObesityHypertension
RelationshipMS ↑, TC ↑, LDL-C ↑, triglyceride ↑, HDL ↓ [17-19]BMI ↑ [20]BP ↑ [21, 22]Ovarian volume and cyst formation ↑;
PCOS ↑; CC resistance ↑[23-26].
Menstrual problems, breakthrough bleeding, anovulation, and infertility↑ [27, 28].Leptin ↑
Possible mechanismTH → SREBP-2 and LDL-receptors ↑ → cholesterol removal from the liver [29];
TH → lipoprotein lipase and hepatic lipase activity ↑ → serum TG and cholesterol↓ [30]; TSH → acting on TSH receptors in the hepatocyte membranes → HMGC ↑ → cholesterol synthesis in the liver ↑ [19]; TSH acts on preadipocyte differentiation and adipogenesis → lipolysis↑→ serum free fatty acid↑ [19].
-T3 acts on arterial smooth muscle cells of blood vessels to cause vasodilation [31].
Hypothyroidism → abnormal sodium metabolism, the sympathetic nervous system activity ↑; glomerular filtration rate↓[32, 33].
Variant FBN3 →TGFβ and Treg ↓ → development of autoimmunity;
anovulation → E/P → autoantibodies ↑; SHBG↓ →free sex hormones↑ [34-36].
Clearance of androstendione and estrone ↓ → aromatization, leading to free estrogen ↑;
TRH ↑ →PRL ↑; GnRH pulse change → LH peak delays and luteum function disorders and coagulation defects [27, 37].
Actions on adipocytes → stimulate leptin secretion [38].
Table 1  Relationship between hypothyroidism and risk factors for EC.
[1] Bashkin A, & Nodelman M (2017). The clinical approach to diagnosis and treatment of hypothyroidism. Harefuah, 156(5): 322.
[2] Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. (2002). Serum tsh, t4, and thyroid antibodies in the united states population (1988 to 1994): national health and nutrition examination survey (nhanes iii). J Clin Endocrinol Metab, 87(2): 489.
[3] Hercbergs AA, Goyal LK, Suh JH, Lee S, Reddy CA, Cohen BH, Stevens GH, et al. (2003). Propylthiouracil-induced chemical hypothyroidism with high-dose tamoxifen prolongs survival in recurrent high-grade glioma: a phase i/ii study. Anticancer Res, 23(1B): 617.
[4] Cristofanilli M, Yamamura Y, Kau SW, Bevers T, Strom S, Patangan M, et al. (2005). Thyroid hormone and breast carcinoma. Primary hypothyroidism is associated with a reduced incidence of primary breast carcinoma. Cancer, 103(6): 1122-8.
[5] Nelson M, Hercbergs A, Rybicki L, Strome M (2006). Association between development of hypothyroidism and improved survival in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg, 132(10): 1041.
[6] Schmidinger M, Vogl UM, Bojic M, Lamm W, Heinzl H, Haitel A, et al. (2011). Hypothyroidism in patients with renal cell carcinoma: blessing or curse? Cancer, 117(3): 534-544.
[7] Sharma DN, Chander S, Gairola M, Kumar L, Parida DK, Pathy S (2001). Medical disorders associated with endometrial carcinoma. J Assoc Physicians India, 49: 630-633.
[8] Brinton LA, Sakoda LC, Frederiksen K, Sherman ME, Graubard BI, Olsen JH, et al. (2007). Relationships of uterine and ovarian tumors to pre-existing chronic conditions. Gynecol Oncol, 107(3): 487-494.
[9] Tangjitgamol S, Khunnarong J, Srijaipracharoen S (2014). Medical morbidities in endometrial cancer patients. Int J Gynecol Cancer, 24(9): 1623-1627.
[10] Kanat-Pektas M, Yenicesu O, Gungor T, Bilge U (2010). Predictive power of sexual hormones and tumor markers in endometrial cancer. Arch Gynecol Obstet, 281(4): 709.
[11] Yurkovetsky Z, Ta’Asan S, Skates S, Rand A, Lomakin A, Linkov F, et al. (2007). Development of multimarker panel for early detection of endometrial cancer. high diagnostic power of prolactin. Gynecol Oncol, 107(1): 58-65.
[12] Vilos GA, Oraif A, Vilos AG, Ettler H, Edris F, Aburafea B (2015). Long-term clinical outcomes after resectoscopic endometrial ablation of nonatypical endometrial hyperplasia in women with abnormal uterine bleeding. J Minim Invasive Gynecol, 22(1): 703-704.
[13] Seebacher V, Hofstetter G, Polterauer S, Reinthaller A, Grimm C, Schwameis R, et al. (2013). Does thyroid-stimulating hormone influence the prognosis of patients with endometrial cancer? a multicentre trial. Br J Cancer, 109(1): 215.
[14] Kang JH, Kueck AS, Stevens R, Curhan G, Vivo ID, Rosner B, et al. (2013). A large cohort study of hypothyroidism and hyperthyroidism in relation to gynecologic cancers. Obstet Gynecol Int, 2013: 743721.
[15] Akhmedkhanov A, Zeleniuchjacquotte A, Toniolo P (2001). Role of exogenous and endogenous hormones in endometrial cancer: review of the evidence and research perspectives. Ann N Y Acad Sci, 943(1): 296.
[16] Lacey-Jv J, Ioffe OB, Rush B, Richesson D, Chatterjee N, Langholz B, et al. (2008). Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan. Br J Cancer, 98(1): 45-53.
[17] Shinkov A, Borissova AM, Kovatcheva R, Atanassova I, Vlahov J, Dakovska L (2014). The prevalence of the metabolic syndrome increases through the quartiles of thyroid stimulating hormone in a population-based sample of euthyroid subjects. Arq Bras Endocrinol Metabol, 58(9): 926-932.
[18] Rodríguez-Castelán J, Anaya-Hernández A, Méndez-Tepepa M, Martínez-Gómez M, Castelán F, Cuevas-Romero E (2016). Distribution of thyroid hormone and thyrotropin receptors in reproductive tissues of adult female rabbits. Endocr Res, 42(1): 59-70.
[19] Chao X, Yang X, Liu W, Yuan H, Yu C, Ling G, et al. (2012). Thyroid stimulating hormone, independent of thyroid hormone, can elevate the serum total cholesterol level in patients with coronary heart disease: a cross-sectional design. Nutr Metab, 9(1): 44.
[20] Knudsen N, Laurberg P, Rasmussen L B, Bülow I, Perrild H, & Ovesen L, et al. (2005). Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab, 90(7), 4019.
[21] Liu D, Jiang F, Shan Z, Wang B, Wang J, Lai Y, et al. (2010). A cross-sectional survey of relationship between serum tsh level and blood pressure. J Hum Hypertens, 24(2): 134-138.
[22] Luboshitzky R, Aviv AP, Lavie L (2002). Risk factors for cardiovascular disease in women with subclinical hypothyroidism. Thyroid, 12(5): 421.
[23] Fitko R, Kucharski J, Szlezyngier B (1995). The importance of thyroid hormone in experimental ovarian cyst formation in gilts. Anim Reprod Sci, 39(2): 159-168.
[24] Muderris II, Boztosun A, Oner G, Bayram F (2011). Effect of thyroid hormone replacement therapy on ovarian volume and androgen hormones in patients with untreated primary hypothyroidism. Ann Saudi Med, 31(2): 145.
[25] Ganie MA, Marwaha RK, Aggarwal R, Singh S (2010). High prevalence of polycystic ovary syndrome characteristics in girls with euthyroid chronic lymphocytic thyroiditis: a case-control study. Eur J Endocrinol, 162(6): 1117.
[26] Ott J, Aust S, Kurz C, Nouri K, Wirth S, Huber JC, et al. (2010). Elevated antithyroid peroxidase antibodies indicating hashimoto’s thyroiditis are associated with the treatment response in infertile women with polycystic ovary syndrome. Fertil Steril, 94(7): 2895.
[27] Dittrich R, Beckmann MW, Oppelt PG, Hoffmann I, Lotz L, Kuwert T, et al. (2011). Thyroid hormone receptors and reproduction. J Reprod Immunol, 90(1): 58-66.
[28] Gerhard I, Becker T, Eggert-Kruse W, Klinga K, Runnebaum B (1991). Thyroid and ovarian function in infertile women. Hum Reprod, 6(3): 338-45.
[29] Shin DJ, Osborne TF (2003). Thyroid hormone regulation and cholesterol metabolism are connected through sterol regulatory element-binding protein-2 (srebp-2). J Biol Chem, 278(36): 34114.
[30] Valdemarsson S, Hansson P, Hedner P, Nilssonehle P (1983). Relations between thyroid function, hepatic and lipoprotein lipase activities, and plasma lipoprotein concentrations. Acta Endocrinol, 104(1): 50-56.
[31] Xiang GD, He YS, Zhao LS, Hou J, Yue L, Xiang HJ. (2006). Impairment of endothelium-dependent arterial dilation in hashimoto’s thyroiditis patients with euthyroidism. Clin Endocrinol, 64(6): 698-702.
[32] Gumieniak O, Perlstein TS, Hopkins PN, Brown NJ, Murphey LJ, Jeunemaitre X, et al. (2004). Thyroid function and blood pressure homeostasis in euthyroid subjects. J Clin Endocrinol Metab, 89(7): 3455-61.
[33] González O, Saracho R, Aguirre R (1996). Changes in renal function in primary hypothyroidism. Am J Kidney Dis, 27(2): 195-198.
[34] Gaberšček S, Zaletel K, Schwetz V, Pieber T, Obermayerpietsch B, Lerchbaum E (2015). Mechanisms in endocrinology: thyroid and polycystic ovary syndrome. Eur J Endocrin, 172(1): 9-21.
[35] Quintero OL, Amadorpatarroyo MJ, Montoyaortiz G, Rojasvillarraga A, Anaya JM (2012). Autoimmune disease and gender: plausible mechanisms for the female predominance of autoimmunity. J Autoimmun, 38(2-3): J109.
[36] Sinha U, Sinharay K, Saha S, Longkumer TA, Baul SN, Pal SK (2013). Thyroid disorders in polycystic ovarian syndrome subjects: a tertiary hospital based cross-sectional study from eastern india. Indian J Endocrinol Metab,17,2(2013-03-28), 17(2): 304-309.
[37] Krassas GE, Poppe K, Glinoer D (2010). Thyroid function and human reproductive health. Endocr Rev, 31(5): 702-755.
[38] Menendez C, Baldelli R, Camiña JP, Escudero B, Peino R, Dieguez C, et al. (2003). Tsh stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol, 176(1): 7-12.
[39] Cooper DS, Biondi B (2012). Subclinical thyroid disease. Singapore Med J, 44(11): 595.
[40] Razvi S, Ingoe L, Keeka G, Oates C, Mcmillan C, Weaver JU (2007). The beneficial effect of l-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab, 92(5): 1715-23.
[41] Cramer DW, Sluss PM (2003). Serum prolactin and tsh in an in vitro fertilization population: is there a link between fertilization and thyroid function? J Assist Reprod Genet, 20(6): 210.
[42] Unuane D, Tournaye H, Velkeniers B, Poppe K (2011). Endocrine disorders & female infertility. Best Pract Res Clin Endocrinol Metab, 25(6): 861-873.
[43] Arojoki M, Jokimaa V, Juuti A, Koskinen P, Irjala K, Anttila L (2000). Hypothyroidism among infertile women in finland. Gynecol Endocrinol, 14(2):127-131.
[44] Bohnet HG, Fiedler K, Leidenberger FA (1981). Subclinical hypothyroidism and infertility. Lancet, 2(8258): 1278.
[45] Wang PP, He XY, Wang R, Wang Z, Wang YG (2014). High leptin level is an independent risk factor of endometrial cancer: a meta-analysis. Cell Physiol Biochem, 34(5):1477-84.
[46] Zhang Y, Liu L, Li C, Ai H (2014). Correlation analysis between the expressions of leptin and its receptor (obr) and clinicopathology in endometrial cancer. Cancer Biomarkers, 14(5): 353-9.
[47] Zhou X, Li H, Chai Y, Liu Z (2015). Leptin inhibits the apoptosis of endometrial carcinoma cells through activation of the nuclear factor κb-inducing kinase/iκb kinase pathway. Int J Gynecol Cancer, 25(5): 770.
[48] Liu Y, Lv LQ, Xiao W, Gong C, Yin J, Wang DH, et al. (2011). Leptin activates STAT3 and ERK1/2 pathways and induces endometrial cancer cell proliferation. J Huazhong Univ Sci Technolog Med Sci, 31(3): 365-370.
[49] Bétry C, Challanbelval MA, Bernard A, Charrié A, Drai J, Laville M, et al. (2015). Increased tsh in obesity: evidence for a bmi-independent association with leptin. Diabetes Metab, 41(3): 248.
[50] Aghajanova L, Stavreus-Evers A, Lindeberg M, Landgren BM, Sparre LS, Hovatta O (2011). Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology. Fertil Steril, 95(1): 230-237.
[51] Sordia-hernandez LH, Morales MA, Gris JM, Herrero J, Hernandez UC, Merino M, et al. (2014). Normal "high" thyroid stimulating hormone (tsh) levels and pregnancy rates in patients undergoing ivf with donor eggs. Clin Exp Obstet Gynecol, 41(5): 517.
[52] Goswami B, Patel S, Chatterjee M, Koner BC, Saxena A (2009). Correlation of prolactin and thyroid hormone concentration with menstrual patterns in infertile women. J Reprod Infertil, 10(3): 207-212.
[1] Yuxiao Liao,Zhao Peng,Liangkai Chen,Yan Zhang,Qian Cheng,Andreas K. Nüssler,Wei Bao,Liegang Liu,Wei Yang. Prospective Views for Whey Protein and/or Resistance Training Against Age-related Sarcopenia[J]. Aging and disease, 2019, 10(1): 157-173.
[2] Szkup Malgorzata, Brodowski Jacek, Aleksander Jerzy Owczarek, Choręza Piotr, Jurczak Anna, Grochans Elzbieta. Searching for Factors Raising the Incidence of Metabolic Syndrome Among 45-60-Year-Old Women[J]. Aging and disease, 2018, 9(5): 831-842.
[3] Bonomini Francesca, Rodella Luigi Fabrizio, Rezzani Rita. Metabolic Syndrome, Aging and Involvement of Oxidative Stress[J]. Aging and disease, 2015, 6(2): 109-120.
[4] Guarner Veronica,Rubio-Ruiz Maria Esther. Aging, Metabolic Syndrome and the Heart[J]. Aging and Disease, 2012, 3(3): 269-279.
[5] Gregory Oxenkrug. Interferon-gamma – Inducible Inflammation: Contribution to Aging and Aging-Associated Psychiatric Disorders[J]. Aging and Disease, 2011, 2(6): 474-486.
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd