Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-8448b6f56d-tj2md Total loading time: 0 Render date: 2024-04-23T17:53:10.138Z Has data issue: false hasContentIssue false

Chapter 1 - Pathophysiology of Uterine Fibroids

Published online by Cambridge University Press:  10 October 2020

By
Mohamed Otify  and
Hilary O. D. Critchley
Edited by
Mostafa Metwally  and
Tin-Chiu Li
Mostafa Metwally
Affiliation:
University of Sheffield
Tin-Chiu Li
Affiliation:
The Chinese University of Hong Kong
Get access

Summary

Uterine fibroids are a major cause of morbidity in women [1]. Fibroids have variable clinical presentations, depending on size and location. These include pelvic pain (20–40% of patients), bleeding (30% of patients), and anaemia. Fibroids are the leading cause of hysterectomy in the United States [2]. Bleeding from fibroids generally presents as abnormal uterine bleeding (AUB) and often prolonged or heavy menstrual bleeding (HMB) [3]. Fibroids that bleed are more frequently submucosal or extend into the endometrial cavity. Other problems related to fibroids include problems with implantation [1], preterm labour, recurrent loss of pregnancy, obstruction of labour, and urinary incontinence [4]. Medical costs for patients with fibroids in the United States were estimated as 4.1–9.4 billion US dollars in 2010 [2].

Type
Chapter
Information
Modern Management of Uterine Fibroids , pp. 1 - 13
Publisher: Cambridge University Press
Print publication year: 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Laughlin, SK, Stewart, EA. Uterine leiomyomas: individualizing the approach to a heterogeneous condition. Obstet Gynecol 2011;117:396–403.CrossRefGoogle ScholarPubMed
Cardozo, ER, Clark, AD, Banks, NK, et al. The estimated annual cost of uterine leiomyomata in the United States. Am J Obstet Gynecol 2012;206:211.e1–9.CrossRefGoogle ScholarPubMed
Whitaker, L, Critchley, HO. Abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol 2016;34:54–65.Google Scholar
Cook, H, Ezzati, M, Segars, JH, McCarthy, K. The impact of uterine leiomyomas on reproductive outcomes. Minerva Ginecol 2010;62:225–36.Google ScholarPubMed
Zimmermann, A, Bernuit, D, Gerlinger, C, Schaefers, M, Geppert, K. Prevalence, symptoms and management of uterine fibroids: an international internet-based survey of 21,746 women. BMC Womens Health 2012;12:6.CrossRefGoogle Scholar
Graphiq. Uterine fibroids. International Statistics on Mortality and Affected Populations [Internet]. Available from: http://global-diseases.healthgrove.com/l/208/Uterine-FibroidsGoogle Scholar
Baird, DD, Dunson, DB, Hill, MC, Cousins, D, Schectman, JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol 2003;188:100–7.Google ScholarPubMed
Chavez, NF, Stewart, EA. Medical treatment of uterine fibroids. Clin Obstet Gynecol 2001;44:372–84.CrossRefGoogle ScholarPubMed
Peddada, SD, Laughlin, SK, Miner, K, et al. Growth of uterine leiomyomata among premenopausal black and white women. Proc Natl Acad Sci USA 2008;105:19887–92.Google Scholar
Davis, BJ, Risinger, JI, Chandramouli, GV, et al. Gene expression in uterine leiomyoma from tumors likely to be growing (from black women over 35) and tumors likely to be non-growing (from white women over 35). PLoS One 2013;8:e63909.Google Scholar
Payson, M, Leppert, P, Segars, J. Epidemiology of myomas. Obstet Gynecol Clin North Am 2006;33:1–11.Google Scholar
Stewart, EA. Uterine fibroids. Lancet 2001;357:293–8.Google Scholar
Walker, CL, Stewart, EA. Uterine fibroids: the elephant in the room. Science 2005;308:1589–92.Google Scholar
Flake, GP, Andersen, J, Dixon, D. Etiology and pathogenesis of uterine leiomyomas: a review. Environ Health Perspect 2003;111:1037–54.Google Scholar
Baird, DD, Harmon, QE, Upson, K, et al. A prospective, ultrasound-based study to evaluate risk factors for uterine fibroid incidence and growth: methods and results of recruitment. J Womens Health (Larchmt) 2015;24:907–15.Google Scholar
Catherino, W, Salama, A, Potlog-Nahari, C, et al. Gene expression studies in leiomyomata: new directions for research. Semin Reprod Med 2004;22:83–90.Google Scholar
Borgfeldt, C, Andolf, E. Transvaginal ultrasonographic findings in the uterus and the endometrium: low prevalence of leiomyoma in a random sample of women age 25–40 years. Acta Obstet Gynecol Scand 2000;79:202–7.Google Scholar
Cramer, SF, Patel, A. The frequency of uterine leiomyomas. Am J Clin Pathol 1990;94:435–8.CrossRefGoogle ScholarPubMed
Laughlin, SK, Schroeder, JC, Baird, DD. New directions in the epidemiology of uterine fibroids. Semin Reprod Med 2010;28:204–17.Google Scholar
Islam, MS, Akhtar, MM, Ciavattini, A, et al. Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: promising options for prevention and treatment of uterine fibroids? Mol Nutr Food Res 2014;58:1667–84.Google Scholar
Wise, LA, Radin, RG, Palmer, JR, et al. Intake of fruit, vegetables, and carotenoids in relation to risk of uterine leiomyomata. Am J Clin Nutr 2011;94:1620–31.Google Scholar
Baird, DD, Hill, MC, Schectman, JM, Hollis, BW. Vitamin D and the risk of uterine fibroids. Epidemiology 2013;24:447–53.Google Scholar
Harris, SS. Vitamin D and African Americans. J Nutr 2006;136:1126–9.Google Scholar
Marshall, LM, Spiegelman, D, Goldman, MB, et al. A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata. Fertil Steril 1998;70:432–9.CrossRefGoogle Scholar
Sener, AB, Seckin, NC, Ozmen, S, et al. The effects of hormone replacement therapy on uterine fibroids in postmenopausal women. Fertil Steril 1996;65:354–7.Google Scholar
Palomba, S, Sena, T, Noia, R, et al. Transdermal hormone replacement therapy in postmenopausal women with uterine leiomyomas. Obstet Gynecol 2001;98:1053–8.Google ScholarPubMed
Yang, CH, Lee, JN, Hsu, SC, et al. Effect of hormone replacement therapy on uterine fibroids in postmenopausal women – a 3-year study. Maturitas 2002;43:35–9.CrossRefGoogle Scholar
Marsh, EE, Bulun, SE. Steroid hormones and leiomyomas. Obstet Gynecol Clin North Am 2006;33:59–67.Google Scholar
Ruddon, RW. What makes a cancer cell a cancer cell? In: Kufe, DW, Pollock, RE, Weichselbaum, RR, et al., editors. Holland-Frei Cancer Medicine, 6th ed. Hamilton, ON: B. C. Decker; 2003. Available from: www.ncbi.nlm.nih.gov/books/NBK12516/Google Scholar
Wong, E. Introduction to neoplasia. 2016. Available from: www.pathophys.org/introneoplasia/Google Scholar
Leppert, PC, Catherino, WH, Segars, JH. A new hypothesis about the origin of uterine fibroids based on gene expression profiling with microarrays. Am J Obstet Gynecol 2006;195:415–20.Google Scholar
Levy, G, Hill, MJ, Beall, S, et al. Leiomyoma: genetics, assisted reproduction, pregnancy and therapeutic advances. J Assist Reprod Genet 2012;29:703–12.Google Scholar
Stewart, EA, Morton, CC. The genetics of uterine leiomyomata: what clinicians need to know. Obstet Gynecol 2006;107:917–21.Google Scholar
Kim, JJ, Sefton, EC, Bulun, SE. Progesterone receptor action in leiomyoma and endometrial cancer. Prog Mol Biol Transl Sci 2009;87:53–85.Google Scholar
Taylor, DK, Holthouser, K, Segars, JH, Leppert, PC. Recent scientific advances in leiomyoma (uterine fibroids) research facilitates better understanding and management. F1000Research 2015;4:183.Google Scholar
Bulun, SE, Noble, LS, Takayama, K, et al. Endocrine disorders associated with inappropriately high aromatase expression. J Steroid Biochem Mol Biol 1997;61:133–9.CrossRefGoogle ScholarPubMed
Bulun, SE. Uterine fibroids. N Engl J Med 2013;369:1344–55.Google Scholar
Stewart, EA, Nowak, RA. Leiomyoma-related bleeding: a classic hypothesis updated for the molecular era. Hum Reprod Update 1996;2:295–306.Google Scholar
Wang, J, Ohara, N, Wang, Z, et al. A novel selective progesterone receptor modulator asoprisnil (J867) down-regulates the expression of EGF, IGF-I, TGFbeta3 and their receptors in cultured uterine leiomyoma cells. Hum Reprod 2006;21:1869–77.Google Scholar
Anania, CA, Stewart, EA, Quade, BJ, Hill, JA, Nowak, RA. Expression of the fibroblast growth factor receptor in women with leiomyomas and abnormal uterine bleeding. Mol Hum Reprod 1997;3:685–91.Google Scholar
Cha, PC, Takahashi, A, Hosono, N, et al. A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids. Nat Genet 2011;43:447–50.CrossRefGoogle ScholarPubMed
Markowski, DN, Helmke, BM, Bartnitzke, S, Loning, T, Bullerdiek, J. Uterine fibroids: do we deal with more than one disease? Int J Gynecol Pathol 2014;33:568–72.CrossRefGoogle ScholarPubMed
Bulun, SE, Moravek, MB, Yin, P, et al. Uterine leiomyoma stem cells: linking progesterone to growth. Semin Reprod Med 2015;33:357–65.Google ScholarPubMed
Ono, M, Qiang, W, Serna, VA, et al. Role of stem cells in human uterine leiomyoma growth. PLoS One 2012;7:e36935.Google Scholar
Markowski, DN, Bartnitzke, S, Loning, T, et al. MED12 mutations in uterine fibroids – their relationship to cytogenetic subgroups. Int J Cancer 2012;131:1528–36.Google Scholar
Halder, SK, Elam, LA, Laknaur, A, Diamond, MP, Al-Hendy, A. Introduction of exon 2 mutant MED12 gene triggers activation of Wnt/β-catenin signaling in normal human uterine smooth muscle cells. Fertil Steril 2015;104(Suppl.):e30.CrossRefGoogle Scholar
Sinclair, DC, Mastroyannis, A, Taylor, HS. Leiomyoma simultaneously impair endometrial BMP-2-mediated decidualization and anticoagulant expression through secretion of TGF-beta3. J Clin Endocrinol Metab 2011;96:412–21.Google Scholar
Moravek, MB, Bulun, SE. Endocrinology of uterine fibroids: steroid hormones, stem cells, and genetic contribution. Curr Opin Obstet Gynecol 2015;27:276–83.Google Scholar
Jorge, S, Chang, S, Barzilai, JJ, Leppert, P, Segars, JH. Mechanical signaling in reproductive tissues: mechanisms and importance. Reprod Sci 2014;21:1093–107.Google Scholar
Munro, MG, Critchley, HO, Broder, MS, Fraser, IS. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011;113:3–13.CrossRefGoogle ScholarPubMed
Wamsteker, K, Emanuel, MH, de Kruif, JH. Transcervical hysteroscopic resection of submucous fibroids for abnormal uterine bleeding: results regarding the degree of intramural extension. Obstet Gynecol 1993;82:736–40.Google Scholar
Morcellation for Myomectomy or Hysterectomy; RCOG Consent Advice No. 13 October 2019.Google Scholar
D’Angelo, E, Prat, J. Uterine sarcomas: a review. Gynecol Oncol 2010;116:131–9.Google Scholar
Kobayashi, H, Uekuri, C, Akasaka, J, et al. The biology of uterine sarcomas: a review and update. Mol Clin Oncol 2013;1:599–609.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×