Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Uterine fibroids

Abstract

Uterine fibroids (also known as leiomyomas or myomas) are common clonal neoplasms of the uterus. Fibroids have both smooth muscle and fibroblast components, in addition to a substantial amount of fibrous extracellular matrix, which all contribute to the pathogenetic process. Fibroids are extremely heterogeneous in their pathophysiology, size, location and clinical symptomatology. They are also a part of a range of disease in which some variants have facets of malignant behaviour but overall are benign. Risk for fibroids is associated with race; black women have a higher risk of developing fibroids earlier in life than their white counterparts and also develop more-severe forms of the disease. Clinically, fibroids account for one-third to half of all hysterectomies and are associated with substantial morbidity and health care costs for women of reproductive age. Indeed, current treatments are primarily surgical and interventional; approximately three-quarters of all fibroid treatments are hysterectomies. However, clinical innovations are emerging in the use of progesterone receptor modulators as a medical therapy. New information is rapidly accumulating about the genetic subgroups that lead to fibroid formation, which might aid further understanding of the clinical heterogeneity of this disease and lead to individualized treatments. This information is a crucial development given the current lack of high-quality evidence on which to base therapeutic decisions.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: The heterogeneity of fibroid disease.
Figure 2: Incidence rates of fibroids in different populations.
Figure 3: Current concepts in the pathogenesis of uterine fibroids.
Figure 4: The role of sex steroids in uterine fibroids.
Figure 5: Imaging modalities for uterine fibroids.
Figure 6: Treatment options for fibroid-associated heavy menstrual bleeding.
Figure 7: Surgical options for fibroid-associated bulk symptoms with or without heavy menstrual bleeding.
Figure 8: Future concepts of fibroid management.

References

  1. 1

    Stewart, E. A. Uterine Fibroids: the Complete Guide (Johns Hopkins Univ. Press, 2007).

    Google Scholar 

  2. 2

    Merrill, R. M. Hysterectomy surveillance in the United States, 1997 through 2005. Med. Sci. Monit. 14, CR24–CR31 (2008).

    PubMed  Google Scholar 

  3. 3

    Borah, B. J., Laughlin-Tommaso, S. K., Myers, E. R., Yao, X. & Stewart, E. A. Association between patient characteristics and treatment procedure among patients with uterine leiomyomas. Obstet. Gynecol. 127, 67–77 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4

    Cardozo, E. R. et al. The estimated annual cost of uterine leiomyomata in the United States. Am. J. Obstet. Gynecol. 206, 211.e1–211.e9 (2012).

    Article  Google Scholar 

  5. 5

    Peddada, S. D. et al. Growth of uterine leiomyomata among premenopausal black and white women. Proc. Natl Acad. Sci. USA 105, 19887–19892 (2008). This paper reports fibroid growth rates using MRI for a racially diverse cohort and examines key differences in growth parameters.

    Article  PubMed  Google Scholar 

  6. 6

    Stewart, E. A. & Nowak, R. A. Leiomyoma-related bleeding: a classic hypothesis updated for the molecular era. Hum. Reprod. Update 2, 295–306 (1996).

    Article  CAS  PubMed  Google Scholar 

  7. 7

    Cramer, S. F. & Patel, A. The frequency of uterine leiomyomas. Am. J. Clin. Pathol. 94, 435–438 (1990).

    Article  CAS  PubMed  Google Scholar 

  8. 8

    Baird, D. D., Dunson, D. B., Hill, M. C., Cousins, D. & Schectman, J. M. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am. J. Obstet. Gynecol. 188, 100–107 (2003). This study documents the difference in ultrasonography-diagnosed fibroid disease for black women and the differences between self-report and imaging diagnosis.

    Article  PubMed  Google Scholar 

  9. 9

    Marshall, L. M. et al. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet. Gynecol. 90, 967–973 (1997).

    Article  CAS  PubMed  Google Scholar 

  10. 10

    Downes, E. et al. The burden of uterine fibroids in five European countries. Eur. J. Obstet. Gynecol. Reprod. Biol. 152, 96–102 (2010).

    Article  PubMed  Google Scholar 

  11. 11

    Borah, B. J., Nicholson, W. K., Bradley, L. & Stewart, E. A. The impact of uterine leiomyomas: a national survey of affected women. Am. J. Obstet. Gynecol. 209, 319.e1–319.e20 (2013).

    Article  Google Scholar 

  12. 12

    Laughlin, S. K., Baird, D. D., Savitz, D. A., Herring, A. H. & Hartmann, K. E. Prevalence of uterine leiomyomas in the first trimester of pregnancy: an ultrasound-screening study. Obstet. Gynecol. 113, 630–635 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13

    Marsh, E. E. et al. Racial differences in fibroid prevalence and ultrasound findings in asymptomatic young women (18–30 years old): a pilot study. Fertil. Steril. 99, 1951–1957 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14

    Selo-Ojeme, D. et al. The incidence of uterine leiomyoma and other pelvic ultrasonographic findings in 2,034 consecutive women in a north London hospital. J. Obstet. Gynaecol. 28, 421–423 (2008).

    Article  CAS  PubMed  Google Scholar 

  15. 15

    Myers, S. L. et al. Self-report versus ultrasound measurement of uterine fibroid status. J. Womens Health (Larchmt) 21, 285–293 (2012).

    Article  Google Scholar 

  16. 16

    Wechter, M. E., Stewart, E. A., Myers, E. R., Kho, R. M. & Wu, J. M. Leiomyoma-related hospitalization and surgery: prevalence and predicted growth based on population trends. Am. J. Obstet. Gynecol. 205, 492.e1–492.e5 (2011).

    Article  Google Scholar 

  17. 17

    Butt, J., Jeffery, S. T. & Van der Spuy, Z. M. An audit of indications and complications associated with elective hysterectomy at a public service hospital in South Africa. Int. J. Gynaecol. Obstet. 116, 112–116 (2012).

    Article  PubMed  Google Scholar 

  18. 18

    Qi, L. et al. Relationship between hysterectomy and admixture in African American women. Am. J. Obstet. Gynecol. 208, 279.e1–279.e7 (2013).

    Article  Google Scholar 

  19. 19

    Wise, L. et al. African ancestry and genetic risk for uterine leiomyomata. Am. J. Epidemiol. 176, 1159–1168 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20

    Laughlin, S. K. et al. Pregnancy-related fibroid reduction. Fertil. Steril. 94, 2421–2423 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21

    Huyck, K. L. et al. The impact of race as a risk factor for symptom severity and age at diagnosis of uterine leiomyomata among affected sisters. Am. J. Obstet. Gynecol. 198, 168.e1–168.e9 (2008).

    Article  Google Scholar 

  22. 22

    Baird, D. D. & Newbold, R. Prenatal diethylstilbestrol (DES) exposure is associated with uterine leiomyoma development. Reprod. Toxicol. 20, 81–84 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. 23

    Lumbiganon, P. et al. Protective effect of depot-medroxyprogesterone acetate on surgically treated uterine leiomyomas: a multicentre case–control study. Br. J. Obstet. Gynaecol. 103, 909–914 (1996).

    Article  CAS  PubMed  Google Scholar 

  24. 24

    Wise, L. A. et al. Reproductive factors, hormonal contraception, and risk of uterine leiomyomata in African-American women: a prospective study. Am. J. Epidemiol. 159, 113–123 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25

    Marshall, L. M. et al. A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata. Fertil. Steril. 70, 432–439 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. 26

    Wise, L. A. et al. Intake of fruit, vegetables, and carotenoids in relation to risk of uterine leiomyomata. Am. J. Clin. Nutr. 94, 1620–1631 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Wise, L. A., Radin, R. G., Palmer, J. R., Kumanyika, S. K. & Rosenberg, L. A prospective study of dairy intake and risk of uterine leiomyomata. Am. J. Epidemiol. 171, 221–232 (2010).

    Article  PubMed  Google Scholar 

  28. 28

    Nesby-O'Dell, S. et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: Third National Health and Nutrition Examination Survey: 1988–1994. Am. J. Clin. Nutr. 76, 187–192 (2002).

    Article  CAS  PubMed  Google Scholar 

  29. 29

    Eggemoen, A. R. et al. Vitamin D deficiency and supplementation in pregnancy in a multiethnic population-based cohort. BMC Pregnancy Childbirth 16, 7 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Baird, D. D., Hill, M. C., Schectman, J. M. & Hollis, B. W. Vitamin D and the risk of uterine fibroids. Epidemiology 24, 447–453 (2013). This study examines the link between vitamin D deficiency and fibroids, a key variable that might explain the racial disparities of this disease.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31

    Laughlin, S. K., Schroeder, J. C. & Baird, D. D. New directions in the epidemiology of uterine fibroids. Semin. Reprod. Med. 28, 204–217 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Faerstein, E., Szklo, M. & Rosenshein, N. Risk factors for uterine leiomyoma: a practice-based case–control study. I. African-American heritage, reproductive history, body size, and smoking. Am. J. Epidemiol. 153, 1–10 (2001).

    Article  CAS  PubMed  Google Scholar 

  33. 33

    Moore, K. R., Smith, J. S., Laughlin-Tommaso, S. K. & Baird, D. D. Cervical neoplasia-related factors and decreased prevalence of uterine fibroids among a cohort of African American women. Fertil. Steril. 101, 208–214 (2014).

    Article  PubMed  Google Scholar 

  34. 34

    Bulun, S. E. Uterine fibroids. N. Engl. J. Med. 369, 1344–1355 (2013). This paper provides an updated review of the pathogenesis of fibroids.

    Article  CAS  PubMed  Google Scholar 

  35. 35

    Ono, M. et al. Paracrine activation of WNT/β-catenin pathway in uterine leiomyoma stem cells promotes tumor growth. Proc. Natl Acad. Sci. USA 110, 17053–17058 (2013).

    Article  CAS  PubMed  Google Scholar 

  36. 36

    Zhou, S. et al. Proteomics identification of annexin A2 as a key mediator in the metastasis and proangiogenesis of endometrial cells in human adenomyosis. Mol. Cell. Proteomics 11, M112.017988 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Holdsworth-Carson, S. J., Zaitseva, M., Vollenhoven, B. J. & Rogers, P. A. Clonality of smooth muscle and fibroblast cell populations isolated from human fibroid and myometrial tissues. Mol. Hum. Reprod. 20, 250–259 (2014).

    Article  CAS  PubMed  Google Scholar 

  38. 38

    Holdsworth-Carson, S. J., Zaitseva, M., Girling, J. E., Vollenhoven, B. J. & Rogers, P. A. Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium. Reproduction 147, 683–692 (2014). This is a key paper delineating the cell types that compose fibroids.

    Article  CAS  PubMed  Google Scholar 

  39. 39

    Leppert, P. C. et al. Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium. Fertil. Steril. 82 (Suppl. 3), 1182–1187 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    Rogers, R. et al. Mechanical homeostasis is altered in uterine leiomyoma. Am. J. Obstet. Gynecol. 198, 474.e1–474.e11 (2008). This is a key paper linking the ECM of fibroids to its functional significance in this disease.

    Article  Google Scholar 

  41. 41

    Ono, M. et al. Role of stem cells in human uterine leiomyoma growth. PLoS ONE 7, e36935 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. 42

    Koumas, L., King, A. E., Critchley, H. O., Kelly, R. W. & Phipps, R. P. Fibroblasts heterogeneity: existence of functionally distinct Thy I+ and Thy I, human female reproductive tract fibroblasts. Am. J. Pathol. 159, 925–935 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Mehine, M. et al. Characterization of uterine leiomyomas by whole-genome sequencing. N. Engl. J. Med. 369, 43–53 (2013). This paper proposes the key genetic subgroups for fibroids.

    Article  CAS  PubMed  Google Scholar 

  44. 44

    Mehine, M., Makinen, N., Heinonen, H. R., Aaltonen, L. A. & Vahteristo, P. Genomics of uterine leiomyomas: insights from high-throughput sequencing. Fertil. Steril. 102, 621–629 (2014).

    Article  CAS  PubMed  Google Scholar 

  45. 45

    Makinen, N. et al. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science 334, 252–255 (2011).

    Article  CAS  PubMed  Google Scholar 

  46. 46

    Halder, S. K. et al. Novel MED12 gene somatic mutations in women from the Southern United States with symptomatic uterine fibroids. Mol. Genet. Genomics 290, 505–511 (2015).

    Article  CAS  PubMed  Google Scholar 

  47. 47

    Borggrefe, T. & Yue, X. Interactions between subunits of the Mediator complex with gene-specific transcription factors. Semin. Cell Dev. Biol. 22, 759–768 (2011).

    Article  CAS  PubMed  Google Scholar 

  48. 48

    Turunen, M. et al. Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK activity. Cell Rep. 7, 654–660 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

    Markowski, D. N. et al. MED12 mutations in uterine fibroids-their relationship to cytogenetic subgroups. Int. J. Cancer 131, 1528–1536 (2012).

    Article  CAS  PubMed  Google Scholar 

  50. 50

    Perot, G. et al. MED12 alterations in both human benign and malignant uterine soft tissue tumors. PLoS ONE 7, e40015 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Makinen, N. et al. MED12 exon 2 mutations in histopathological uterine leiomyoma variants. Eur. J. Hum. Genet. 21, 1300–1303 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. 52

    Gattas, G. J., Quade, B. J., Nowak, R. A. & Morton, C. C. HMGIC expression in human adult and fetal tissues and in uterine leiomyomata. Genes Chromosomes Cancer 25, 316–322 (1999).

    Article  CAS  PubMed  Google Scholar 

  53. 53

    Hodge, J. C. et al. Uterine leiomyomata and decreased height: a common HMGA2 predisposition allele. Hum. Genet. 125, 257–263 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  54. 54

    Markowski, D. N. et al. HMGA2 and p14Arf: major roles in cellular senescence of fibroids and therapeutic implications. Anticancer Res. 31, 753–761 (2011).

    PubMed  Google Scholar 

  55. 55

    Peng, Y. et al. Antiproliferative effects by Let-7 repression of high-mobility group A2 in uterine leiomyoma. Mol. Cancer Res. 6, 663–673 (2008).

    Article  CAS  PubMed  Google Scholar 

  56. 56

    Moravek, M. B. & Bulun, S. E. Endocrinology of uterine fibroids: steroid hormones, stem cells, and genetic contribution. Curr. Opin. Obstetr. Gynecol. 27, 276–283 (2015).

    Article  Google Scholar 

  57. 57

    Bertsch, E. et al. MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma. Mod. Pathol. 27, 1144–1153 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Zaitseva, M., Vollenhoven, B. J. & Rogers, P. A. Retinoids regulate genes involved in retinoic acid synthesis and transport in human myometrial and fibroid smooth muscle cells. Hum. Reprod. 23, 1076–1086 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. 59

    Kurman, R. J. Blaustein's Pathology of the Female Genital Tract (Springer, 2002).

    Google Scholar 

  60. 60

    Sanz-Ortega, J., Vocke, C., Stratton, P., Linehan, W. M. & Merino, M. J. Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome. Am. J. Surg. Pathol. 37, 74–80 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  61. 61

    Walker, C. L. & Stewart, E. A. Uterine fibroids: the elephant in the room. Science 308, 1589–1592 (2005).

    Article  CAS  PubMed  Google Scholar 

  62. 62

    Navarro, A. et al. Genome-wide DNA methylation indicates silencing of tumor suppressor genes in uterine leiomyoma. PLoS ONE 7, e33284 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. 63

    Maekawa, R. et al. Genome-wide DNA methylation analysis reveals a potential mechanism for the pathogenesis and development of uterine leiomyomas. PLoS ONE 8, e66632 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Benassayag, C. et al. Estrogen receptors (ERα/ERβ) in normal and pathological growth of the human myometrium: pregnancy and leiomyoma. Am. J. Physiol. 276, E1112–E1118 (1999).

    CAS  PubMed  Google Scholar 

  65. 65

    Hsieh, Y. Y. et al. Estrogen receptor thymine-adenine dinucleotide repeat polymorphism is associated with susceptibility to leiomyoma. Fertil. Steril. 79, 96–99 (2003).

    Article  PubMed  Google Scholar 

  66. 66

    Ishikawa, H. et al. High aromatase expression in uterine leiomyoma tissues of African-American women. J. Clin. Endocrinol. Metab. 94, 1752–1756 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Donnez, J. et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N. Engl. J. Med. 366, 421–432 (2012).

    Article  CAS  PubMed  Google Scholar 

  68. 68

    Donnez, J. et al. Long-term treatment of uterine fibroids with ulipristal acetate. Fertil. Steril. 101, 1565–1573.e18 (2014).

    Article  CAS  PubMed  Google Scholar 

  69. 69

    Ishikawa, H. et al. Progesterone is essential for maintenance and growth of uterine leiomyoma. Endocrinology 151, 2433–2442 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. 70

    Yin, P. et al. Genome-wide progesterone receptor binding: cell type-specific and shared mechanisms in T47D breast cancer cells and primary leiomyoma cells. PLoS ONE 7, e29021 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Yin, P. et al. Transcription factor KLF11 integrates progesterone receptor signaling and proliferation in uterine leiomyoma cells. Cancer Res. 70, 1722–1730 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Hoekstra, A. V. et al. Progestins activate the AKT pathway in leiomyoma cells and promote survival. J. Clin. Endocrinol. Metab. 94, 1768–1774 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Brakta, S., Diamond, J. S., Al-Hendy, A., Diamond, M. P. & Halder, S. K. Role of vitamin D in uterine fibroid biology. Fertil. Steril. 104, 698–706 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Halder, S. K., Goodwin, J. S. & Al-Hendy, A. 1,25-Dihydroxyvitamin D3 reduces TGF-β3-induced fibrosis-related gene expression in human uterine leiomyoma cells. J. Clin. Endocrinol. Metab. 96, E754–E762 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. 75

    Zaitseva, M., Vollenhoven, B. J. & Rogers, P. A. Retinoic acid pathway genes show significantly altered expression in uterine fibroids when compared with normal myometrium. Mol. Hum. Reprod. 13, 577–585 (2007).

    Article  CAS  PubMed  Google Scholar 

  76. 76

    Catherino, W. H. & Malik, M. Uterine leiomyomas express a molecular pattern that lowers retinoic acid exposure. Fertil. Steril. 87, 1388–1398 (2007).

    Article  CAS  PubMed  Google Scholar 

  77. 77

    Wei, J. et al. Ethnic differences in expression of the dysregulated proteins in uterine leiomyomata. Hum. Reprod. 21, 57–67 (2006).

    Article  PubMed  Google Scholar 

  78. 78

    Lan, M. et al. In vivo evidence of the androgen receptor in association with myometrial cell proliferation and apoptosis. Reprod. Sci. 23, 264–271 (2016).

    Article  CAS  PubMed  Google Scholar 

  79. 79

    Wong, J., Gold, E., Johnson, W. & Lee, J. Circulating sex hormones and risk of uterine fibroids: Study of Women's Health Across the Nation (SWAN). J. Clin. Endocrinol. Metab. 101, 123–130 (2016).

    Article  CAS  PubMed  Google Scholar 

  80. 80

    Yin, H. et al. Expression profiling of nuclear receptors identifies key roles of NR4A subfamily in uterine fibroids. Mol. Endocrinol. 27, 726–740 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. 81

    Zaitseva, M. et al. Aberrant expression and regulation of NR2F2 and CTNNb1 in uterine fibroids. Reproduction 146, 91–102 (2013).

    Article  CAS  PubMed  Google Scholar 

  82. 82

    Weston, G. et al. Fibroids display an anti-angiogenic gene expression profile when compared with adjacent myometrium. Mol. Hum. Reprod. 9, 541–549 (2003).

    Article  CAS  PubMed  Google Scholar 

  83. 83

    Hodge, J. C. et al. Expression profiling of uterine leiomyomata cytogenetic subgroups reveals distinct signatures in matched myometrium: transcriptional profilingof the t(12;14) and evidence in support of predisposing genetic heterogeneity. Hum. Mol. Genet. 21, 2312–2329 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. 84

    Fleischer, R., Weston, G. C., Vollenhoven, B. J. & Rogers, P. A. Pathophysiology of fibroid disease: angiogenesis and regulation of smooth muscle proliferation. Best Pract. Res. Clin. Obstetr. Gynaecol. 22, 603–614 (2008).

    Article  Google Scholar 

  85. 85

    Lee, B. S. & Nowak, R. A. Human leiomyoma smooth muscle cells show increased expression of transforming growth factor-β3 (TGFβ3) and altered responses to the antiproliferative effects of TGFβ. J. Clin. Endocrinol. Metab. 86, 913–920 (2001).

    CAS  PubMed  Google Scholar 

  86. 86

    Sinclair, D. C., Mastroyannis, A. & Taylor, H. S. Leiomyoma simultaneously impair endometrial BMP-2-mediated decidualization and anticoagulant expression through secretion of TGF-β3. J. Clin. Endocrinol. Metab. 96, 412–421 (2011).

    Article  CAS  PubMed  Google Scholar 

  87. 87

    Vollenhoven, B. J., Herington, A. C. & Healy, D. L. Messenger ribonucleic acid expression of the insulin-like growth factors and their binding proteins in uterine fibroids and myometrium. J. Clin. Endocrinol. Metab. 76, 1106–1110 (1993).

    CAS  PubMed  Google Scholar 

  88. 88

    Varghese, B. V. et al. Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway. Proc. Natl Acad. Sci. USA 110, 2187–2192 (2013).

    Article  CAS  PubMed  Google Scholar 

  89. 89

    Nowak, R. A., Mora, S., Diehl, T., Rhoades, A. R. & Stewart, E. A. Prolactin is an autocrine or paracrine growth factor for human myometrial and leiomyoma cells. Gynecol. Obstet. Invest. 48, 127–132 (1999).

    Article  CAS  PubMed  Google Scholar 

  90. 90

    Everitt, J. I., Wolf, D. C., Howe, S. R., Goldsworthy, T. L. & Walker, C. Rodent model of reproductive tract leiomyomata. Clinical and pathological features. Am. J. Pathol. 146, 1556–1567 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91

    Howe, S. R. et al. Rodent model of reproductive tract leiomyomata. Establishment and characterization of tumor-derived cell lines. Am. J. Pathol. 146, 1568–1579 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92

    Hassan, M. H. et al. Memy I: a novel murine model for uterine leiomyoma using adenovirus-enhanced human fibroid explants in severe combined immune deficiency mice. Am. J. Obstet. Gynecol. 199, 156.e1–156.e8 (2008).

    Article  CAS  Google Scholar 

  93. 93

    Wang, G. et al. Nonobese diabetic/severe combined immunodeficient murine xenograft model for human uterine leiomyoma. Fertil. Steril. 101, 1485–1492 (2014).

    Article  CAS  PubMed  Google Scholar 

  94. 94

    Machado, S. A. et al. Validation of the aging hen (Gallus gallus domesticus) as an animal model for uterine leiomyomas. Biol. Reprod. 87, 86 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  95. 95

    Munro, M. G., Critchley, H. O., Broder, M. S. & Fraser, I. S. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int. J. Gynaecol. Obstetr. 113, 3–13 (2011).

    Article  Google Scholar 

  96. 96

    Cantuaria, G. H., Angioli, R., Frost, L., Duncan, R. & Penalver, M. A. Comparison of bimanual examination with ultrasound examination before hysterectomy for uterine leiomyoma. Obstet. Gynecol. 92, 109–112 (1998).

    Article  CAS  PubMed  Google Scholar 

  97. 97

    Kramer, M. et al. Incidence, risk factors, and temporal trends in severe postpartum hemorrhage. Am J. Obstet. Gynecol. 209, 449.e1–449.e7 (2013).

    Article  Google Scholar 

  98. 98

    Stout, M. J. et al. Leiomyomas at routine second-trimester ultrasound examination and adverse obstetric outcomes. Obstet. Gynecol. 116, 1056–1063 (2010).

    Article  PubMed  Google Scholar 

  99. 99

    Ciavattini, A. et al. Number and size of uterine fibroids and obstetrics outcomes. J. Matern. Fetal Neonatal Med. 28, 484–488 (2014).

    Article  PubMed  Google Scholar 

  100. 100

    Ferreira, J. et al. The evolution of fetal presentation during pregnancy: a retrospective, descriptive cross sectional study. Acta Obstet. Gynecol. Scand. 94, 660–663 (2015).

    Article  PubMed  Google Scholar 

  101. 101

    Puri, K., Famuyide, A. O., Erwin, P. J., Stewart, E. A. & Laughlin-Tommaso, S. K. Submucosal fibroids and the relation to heavy menstrual bleeding and anemia. Am J. Obstet. Gynecol. 210, 38.e1–38.e7 (2014).

    Article  Google Scholar 

  102. 102

    Myers, E. et al. Management of Uterine Fibroids (Agency for Healthcare Research and Quality, 2001).

    Google Scholar 

  103. 103

    Fonseca-Moutinho, J. A., Barbosa, L. S., Torres, D. G. & Nunes, S. M. Abnormal uterine bleeding as a presenting symptoms is related to multiple uterine leiomyoma: an ultrasound-based study. Int. J. Womens Health 18, 689–694 (2013).

    Article  Google Scholar 

  104. 104

    Cicinelli, E. et al. Transabdominal sonohysterography, transvaginal sonography, and hysteroscopy in the evaluation of submucous myomas. Obstet. Gynecol. 85, 42–47 (1995).

    Article  CAS  PubMed  Google Scholar 

  105. 105

    Becker, E. Jr et al. The added value of transvaginal sonogysterography over transvaginal sonography alone in women with known or suspected leiomyoma. J. Ultrasound Med. 21, 237–247 (2002).

    Article  PubMed  Google Scholar 

  106. 106

    Dueholm, M., Lundorf, E., Hansen, E., Ledertoug, S. & Olesen, F. Evaluaiton of the uterine cavity with magnetic resonance imaging, transvaginal sonography, hysterosonographic examination, and diagnostic hysterocopy. Fertil. Steril. 76, 350–357 (2001).

    Article  CAS  PubMed  Google Scholar 

  107. 107

    Dudiak, C. M. et al. Uterine leiomyomas in the infertile patient: preoperative localization with MR imaging versus US and hysterosalpingography. Radiology 167, 627–630 (1988).

    Article  CAS  PubMed  Google Scholar 

  108. 108

    Nanda, S., Chadha, N., Sen, J. & Sangwan, K. Transvaginal sonography and saline infusion sonohysterograhy in the evaluation of abnormal uterine bleeding. Aust. N. Z. J. Obstet. Gynaecol. 42, 530–534 (2002).

    Article  PubMed  Google Scholar 

  109. 109

    Spielmann, A. L., Keogh, C., Forster, B. B., Martin, M. L. & Machan, L. S. Comparison of MRI and sonography in the preliminary evaluation for fibroid embolization. Am. J. Roentgenol 187, 1499–1504 (2006).

    Article  Google Scholar 

  110. 110

    Toledo, G. & Oliva, E. Smooth muscle tumors of the uterus: a practical approach. Arch. Pathol. Lab. Med. 132, 595–605 (2008).

    PubMed  Google Scholar 

  111. 111

    Clement, P. B. & Young, R. H. Atlas of Gynecologic Surgical Pathology 3rd edn (Elsevier, 2014).

    Google Scholar 

  112. 112

    Levy, G., Hill, M. J., Plowden, T. C., Catherino, W. & Armstrong, A. Biomarkers in uterine leiomyoma. Fertil. Steril. 99, 1146–1152 (2013).

    Article  CAS  PubMed  Google Scholar 

  113. 113

    Taran, F. A., Weaver, A. L., Coddington, C. C. & Stewart, E. A. Understanding adenomyosis: a case control study. Fertil. Steril. 94, 1223–1228 (2010).

    Article  PubMed  Google Scholar 

  114. 114

    Brosens, J. J., de Souza, N. M. & Barker, F. G. Uterine junctional zone: function and disease. Lancet 346, 558–560 (1995).

    Article  CAS  PubMed  Google Scholar 

  115. 115

    Dueholm, M. et al. Reproducibility of evaluation of the uterus by transvaginal sonography, hysterosonographic examination, hysteroscopy and magnetic resonance imaging. Hum. Reprod. 17, 195–200 (2002).

    Article  PubMed  Google Scholar 

  116. 116

    Wright, J. D. et al. Uterine pathology in women undergoing minimally invasive hysterectomy using morcellation. JAMA 312, 1253–1255 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  117. 117

    Matsuda, M. et al. Preoperative diagnosis of usual leiomyoma, atypical leiomyoma, and leiomyosarcoma. Sarcoma 2014, 498682 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. 118

    Santos, P. & Cunha, T. Uterine sarcomas: clinical presentation and MRI features. Radiology 21, 4–9 (2015).

    Google Scholar 

  119. 119

    US FDA. Updated laparoscopic uterine power morcellation in hysterectomy and myomectomy: FDA safety communication. FDAhttp://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm424443.htm (2014).

  120. 120

    Stewart, E. A. Clinical practice. Uterine fibroids. N. Engl. J. Med. 372, 1646–1655 (2015). This is an updated review of the clinical diagnosis and treatment of fibroids.

    Article  CAS  PubMed  Google Scholar 

  121. 121

    Malik, M., Webb, J. & Catherino, W. H. Retinoic acid treatment of human leiomyoma cells transformed the cell phenotype to one strongly resembling myometrial cells. Clin. Endocrinol. (Oxf.) 69, 462–470 (2008).

    Article  CAS  Google Scholar 

  122. 122

    Halder, S. K., Sharan, C. & Al-Hendy, A. 1,25-Dihydroxyvitamin D3 treatment shrinks uterine leiomyoma tumors in the Eker rat model. Biol. Reprod. 86, 116 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. 123

    Malik, M., Mendoza, M., Payson, M. & Catherino, W. Curcumin, a nutritional supplement with antineoplastic activity, enhances leiomyoma cell apoptosis and decreases fibronectin expression. Fertil. Steril. 91, 2177–2184 (2009).

    Article  CAS  PubMed  Google Scholar 

  124. 124

    Lee, T. et al. Inhibitory effects of Scutellaria barbatta D. Don on human unterine leiomyomal smooth muscle cell proliferation through cell cycle analysis. Int. Immunopharmacol. 4, 447–454 (2004).

    Article  CAS  PubMed  Google Scholar 

  125. 125

    K.Im, D. et al. Induction of growth inhibition and apoptosis in human leiomyoma cells by isoliquiritigenin. Reprod. Sci. 15, 552–558 (2008).

    Article  CAS  Google Scholar 

  126. 126

    Roshdy, E. et al. Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study. Int. J. Womens Health 5, 477–486 (2013).

    PubMed  PubMed Central  Google Scholar 

  127. 127

    Kim, C. et al. Euonymus alatus (Thunb.) Sieb induces apoptosis via mitochondrial pathway as prooxidant in human uterine leiomyomal smooth muscle cells. Int. J. Gynecol. Cancer 16, 843–848 (2006).

    Article  CAS  PubMed  Google Scholar 

  128. 128

    Gliklich, R. E. et al. Identification of Future Needs in the Comparative Management of Uterine Fibroid Disease. A Report on the Priority-Setting Process, Preliminary Data Analysis, and Research Plan (Agency for Healthcare Research and Quality, 2011). This is a comprehensive assessment of the evidence, or lack thereof, for treatment of uterine fibroids.

    Google Scholar 

  129. 129

    American College of Obstreticians and Gynecologists. ACOG practice bulletin. Alternatives to hysterectomy in the management of leiomyomas. Obstet. Gynecol. 112, 387–400 (2008).

    Article  Google Scholar 

  130. 130

    Marret, H. et al. Therapeutic management of uterine fibroid tumors: updated French guidelines. Eur. J. Obstetr. Gynecol. Reprod. Biol. 165, 156–164 (2012).

    Article  Google Scholar 

  131. 131

    Perez-Lopez, F. R. et al. EMAS position statement: management of uterine fibroids. Maturitas 79, 106–116 (2014). This is a comprehensive, updated and annotated review of guidelines for fibroid treatment.

    Article  PubMed  Google Scholar 

  132. 132

    Laughlin, S. K., Hartmann, K. E. & Baird, D. D. Postpartum factors and natural fibroid regression. Am. J. Obstet. Gynecol. 204, 496.e1–496.e6 (2011).

    Article  Google Scholar 

  133. 133

    Flake, G. P. et al. The natural history of uterine leiomyomas: morphometric concordance with concepts of interstitial ischemia and inanosis. Obstet. Gynecol. Int. 2013, 285103 (2013).

    PubMed  PubMed Central  Google Scholar 

  134. 134

    Wamsteker, K., Emanuel, M. H. & de Kruif, J. H. Transcervical hysteroscopic resection of submucous fibroids for abnormal uterine bleeding: results regarding the degree of intramural extension. Obstet. Gynecol. 82, 736–740 (1993).

    CAS  PubMed  Google Scholar 

  135. 135

    Lethaby, A., Duckitt, K. & Farquhar, C. Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst. Rev. 1, CD000400 (2013).

    Google Scholar 

  136. 136

    Lukes, A. S. et al. Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial. Obstet. Gynecol. 116, 865–875 (2010).

    Article  PubMed  Google Scholar 

  137. 137

    Eder, S., Baker, J., Gersten, J., Mabey, R. G. & Adomako, T. L. Efficacy and safety of oral tranexamic acid in women with heavy menstrual bleeding and fibroids. Womens Health (Lond. Engl.) 9, 397–403 (2013).

    Article  CAS  Google Scholar 

  138. 138

    Sangkomkamhang, U. S., Lumbiganon, P., Laopaiboon, M. & Mol, B. W. Progestogens or progestogen-releasing intrauterine systems for uterine fibroids. Cochrane Database Syst. Rev. 2, CD008994 (2013).

    Google Scholar 

  139. 139

    Lethaby, A. E., Cooke, I. & Rees, M. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst. Rev. 4, CD002126 (2005).

    Google Scholar 

  140. 140

    Kriplani, A., Awasthi, D., Kulshrestha, V. & Agarwal, N. Efficacy of the levonorgestrel-releasing intrauterine system in uterine leiomyoma. Int. J. Gynaecol. Obstet. 116, 35–38 (2012).

    Article  CAS  PubMed  Google Scholar 

  141. 141

    Socolov, D. et al. Levonorgestrel releasing-intrauterine system for the treatment of menorrhagia and/or frequent irregular uterine bleeding associated with uterine leiomyoma. Eur. J. Contracept. Reprod. Health Care 16, 480–487 (2011).

    Article  CAS  PubMed  Google Scholar 

  142. 142

    Youm, J., Lee, H. J., Kim, S. K., Kim, H. & Jee, B. C. Factors affecting the spontaneous expulsion of the levonorgestrel-releasing intrauterine system. Int. J. Gynaecol. Obstetr. 126, 165–169 (2014).

    Article  CAS  Google Scholar 

  143. 143

    Mercorio, F. et al. The effect of a levonorgestrel-releasing intrauterine device in the treatment of myoma-related menorrhagia. Contraception 67, 277–280 (2003).

    Article  CAS  PubMed  Google Scholar 

  144. 144

    Perez-Lopez, F. R. Long-term consequences of LNG-IUS versus hysterectomy for menorrhagia. Climacteric 17, 308–309 (2014).

    Article  PubMed  Google Scholar 

  145. 145

    Qin, J., Yang, T., Kong, F. & Zhou, Q. Oral contraceptive use and uterine leiomyoma risk: a meta-analysis based on cohort and case–control studies. Arch. Gynecol. Obstet. 288, 139–148 (2013).

    Article  CAS  PubMed  Google Scholar 

  146. 146

    Donnez, J. et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N. Engl. J. Med. 366, 409–420 (2012).

    Article  CAS  PubMed  Google Scholar 

  147. 147

    Mutter, G. L. et al. The spectrum of endometrial pathology induced by progesterone receptor modulators. Mod. Pathol. 21, 591–598 (2008).

    Article  CAS  PubMed  Google Scholar 

  148. 148

    Dinh, A., Sriprasert, I., Williams, A. R. & Archer, D. F. A review of the endometrial histologic effects of progestins and progesterone receptor modulators in reproductive age women. Contraception 91, 360–367 (2015).

    Article  CAS  PubMed  Google Scholar 

  149. 149

    Luyckx, M. et al. First series of 18 pregnancies after ulipristal acetate treatment for uterine fibroids. Fertil. Steril. 102, 1404–1409 (2014).

    Article  CAS  PubMed  Google Scholar 

  150. 150

    Steinauer, J., Pritts, E. A., Jackson, R. & Jacoby, A. F. Systematic review of mifepristone for the treatment of uterine leiomyomata. Obstet. Gynecol. 103, 1331–1336 (2004).

    Article  CAS  PubMed  Google Scholar 

  151. 151

    Engman, M. et al. GSTM1 gene expression correlates to leiomyoma volume regression in response to mifepristone treatment. PLoS ONE 8, e80114 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. 152

    Carr, B. R. et al. An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial. J. Clin. Endocrinol. Metab. 76, 1217–1223 (1993).

    CAS  PubMed  Google Scholar 

  153. 153

    Perez-Lopez, F. R. Ulipristal acetate in the management of symptomatic uterine fibroids: facts and pending issues. Climacteric 18, 177–181 (2015).

    Article  CAS  PubMed  Google Scholar 

  154. 154

    Lethaby, A. E. & Vollenhoven, B. J. An evidence-based approach to hormonal therapies for premenopausal women with fibroids. Best Pract. Res. Clin. Obstetr. Gynaecol. 22, 307–331 (2008).

    Article  Google Scholar 

  155. 155

    Muzii, L. et al. GnRH analogue treatment before hysteroscopic resection of submucous myomas: a prospective, randomized, multicenter study. Fertil. Steril. 94, 1496–1499 (2010).

    Article  CAS  PubMed  Google Scholar 

  156. 156

    Kamath, M. S., Kalampokas, E. E. & Kalampokas, T. E. Use of GnRH analogues pre-operatively for hysteroscopic resection of submucous fibroids: a systematic review and meta-analysis. Eur. J. Obstet. Gynecol. Reprod. Biol. 177, 11–18 (2014).

    Article  CAS  PubMed  Google Scholar 

  157. 157

    Flierman, P. A., Oberye, J. J., van der Hulst, V. P. & de Blok, S. Rapid reduction of leiomyoma volume during treatment with the GnRH antagonist ganirelix. BJOG 112, 638–642 (2005).

    Article  CAS  PubMed  Google Scholar 

  158. 158

    Palomba, S. et al. Effectiveness of combined GnRH analogue plus raloxifene administration in the treatment of uterine leiomyomas: a prospective, randomized, single-blind, placebo-controlled clinical trial. Hum. Reprod. 17, 3213–3219 (2002).

    Article  CAS  PubMed  Google Scholar 

  159. 159

    Palomba, S. et al. Raloxifene administration in premenopausal women with uterine leiomyomas: a pilot study. J. Clin. Endocrinol. Metab. 87, 3603–3608 (2002).

    Article  CAS  PubMed  Google Scholar 

  160. 160

    Hilario, S. G., Bozzini, N., Borsari, R. & Baracat, E. C. Action of aromatase inhibitor for treatment of uterine leiomyoma in perimenopausal patients. Fertil. Steril. 91, 240–243 (2009).

    Article  CAS  PubMed  Google Scholar 

  161. 161

    Varelas, F. K., Papanicolaou, A. N., Vavatsi-Christaki, N., Makedos, G. A. & Vlassis, G. D. The effect of anastrazole on symptomatic uterine leiomyomata. Obstet. Gynecol. 110, 643–649 (2007).

    Article  CAS  PubMed  Google Scholar 

  162. 162

    Coutinho, E. M. Gestrinone in the treatment of myomas. Acta Obstet. Gynecol. Scand. Suppl. 150, 39–46 (1989).

    Article  CAS  PubMed  Google Scholar 

  163. 163

    Brucker, S. Y. et al. Laparoscopic radiofrequency volumetric thermal ablation of fibroids versus laparoscopic myomectomy. Int. J. Gynaecol. Obstetr. 125, 261–265 (2014).

    Article  Google Scholar 

  164. 164

    Bergamini, V. et al. Laparoscopic radiofrequency thermal ablation: a new approach to symptomatic uterine myomas. Am. J. Obstet. Gynecol. 192, 768–773 (2005).

    Article  PubMed  Google Scholar 

  165. 165

    Gupta, J. K., Sinha, A., Lumsden, M. A. & Hickey, M. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database Syst. Rev. 5, CD005073 (2012).

    Google Scholar 

  166. 166

    van der Kooij, S. M., Bipat, S., Hehenkamp, W. J., Ankum, W. M. & Reekers, J. A. Uterine artery embolization versus surgery in the treatment of symptomatic fibroids: a systematic review and metaanalysis. Am J. Obstet. Gynecol. 205, 317.e1–317.e8 (2011).

    Article  Google Scholar 

  167. 167

    Mara, M. et al. Midterm clinical and first reproductive results of a randomized controlled trial comparing uterine fibroid embolization and myomectomy. Cardiovasc. Intervent. Radiol. 31, 73–85 (2008).

    Article  PubMed  Google Scholar 

  168. 168

    Pisco, J. M., Duarte, M., Bilhim, T., Cirurgiao, F. & Oliveira, A. G. Pregnancy after uterine fibroid embolization. Fertil. Steril. 95, 1121.e5–1121.e8 (2011).

    Article  Google Scholar 

  169. 169

    Hehenkamp, W. J. et al. Loss of ovarian reserve after uterine artery embolization: a randomized comparison with hysterectomy. Hum. Reprod. 22, 1996–2005 (2007).

    Article  CAS  PubMed  Google Scholar 

  170. 170

    Rabinovici, J. et al. Pregnancy outcome after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for conservative treatment of uterine fibroids. Fertil. Steril. 93, 199–209 (2010).

    Article  PubMed  Google Scholar 

  171. 171

    Quinn, S. D., Vedelago, J., Gedroyc, W. & Regan, L. Safety and five-year re-intervention following magnetic resonance-guided focused ultrasound (MRgFUS) for uterine fibroids. Eur. J. Obstetr. Gynecol. Reproduct. Biol. 182, 247–251 (2014).

    Article  CAS  Google Scholar 

  172. 172

    Gorny, K. R. et al. Incidence of additional treatments in women treated with MR-guided focused US for symptomatic uterine fibroids: review of 138 patients with an average follow-up of 2.8 years. J. Vasc. Interv. Radiol. 25, 1506–1512 (2014).

    Article  PubMed  Google Scholar 

  173. 173

    Rocca, W. A. & Ulrich, L. G. Oophorectomy for whom and at what age? Primum non nocere. Maturitas 71, 1–2 (2012).

    Article  PubMed  Google Scholar 

  174. 174

    Rocca, W. A., Grossardt, B. R., Shuster, L. T. & Stewart, E. A. Hysterectomy, oophorectomy, estrogen, and the risk of dementia. Neurodegenerat. Dis. 10, 175–178 (2012).

    Article  Google Scholar 

  175. 175

    Ghant, M. S. et al. Beyond the physical: a qualitative assessment of the burden of symptomatic uterine fibroids on women's emotional and psychosocial health. J. Psychosom. Res. 78, 499–503 (2015).

    Article  PubMed  Google Scholar 

  176. 176

    Marsh, E. E., Brocks, M. E., Ghant, M. S., Recht, H. S. & Simon, M. Prevalence and knowledge of heavy menstrual bleeding among African American women. Int. J. Gynaecol. Obstetr. 125, 56–59 (2014).

    Article  Google Scholar 

  177. 177

    Stewart, E. A., Nicholson, W. K., Bradley, L. & Borah, B. J. The burden of uterine fibroids for African-American women: results of a national survey. J. Womens Health (Larchmt) 22, 807–816 (2013). This paper articulates the differential clinical burden of fibroids for women of African descent compared with other women.

    Article  Google Scholar 

  178. 178

    Spies, J. B. et al. The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata. Obstet. Gynecol. 99, 290–300 (2002).

    PubMed  Google Scholar 

  179. 179

    Harding, G., Coyne, K. S., Thompson, C. L. & Spies, J. B. The responsiveness of the uterine fibroid symptom and health-related quality of life questionnaire (UFS-QOL). Health Qual. Life Outcomes 6, 99 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  180. 180

    Laughlin-Tommaso, S. K., Borah, B. J. & Stewart, E. A. Effect of menses on standardized assessment of sexual dysfunction among women with uterine fibroids: a cohort study. Fertil. Steril. 104, 435–439 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  181. 181

    Coronado, G. D., Marshall, L. M. & Schwartz, S. M. Complications in pregnancy, labor, and delivery with uterine leiomyomas: a population-based study. Obstet. Gynecol. 95, 764–769 (2000).

    CAS  PubMed  Google Scholar 

  182. 182

    Klatsky, P. C., Tran, N. D., Caughey, A. B. & Fujimoto, V. Y. Fibroids and reproductive outcomes: a systematic literature review from conception to delivery. Am. J. Obstet. Gynecol. 198, 357–366 (2008).

    Article  PubMed  Google Scholar 

  183. 183

    Johnson, G., MacLehose, R. F., Baird, D. D., Laughlin-Tommaso, S. K. & Hartmann, K. E. Uterine leiomyomata and fecundability in the Right from the Start study. Hum. Reprod. 27, 2991–2997 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  184. 184

    ACOG Committee on Practice Bulletins-Gynecology. ACOG practice bulletin. Alternatives to hysterectomy in the management of leiomyomas. Obstetr. Gynecol. 112, 387–400 (2008).

    Article  Google Scholar 

  185. 185

    Pritts, E. A., Parker, W. H. & Olive, D. L. Fibroids and infertility: an updated systematic review of the evidence. Fertil. Steril. 91, 1215–1223 (2009).

    Article  PubMed  Google Scholar 

  186. 186

    Metwally, M., Cheong, Y. C. & Horne, A. W. Surgical treatment of fibroids for subfertility. Cochrane Database Syst. Rev. 11, CD003857 (2012).

    PubMed  Google Scholar 

  187. 187

    Bosteels, J. et al. Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities. Cochrane Database Syst. Rev. 1, CD009461 (2013).

    Google Scholar 

  188. 188

    Fisher, B. From Halsted to prevention and beyond: advances in the management of breast cancer during the twentieth century. Eur. J. Cancer 35, 1963–1973 (1999).

    Article  CAS  PubMed  Google Scholar 

  189. 189

    Hodge, J. C., Pearce, K. E., Clayton, A. C., Taran, F. A. & Stewart, E. A. Uterine cellular leiomyomata with chromosome 1p deletions represent a distinct entity. Am J. Obstet. Gynecol. 210, 572.e1–573.e7 (2014).

    Article  CAS  Google Scholar 

  190. 190

    Ruta, D. A. et al. Assessment of patients with menorrhagia: how valid is a structured clinical history as a measure of health status? Qual. Life Res. 4, 33–40 (1995).

    Article  CAS  PubMed  Google Scholar 

  191. 191

    Zakherah, M. S., Sayed, G. H., El-Nashar, S. & Shaaban, M. Pictorial blood loss assessment chart in the evaluation of heavy menstrual bleeding: diagnotic accuracy compared to alkaline hematin. Gynecol. Obstet. Invest. 71, 281–284 (2011).

    Article  PubMed  Google Scholar 

  192. 192

    Moos, R. H. The development of a menstrual distress questionnaire. Psychosomat. Med. 30, 853–867 (1968).

    Article  CAS  Google Scholar 

  193. 193

    Rosen, R. et al. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J. Sex. Marital Ther. 26, 191–208 (2000).

    Article  CAS  PubMed  Google Scholar 

  194. 194

    Lukacz, E. S. et al. The use of Visual Analog Scale in urogynecologic research: a psychometric evaluation. Am. J. Obstet. Gynecol. 191, 165–170 (2004).

    Article  PubMed  Google Scholar 

  195. 195

    Melzack, R. The short-form McGill Pain Questionnaire. Pain 30, 191–197 (1987).

    Article  CAS  Google Scholar 

  196. 196

    Eskenazi, B. et al. Serum dioxin concentrations and risk of uterine leiomyoma in the Seveso Women's Health Study. Am. J. Epidemiol. 166, 79–87 (2007).

    Article  PubMed  Google Scholar 

  197. 197

    Bower, J. K., Schreiner, P. J., Sternfeld, B. & Lewis, C. E. Black–white differences in hysterectomy prevalence: the CARDIA study. Am. J. Public Health 99, 300–307 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  198. 198

    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. 79, 202–207 (2000).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

E.A.S. has received research support from the US NIH (R01HD060503, P50HS023418 and R01HD074711) and from Insightec Inc. The authors acknowledge the technical assistance of D. Littlefield.

Author information

Affiliations

Authors

Contributions

Introduction (E.A.S.); Epidemiology (S.K.L.-T.); Mechanisms/pathophysiology (E.A.S., B.V. and D.V.); Diagnosis, screening and prevention (W.H.C.); Management (E.A.S. and S.L.); Quality of life (E.A.S. and S.L.); Outlook (E.A.S.); Overview of Primer (E.A.S.).

Corresponding author

Correspondence to Elizabeth A. Stewart.

Ethics declarations

Competing interests

E.A.S. is a consultant for AbbVie, Allergan, Astellas Pharma, Bayer Health Care, Gynesonics and Viteava and has received royalties from UpToDate and the Massachusetts Medical Society. S.K.L.-T. has received research support from InSightec and support for consulting from Truven Health Analytics and for serving on the data monitoring board for ULTRA trail from HALT medical. She is an author for UpToDate. W.H.C. has received research support from Bayer Schering Pharma and Patient-Centered Outcomes Research Institute (PCORI), and is a consultant for AbbVie Pharmaceuticals and Actavis. He is an oral boards examiner for the American Board of Obstetrics and Gynecology and a content Review Committee for the American Society of Reproductive Medicine. S.L., B.V. and D.G. declare no competing interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Stewart, E., Laughlin-Tommaso, S., Catherino, W. et al. Uterine fibroids. Nat Rev Dis Primers 2, 16043 (2016). https://doi.org/10.1038/nrdp.2016.43

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing