Current Understanding of Pathogenesis, Histopathology, Diagnosis, and Treatment Options of Uterine Fibroids-Review

Abstract

Uterine fibroids are the most common benign monoclonal tumors of the uterus..They are associated with a significant morbidity rate and affect women mainly during their reproductive age. These tumors are usually asymptomatic however, they may present as heavy or prolonged menstrual bleeding, abnormal uterine bleeding, consequent anaemia, pelvic pain, infertility, and/or recurrent abortions. Despite many factors playing a role in the development and incidence of these common tumors namely; modifications in growth factor expression, abnormalities in the vascular system, and tissue reaction to injury and even genetics, a clear understanding of the pathogenesis of uterine fibroids is yet to be achieved. However, there has been significant progress made towards understanding their origin witnessed in recent years which has provided more options for the treatment of uterine fibroids including medical, surgical, and radiological interventions. This article briefly reviews the current knowledge of pathology, histology, and diagnosis of uterine fibroids while highlighting their treatment options.

Keywords

• Uterine fibroids
• Pathogenesis
• Classification
• Treatment

References

1. Al-Hendy, A., & Salama, S. A. (2006). Ethnic distribution of estrogen receptor-α polymorphism is associated with a higher prevalence of uterine leiomyomas in black Americans. Fertility and Sterility, 86(3), 686–693. https://doi.org/10.1016/j.fertnstert.2006.01.052
2. Baird, D. D., & Dunson, D. B. (2003). Why is parity protective for uterine fibroids? Epidemiology, 14(2), 247–250. https://doi.org/10.1097/00001648-200303000-00021
3. Baird, D. D., Dunson, D. B., Hill, M. C., Cousins, D., & Schectman, J. M. (2007). Association of physical activity with development of uterine leiomyoma. American Journal of Epidemiology, 165(2), 157–163. https://doi.org/10.1093/aje/kwj363
4. Borahay, M. A., Al Hendy, A., Kilic, G. S., & Boehning, D. (2015). Signaling pathways in leiomyoma: Understanding pathobiology and implications for therapy. Molecular Medicine, 21, 242–256. https://doi.org/10.2119/molmed.2014.00053
5. Borahay, M. A., Asoglu, M. R., Mas, A., Adam, S., Kilic, G. S., & Al-Hendy, A. (2017). Estrogen Receptors and Signaling in Fibroids: Role in Pathobiology and Therapeutic Implications. Reproductive Sciences, 24(9), 1235–1244. https://doi.org/10.1177/1933719116678686
6. Boynton-Jarrett, R., Rich-Edwards, J. W., Jun, H. J., Hibert, E. N., & Wright, R. J. (2011). Abuse in childhood and risk of uterine leiomyoma: The role of emotional support in biologic resilience. Epidemiology, 22(1), 6–14. https://doi.org/10.1097/EDE.0b013e3181ffb172
7. Brasky, T. M., Bethea, T. N., Wesselink, A. K., Wegienka, G. R., Baird, D. D., & Wise, L. A. (2020). Dietary Fat Intake and Risk of Uterine Leiomyomata: A Prospective Ultrasound Study. American Journal of Epidemiology, 189(12), 1538–1546. https://doi.org/10.1093/aje/kwaa097
8. Bulman, J. C., Ascher, S. M., & Spies, J. B. (2012). Current concepts in uterine fibroid embolization. Radiographics, 32(6), 1735–1750. https://doi.org/10.1148/rg.326125514

9. Chiaffarino, F., Ricci, E., Cipriani, S., Chiantera, V., & Parazzini, F. (2016). Cigarette smoking and risk of uterine myoma: Systematic review and meta-analysis. European Journal of Obstetrics and Gynecology and Reproductive Biology, 197, 63–71. https://doi.org/10.1016/j.ejogrb.2015.11.023
10. Ciebiera, M., Włodarczyk, M., Wrzosek, M., Męczekalski, B., Nowicka, G., Łukaszuk, K., … Jakiel, G. (2017). Role of transforming growth factor β in uterine fibroid biology. International Journal of Molecular Sciences, Vol. 18, pp. 1–16. https://doi.org/10.3390/ijms18112435
11. Davis, B. J., Risinger, J. I., Chandramouli, G. V. R., Bushel, P. R., Baird, D. D., & Peddada, S. D. (2013). 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, 8(6). https://doi.org/10.1371/journal.pone.0063909
12. Donnez, J., Courtoy, G. E., Donnez, O., & Dolmans, M. M. (2018). Ulipristal acetate for the management of large uterine fibroids associated with heavy bleeding: a review. Reproductive BioMedicine Online, 37(2), 216–223. https://doi.org/10.1016/j.rbmo.2018.04.040
13. Donnez, J., & Dolmans, M. M. (2016). Uterine fibroid management: From the present to the future. Human Reproduction Update, 22(6), 665–686. https://doi.org/10.1093/humupd/dmw023
14. Duhan, N. (2011). Current and emerging treatments for uterine myoma - An update. International Journal of Women’s Health, 3(1), 231–242. https://doi.org/10.2147/ijwh.s15710
15. Farris, M., Bastianelli, C., Rosato, E., Brosens, I., & Benagiano, G. (2019, January 23). Uterine fibroids: An update on current and emerging medical treatment options. Therapeutics and Clinical Risk Management, Vol. 15, pp. 157–178. Dove Press. https://doi.org/10.2147/TCRM.S147318
16. Flake, G. P., Andersen, J., & Dixon, D. (2003). Etiology and pathogenesis of uterine leiomyomas: A review. Environmental Health Perspectives, Vol. 111, pp. 1037–1054. https://doi.org/10.1289/ehp.5787
17. Frydenberg, H., Flote, V. G., Larsson, I. M., Barrett, E. S., Furberg, A. S., Ursin, G., … Thune, I. (2015). Alcohol consumption, endogenous estrogen and mammographic density among premenopausal women. Breast Cancer Research, 17(1), 1–12. https://doi.org/10.1186/s13058-015-0620-1
18. Gupta, J. K., Sinha, A., Lumsden, M. A., & Hickey, M. (2014). Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database of Systematic Reviews, 2014(12). https://doi.org/10.1002/14651858.CD005073.pub4
19. Halder, S. K., Goodwin, J. S., & Al-Hendy, A. (2011). 1,25-Dihydroxyvitamin D3 reduces TGF-β3-induced fibrosis-related gene expression in human uterine leiomyoma cells. Journal of Clinical Endocrinology and Metabolism, 96(4), 754–762. https://doi.org/10.1210/jc.2010-2131
20. Halder, S. K., Osteen, K. G., & Al-Hendy, A. (2013). 1,25-Dihydroxyvitamin D3 Reduces Extracellular Matrix-Associated Protein Expression in Human Uterine Fibroid Cells1. Biology of Reproduction, 89(6), 1–13. https://doi.org/10.1095/biolreprod.113.107714
21. He, Y., Zeng, Q., Dong, S., Qin, L., Li, G., & Wang, P. (2013). Associations between uterine fibroids and lifestyles including diet, physical activity and stress: A case-control study in China. Asia Pacific Journal of Clinical Nutrition, 22(1), 109–117. https://doi.org/10.6133/apjcn.2013.22.1.07
22. Herndon, C. N., Aghajanova, L., Balayan, S., Erikson, D., Barragan, F., Goldfien, G., … Giudice, L. C. (2016). Global Transcriptome Abnormalities of the Eutopic Endometrium from Women with Adenomyosis. Reproductive Sciences, 23(10), 1289–1303. https://doi.org/10.1177/1933719116650758
23. Holdsworth-Carson, S. J., Zaitseva, M., Vollenhoven, B. J., & Rogers, P. A. W. (2014). Clonality of smooth muscle and fibroblast cell populations isolated from human fibroid and myometrial tissues. Molecular Human Reproduction, 20(3), 250–259. https://doi.org/10.1093/molehr/gat083
24. Islam, M. S., Ciavattini, A., Petraglia, F., Castellucci, M., & Ciarmela, P. (2018). Extracellular matrix in uterine leiomyoma pathogenesis: A potential target for future therapeutics. Human Reproduction Update, 24(1), 59–85. https://doi.org/10.1093/humupd/dmx032
25. Islam, M. S., Protic, O., Giannubilo, S. R., Toti, P., Tranquilli, A. L., Petraglia, F., … Ciarmela, P. (2013). Uterine leiomyoma: Available medical treatments and new possible therapeutic options. Journal of Clinical Endocrinology and Metabolism, 98(3), 921–934. https://doi.org/10.1210/jc.2012-3237
26. Islam, M. S., Protic, O., Stortoni, P., Grechi, G., Lamanna, P., Petraglia, F., … Ciarmela, P. (2013). Complex networks of multiple factors in the pathogenesis of uterine leiomyoma. Fertility and Sterility, 100(1), 178–193. https://doi.org/10.1016/j.fertnstert.2013.03.007
27. Iwahashi, M., & Muragaki, Y. (2011). Increased type i and v collagen expression in uterine leiomyomas during the menstrual cycle. Fertility and Sterility, 95(6), 2137–2139. https://doi.org/10.1016/j.fertnstert.2010.12.028
28. Jacoby, V. L., Fujimoto, V. Y., Giudice, L. C., Kuppermann, M., & Washington, A. E. (2010). Racial and ethnic disparities in benign gynecologic conditions and associated surgeries. American Journal of Obstetrics and Gynecology, 202(6), 514–521. https://doi.org/10.1016/j.ajog.2010.02.039
29. Jayes, F. L., Liu, B., Feng, L., Aviles-Espinoza, N., Leikin, S., & Leppert, P. C. (2019). Evidence of biomechanical and collagen heterogeneity in uterine fibroids. PLoS ONE, 14(4), 1–16. https://doi.org/10.1371/journal.pone.0215646
30. Joseph, D. S., Malik, M., Nurudeen, S., & Catherino, W. H. (2010). Myometrial cells undergo fibrotic transformation under the influence of transforming growth factor β-3. Fertility and Sterility, 93(5), 1500–1508. https://doi.org/10.1016/j.fertnstert.2009.01.081
31. Khalid, A., Qureshi, H. J., Nazir, S., & Lone, K. P. (2017). Effect of second hand smoke exposure on serum estradiol and progesterone levels in women having first trimester spontaneous abortions. Pakistan Journal of Medical and Health Sciences, 11(1), 163–167.
32. Khan, A. T., Shehmar, M., & Gupta, J. K. (2014). Uterine fibroids: Current perspectives. International Journal of Women’s Health, 6(1), 95–114. https://doi.org/10.2147/IJWH.S51083
33. Lam, S. J., Best, S., & Kumar, S. (2014). The impact of fibroid characteristics on pregnancy outcome. American Journal of Obstetrics and Gynecology, 211(4), 395.e1-395.e5. https://doi.org/10.1016/j.ajog.2014.03.066
34. Laughlin, S. K., Herring, A. H., Savitz, D. A., Olshan, A. F., Fielding, J. R., Hartmann, K. E., & Baird, D. D. (2010). Pregnancy-related fibroid reduction. Fertility and Sterility, 94(6), 2421–2423. https://doi.org/10.1016/j.fertnstert.2010.03.035
35. Laughlin, S. K., Schroeder, J. C., & Baird, D. D. (2010). New directions in the epidemiology of uterine fibroids. Seminars in Reproductive Medicine, 28(3), 204–217. https://doi.org/10.1055/s-0030-1251477
36. Laughlin, S. K., & Stewart, E. A. (2011). Uterine leiomyomas: Individualizing the approach to a heterogeneous condition. Obstetrics and Gynecology, 117(2 PART 1), 396–403. https://doi.org/10.1097/AOG.0b013e31820780e3
37. Leppert, P. C., Baginski, T., Prupas, C., Catherino, W. H., Pletcher, S., & Segars, J. H. (2004). Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium. Fertility and Sterility, 82(SUPPL. 3), 1182–1187. https://doi.org/10.1016/j.fertnstert.2004.04.030
38. Leppert, P. C., Jayes, F. L., & Segars, J. H. (2014). The Extracellular Matrix Contributes to Mechanotransduction in Uterine Fibroids. Obstetrics and Gynecology International, 2014, 1–12. https://doi.org/10.1155/2014/783289
39. Lethaby, A., & Vollenhoven, B. (2015). Fibroids (uterine myomatosis, leiomyomas). BMJ Clinical Evidence, 2015(November 2006), 1–26.
40. Levy, B. S. (2020). Modern Management of Uterine Fibroids. In M. Metwally & T.-C. Li (Eds.), Acta Obstetricia et Gynecologica Scandinavica (Vol. 87). Cambridge University Press. https://doi.org/https://doi.org/10.1017/9781108332798
41. Lucero, J., Harlow, B. L., Barbieri, R. L., Sluss, P., & Cramer, D. W. (2001). Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use. Fertility and Sterility, 76(4), 723–729. https://doi.org/10.1016/S0015-0282(01)02005-2
42. Lumsden, M. A., Hamoodi, I., Gupta, J., & Hickey, M. (2015). Fibroids: Diagnosis and management. BMJ (Online), 351. https://doi.org/10.1136/bmj.h4887
43. Malik, M., Segars, J., & Catherino, W. H. (2012). Integrin β1 regulates leiomyoma cytoskeletal integrity and growth. Matrix Biology, 31(7–8), 389–397. https://doi.org/10.1016/j.matbio.2012.09.005
44. Marshall, L. M., Spiegelman, D., Goldman, M. B., Manson, J. A. E., Colditz, G. A., Barbieri, R. L., … Hunter, D. J. (1998). A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata. Fertility and Sterility, 70(3), 432–439. https://doi.org/10.1016/S0015-0282(98)00208-8
45. Mas, A., Cervello, I., Gil-Sanchis, C., & Simón, C. (2014). Current understanding of somatic stem cells in leiomyoma formation. Fertility and Sterility, 102(3), 613–620. https://doi.org/10.1016/j.fertnstert.2014.04.051
46. Medikare, V., Kandukuri, L. R., Ananthapur, V., Deenadayal, M., & Nallari, P. (2011). The genetic bases of uterine fibroids; a review. Journal of Reproduction and Infertility, 12(3), 181–191.
47. Moore, K. R., Cole, S. R., Dittmer, D. P., Schoenbach, V. J., Smith, J. S., & Baird, D. D. (2015). Self-reported reproductive tract infections and ultrasound diagnosed uterine fibroids in African-American Women. Journal of Women’s Health, 24(6), 489–495. https://doi.org/10.1089/jwh.2014.5051
48. Moro, E., Esposti, E. D., Borghese, G., Manzara, F., Zanello, M., Raimondo, D., … Seracchioli, R. (2019). The impact of hormonal replacement treatment in postmenopausal women with uterine fibroids: A state-of-the-art review of the literature. Medicina (Lithuania), 55(9). https://doi.org/10.3390/medicina55090549
49. Nagata, C., Nakamura, K., Oba, S., Hayashi, M., Takeda, N., & Yasuda, K. (2009). Association of intakes of fat, dietary fibre, soya isoflavones and alcohol with uterine fibroids in Japanese women. British Journal of Nutrition, 101(10), 1427–1431. https://doi.org/10.1017/S0007114508083566
50. Nivethithai, P., Sr, N., & Bv, R. (2010). APTI Uterine Fibroids : A Review. 3(1), 6–11.
51. Omar, M. K., Yang, Q., Laknaur, A., & Al-Hendy, A. (2016). Myometrial progesterone hyper-responsivness is associated with increased risk for the development of human uterine fibroids. Fertility and Sterility, 106(3), e96. https://doi.org/10.1016/j.fertnstert.2016.07.280
52. Ono, M., Qiang, W., Serna, V. A., Yin, P., Coon, J. S., Navarro, A., … Bulun, S. E. (2012). Role of stem cells in human uterine leiomyoma growth. PLoS ONE, 7(5). https://doi.org/10.1371/journal.pone.0036935
53. Paffoni, A., Somigliana, E., Vigano’, P., Benaglia, L., Cardellicchio, L., Pagliardini, L., … Fedele, L. (2013). Vitamin D status in women with uterine leiomyomas. Journal of Clinical Endocrinology and Metabolism, 98(8), 1374–1378. https://doi.org/10.1210/jc.2013-1777
54. Palomba, S., Orio, F., Russo, T., Falbo, A., Tolino, A., Lombardi, G., … Zullo, F. (2005). Antiproliferative and proapoptotic effects of raloxifene on uterine leiomyomas in postmenopausal women. Fertility and Sterility, 84(1), 154–161. https://doi.org/10.1016/j.fertnstert.2004.12.058
55. Pan, Q., Luo, X., & Chegini, N. (2007). Genomic and proteomic profiling I: Leiomyomas in African Americans and Caucasians. Reproductive Biology and Endocrinology, 5, 1–15. https://doi.org/10.1186/1477-7827-5-34
56. Parazzini, F., Negri, E., La Vecchia, C., Rabaiotti, M., Luchini, L., Villa, A., & Fedele, L. (1996). Uterine myomas and smoking: Results from an Italian study. Journal of Reproductive Medicine for the Obstetrician and Gynecologist, 41(5), 316–320. Retrieved from https://europepmc.org/article/med/8725755
57. Parker, W. H. (2007). Etiology, symptomatology, and diagnosis of uterine myomas. Fertility and Sterility, 87(4), 725–736. https://doi.org/10.1016/j.fertnstert.2007.01.093
58. Pascual Botia, C., Camarasa, S. C., Raga Baixauli, F., & Sanchez, A. C. (2017). Uterine Fibroids Review: Understanding their Origins to Better Understand their Future Treatments. Journal of Tumor Research, 03(03). https://doi.org/10.35248/2684-1258.17.3.130
59. Perrine Susan. (2005). 基因的改变NIH Public Access. Bone, 23(1), 1–7. https://doi.org/10.1038/jid.2014.371
60. Premkumar, A., Venzon, D. J., Avila, N., Johnson, D. V., Remaley, A. T., Forman, M. R., … Stratton, P. (2007). Gynecologic and hormonal effects of raloxifene in premenopausal women. Fertility and Sterility, 88(6), 1637–1644. https://doi.org/10.1016/j.fertnstert.2007.01.095
61. Reis, F. M., Bloise, E., & Ortiga-Carvalho, T. M. (2016). Hormones and pathogenesis of uterine fibroids. Best Practice and Research: Clinical Obstetrics and Gynaecology, 34(November), 13–24. https://doi.org/10.1016/j.bpobgyn.2015.11.015
62. Ritchie, J., & Nelson, A. L. (2017). Severe Anemia from Heavy Menstrual Bleeding Requires Heightened Attention. Clinics in Mother and Child Health, 14(1), 1–2. https://doi.org/10.4172/2090-7214.1000256
63. Sabry, M., Halder, S. K., Ait Allah, A. S. A., Roshdy, E., Rajaratnam, V., & Al-Hendy, A. (2013). Serum vitamin D3 level inversely correlates with uterine fibroid volume in different ethnic groups: A cross-sectional observational study. International Journal of Women’s Health, 5(1), 93–100. https://doi.org/10.2147/IJWH.S38800
64. Samadi, A. R., Lee, N. C., Dana Flanders, W., Boring, J. R., & Parris, E. B. (1996). Risk factors for self-reported uterine fibroids: A case-control study. American Journal of Public Health, 86(6), 858–862. https://doi.org/10.2105/AJPH.86.6.858
65. Seshadri, S., El-Toukhy, T., Douiri, A., Jayaprakasan, K., & Khalaf, Y. (2015). Diagnostic accuracy of saline infusion sonography in the evaluation of uterine cavity abnormalities prior to assisted reproductive techniques: A systematic review and meta-analyses. Human Reproduction Update, 21(2), 262–274. https://doi.org/10.1093/humupd/dmu057
66. Sharan, C., Halder, S. K., Thota, C., Jaleel, T., Nair, S., & Al-Hendy, A. (2011). Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase. Fertility and Sterility, 95(1), 247–253. https://doi.org/10.1016/j.fertnstert.2010.07.1041
67. Sinclair, D. C., Mastroyannis, A., & Taylor, H. S. (2011). Leiomyoma simultaneously impair endometrial BMP-2-mediated decidualization and anticoagulant expression through secretion of TGF-β3. Journal of Clinical Endocrinology and Metabolism, 96(2), 412–421. https://doi.org/10.1210/jc.2010-1450
68. Sommer, E. M., Balkwill, A., Reeves, G., Green, J., Beral, D. V., & Coffey, K. (2015). Effects of obesity and hormone therapy on surgically-confirmed fibroids in postmenopausal women. European Journal of Epidemiology, 30(6), 493–499. https://doi.org/10.1007/s10654-015-0016-7
69. Sparic, R., Mirkovic, L., Malvasi, A., & Tinelli, A. (2016). Epidemiology of uterine myomas: A review. International Journal of Fertility and Sterility, 9(4), 424–435. https://doi.org/10.22074/ijfs.2015.4599
70. Stewart, E. A., Cookson, C. L., Gandolfo, R. A., & Schulze-Rath, R. (2017). Epidemiology of uterine fibroids: a systematic review. BJOG: An International Journal of Obstetrics and Gynaecology, 124(10), 1501–1512. https://doi.org/10.1111/1471-0528.14640
71. Stewart, Elizabeth A., & Nowak, R. A. (1996). Leiomyoma-related bleeding: A classic hypothesis updated for the molecular era. Human Reproduction Update, 2(4), 295–306. https://doi.org/10.1093/humupd/2.4.295
72. Taran, F. A., Brown, H. L., & Stewart, E. A. (2010). Racial diversity in uterine leiomyoma clinical studies. Fertility and Sterility, 94(4), 1500–1503. https://doi.org/10.1016/j.fertnstert.2009.08.037
73. Thorne, J. T., Segal, T. R., Chang, S., Jorge, S., Segars, J. H., & Leppert, P. C. (2015). Dynamic Reciprocity Between Cells and Their Microenvironment in Reproduction1. Biology of Reproduction, 92(1), 1–10. https://doi.org/10.1095/biolreprod.114.121368
74. Tinelli, A., Vinciguerra, M., Malvasi, A., Andjić, M., Babović, I., & Sparić, R. (2021). Uterine fibroids and diet. International Journal of Environmental Research and Public Health, Vol. 18, pp. 1–15. https://doi.org/10.3390/ijerph18031066
75. Välimäki, N., Kuisma, H., Pasanen, A., Heikinheimo, O., Sjöberg, J., Bützow, R., … Aaltonen, L. A. (2018). Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability. ELife, 7, 1–50. https://doi.org/10.7554/eLife.37110
76. Vessey, M. P. (1986). Risk factors for uterine fibroids: Reduced risk associated with oral contraceptives. British Medical Journal (Clinical Research Ed.), 293(6543), 359–362. https://doi.org/10.1136/bmj.293.6543.359
77. Vitner, D., Filmer, S., Goldstein, I., Khatib, N., & Weiner, Z. (2013). A comparison between ultrasonography and hysteroscopy in the diagnosis of uterine pathology. European Journal of Obstetrics and Gynecology and Reproductive Biology, 171(1), 143–145. https://doi.org/10.1016/j.ejogrb.2013.08.024
78. Wang, Y., Feng, G., Wang, J., Zhou, Y., Liu, Y., Shi, Y., … Li, Z. (2015). Differential effects of tumor necrosis factor-α on matrix metalloproteinase-2 expression in human myometrial and uterine leiomyoma smooth muscle cells. Human Reproduction, 30(1), 61–70. https://doi.org/10.1093/humrep/deu300
79. Williams, A. R. W. (2017). Uterine fibroids – what’s new? F1000Research, 6, 2109. https://doi.org/10.12688/f1000research.12172.1
80. Windham, G. C., Mitchell, P., Anderson, M., & Lasley, B. L. (2005). Cigarette smoking and effects on hormone function in premenopausal women. Environmental Health Perspectives, 113(10), 1285–1290. https://doi.org/10.1289/ehp.7899
81. Wise, L. A., & Laughlin-tommaso, S. K. (2016). Epidemiology of Uterine Fibroids. Clinical Obstetrics & Gynecology, 59(1), 2–24. https://doi.org/10.1097/grf.0000000000000164
82. Wise, L. A., Palmer, J. R., Harlow, B. L., Spiegelman, D., Stewart, E. A., Adams-Campbell, L. L., & Rosenberg, L. (2004). Risk of uterine leiomyomata in relation to tobacco, alcohol and caffeine consumption in the Black Women’s Health Study. Human Reproduction, 19(8), 1746–1754. https://doi.org/10.1093/humrep/deh309
83. Wise, L. A., Palmer, J. R., Harlow, B. L., Spigelman, D., Stewart, E. A., Adams-Campbell, L. L., & Rosenberg, L. (2004). Reproductive Factors, Hormonal Contraception, and Risk of Uterine Leiomyomata in African-American Women: A Prospective Study. American Journal of Epidemiology, 159(2), 113–123. https://doi.org/10.1093/aje/kwh016
84. Wise, L. A., Palmer, J. R., Ruiz-Narvaez, E., Reich, D. E., & Rosenberg, L. (2013). Is the observed association between dairy intake and fibroids in African Americans explained by genetic ancestry? American Journal of Epidemiology, 178(7), 1114–1119. https://doi.org/10.1093/aje/kwt091
85. Wynn, T. A., & Wynn, T. A. (2007). Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases Find the latest version : Review series introduction Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. Journal Of Clinical Investigation, 117(3), 524–529. https://doi.org/10.1172/JCI31487.524
86. Yan, L., Ding, L., Li, C., Wang, Y., Tang, R., & Chen, Z. J. (2014). Effect of fibroids not distorting the endometrial cavity on the outcome of in vitro fertilization treatment: A retrospective cohort study. Fertility and Sterility, 101(3), 716-721.e6. https://doi.org/10.1016/j.fertnstert.2013.11.023