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Factors Predisposing Women to Fibroids

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Uterine leiomyomata, or fibroids, are very common, affecting approximately 70% of women at some point in their lives.1 However, many cases go undiagnosed, increasing the probable incidence.1

In general, genetics and ovarian hormone exposure are the known antecedents for the development of fibroids.2 The heavy bleeding associated with fibroids can cause anemia, fatigue, and pain.1 Women with uterine fibroids report a decreased quality of life, difficulty getting diagnosed, and concerns about available treatment options.3

Often, women with fibroids want to avoid hysterectomy.3 However, in the US, uterine fibroids are the top cause of hysterectomies.3 Yet it is well known that even when the ovaries are conserved, hysterectomies can greatly increase other health risks like cardiovascular and metabolic conditions, including congestive heart failure.4 What risk factors may play a role, and what options other than hysterectomy are available to clinicians?

Risk Factors for fibroid development

Factors that predispose women to fibroids are not yet well understood,5 but research has identified that modifiable lifestyle factors and antecedents play a role. Increased blood pressure correlates with the increased risk of fibroids, due to changes in atherogenesis.5 High serum lipids and metabolic syndrome also increase the risk of fibroids, suggesting a cardiometabolic connection.6 Low vitamin D levels may also increase risk for fibroids.7 In addition, cytokines show different seasonal variance in women with and without fibroids, suggesting that a highly inflamed immune system may play a role in fibroid formation.7

African-American women are much more likely to develop fibroids, and to report more severe symptoms.8,9 Adding to this connection, central centrifugal cicatricial alopecia (which primarily affects black women) is highly correlated with uterine fibroids, suggesting a similar underlying pathophysiological mechanism.10

Either as part of an inflammatory milieu or otherwise, toxins also likely play a role in the development of fibroids, including exposure to air pollution. One large-scale, longitudinal study demonstrated that exposure to high amounts of air pollution [particulate matter (PM) 2.5] correlated with an increased risk of fibroids.11 Heavy metals,12 persistent organic pollutants (POPs),12,13 and possibly PCBs13 are also correlated with uterine fibroid development. Estimates are that at least 23% of child-bearing women are exposed to three or more toxicants above the level of known safety.14 Critical windows of exposure may affect long-term hormonal patterns, especially pre-menarche exposures.15 A significant, dose-dependent connection between hair relaxers and fibroid risk also suggests that some African-American women may be exposed to more and different chemicals than many white women.16

Treatment Considerations

One of the emerging non-surgical treatments for fibroids is modulating progesterone. In one study, perioperative treatment with the progesterone receptor modulator ulipristal acetate (or UPA) resulted in 61% of women electing not to continue with surgery, as their symptoms were adequately managed.17  

Fibroids themselves alter the expression patterns of estrogen and androgen receptors.18 For that reason, it’s important to help patients restore hormonal balance even after fibroids and their symptoms are adequately treated.

Best practices for treating fibroids have not yet been established.19 From a Functional Medicine perspective, fibroids likely indicate hormonal imbalance, and several lifestyle interventions can assist in treatment, including improved nutrition (which may also reduce cardiometabolic risk), reduced exposure to toxins (particularly androgenic toxins), and anti-inflammatory interventions (including botanicals and lifestyle interventions). For the many women who suffer from fibroids but wish to avoid hysterectomy, these low-harm therapies may provide the relief they seek.

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References

  1. Stewart EA, Cookson CL, Gandolfo RA, Schulze-Rath R. Epidemiology of uterine fibroids: a systematic review. BJOG. 2017;124(10):1501-1512. doi:10.1111/1471-0528.14640
  2. Vercellini P, Frattaruolo MP. Uterine fibroids: from observational epidemiology to clinical management. BJOG. 2017;124(10):1513. doi:10.1111/1471-0528.14730
  3. Borah BJ, Nicholson WK, Bradley L, Stewart EA. The impact of uterine leiomyomas: a national survey of affected women. Am J Obstet Gynecol. 2013;209(4):319.e1-319.e20. doi:10.1016/j.ajog.2013.07.017
  4. Laughlin-Tommaso SK, Khan Z, Weaver AL, Smith CY, Rocca WA, Stewart EA. Cardiovascular and metabolic morbidity after hysterectomy with ovarian conservation: a cohort study. Menopause. 2018;25(5):483-492. doi:10.1097/GME.0000000000001043
  5. Boynton-Jarrett R, Rich-Edwards J, Malspeis S, Missmer SA, Wright R. A prospective study of hypertension and risk of uterine leiomyomata. Am J Epidemiol. 2005;161(7):628-638. doi:10.1093/aje/kwi072
  6. Uimari O, Auvinen J, Jokelainen J, et al. Uterine fibroids and cardiovascular risk. Hum Reprod. 2016;31(12):2689-2703. doi:10.1093/humrep/dew249
  7. Wegienka G, Baird DD, Cooper T, Woodcroft KJ, Havstad S. Cytokine patterns differ seasonally between women with and without uterine leiomyomata. Am J Reprod Immunol. 2013;70(4):327-335. doi:10.1111/aji.12127
  8. Commandeur AE, Styer AK, Teixeira JM. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth. Hum Reprod Update. 2015;21(5):593-615. doi:10.1093/humupd/dmv030
  9. Stewart EA, Nicholson WK, Bradley L, Borah BJ. The burden of uterine fibroids for African-American women: results of a national survey. J Womens Health (Larchmt). 2013;22(10):807-816. doi:10.1089/jwh.2013.4334
  10. Dina Y, Okoye GA, Aguh C. Association of uterine leiomyomas with central centrifugal cicatricial alopecia. JAMA Dermatol. 2018;154(2):213-214. doi:10.1001/jamadermatol.2017.5163
  11. Mahalingaiah S, Hart JE, Laden F, et al. Air pollution and risk of uterine leiomyomata. Epidemiology. 2014;25(5):682-688. doi:10.1097/EDE.0000000000000126
  12. Qin YY, Leung CK, Leung AO, Wu SC, Zheng JS, Wong MH. Persistent organic pollutants and heavy metals in adipose tissues of patients with uterine leiomyomas and the association of these pollutants with seafood diet, BMI, and age. Environ Sci Pollut Res Int. 2010;17(1):229-240. 
  13. Trabert B, Chen Z, Kannan K, et al. Persistent organic pollutants (POPs) and fibroids: results from the ENDO study. J Expo Sci Environ Epidemiol. 2015;25(3):278-285. doi:10.1038/jes.2014.31
  14. Thompson MR, Boekelheide K. Multiple environmental chemical exposures to lead, mercury and polychlorinated biphenyls among childbearing-aged women (NHANES 1999–2004): body burden and risk factors. Environ Res. 2013;121:23-30. doi:10.1016/j.envres.2012.10.005
  15. Mahalingaiah S, Missmer SE, Cheng JJ, Chavarro J, Laden F, Hart JE. Perimenarchal air pollution exposure and menstrual disorders. Hum Reprod. 2018;33(3):512-519. doi:10.1093/humrep/dey005
  16. Wise LA, Palmer JR, Reich D, Cozier YC, Rosenberg L. Hair relaxer use and risk of uterine leiomyomata in African-American women. Am J Epidemiol. 2012;175(5):432-440. doi:10.1093/aje/kwr351
  17. Fernandez H, Schmidt T, Powell M, Costa AP, Arriagada P, Thaler C. Real world data of 1473 patients treated with ulipristal acetate for uterine fibroids: Premya study results. Eur J Obstet Gynecol Reprod Biol. 2017;208:91-96. doi:10.1016/j.ejogrb.2016.11.003
  18. Wong JY, Gold EB, Johnson WO, Lee JS. Circulating sex hormones and risk of uterine fibroids: Study of Women’s Health Across the Nation (SWAN). J Clin Endocrinol Metab. 2016;101(1):123-130. doi:10.1210/jc.2015-2935
  19. Al-Hendy A, Myers ER, Stewart E. Uterine fibroids: burden and unmet medical need. Semin Reprod Med. 2017;35(6):473-480. doi:10.1055/s-0037-1607264

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