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Factors Predisposing Women to Fibroids

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Uterine leiomyomata, or fibroids, are very common, affecting up to 70% or even 80% of women at some point in their lives.1,2 Despite this lifetime prevalence, many cases go undiagnosed, increasing the probable incidence,1 while clinical guidelines appear to lack consensus on optimal evidence-based treatment strategies.3

In general, genetics and ovarian hormone exposure are likely antecedents for the development of fibroids.2 Studies have shown a notable difference in the prevalence and presentation of fibroids based on race, with Black women experiencing larger fibroids more often and at a younger age than some other racial populations.1,2,4 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.5

Often, women with fibroids want to avoid hysterectomy.5 However, in the United States, uterine fibroids are one of the most common reasons for a hysterectomy,5 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.6 What risk factors may play a role in the development of uterine fibroids, and what options other than hysterectomy are available for patients?

Risk Factors

The underlying cause of uterine fibroids and the mechanisms of their growth are not fully known, and those factors that predispose women to fibroid development continue to be studied. Age, race, and family history are a few of the noted risk factors that are not modifiable; however, certain lifestyle factors that are modifiable may play a role in fibroid development.4,7 Increased blood pressure correlates with the increased risk of fibroids2,4 due to changes in atherogenesis.8 High serum lipids and metabolic syndrome also increase the risk of fibroids, suggesting a cardiometabolic connection.9 Low vitamin D levels may also increase risk for fibroids.10,11 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.10

As mentioned, Black women are much more likely to develop fibroids. In addition, they are also more likely to report more severe symptoms.4,12,13 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.14

ENVIRONMENTAL EXPOSURES

Either as part of an inflammatory milieu or otherwise, environmental toxicants also likely play a role in the development of fibroids, including exposures to polluted drinking water15 and 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.16 Heavy metals,17 persistent organic pollutants (POPs),17,18 and possibly PCBs18 are also correlated with uterine fibroid development. Reports estimate that at least 23% of child-bearing women are exposed to three or more toxicants above the level of known safety.19 Critical windows of exposure may affect long-term hormonal patterns, especially pre-menarche exposures.20 A significant, dose-dependent connection between hair relaxers and fibroid risk also suggests that some Black women may be exposed to more and different chemicals than many white women.21

Treatment Considerations

Healthy lifestyle factors may not only play a preventative role in fibroid risk but may also be part of an effective treatment plan. Improving gut health and detoxification efficiency, addressing hormone imbalances and normalizing insulin, and implementing the most effective exercise and nutritional plan for an individual patient are all components of a foundational functional medicine approach to decreasing fibroids.

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.22 Fibroids themselves alter the expression patterns of estrogen and androgen receptors.23 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;24 however, from a functional medicine perspective, interventions that prioritize an anti-inflammatory approach, improve modifiable lifestyle factors, and reduce exposure to environmental toxicants are treatment approaches to be considered. For the many women who suffer from fibroids but wish to avoid hysterectomy, these low-harm therapies may provide the relief they seek.

"LEARN

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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. Giuliani E, As-Sanie S, Marsh EE. Epidemiology and management of uterine fibroids. Int J Gynaecol Obstet. 2020;149(1):3-9. doi:10.1002/ijgo.13102
  3. Amoah A, Joseph N, Reap S, Quinn SD. Appraisal of national and international uterine fibroid management guidelines: a systematic review. BJOG. 2022;129(3):356-364. doi:10.1111/1471-0528.16928
  4. Eunice Kennedy Shriver National Institute of Child Health and Human Development. What are the risk factors for uterine fibroids? National Institutes of Health. Reviewed November 2, 2018. Accessed April 8, 2022. https://www.nichd.nih.gov/health/topics/uterine/conditioninfo/people-affected
  5. 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
  6. 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
  7. Pavone D, Clemenza S, Sorbi F, Fambrini M, Petraglia F. Epidemiology and risk factors of uterine fibroids. Best Pract Res Clin Obstet Gynaecol. 2018;46:3-11. doi:10.1016/j.bpobgyn.2017.09.004
  8. 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
  9. 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
  10.  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
  11.  Vahdat M, Allahqoli L, Mirzaei H, et al. The effect of vitamin D on recurrence of uterine fibroids: a randomized, double-blind, placebo-controlled pilot study. Complement Ther Clin Pract. 2022;46:101536. doi:10.1016/j.ctcp.2022.101536
  12.  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
  13.  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
  14.  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
  15.  Hammarstrand S, Jakobsson K, Andersson E, et al. Perfluoroalkyl substances (PFAS) in drinking water and risk for polycystic ovarian syndrome, uterine leiomyoma, and endometriosis: a Swedish cohort study. Environ Int. 2021;157:106819. doi:10.1016/j.envint.2021.106819
  16. 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
  17.  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.
  18.  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
  19.  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
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  22.  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
  23.  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
  24.  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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