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UTERINE FIBROIDS; COMPLIMENTARY & ALTERNATIVE THERAPIES

Brittany Pinkos

Hannah Sabella

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CONDITION DEFINED

Leiomyoma originating from the myometrium of the uterus

Cervical fibroid
Intramural fibroid
Pedunculated fibroid
Submucosal fibroid
Subserosal fibroid

PubMed Health; Stewart, 2001

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SIGNS & SYMPTOMS

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PREVALENCE

Race	Incidence*	Population of Women**	New Cases Diagnosed
African American	30.6 per 1,000	18,309,891	560,283
White	8.9 per 1,000	98,476,381	876,440
Asian	8.0 per 1,000	5,489,427	43,915
Hispanic	11.0 per 1,000	16,089,357	176,983
American/Indian & Alaskan Native	Not determined	1,201,635	Not determined
*’Incidence’ is the number of new diagnoses of fibroids made each year for every 1,000 woman years, as confirmed by ultrasound of hysterectomy. Source: Marshall LM, Spiegelman D, Barbieri RL, Goldman MB, Manson JE, Colditz GA, Willett WC, Hunter DJ. “Variation in the incidence of uterine leiomyoma among premenopausal women by age and race.” Obstet Gynecol. 1997 Dec;90(6):967-73.
Source: National Women’s Law Center, “Making the Grade on Women’s Health 2001.”

Clinically apparent in about 25% (as of 2001)
Modern imaging techniques and examination of surgical specimens suggests that undiagnosed rates may reach upwards of 77%.
As we’ll discuss, diagnosis is not always warranted for this condition, making prevalence difficult to track.
This chart shows the incidence (new cases) of uterine fibroids diagnosed by ultrasound among different populations

It’s important to note that treatment with CAM may not always be for the fibroids, as they may be undiagnosed and unknown to the individual, but for the severity of symptoms that accompany fibroids.
Black women are significantly more likely than white women to have myomas, and they tend to be younger at the time of diagnosis and require hysterectomy.

Source: http://www.nuff.org/bod.htm – National Uterine Fibroids Foundation

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ETIOLOGY

Myomas respond to the gonadal steroids estrogen and progesterone, and their epidemiology parallels the ontogeny and life-cycle changes in reproductive hormones.
Higher BMI promotes estrogenic factors, increasing risk of fibroid development
reproductive factors:

Woman is at decrease risk if she is “parous” – having one or more pregnancies extending beyond 20 weeks decreases chance of myoma formation
Fibroids contain more estrogen and progesterone receptors than normal uterine muscle cells do
contraceptives –

Exposure to oral contraceptives between the ages of 13 and 16 years led to increased relative risk of myomas, whereas use in general showed protection in direct proportion to duration of use.

Myomas do not occur pre-puberty, and symptoms tend to be relieved at time of menopause

In the case of hormone replacement therapy, post-menopausal women may develop symptomatic fibroids

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PATHOPHYSIOLOGY�TRANSFORMATION OF NORMAL MYOCYTES INTO ABNORMAL MYOCYTES�ABNORMAL MYOCYTE GROWTH INTO APPARENT TUMORS

Stewart, 2001

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PATHOPHYSIOLOGY�GENETIC & HORMONAL

Genetic

HMGIC gene

bFGF – basic fibroblast growth factor

TGF-B – transforming growth factor B
GM-CSF – granulocyte-macrophage colony-stimulating factor

Hormonal

Levels of ER and PR in fibroid tissue
Regulated by levels of circulating sex steroids

Stewart, 2001; Englund, 1998

HORMONAL – source: http://press.endocrine.org/doi/full/10.1210/jcem.83.11.5287

Higher content of estrogen and progesterone receptors in fibroid tissues
Can be treated with endocrine disruptors (EDs) or environmental estrogens

Found in plastics (BPA), detergents and surfactants, pesticides (DDT), industrial chemicals (PCBs) and phytoestrogens (genistein, coumesterol)

source: http://toxsci.oxfordjournals.org/content/81/1/139.full

Estrogen stimulates cell division, excessive amounts can lead to tumor development
Polyphenols decrease estrogen levels
Phytoestrogens are estrogens found in plants

GENETIC

HMGIC gene

Dysregulated in the subgroup of myomas contributing to fibroids
Characterised by gene translocation, hereditary predisposition

bFGF

Myomas have higher amounts of mRNA for this angiogenic growth factor than a matched myometrium
In fact, a reservoir of bFGF protein is stored in the extracellular matrix that characterizes myomas

TGF-B & GM-CSF

Myomas have higher amounts of TGF-B and receptor mRNA than myometrium when obtained during the secretory phase of the menstrual cycle
GM-CSF acting directly and through the increase in expression of TGF-B may differentially stimulate myomas and normal myometrium

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CONVENTIONAL TREATMENT

Source for Image: http://www.einstein.edu/fibroid-center/fibroid-algorithm/

Several factors determine treatment, including the size and location of the myomas, the presenting symptoms, & the age and reproductive desires of the patients.

The flow chart helps to illustrate the conditions in which each treatment method may be indicated as the best option for the patient.

American Academy of Family Physicians (http://www.aafp.org/afp/2007/0515/p1503.html)

Gonadotropin-releasing hormone agonsists – decreases sizes of tumors before hysterectomy, myomectomy, or myolysis
Hysterectomy – surgical removal of the uterus, unable to conceive afterwards
Myolysis – in situ destruction of tumors by heat, laser, or cryotherapy
Myomectomy – surgical or endoscopic excision of tumors
Uterine artery embolization – radiologic procedure to occlude uterine arteries
Hormones – can shrink/limit tumor growth → thus, many of the alternative options for treatment share a close relationship with the primary female/reproductive hormone, estrogen

Source: http://archive.ahrq.gov/downloads/pub/evidence/pdf/uterupdate/uterup.pdf

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REPORTED CAM USAGE

Reproductive Health & Suspected CAM Prevalence		Popular CAMs
Infertility	29%	Acupuncture, herbal therapy, body work, meditation
Heavy menstrual bleeding	--	Ginger, Licorice, Omega-3, Magnesium, Iron
PMS symptoms	--	Calcium, Magnesium, Chaste berry, St. John’s Wort, Acupuncture, Evening primrose oil
Ovarian cysts	--	Avoid plastic food containers, Chaste berry, Iodine, Red Clover, Dandelion

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GREEN TEA EXTRACT-EGCG

Epigallocatechin Gallate (EGCG) is a polyphenol found in green tea and also fruits and vegetables
EGCG has anti-inflammatory, anti proliferative and antioxidant effects
Known to decrease tumor volume and size in mice and human subjects

Also reduced symptom severity

Has been shown safe and effective in treating other conditions as well

Obgyn.net

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GREEN TEA EXTRACT- STUDY 1

Methods

39 reproductive women aged 18-50, fibroid measuring 2 cm or larger
Doubled blinded, placebo controlled randomized clinical trail

Assigned to 800 mg green tea extract (45% ECGC) or 800 mg brown rice (placebo)

Results

Treatment showed significant reduction in total UF volume
EGCG significantly treatment symptom severity and HRQL
Anemia was significantly improved
Blood loss significantly decreased

Conclusion: EGCG shows a promising safe and effective therapy for women with symptomatic uterine fibroids

Roshdy, 2013

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GREEN TEA EXTRACT- OTHER STUDIES

Studies previously been done on mice

Results show that ECGC effectively inhibit proliferation and induces apoptosis

Studies done on cultured human leiomyoma cells

Results suggest EGCG to be a potential anit-uterine fibroid agent

Zhang, 2010

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FLAXSEED

Abundant source of phytoestrogens, mainly lignans

Chemical structures resembling endogenous estrogens

Studies show flax helps the body produce less unhealthy estrogen
Flax can decrease estrogens effect by blocking estrogen receptors on fibroid cells
Lignans have estrogen antagonist/agonist actions

Also have antioxidants properties

Lahey.org

American Journal of Nutrition

http://ajcn.nutrition.org/content/79/2/318.full

http://clincancerres.aacrjournals.org/content/13/3/1061.short

http://onlinelibrary.wiley.com/doi/10.1002/ijc.21067/full

https://lahey.org/Departments_and_Locations/Departments/Gynecology/Ebsco_Content/Uterine_Fibroids.aspx?chunkiid=24390

http://www.healthy.net/Health/Article/Healing_Fibroids_Naturally/8110/2

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074428/

http://www.ncbi.nlm.nih.gov/pubmed/8077314

Citation: http://toxsci.oxfordjournals.org/content/80/1/14.full

Phytoestrogens can be pleiotropic (one gene defect causes affects over multiple systems) on cellular signaling and some estrogen-dependent diseases, but could potentially encourage tumor growth

Most commonly studied are soy phytoestrogens – resveratrol, genistein, coumestrol, equol, and dialdzein

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FLAXSEED- STUDY 1

Methods:

The diet of 46 postmenopausal women was supplement with either placebo, soy (25 g soy flour) or flaxseed (25 g ground flaxseed) muffins for 16 wk
Urine samples were measured to determine estrogen excretion

Results:

Urinary concentrations of 2-hydroxyestrone significantly increased in flaxseed group
Flaxseed group, ratio of 2-hydroxyestrone to 16-a was positively correlated with urinary lignin excretion

Conclusion: Supplementation with flaxseed can modify urinary estrogen metabolites greater than with soy supplementation

Flaxseed is associated with increase in urinary lignan excretion

Brooks, 2004

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FLAXSEED- OTHER STUDIES

Other studies have been done on flaxseed and breast cancer

Showed to reduce tumor growth and metastasis in mice with established ER- human breast cancer due to lignan and flaxseed oil components
Promising that flaxseed could reduce fibroid tumor growth

Wang, 2005

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CURCUMIN

Active ingredient in turmeric
Shown to inhibit fibroid cell growth
Decreases levels of fibronectin- component of extracellular matrix that contributes to fibroid progression
Can help treat and prevent liver damage

Helps liver to be healthy enough to remove toxins and excess estrogen

Side effects could include allergic reaction to turmeric

Ncbi.nlm.nih.gov

Fibroidnaturaltreatment.com

Lifeextension.com

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CURCUMIN- STUDY1

Methods:

Eker rat-derived uterine leiomyoma cell lines (ELT-3) were used
Cell proliferation and activation of peroxisome proliferator-activated receptor gamma (PPARY) were measured

Results

ELT-3 significantly inhibited
PPARY was expressed and curcumin acted as a ligand

Conclusion: Findings showed that in vitro curcumin showed an inhibitory effect on ELT-3 cell proliferation

Tsuiji, 2011

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OTHER PROMISING THERAPIES

Bromelain
Choline
Chaste berry (Vitex)
Antioxidants- vitamin E, vitamin C
Chinese herbal therapy
Dandelion root
Milk thistle
Nettle
Red Raspberry

Altmd.com

Uterine-fibroids.org

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EFFICACIOUS OR PROMISING ALTERNATIVE THERAPIES (BEYOND NATURAL PRODUCTS)

Acupuncture
Sitz baths
Aroma therapy
Massage

Uterine-fibroids.org

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RECOMMENDATIONS & DOSING

Upper limits

Flaxseed

Green Tea extract 725 mg daily
Flaxseed 5-38 g/day
Curcumin 400-630 mg daily

Lifeextension.com

Lahey.org

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ISSUES & CONCERNS // DIET NOTES

Flaxseed not associated with adverse effects

Too much can be chemo preventive or cancer-promoting

Important to determine efficacy and safety of product being used

Diet notes:
Eat more fruits, green or sea vegetables, whole grains, nuts and seeds
Consume more soy products?
Avoid foods high in fat and sugar
Avoid produce sprayed with insecticides

Lahey.org

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REFERENCES (AMA FORMAT)

Brooks JD, Ward WE, Lewis JE, Hilditch J, Nickell L, Wong E, Thompson LU. Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with equal amount of soy. The American Journal of Clinical Nutrition. 2004;79(2)318-325.
Englund K, Blanck A, Gustavsson I, Lundkvist U, Sjoblom P, Norgren, Lindblom B. Sex Steroid Receptors in Human Myometrium and Fibroids: Changes during the Menstrual Cycle and Gonadotropin-Releasing Hormone Treatment. Journal of Clinical Endocrinology & Metabolism. 1998;83(11).
Greenlee RT, Kessel B, Williams CR, Riley TL, Ragard LR, Hartge P,… Reding DJ. Prevalence, incidence, and natural history of simple ovarian cysts among women over age 55 in a large cancer screening trial. Am J Obstet Gynecol. 2011;202(4):373.
Mueller SO, Simon S, Chae K, Metzler M, Korach KS. Phytoestrogens and Their Human Metabolites Show Distinct Agonistic and Antagonistic Properties on Estrogen Receptor a (Era) and ERB in Human Cells. Toxicol Sci. 2004:80(1);14-25.
Pubmed Health Website. Uterine Fibroids. Accessed 16 May 2015. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024647/
Roshdy E, Rajaratam V, Maitra S, Sabry M, Allah ASA, Al-Hendy. Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study. International Journal of Women’s Health. 2013;5:477-486
Smith JF, Eisenberg ML, Millstein SG, Nachtigall RD, Shindel AW, Wing H,… Katz PP. The use of complementary and alternative fertility treatment in couples seeking fertility care: data from a prospective cohort in the United States. Fertil Steril. 2010;93(7):2169-74.
Stewart EA. Uterine Fibroids. The Lancet. 2001;357:293-298.
Tsuiji K, Takeda T, Li B, Wakabayashi A, Kondo A, Kimura T, Yaegashi N. Inhibitory effect of curcumin on uterine leiomyoma cell proliferation. Gynecol Endocriol. 2011;27(2):512-517.
Wang L, Chen J, Thompson LU. The inhibitory effect on the growth and metastasis of estrogen receptor negative human breast cancer xenografts to both it lignan and oil components. International Journal of Cancer. 2005;116(5)793-798
Yurino H, Ishikawa S, Sato T, Akadegawa K, Ito T, Ueha S, Inadera H, Matsushima K. Toxicol Sci. 2004;81(1):139-147.