Use of this content is subject to the Terms and Conditions

Rakel: Integrative Medicine, 2nd ed.

Copyright © 2007 Saunders, An Imprint of Elsevier

chapter 57 – Uterine Fibroids

Allan Warshowsky, MD, FACOG, ABHM
Pathophysiology 619
Prevalence and Etiology of Uterine Fibroids 619
Hormonal Changes in the Normal Ovulatory Menstrual Cycle 619
Estrogen Dominance 620
Determining Whether a Fibroid Has Malignant Potential 623
Integrative Therapy 623
Nutrition 623
Lifestyle 624
Botanicals 624
Specific Herbal Therapies for Specific Symptoms 625
Complementary and Alternative Medicine Studies on Fibroid Tumors of the Uterus 626
Supplements 626
Mind-Body Approaches 628
Pharmaceuticals 628
Surgical Treatment 629
Therapies to Consider 630
Prevention Prescription 630
Therapeutic Review 630
Pathophysiology
Prevalence and Etiology of Uterine Fibroids

Prevalence estimates for uterine fibroids indicate that they affect 5.4% to 77% of women,
depending on the method of diagnosis. A fibroid can be very small and difficult to feel,
[1]

especially in an obese woman, or as large as a watermelon. Most gynecologists do not

consider fibroids a problem until they are the size of a 12-week pregnancy or are causing
significant symptoms, such as bleeding and painful menstruation. Hysterectomy has been
the procedure of choice for large fibroid tumors. Approximately 300,000 hysterectomies are
performed per year for fibroid tumors. Hysterectomy is not a benign procedure; in 1975,
1700 deaths occurred in the 787,000 hysterectomies performed. Conventional medicine has
[2]

little else to offer other than a “watch and wait” attitude to women who suffer from small
fibroids. If fibroids are approached holistically when initially observed, however, much of
the disability and invasive surgical procedures can be avoided.
Hormonal Changes in the Normal Ovulatory Menstrual Cycle

(…)
 We must also consider the association of ovarian hormones with the thyroid and adrenal
glands. Alterations of thyroid function invariably cause menstrual irregularities of all kinds.
The benign dermoid tumor of the ovary is often associated with thyroid tissue and can even
contribute to the condition called “thyroid storm.” Low progesterone-to-estradiol (P/E2)
ratios are associated with reduced conversion of thyroxin (T4) to triiodothyronine (T3) or
activated thyroid hormone. Therefore hypothyroidism can at least be an indicator of sex
hormone imbalance. The adrenal glands are also connected with sex hormone production
and metabolism and must be evaluated along with the thyroid and ovarian hormones.

(…)

Vitamin D research has also begun to shed some light on the higher incidence of fibroids in
African-American and other dark-skinned women. Low vitamin D levels are associated
with inflammatory imbalances and have been shown to be associated with higher incidence
of epithelial cancers such as those of breast, colon, and prostate. Vitamin D is necessary for
healthy cell apoptosis or regulated cell death and also has profound effects on healthy
glucose metabolism. Later discussion explains how unhealthy glucose metabolism can
contribute to fibroid growth through the development of insulin resistance. It is important
[6]

to measure 25-hydroxyvitamin D, because it is the form that circulates to all cells of the
body. The optimal range of 25-hydroxyvitamin D is probably between 40 and 100 IU. [7]

Replenishment is with Vitamin D3 at the range of 50,000 IU/month for 3 months, at which
time the measurement should be repeated. [8]

Studies by Elizabeth Stewart in Boston have strengthened the connection between systemic
inflammation and fibroid growth. She has shown that various growth factors, such as
fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor,
which are concentrated in fibroid cells, are responsive to inflammatory mediators. These
stimulated growth factors increase blood vessel growth to the myomata and stimulate
growth. All successful tumors increase their own blood supply, enabling growth.
Controlling vascularity can then reduce the growth of the tumor or fibroid. [9]

The theorized “gut connection” to fibroid growth concerns bacterial

imbalance, which creates a dysbiotic intestinal environment and then
gut-associated inflammatory mediators. These inflammatory mediators are IL-
2, IL-6, TNF-α, and other leukotrienes and cytokines. They bathe the pelvis, where nature's
fertilizer, estradiol, stimulates the growth of atypical cells that develop into autonomously
growing leiomyomata. The intestinal dysbiosis with bacterial and yeast overgrowth also
contributes to estrogen dominance through the estrogenic effects of bacterial toxins and
yeast mycotoxins.

Estrogen Dominance
Estrogen dominance is a term coined by the late Dr. John Lee ( Fig. 57-1 ). It indicates
[10]

conditions associated with stronger estrogen effects than can be balanced with existing
progesterone. Fibroids are just one condition associated with estrogen dominance ( Table
57-1 ). Other conditions associated with estrogen dominance are as follows:

• Autoimmune diseases—Hashimoto's disease, systemic lupus erythematosus

• Fibrocystic breast problems
• Gallbladder disease
• Cervical dysplasias and other hormone-dependent cancers
• Endometriosis
• Infertility
• Menstrual irregularities
• Polycystic ovary syndrome
• Premenstrual syndrome
 FIGURE 57-1 The fibroid that can be felt and measured is the physical manifestation of estrogen dominance and inflammation. Estrogen dominance and inflammation in the body are created and
supported by the underlying sugar dysregulation, intestinal dysbiosis, detoxification errors, environmental factors, and genetics.

TABLE 57-1 -- Factors that Promote Estrogen Dominance and Subsequent Fibroid
Growth
Poor dietary choices [*]
Low-isoflavone, low-fiber foods (constipation)
High-glycemic-index foods
Hormone-rich meats, poultry, and dairy
 Excessive inflammation-causing saturated fats
Excessive-gluten grains
Intestinal dysbiosis High-β-glucuronidase levels [†]

Estrogen-like mycotoxins
Intestinal parasites
Sugar dysregulation Insulin resistance
Low sex hormone–binding globulin
Anovulation with low progesterone/ estradiol ratios
Environmental issues [‡]
Xenobiotics
Polychlorinated biphenyls (PCBs), dioxins, heavy metals
Birth control pills and hormone replacement therapy [§]

Violence and sex effects on limbic system

Stress High cortisol levels contributing to low progesterone
Reduced estrogen detoxification Leads to estrogen dominance
*
Goldin BR, Adlercreutz H, Gorbach SL, et al: Estrogen excretion patterns and plasma levels in vegetarian and omnivorous women. N Engl J Med 307:1542–1547, 1982.
†
Minton JP, Walaszek Z, Hanausek-Walaszek M, Webb TE: β-glucuronidase levels in patients with fibrocystic breast disease. Breast Cancer Res Treat 8:217–222, 1986.
‡
Wolff MS, Toniolo PG, Lee EW, et al: Blood levels of organochlorine residues and risk of breast cancer. J Natt Cancer Inst 85:648–652, 1993.
§
Gruber CJ, Tschugguel W, Schneeberger C, Huber JC: Production and actions of estrogens. N Engl J Med 346:340–352, 2002.

Effects of Diet, Digestion, Absorption, and the Intestinal Environment on Hormone Balance

Hormone imbalance and estrogen dominance are often associated with intestinal dysbiosis.
Intestinal dysbiosis designates an unhealthy gut environment often associated with greater
intestinal permeability. Signs and symptoms of dysbiosis include all kinds of digestive
issues, such as bad breath, body odor, bloating, gas, nausea, and constipation. Conditions
associated with intestinal dysbiosis include attention deficit–hyperactivity disorder, anxiety
and nervousness, brain fog and confusion, digestive problems, irritable bowel syndrome and
inflammatory bowel disease, immune disorders (autoimmune disease, allergies, recurrent
infections), liver dysfunction, malaise and fatigue, chronic fatigue and immune dysfunction
syndrome (fibromyalgia, multiple chemical sensitivity), muscle and joint aches and pains,
skin conditions, and just feeling “toxic.”

Intestinal dysbiosis can be caused by antacid abuse, antibiotics, chronic stress, eating
practices that do not enhance digestion and absorption (eating on the run), hypochlorhydria,
intestinal infection, and birth control pills.

Intestinal dysbiosis can contribute to estrogen dominance via several mechanisms. β-

Glucuronidase is an enzyme produced by pathogenic gut bacteria. It cleaves the glucuronic [11]

acid molecule that was helping transport estrogen out of the body, allowing the estrogen to
reenter the body and thereby raising total body estrogen and putting more stress on the liver
and its detoxification capacities. Pathogenic intestinal bacteria and pathogenic yeast can
also produce toxins that have estrogenic effects. Concomitant inflammation can increase
estrogen production and the growth factors that reside in the fibroid tissue and support
angiogenesis.
 Intestinal dysbiosis is treated with an intestinal restoration program such as the 4-R program
described by Bland. The 4 R's signify:
[12]

• Remove irritants affecting the gut.

• Replace betaine hydrochloride, enzymes, bile salts, and fiber
• Re-inoculate with probiotics
• Repair, which is done with gut restorative

For further information, see Chapter 86 , Adverse Food Reactions and the Elimination Diet.

It is uncommon for a woman to have symptomatic fibroids and not to have functional
intestinal dysfunction and associated dysbiosis.
Effects of Insulin Resistance on Hormone Balance and Estrogen Dominance

Elevations of insulin and insulin-like growth factor-1 (IGF-1) can also contribute to
estrogen dominance and fibroid growth. (…) It is associated with these laboratory markers:

• Elevation of fasting insulin/blood glucose

• Elevation of fasting fructosamine
• High hemoglobin A1C measurement (> 6%)
• Increases in inflammatory mediators: IL-2, IL-6, TNF-α, LTB4
• Increases in levels of prostaglandin-2 series—increasing inflammation
• Greater estrogen production in adipocytes—this is in the form of estrone (E1)
• Estrogen dominance—this is most apparent in polycystic ovary syndrome, which is
highly associated with insulin resistance
• Drop in level of sex hormone–binding globulin—which raises the amount of free
estradiol available at the cellular level [14]

• Rise in level of aromatase enzyme—which increases conversion of testosterone and

androstenedione to estradiol and estrone, which will also increase estrogen dominance

Insulin sensitivity can be improved by a variety of methods; they are all thoroughly
discussed in Chapter 35 , Insulin Resistance and the Metabolic Syndrome.

Errors in Liver Detoxification and the Likelihood of Hormone Imbalance and Estrogen
Dominance

Healthy detoxification consists of a phase 1, in which lipid-soluble substances—toxins,

hormones, and drugs—are transformed into intermediate substances by the cytochrome P450
set of enzymes. This enzyme system can be upregulated or downregulated by various
[15]

drugs, stressors, and herbs. An example in the world of estrogen dominance

and uterine fibroids is the effect of gluten grains on estrogen
metabolism. Gluten, in the grains that most of us consume, reduces
 cytochrome P450 3A4, leading to reduced estrogen metabolism and
subsequent estrogen dominance.
The intermediate substances must then be made water soluble. In phase 2 of the
detoxification process, the intermediates are conjugated with amino acids like glucuronic
acid, glutathione, and glycine, or undergo processes such as methylation, sulfation,
acetylation, and sulfoxidation. These now water-soluble substances can then be excreted in
[16]

stool, urine, or sweat or via the lungs.

The estrogen–glucuronic acid molecule is cleaved in the unhealthy gut by elevated amounts
of the enzyme β-glucuronidase, which is produced by imbalanced gut bacteria.

Phase 1 and phase 2 detoxification errors can be determined not by conventional enzyme
levels but with functional diagnostic tests available from Genova Diagnostics and
Metametrix Clinical Laboratory. Such tests measure how specific substances are cleared
through the body.

Estrogen metabolites or their intermediaries consist of the catechol (hydroxy) estrogens.

The anticarcinogenic estrogen modulator 2-hydroxyestrone (2OH-E1) comes from natural
estrogens; high levels of this substance may reduce risk of breast cancer. Higher amounts of
4-hydroxyestrone (4OH-E1) occur with metabolism of Premarin to form DNA-damaging
quinones. Epigallocatechin gallates (green tea) convert quinones to mercapturates. 16α-
Hydroxyestrone (16OH-E1) forms a very strong bond with estrogen receptor; it has
carcinogenic potential. Elevations of 16α-hydroxyestrone indicate high bone density. The
ratio of these three hydroxyestrogens, which can be measured in urine (Metametrix Clinical
Laboratory) or blood (Genova Diagnostics), can help evaluate risks in estrogen dominance
conditions. In menstruating women, the 2OH-E1-to-16OH-E1 ratio should be evaluated
during the luteal phase of the cycle. The following factors increase either this ratio or the
level of 2OH-E1:

• A diet rich in the cruciferous vegetables (broccoli, Brussels sprouts, kale, cabbage,
cauliflower)
• Indole-3-carbinol (I3C), which comes from cruciferous vegetables (broccoli, Brussels
sprouts, cabbage, kale); intake should be 200 to 800 mg/day DIM (diindolylmethane), its
form activated by stomach acid; may be used alone or in conjunction with I3C.
• Epigallocatechin gallates (green tea extract)
• Isoflavones, including soy, flaxseed, and kudzu [17]

• Omega-3 fatty acids

TABLE 57-2 -- Tests to Consider for Evaluation of a Patient with Fibroid Tumors of the
Uterus [*]

25-hydroxyvitamin D measurement [6]

Low levels can increase fibroid growth by several
mechanisms

Vitamin A measurement
Iron or total iron-binding capacity
measurement, ferritin measurement
Progesterone/estradiol ratio (100–300:1)
Luteal-phase progesterone measurement
Thyroid function testing
Comprehensive digestive stool analysis
Phase 1 and phase 2 detoxification
evaluation
Transvaginal and abdominal
ultrasonography
Anti–malignin antibody in serum (AMAS) Can be helpful in ruling out sarcomatous change
test
Testing for celiac disease (anti-gliadin
antibodies)
*
Superscript numbers indicate chapter references.
(see text)
[36]
Low levels shown to increase menorrhagia
Low iron stores reduce myometrial contractility and
increase menstrual blood loss
Low luteal-phase progesterone level supports estrogen
dominance and fibroid growth
Hypothyroidism is associated with all sorts of
menstrual dysfunction
Intestinal dysbiosis is a cause of estrogen dominance
through several mechanisms as discussed
Unhealthy estrogen metabolism contributes to
estrogen dominance
To determine the size and location of fibroids and rule
out ovarian tumors
Gluten grain sensitivity is common in fibroid tumor
sufferers and can lead to further estrogen dominance

The AMAS (anti-malignin antibody in serum) test (Oncolab, Boston, Mass) is approved
by the U.S. Food and Drug Administration (FDA) for detection of malignin, a protein
produced by malignant cells.

Integrative Therapy
Nutrition

The patient should begin a hormone-balancing diet, involving foods with low inflammation
effects, low acidity, and a low glycemic load.
Foods That Increase Estrogen Dominance

Acidic, inflammatory foods, such as red meats, poultry, and dairy products, are sources of
arachidonic acid, which can increase the inflammatory prostaglandins and other
inflammatory mediators, helping to support fibroid growth. Avoiding the commercial meat
products also reduces exposure to the added hormones in these products. Small amounts of[20]

range-fed meats can be added back as inflam-mation subsides. (See Chapter 88 , The Anti-
Inflammatory [Omega-3] Diet.)

Sweets and other foods with a high glycemic index will raise insulin levels, increase
estrogen dominance, and also support fibroid growth. It is also imperative to eat a breakfast
containing good quality protein, fats, and carbohydrates in combination to avoid
 hypoglycemic stress–induced cortisol and epinephrine elevations, which via
gluconeogenesis will deplete lean muscle and increase the tendency for insulin resistance.
(See Chapter 87 , Glycemic Index and Glycemic Load.)

Gluten grains, especially wheat, rye, and barley, contain genetically

engineered gluten that is much stronger than that in the more ancient
gluten grains such as spelt. These grains can increase estrogens via
the cytochrome P450 3A4 enzyme system and can also affect thyroid
hormone. All people with chronic estrogen dominance need to be
tested for gluten sensitivity.
Alcohol is all right if consumed in moderation. Studies show that women consuming more
than five alcoholic drinks per week have a higher risk of breast cancer. This increase is
probably due to the effect of alcohol on detoxification of estrogens. Organic coffee in
moderation (1 to 2 cups per day) is safe. Artificial ingredients, colorings, flavorings, and
preservatives should be eliminated. Margarines and other sources of trans fatty acids are
likewise unhealthy and must be avoided.
Foods That Reduce Estrogen Dominance

Deep sea, cold-water fish, such as salmon, sardines, mackerel, and cod, have good amounts
of the omega-3 oils. Because heavy metals like mercury contribute to estrogen dominance,
[21]

I do recommend eating fish with lower levels of mercury.

Seeds and nuts, especially flaxseed, contain isoflavones much like soy. They tend to be
[22]

hormone balancing. I recommend 2 tablespoons of flaxseed per day added to a soy- or

kudzu-containing protein powder shake first thing in the morning. Seeds and nuts such as
pumpkin seeds, sunflower seeds, hemp seeds, and walnuts are also good sources of omega-3
oils. [23]

Cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, and cauliflower support
healthy estrogen metabolism.

Legumes such as adzuki beans, peas, lentils, and edamame all have hormone-modulating
flavonoids and can safely be eaten. [24]

I have been consistently impressed by the elimination of symptoms related to estrogen

dominance by the elimination of high-glycemic carbohydrates and gluten grains. The
symptoms that seem to be most affected are fatigue, insomnia, and mood issues.

Copyright © 2009 Elsevier Inc. All rights reserved. - www.mdconsult.com

Bookmark URL: /das/book/0/view/1494/104.html

xa.yimg.com/kq/groups/14152481/1954738889/.../Uterine+Fibroids.doc