Uterine Fibroids

2011

Uterine fibroids (properly called leiomyomata or myomas) are solid, well-defined benign monoclonal tumors of the smooth muscle cells of the uterus. They range in size from microscopic to many pounds in weight, and may be singular or clustered. Multiple myomas in the same uterus are not clonally related. Fibroid size is described in comparison to a pregnant uterus (i.e., a fibroid the size of a 16-week pregnancy). As many as 20% to 40% of all women develop fibroids by age 40. Approximately 17% of all hysterectomies performed in the United States are for uterine myomas, with a peak incidence of surgery occurring for women around age 45, making fibroids the primary annual cause of pre-menopausal hysterectomy in the United States. They are rare in a premenarchal young women and shrinkage typically occurs in post-menopausal women with the natural decline in estrogen levels, unless stimulated by exogenous estrogen (foreign estrogens usually a result of environmental exposure, for example, from pesticides or plastics). For unknown reasons, fibroids are two to three times more common in black women than white, Asian, and Hispanic women. Fibroids are classified according to their site of growth in the uterine or surrounding tissue as submucosal, intramural, and subserous. They also may occur in the cervix (cervical fibroids), between the uterine broad ligaments (interligamentous fibroids), or they may be attached to a stalk (pedunculated fibroids) and protrude into the uterine cavity (pedunculated submucosal fibroids) or through the cervix.

The exact etiology of uterine fibroids remains undetermined. Leiomyomas are hormone dependent. This is evidenced by the fact that they develop during hormon-ally active years and decline during menopause, fibroid tissue has an increased number of estrogen and progesterone receptors, fibroid tissue is hyperestrogenic, hypersensitive to estrogen, and does not possess the normal regulatory mechanism that limits estrogen response, the peak mitotic activity occurs during the luteal phase, and they respond to treatment with gonadotropin-releasing hormone (GnRH) agonists. Growth factor also plays a role in leiomyomata development. As estrogen and progesterone levels rise, insulin is released causing the transient hypoglycemia commonly experienced premen-strually. When plasma glucose levels fall, pituitary growth hormone is released, exerting bodywide effects. Its action on hepatocytes causes the release of insulinlike growth factors (IGFs). In a study by Vollenhoven et al., it is postulated that the net effect of these changes increases the bioavailability of free (bioactive) insulinlike growth factor, which may play a major role in promoting fibroid growth. A further study by De Leo and Morgante states that concentrations of epidermal growth factor, insulin-like growth factor 1 (IGF 1), and platelet-derived growth factor (PDGF AB) are present in myomatous tissues together with their receptors. Prolactin also may be a factor. Leiomyomata express a number of hormones, including parathyroid hormone-related protein (a growth factor), prolactin, and insulinlike growth factor.

Factors that might increase fibroid development and growth include:

• Increased lifetime estrogen exposure due to early age at menarche, fewer pregnancies, increased follicular phase, or obesity

• Exposure to exogenous estrogens [i.e., environmental exposure (plastics, pesticides, hormones through meat and dairy, etc.) or medical exposure (HRT, etc.)]

• Poor enterohepatic estrogen clearance

Hypertension

• Pelvic inflammatory disease

• IUD use with infectious complications

• Perineal talc use

The use of oral contraceptives is not associated with any changes in fibroid size, and may even be protective; however, one study reported a slight increase in risk with a history of OC use beginning in the early teenage years.

Pathophysiology

Myoma risk is inversely related to increasing parity and age at last pregnancy, and is decreased by smoking (due to its inhibition of estrogen) and increased by obesity (likely due to increased estrogen levels) and hypertension.’ Fibroids occur in 1% to 2% of pregnancies. However, it is uncertain whether this relationship is entirely causal. Infertility, as well as early pregnancy loss, may be due to mechanical obstruction of implantation or distortion of the cervix or endometrium. Once a pregnancy is established, it is rare for myomata to interfere with its progress, and most proceed uncomplicated. However, a higher rate of cesarean section has been noted, and premature labor may result from very large myomata. Degeneration of fibroids, caused by hemorrhagic infarction, may rarely occur during late pregnancy and is marked by pain, and also may be accompanied by rebound tenderness, fever, nausea, vomiting, and leukocytosis. Treatment consists of rest and analgesia; surgery is a last resort.

Anemia and fatigue can be caused by excessive blood loss associated with fibroids. Pressure on the bowel or bladder can cause constipation, urinary frequency, and dyspareunia. Large fibroids may mask the diagnosis of serious gynecologic neoplasm. Rapidly growing fibroids may indicate a more serious pathology such as leiosar-coma and should be investigated. Malignancy is rarely associated with uterine fibroids; however, they occur with increased frequency in endometrial hyperplasia and are associated with a fourfold increased risk of developing endometrial cancer.

Symptoms

Most women with myomas are asymptomatic, never knowing that they have them unless informed of such by gynecologic examination. This was actually discovered based on ultrasound and autopsy results revealing that many more women had fibroids than had ever been diagnosed or treated for symptoms. The most common symptoms are menorrhagia and the physical effects caused by large myomata such as increased pelvic pressure, frequent urination, difficulty with defecation, and dyspareunia with deep penetration.,s Abnormal uterine bleeding is present in about 30% of all patients, and periods are typically heavy and prolonged, often with premenstrual and postmenstrual spotting. Uterine bleeding caused by myomas can be associated with significant social, emotional, financial, and medical difficulties; women’s concerns should be addressed. Some women experience dysmenorrhea. Metrorrhagia, may occur, but should be evaluated with an endometrial biopsy to rule out other endometrial disease. About 2% to 10% of women experience infertility as a result of fibroids, ostensibly due to abnormal uterine of tubal motility, interference with sperm movements, or abnormal uterine blood flow. Fibroid degeneration, torsion, or compression of a nerve against the pelvis caused by encroachment by a fibroid can lead to significant pain.

Diagnosis

Diagnosis can be determined by:

• Pelvic bimanual examination: Large fibroids (greater than a 12- to 14-week gestation) can be manually palpated and felt as an enlarged uterus, lump, or mass.

• Ultrasound scan: It is useful to monitor size and growth rate of fibroids. Repeat scans should be done during the same phase of the menstrual cycle.

• Laparoscopy: This is important if the mass is indistinguishable from the ovaries.

• The differential diagnosis includes:

• Ovarian neoplasm

• Tubo-ovarian inflammatory mass

• Diverticulum inflammatory mass

• Endometrial carcinoma

Uterine Fibroids: Conventional Treatment

Uterine Fibroids: Botanical Treatment

Case History: Uterine Fibroids

Nutritional Considerations

Obesity / Weight Management

Obesity is a risk factor for fibroid development. Therefore, dietary and lifestyle strategies should be aimed at weight reduction and healthy weight maintenance.

Xenoestrogens / Endocrine Disruptors

Avoid xenoestrogen ingestion from pesticide and herbicide residue by eating organically cultivated foods and avoiding foods in plastic containers. Xenoestrogens are found most concentrated in the fat of meat, farmed fish, and nonorganic dairy products. Eating primarily organic meat, dairy, and produce, washing fruits and vegetables thoroughly before eating, and minimizing the use of soft plastics, such as for food storage, can help reduce xenoestrogen intake.

Estrogen Biotransformation and Diet

Metabolism and detoxification of estrogen in the body ultimately determines its biological effects. Estrogen biotransformation occurs mainly in the liver through phase I hydroxylation and phase II methylation and glucuroni-dation, allowing estrogen to become a water-soluble, excretable compound. This is predominantly excreted by the liver in bile (see Dietary Fiber). Phase I detoxification yields three estrogen metabolites with highly variable biological activity: 2-hydroxyestrone (2-HE), 16-alpha-hydroxyestrone (16α-HE), and 4-hydroxyestrone (4-HE). 2-HE is a beneficial estrogen metabolite in that among its effects, it competitively binds estrogen sites, blocking more potent estrogens. Conversely, 4-HE and 16α-HE are potent estrogens that may promote the growth of estrogen-sensitive tissue. Dietary consumption of cruciferous vegetables, such as broccoli and cabbage, as well as green tea, garlic, and rosemary can increase the amount of 2-HE by modifying P450 activity in phase I, and have antioxidant effects as well.

Dietary Fiber

Once estrogen metabolites are excreted by the liver in bile, the metabolites are soaked up by fiber in the small intestines and excreted via defecation. If the diet lacks fiber, bile, along with the estrogen metabolites are reab-sorbed, adding an unnecessary estrogen burden to the body. Soluble fiber such as the lignins found in flax seeds also increases sex hormone binding globulin (SHBG), decreasing the amount of available active estrogen, as estrogen bound to SHBG is rendered inactive. Brassicae vegetables such as cabbage and broccoli contain indole glucosinolates, which when chewed, are degraded by a plant enzyme into a variety of indole structures. When degraded in the body, these structures induce cytochrome P450 expression (CY1A1) in hepatic and extrahepatic tissue, leading to greater conversion of 2-hydroxyestrone (2-HE), and decreasing the availability of E1 for conversion to 16-HE, thereby reducing the estrogen burden overall. This is partly associated with the anticancer effects associated with these foods.

Dietary Antioxidants

The conversion of estradiol to catechol estrogens via 4-hydroxylation stimulates an oxidant stress response induced by free radicals. This activity is markedly increased in fibroid tissue. Therefore, daily intake of foods containing the vitamins A, C, and E, and the minerals zinc, selenium, and a range of phytochemicals would be appropriate supportive treatment, as would inclusion of antioxidant adaptogen herbs.

Additional Therapies

Exercise not only encourages weight reduction but also improves pelvic circulation, promotes uterine muscular tone, promotes regular bowel elimination, and reduces stress. Herbalists often recommend specific yoga postures or Kegel exercises to assist in improving pelvic circulation particularly. Vigorous walking, hip circling, pelvic thrusts, and belly dancing can all be useful to improve pelvic circulation.

Uterine Fibroids: Treatment Summary