Uterine Fibroids

Uterine fibroids (also known as leiomyomas) are solid pelvic tumors composed of connective tissue and muscle ^[1]. Leiomyomas vary in terms of size, shape, and location; if one leiomyoma is discovered chances are multiple exist. Leiomyomas are either submucosal (under the endometrium), intramural (within the uterine wall), or subserosal (in the outer wall of the uterus). They can be intraligamentous (in the cervix between the two layers of broad ligament), pedunculated and dangling from a stalk into the uterine cavity (pedunculated submucous), or pedunculated on the outside of the uterine wall (pedunculated subserous). These tumors are usually benign growths with very limited malignant potential ^[2].

Age, nulliparity, black race, and obesity appear to be risk factors for leiomyoma development ^[3]. Early age of menarche is also positively associated with leiomyoma growth, size, and number ^[4]. Leiomyomas occur in 20 to 25 percent of women by the age of 40, and in over 50 percent of women overall ^[2]. These tumors are the most common of the female reproductive tract, found in up to 70% Caucasians and 80% African-American women by the age of 50. ^[3] Meanwhile, being overweight is correlated with leiomyoma growth due to higher levels of estrogen production in fat cells. Women with a body mass greater than 25 are more susceptible to leiomyomas ^[1]. Leiomyomas are the most common indication for surgery in women, and account for one-third of hysterectomies each year. Leiomyomas are thought to be the cause of 2 to 10 percent of infertility cases ^[2].

Pathophysiology

A genetic predisposition to leiomyomas may be possible since familial association has been shown. Studies reveal that single nucleotide polymorphisms are associated with uterine leiomyoma diagnosis: in particular, a translocation between chromosomes 12 and 14 ^[3]. Meanwhile, the possibility of angiogenesis and vascularization has been studied in recent years. Angiogenesis is the formation of new blood vessels from previous ones, and is essential for tissue growth and development. These two factors have been regarded as crucial in controlling leiomyoma growth. Leiomyomas appear to have an abnormal vasculature which is responsible for their state of hypoxia, relative to the surrounding tissues ^[3]. A disrupted extracellular matrix (ECM) is also suggestible: the bulk of such tumors consist of excessive and disrupted ECM ^[5]. In addition, the observation that leiomyomas resemble scar tissue highlights the importance of tissue remodeling, fibrosis, and the inflammatory response in the development and progression of these tumors ^[4].

The growth of leiomyomas also appears to be stimulated by estrogen: they arise during the reproductive years and regress during the post-menopausal period. Estrogen levels drastically decline during the post-menopausal period, providing further evidence supporting the key role of estrogen in growth. Leiomyoma growth is also seen during the perimenopausal period, and this is likely due to anovulatory cycles with a relative estrogen excess. Studies suggest that estrogen receptors are found in higher concentrations in fibroid tissue compared to the surrounding myometrium and endometrium. One study demonstrated a significantly lower conversion of estradiol into estrone in fibroids, suggesting that estradiol increases within the fibroid may play a role in growth. Fibroids do not lead to cancer but are associated with a fourfold increased risk of endometrial carcinoma. The most likely explanation being that there is not enough progesterone to oppose estrogen in both conditions ^[2].

A growth in the size of fibroids is also seen during initial pregnancy. In one study, the volume of fibroids doubled within 6-7 weeks gestation. However, a similar growth pattern was not observed throughout the course of pregnancy ^[6]. Although both estrogen and progesterone levels are elevated during pregnancy, the increased blood supply during pregnancy leads to an overall stimulating effect on the fibroids. Progesterone generally opposes estrogen; however its effect is minimal during pregnancy. Fibroids may physically interfere with implantation of the zygote and cause compression of the fallopian tubes. They may also cause periodic anovulation or abnormal uterine blood flow. Fibroids can also interfere with fetus growth and cause growth retardation, premature rupture of membranes, retained placenta, postpartum hemorrhage, and abnormal labor ^[2].

Diagnosis

The exact cause and cure for fibroids remains unknown. However, in some cases it may be easy to pinpoint factors that are influencing the growth of these tumors ^[2]. Most leiomyomas are asymptomatic ^[3]. In fact, only 20 to 50 percent of patients with fibroids experience related-symptoms ^[4]. If symptoms are present, they generally include a vague feeling of discomfort including a feeling of pressure (pelvic pain or discomfort), congestion, bloating, heaviness, pain with vaginal sex, urinary frequency, backache, abdominal enlargement, dysmenorrhea, and abnormal bleeding. Feelings of pressure pain result when the uterus becomes excessively enlarged with fibroids, and if a single fibroid is larger than 5 cm ^[2]. Systemic symptoms may also arise, including: anemia from excessive blood loss, compression of the bladder resulting in kidney enlargement, and bowel obstruction ^[1]. Fibroids may be palpated by the healthcare provider during a pelvic exam. The exam itself does not necessarily elicit pain; however, the uterus may be irregularly shaped with protrusions ^[2]. Leiomyomas can range in consistency from being soft or hard, and are generally not tender to touch ^[1]. A pelvic ultrasound is the gold standard diagnostic tool to confirm the presence of a leiomyoma. However, a transvaginal ultrasound is more accurate in determining characteristics ^[4]. An ultrasound is able to determine the number, size, and location of leiomyomas. It also detects if the uterus is enlarged and if the ovaries are of normal size. One drawback is that the small fibroids (less than 2cm) are not easily detected by ultrasound ^[2].

Following initial diagnosis, a follow-up ultrasound should be carried out 4 to 6 months later in order to determine the type of, size, location, and rate of growth of the fibroid(s) ^[1]. The process is called ‘mapping’ ^[4]. An annual pelvic exam is sufficient for monitoring thereafter. Surgical options include myomectomy and hysterectomy. Myomectomy is commonly performed on women wanting to conceive, as the procedure simply involves removal of the leiomyoma from the uterus ^[1]. Removal of leiomyomas is correlated with an increased likelihood of fertility ^[4]. However, the reformation of these tumors following surgical removal is an ongoing problem ^[7]. It is estimated that 60% of fibroids will recur 3 to 5 years following surgery ^[4]. On the other hand, a hysterectomy involves removal of the uterus and is performed on women who do not wish to conceive in the future ^[8]. Uterine leiomyomas are the single most common indication for hysterectomies. 

Natural Treatments

There currently is no natural treatment that can cure uterine fibroids. Several natural treatments exist that are able to help patients cope with the symptoms and prevent progression of uterine fibroids.

Dietary Modifications

1. Decrease saturated fats: Diets high in saturated fats are associated with higher blood levels of estrogen ^[2]. Sources of saturated fat include: cheese, butter, milk, dairy, meat, and lard ^[1].
2. Avoid acidic foods: Acidic foods such as red meat, poultry, and dairy products are sources of arachidonic acid. Arachidonic acid is inflammatory in nature and increases other inflammatory mediators that help support fibroid growth through angiogenesis ^[9].
3. Increase fiber intake: Low-fiber diets are associated with elevated estrogen levels and poor excretion of estrogen. Fiber helps to bind estrogen ^[2].
4. Increase cruciferous vegetables: These vegetables contain indole-3-carbinol (I3C) which is important for healthy liver detoxification. I3C also helps the liver to metabolize and excrete excess amounts of estrogen within the body. Broccoli, Brussel sprouts, kale, cabbage, cauliflower, and collard greens are known examples.
5. Increase soy intake: It is known that soy contains phytoestrogens, and phytoestrogens have a weak estrogenic effect. However, studies have shown that phytoestrogens can be estrogenic as well as anti-estrogenic, depending on the tissue or organ. Soy isoflavones appear to be anti-estrogenic in the uterus, with the possible exception of when they are used in high doses daily long-term. Isoflavones compete with endogenous estrogen to bind to estrogen receptors. Their weak estrogenic effect makes them antagonistic, unless used in high doses for extended periods of time ^[2].
6. Decrease sugar and high-glycemic food intake: These foods are particularly “stressful” to the body. Insulin-growth factor-1 (IGF-1) is a hormone that is produced by the liver and is found in higher concentrations in patients with fibroids; it is believed to work with estrogen to stimulate growth. IGF-1 levels can minimized by avoiding sugar and high-glycemic foods ^[1].

Lifestyle Modifications

Exercise is important to help the body detoxify and improve estrogen metabolism. It is recommended that one exercise 40 minutes per day to promote weight loss in the obese, and to increase blood flow to the uterus and liver. Exercise will also help stimulate bowel movements, and this is another effective way the body excretes excess estrogen. Two to three bowel movements per day is ideal to help excrete toxin build-up ^[1].

Supplements

1. Vitamin D: Evidence-based medicine suggests that vitamin D inhibits leiomyoma growth. It also appears to induce programmed-cell death in leiomyoma cells, and may act as an anti-fibrotic factor. Studies examined vitamin D levels in healthy women with fibroids, and found that there was a correlation between disease severity and vitamin D levels ^[10]. A negative correlation between vitamin D levels and total leiomyoma volume was also detected ^[11].
2. Castor oil packs: Apply castor oil packs to the uterus, abdomen, and liver 5 nights a week for 20 to 60 minutes per session. Castor oil packs work through the lymphatic system and reduce inflammation ^[9].
3. Green tea: Epigallocatechin gallate (EGCG) is the primary catechin found in green tea. Catechins are a group of bioflavonoids which exhibit antioxidant and anti-inflammatory properties ^[11]. In one study, human leiomyoma cells were cultured and exposed to EGCG. The cells showed a dose- and time-dependent inhibition of cell proliferation. This evidence suggests that EGCG may be a good anti-fibroid agent acting through multiple signal transduction pathways ^[12].
4. Curcumin: Curcumin is a dietary spice with anti-inflammatory, anti-fibrosis, and anti-neoplastic activity ^[10]. Studies reveal that curcumin induces cell apoptosis and inhibits leiomyoma cell proliferation without impacting normal myometrial cells of the uterus. Curcumin also inhibits the production of factors which are involved in disrupted ECM formation ^[5].

Conclusion

Several theories exist in an attempt to explain the pathogenesis of uterine leiomyomas. One or more of these theories may be correct, and more research is needed in order to arrive at a conclusion. A genetic predisposition, disruption in angiogenesis and vascularization, ECM disruption, and estrogen dominance are all possible factors which may contribute to the growth of fibroids. Modifications can be made to help shrink and prevent progression of fibroid growth. Please consult with your healthcare provider before commencing any therapy to make sure the modification is safe. Natural supplements are not always risk-free and therefore a thorough medical history needs to be obtained prior to prescribing.