Uterine leiomyomas, or fibroids, are benign tumors of the uterus composed of smooth muscle and connective tissue. Fibroids are the most common pelvic tumor in females. Most women develop some degree of fibroids in their lifetimes, and up to one-third of these women will become symptomatic. ,
Fibroids are classified by anatomic location as intramural (within the myometrium), submucosal (underlying the endometrium), or subserosal (underlying the uterine serosa). There is no identifiable cause of uterine fibroids. However, estrogen is necessary for their growth; many grow during pregnancy and then recede at menopause. Further, higher parity and low-dose oral contraceptive use have been shown to decrease the risk of fibroid formation.
Most uterine fibroid cases are asymptomatic. However, symptoms may include uterine bleeding, resulting in prolonged or heavy menstrual flow and possibly anemia; dysmenorrhea; urinary frequency and urgency; constipation; dyspareunia; and abdominal tenderness. Complications of pregnancy may be more common in women with fibroids, including miscarriage, placental abruption, and premature labor.
Age. Fibroids occur during the reproductive years, most commonly becoming clinically apparent during the fourth and fifth decades of life. They do not occur in prepubescent girls and usually shrink at menopause.
Pregnancy. Parity appears to decrease the risk of fibroids.
Early menarche. Menarche before age 10 is associated with increased risk of developing fibroids.
Oral contraceptive pills. Although these appear to be protective, the Nurses’ Health Study showed an increased risk in women who used oral contraceptive pills at ages 13-16. Low-dose oral contraceptives and menopausal hormone therapy are not contraindicated in women with fibroids.
Obesity. Most studies suggest that higher BMI confers higher risk and that the risk is most related to weight gain in adulthood.
Diet. Ham and red meat appear to significantly increase risk while fruit and vegetable consumption decreases risk (see Nutritional Considerations). Soy intake does not appear to increase risk.
Exercise. Women who engaged in at least 7 hours per week of physical activity were found to have a 40% decreased risk of having fibroids.
Fibroids may be suspected from the patient history, and a bimanual pelvic exam often confirms the diagnosis. The uterus is generally enlarged, mobile, and asymmetric. Extremely large fibroids may cause a palpable uterus on abdominal exam. Imaging studies are used to confirm the diagnosis and rule out other types of pelvic or adnexal masses.
Transvaginal ultrasound can be used to detect and localize fibroids. However, for women with large uteri or more than 4 fibroids, it is less precise than MRI.
Sonohysterography can better characterize submucosal fibroids than transvaginal ultrasound.
Pelvic MRI best localizes all types of fibroids, accurately assesses their size, and distinguishes fibroids from other growths (e.g., ovarian tumors) and from other uterine muscle pathology. However, this modality is typically reserved for surgical planning, due to expense
Hysterosalpingography is best reserved for fertility evaluations. It defines the contour of the endometrium and patency of the fallopian tubes.
Hysteroscopy provides direct visualization inside the uterus and can diagnose submucosal fibroids.
Most uterine fibroids are asymptomatic and need not be treated. Intervention depends upon a number of factors, including age (women approaching menopause may not require therapy, as fibroids typically regress spontaneously), fertility concerns, the location and size of the fibroids and severity of symptoms. If intervention is undertaken, the goal is to alleviate symptoms or improve odds of a successful pregnancy.
Myomectomy, via hysteroscopy, laparoscopy, laparotomy or robotic assisted procedures, preserves childbearing potential. However, new fibroids can develop after removal of existing ones.
Hysterectomy is a definitive treatment that offers clear symptomatic improvement. Fibroids are one of the most common reasons for hysterectomy. The primary indication is uncontrollable bleeding. Other indications include: concurrent risks for any type of gynecologic cancer (cervical, endometrial, ovarian), significant symptoms, and failure of minimally invasive procedures. The morbidity of hysterectomy is highest among all treatment options.
Other options for women who do not desire pregnancy include endometrial ablation with or without hysteroscopic myomectomy, cryotherapy, uterine artery embolization, or magnetic resonance-guided ultrasonic ablation.
Gonadotropin-releasing hormone (GnRH) analogs (e.g., leuprolide) can shrink fibroids prior to surgical removal. Symptoms will usually return with discontinuation of therapy. GnRH analogs are generally not recommended for long-term management.
Low-dose combined oral contraceptive pills may be useful in controlling menstrual bleeding and may provide symptomatic relief. Oral contraceptives do not decrease the size of fibroids, and some evidence suggests they may actually support fibroid growth.
There is less data available on the usefulness of other types of hormonal contraceptives.
GnRH antagonists, which have effects similar to those of GnRH analogs, have shown positive results in clinical trials but are currently available only in doses required for ovulation induction and are administered through daily injections.
Progesterone receptor modulators (PRMs). Progesterone can stimulate fibroid growth. PRMs were once thought to be a treatment option, but these drugs have been shown to cause endometrial hyperplasia. Mifepristone is a widely studied PRM and has been shown to significantly reduce uterine volume, but is not FDA approved for treating fibroids and there are no current appropriate dosing options in the U.S. Ulipristal acetate, another PRM, has shown promise as a medical treatment option, but is not FDA approved for fibroid treatment. There is little evidence regarding long-term safety.
Aromatase inhibitors may be efficacious and carry fewer side effects than other hormonal therapies, but more information is necessary to determine long-term risks and cost-effectiveness.
Adrogenic steroids (danazol) can shrink fibroids but have significant side effects, including weight gain, depression, dyslipidemia and elevated liver enzymes.
Raloxiphene, a selective estrogen receptor modulator, appears to offer benefit to postmenopausal women, but further trials are needed to establish its effect for premenopausal women.
Pain can be treated with nonsteroidal anti-inflammatory drugs.
Evidence for a direct effect of diet on fibroid risk or progression is very limited. However, the excessive production of certain growth factors (insulin-like growth factor I, epidermal growth factor) is a risk factor for fibroid growth, and evidence indicates that these may be the effectors of estrogen- and progesterone-mediated fibroid growth. Diets low in fat and high in fiber (e.g., vegetarian diets) have the ability to modulate blood hormone concentration and activity and reduce levels of growth factors. These effects may underlie the results of studies that have found higher risk for fibroids in women who eat red meat more often than do others, and in those who are overweight, as described below. However, this does not necessarily mean that a diet change, even if effective, will alleviate symptoms rapidly enough to obviate other treatments.
Epidemiologic studies indicate that the following factors are associated with reduced risk of fibroids:
Avoiding meat. In one study, women who ate more than one serving per day of red meat had a 70% greater risk for uterine myoma, compared with women who ate the least red meat. In other studies, higher fish consumption was associated with a significantly higher incidence of fibroids , Hypothesized mechanisms include (1) the tendency of fatty, low-fiber foods to increase estrogen concentrations or activity; (2) estrogenic chemicals found in fatty fish (e.g., polychlorinated biphenyls, PCBs); (3) and an increase in growth factors promoted by animal protein consumption.
Increasing fruit and vegetable intake. In the Black Women’s Health Study, the intake of fruits and vegetables was inversely associated with the risk of being diagnosed with uterine fibroids.
Limiting alcohol. Alcohol appears to increase the risk for fibroids. This risk is positively correlated with the number of years of alcohol intake and specifically with beer consumption. Compared with women who abstained from alcohol, those who drank one or more beers per day had a greater than 50% increased risk for leiomyomata.
Physical activity prescription that promotes weight loss (in overweight patients).
Dietary contributors to fibroids are still under investigation. However, the changes that appear to be helpful—limiting meat and alcohol and increasing vegetables—can be beneficial for the whole family, and are most sustainable when the family makes these changes together.