Diagnosis and management of uterine fibroids.

In 2004 U.S. Secretary of State Condoleezza Rice underwent a procedure called uterine artery embolization (UAE) at Georgetown University Hospital in Washington, District of Columbia. Rice's treatment brought attention to uterine fibroids, which not only disproportionately affect African American women, (2) but also affect 25% of all women in the United States. (3) According to reports, the procedure took approximately 90 minutes and was a success. (4)

Uterine fibroids are the most common growth found in a woman's pelvis, and their exact cause remains unknown. They affect approximately 15% to 20% of fertile women, but occur most commonly in women aged 30 to 40 years. (2) The American College of Obstetricians and Gynecologists estimates that 25% to 50% of all women have some form of uterine fibroids. (5) Although some women are asymptomatic, the most common symptoms are bleeding, pelvic pressure and infertility--all of which substantially impact quality of life.

The presence of fibroids does not increase a woman's risk for developing uterine cancer, and fibroids are almost always benign, with less than 0.1% becoming cancerous. (6) Uterine fibroids are a paramount health issue, however, because they are the primary indication for hysterectomy in premenopausal women. (7) In addition to rendering a woman infertile, hysterectomies can cause long-term psychological effects by disrupting hormone production and thus creating the need for hormone replacement therapy.

Nearly one-third of all hysterectomies performed in the United States are due to uterine fibroids. (8) Although the rate of hysterectomy is declining, hysterectomy remains the second most frequently performed surgery in America, second only to cesarean delivery. The estimated expense to the United States health care system associated with fibroids is $2.1 billion in direct costs annually, of which $1.7 billion is the direct result of inpatient hospital costs. (9)

Fibroids in African American Women

African America women have the highest incidence of fibroids (2 to 3 times higher than white women). (2) Fibroids occur at a younger age in African American women and increase in size more rapidly. (5) Among the African American population affected by the condition, approximately 50% have fibroids of a significant size. (8)

Recently, physiological research has linked fibroids with keloids, which is a wound-healing disorder that also disproportionately affects African Americans. Investigators at the National Institute of Child Health and Human Development, a division of the National Institutes of Health (NIH), identified similarities in the abnormal formation of connective tissue of both fibroids and keloids, indicating the possibility of genetic predisposition for the 2 conditions. This finding supports information from the Fibroid Growth Study, conducted in part by the NIH, revealing that fibroid growth greater than 3 inches (5 cm) was due largely to deposition of connective tissue rather than an increase in the number of cells. (9)

Anatomy of Fibroids

Fibroids, or leiomyomata uteri, are benign clonal tumors in the uterus made up of smooth muscle cells that can have hard (like stone) to soft (like rubber) texture. They vary in size from microscopic to more than 5 to 6 inches wide (5) and can weigh as much as several pounds. (2) Although it is possible for a single fibroid to develop, usually a woman will have more than 1 or a cluster of several (see Figure 1). (2) Fibroids can grow large enough to distort the uterus and even to fill the pelvis or abdomen; they can remain small for a number of years then suddenly increase in size or they may increase steadily in size over time. In extreme cases, fibroids can cause the uterus to increase in size to that of a 5-month pregnancy. (8) Fibroids are measured according to the size they cause the uterus to be during a typical pregnancy.

Anatomy of the Uterus

The uterus is the major female reproductive organ, composed primarily of muscle tissue. Located in the pelvic cavity, it is supported by the broad, round and cardinal ligaments, as well as by the rectouterine and vesicouterine folds. The uterus has 3 layers: the serosa, the myometrium and the endometrium. The serosa is the outermost layer that consists of membrane that merges with the ligaments that suspend the uterus in the pelvis. The middle layer, or myometrium, forms a thick wall made up of smooth muscle cells. The endometrium, also known as the mucosa, is a layer of cells that forms the inner uterine lining. It includes glands and chemical receptors. Fibroids occur in all 3 uterine layers.

The function of the uterus is to harbor a developing fetus, which descends as an ovum from the oviducts (fallopian tubes) and becomes implanted in the endometrial walls of the uterus. Under the influence of female sex hormones such as estrogen, the walls swell and engorge with blood during pregnancy to nourish the fetus inside the uterus during the 9-month human gestation period. The uterus is a small but important organ that weighs only about 2.2 pounds (1 kg), even during pregnancy, and is approximately 3 inches (7.5 cm) long in nonpregnant women.

[FIGURE 1 OMITTED]

The role of the uterus is not just confined to reproduction, however. The uterus secretes female sex hormones necessary for homeostatic function. This secretion is in response to menstrual cycle function and usually ceases after menopause. However, if the uterus or ovaries are removed before menopause, as with hysterectomy, hormones may be supplemented with oral hormone therapy. The uterus also may play a part in female sexual function, although more information is needed to substantiate such a hypothesis.

Fibroid Types

There are 4 types of fibroids, all of which are classified by their location within the uterus: intramural, subserosal, submucosal and pedunculated (see Table 1 and Figure 2). Intramural fibroids are most common and grow inside the myometrium. If they are smaller than 4 to 5 cm in diameter and do not encroach upon the endometrium, intramural fibroids are relatively harmless to fertility. (10)

Subserosal fibroids grow outward from the myometrium into the abdominal cavity. They can be as large as 5 to 7 cm in diameter and have little or no effect on fertility. (10) If they grow larger than 7 cm (2.76 inches), a woman may experience bulk symptoms, such as frequent urination or constipation, if the fibroids compress nearby pelvic structures, such as the bladder, sciatic nerve or bowels. (11)

Submucosal fibroids are found just under the mucosal lining and grow inward to take up space in the uterine cavity. These fibroids are the least common but cause the most complications. (12) A small submucosal fibroid can cause heavy bleeding and prolonged menstruation (menorrhagia). It is likely to affect fertility by distorting the endometrial cavity and therefore should be removed before pregnancy is attempted. (10) Prolonged and severe menorrhagia is the most common symptom of submucosal fibroids.

Fibroids that are pedunculated, which means having or growing from a peduncle or stalk, differ from the other types of fibroids because they are not embedded in the tissue, but rather are tumors attached to the uterus by a stem-like structure. The stem can become twisted, causing a kink in the blood vessels feeding the fibroid. This results in acute, severe pain that may necessitate surgery to remove the fibroid.

[FIGURE 2 OMITTED]

Causes of Fibroids

A definite cause of uterine fibroids is still under investigation. Fibroids have been linked to increased production of the female hormone estrogen, (13) and they rarely occur in women younger than 20 years old or those who are postmenopausal. (2) The incidence and size of fibroids have been shown to increase with age. (14)

Estrogen can be affected by natural events, like menstruation and menopause, as well as by certain medications. Factors associated with fibroids in both African American and white women include early menopause, fewer births after age 24, alcohol consumption and a physically inactive lifestyle. (9) A study by the NIH at Vanderbilt University is currently underway to investigate the role of environmental toxins on uterine gene expression. (9) Researchers hypothesized that the exact cause of fibroids is most likely a combination of several factors: hormonal, genetic and environmental. (6)

Pregnancy and Fibroids

Fibroids have been shown to increase in size during pregnancy, likely due to a pregnancy-related increase in estrogen. (6) However, according to Ouyang et al, (12) the current literature on fibroids tends to underestimate the prevalence of fibroids in pregnancy and overestimate the complications attributed to them. Ouyang stated that, although fibroids do tend to grow larger during pregnancy, this change is not significant. Nevertheless, the fibroids that do increase in size do so only during the first trimester. (12) During pregnancy, fibroids can be both diagnosed and treated effectively. (15)