Red M. Alinsod, M.D., FACOG, ACGE
South Coast Urogynecology
The Women's Center
31852 Coast Highway, Suite 200
Laguna Beach, California 92651
949-499-5311 Main
949-499-5312 Fax
www.urogyn.org
Uterine Fibroids and Hysterectomy
WHAT ARE UTERINE FIBROIDS?
A uterine fibroid (known medically as a leiomyoma, or simply myoma) is a benign (noncancerous) growth composed of smooth muscle and connective tissue. The size of a fibroid varies from that of a pinhead to larger than a melon. Fibroid weights of more than 20 pounds have been reported.
Fibroids originate from the thick wall of the uterus and are categorized by the direction in which they grow:
• Intramural fibroids grow within the middle and thickest layer of the uterus (called the myometrium). They are the most common fibroids.
• Subserosal fibroids grow out from the thin outer fibrous layer of the uterus (called the serosa). Subserosal can be either stalk-like ( pedunculated) or broad-based ( sessile). These are the second most common fibroids.
• Submucous fibroids grow from the uterine wall toward and into the inner lining of the uterus (the endometrium). Submucous fibroids can also be stalk-like or broad-based. Only about 5% of fibroids are submucous.
The Female Reproductive System
The Primary Organs and Structures in the Reproductive System
The primary structures in the reproductive system are as follows:
• The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix.
• When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy the walls of the uterus are pushed apart as the fetus grows.
• The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina.
• Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary.
• Ovaries are egg-producing organs that hold between 200,000 and 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.
The inner lining of the uterus is called the endometrium, and during pregnancy it thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed as part of the menstrual flow. Menstrual flow also consists of blood and mucus from the cervix and vagina.
Reproductive Hormones
The hypothalamus (an area in the brain) and the pituitary gland regulate the reproductive hormones. The pituitary gland is often referred to as the master gland because of its important role in many vital functions, many of which require hormones. In women, six key hormones serve as chemical messengers that regulate the reproductive system:
• The hypothalamus first releases the gonadotropin-releasing hormone (GnRH).
• This chemical, in turn, stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
• Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH and complete the hormonal group necessary for reproductive health.
WHAT CAUSES UTERINE FIBROIDS?
Inherited genetic factors may be important in many cases of fibroids. Researchers are investigating unique genetic factors that regulate hormones. Proteins called growth factors may be responsible for some of the abnormalities leading to uterine muscle overgrowth and fibroids. Scientists have identified chromosomes carrying a total of 145 genes that may have an effect on fibroid growth. Some experts report that uterine fibroids are inherited from paternal genes (the father's side).
Female Hormones
Uterine fibroids often grow during pregnancy and they degenerate after menopause. From these observations and certain studies researchers are fairly certain that the female hormones, both estrogen and progesterone, play a role in their growth. Their role, however, is not clear. Some theories about the relationship to fibroids and estrogen include the following:
Estrogen patterns in fibroids are similar to those in pregnancy. That is, like smooth muscle cells in the uterus during pregnancy, fibroid cells exposed to female hormones do not respond normally to signals that would make them self-destruct and return to a nonpregnant state. (This natural self-destruction is a process called apoptosis). Instead, they continue to grow.
Some evidence suggests that estrogen may inhibit a tumor-suppressor gene called p53 in fibroid tissue, therefore triggering cell proliferation leading to fibroid growth. (P53 plays a role in some cancer-cell growth, although in this case the process is not malignant.)
Growth Factors
The formation of fibroids may be attributable to abnormalities in substances called growth factors. These are special proteins secreted by different cell types and are responsible for cell-to-cell interaction. Many of these substances regulate a process called angiogenesis, which causes new blood vessels to sprout from pre-existing ones. The production of new blood vessels then feeds any existing growth, such as fibroids.
The growth factors that appear to play an important role in many female reproductive disorders are Basic Fibroblast Growth Factor (BFGF) and Vascular Endothelial Growth Factor (VEGF). BFGFs are involved in the proliferation of cells that form connective tissue, which supports the body's organs and structure. VEGFs are involved with cell growth in smooth muscles that line blood vessels. There is some evidence that they play role in uterine fibroids.
Other growth factors being studied specifically for fibroids are Insulin-like Growth Factor (IGF)-I, Epidermal Growth Factor (EGF), Platelet Derived Growth Factor, and Transforming Growth Factor (TGF). TGF is proving to have multiple effects that may of particular importance in the development of fibroids.
WHAT ARE THE SYMPTOMS OF UTERINE FIBROIDS?
Less than 25% of patients with fibroids experience symptoms. When they do, they include the following:
• The most common symptom is prolonged and heavy bleeding during menstruation. This is caused by fibroid growth bordering the uterine cavity. In severe cases, heavy bleeding may last as long as two weeks. (Fibroids rarely bleed between periods, except in a few cases of very large fibroids.)
• Large fibroids can also cause pressure and pain in the abdomen or lower back that sometimes feels like menstrual cramps.
• As the fibroids grow larger, some women feel them as hard lumps in the lower abdomen.
• Very large fibroids may give the abdomen the appearance of pregnancy and cause a feeling of heaviness and pressure. In fact, large fibroids are defined by comparing the size of the uterus to the size it would be at specific months during gestation.
• Unusually large fibroids may press against the bladder and urinary tract and cause frequent urination or the urge to urinate, particularly during the night when a woman is lying down.
• Abnormal pain during intercourse (called dyspareunia).
• If the fibroids press on the ureters (the tubes going from the kidneys to the bladder), obstruction or blockage of urine may result.
• Fibroid pressure against the rectum can cause constipation.
WHO GETS FIBROIDS?
Uterine fibroids are the most common tumor found in female reproductive organs. It is estimated that over 50% of women between the ages of 30 and 50 have fibroids, although they cause symptoms in only about 25%. A number of possible risk factors have been identified, but very little research exists to confirm or develop information on them.
Being African American
Uterine fibroids are particularly common in African-American women, with an estimated prevalence of 50% to 75%. These women are also more likely to have severe pain, anemia, and larger and more numerous fibroids than women in other population groups. Although genetics may play a role, women of African descent who live in other countries do not appear to have as high an incidence of fibroids. This suggests that diet or other environmental factors are at work in the development of fibroids in African-American women.
High Exposure to Estrogen
Fibroids can start to grow soon after puberty, although usually they are detected when a woman reaches young adulthood. Women with fibroids are at risk for accelerated fibroid growth when estrogen levels are high or when lifestyle behaviors keep estrogen levels high.
Some examples of risk factors for fibroids that are also associated with high estrogen exposure include the following:
• Early onset of menstrual period (before age 12).
• Being overweight and sedentary.
• Never being pregnant. The risk for fibroids decreases with more children. (This risk factor, however, may be due to a greater risk for infertility caused by fibroids in the first place.)
Combined Oral Contraceptives. Combined oral contraceptives contain estrogen and progesterone and the evidence on their effects on fibroids have been conflicting. Early reports suggested they might be a risk factor. Most studies conducted more recently, however, have found no association and some even suggest that the newer low-dose OC combinations may be protective.
Hormone Replacement Therapy. Hormone replacement therapies (HRT) contain estrogen alone or estrogen plus progesterone. After menopause, fibroids usually shrink. Researchers, then, are investigating whether the hormones used in HRT could cause existing fibroids to persist or even grow. Some studies, but not all, have found greater fibroid growth with the use of patch-administered hormone agents. (In one of the studies taking oral estrogen however, had no effect.) A 2001 systematic review of studies reported some fibroid growth in women taking HRT, but usually without any significant symptoms. In summary, if HRT has an effect on fibroid growth, it is unlikely to be severe. Any increase in fibroid growth during menopause must be evaluated surgically by a gynecologist since such growth, even if a woman is on hormone replacement therapy, may mean cancer.
Other Risk Factors
Studies report a higher incidence of fibroids in women with high blood pressure and obesity. Both fibroids and hypertension are associated with a thicker uterus, but it is not clear if or how these conditions are related. There is also a weak association between fibroids and diabetes.
HOW SERIOUS ARE UTERINE FIBROIDS?
Effect on Fertility. The effect of fibroids on fertility is controversial. A 2002 analysis suggested that they may account for infertility in only 1% to 2.4% of women who are having trouble conceiving. Large fibroids may cause infertility in the following way:
• By impairing the uterine lining.
• By blocking the fallopian tubes.
• By distorting the shape of the uterine cavity.
• By altering the position of the cervix and preventing sperm from reaching the uterus.
Some evidence suggests that even small fibroids may reduce the chances of pregnancy in women who are undergoing assisted reproductive techniques. Treatments to reduce fibroids may be helpful in such women, although there has been little research on this subject.
Effect on Pregnancy. Fibroids pose some risk to a pregnancy:
• A cesarean section may be required in cases where multiple fibroids, particularly those located in the lower part of the uterus, block the vagina during pregnancy. Fortunately, this is a rare occurrence.
• Multiple fibroids can also increase the risk for miscarriage. In one 2001 study the presence of intramural fibroids halved the chances for a successful pregnancy. (The largest fibroid observed in the study was less than an inch.)
• Fibroids can degenerate during pregnancy causing pain and may cause premature labor.
Anemia
Anemia from iron deficiency can develop if fibroids cause excessively heavy bleeding. Oddly enough, smaller fibroids, usually submucous, are more likely to cause abnormally heavy bleeding than larger ones.
Most cases of anemia are mild, but even mild anemia can cause weakness and fatigue. Moderate to severe anemia can also cause shortness of breath, rapid heart rate, lightheadedness, headaches, ringing in the ears (tinnitus), irritability, pale skin, restless legs syndrome, and mental confusion. Heart problems can occur in prolonged and severe anemia that is not treated. Pregnant women, who are anemic, particularly in the first trimester, have an increased risk for a poor pregnancy outcome.
Urinary Tract Infection
Large fibroids that press against the bladder occasionally result in urinary tract infections. Pressure on the ureters may cause urinary obstruction and kidney damage.
Severe Pain
Fibroids can cause cramping during a period, which can be quite intense at times.
Pain can also develop if the blood supply is cut off from the fibroid tissue. In such cases, the cells blacken and die (called necrosis) from lack of oxygen. This event may occur under the following circumstances:
• A very large fibroid outgrows its own blood supply.
• A pedunculated fibroid (one that grows on a stem from the uterine wall) becomes twisted, thus cutting off its blood supply.
• Pregnancy occurs, in which the risk for fibroid cell degeneration and necrosis increases.
Leiomyomas that Spread Outside the Organ
Rarely, a fibroid breaks away from the uterus and develops in other locations. They are typically one of the following:
• Benign Metastasizing Leiomyoma or BML (which usually spreads to the lung).
• Disseminated Peritoneal Leiomyomatosis (which spreads to the abdominal wall).
Neither is cancerous, although there is some evidence that BML, which often occurs after menopause, may represent a slow-growing variant of leiomyosarcoma.
Uterine Cancer
Fibroids are nearly always benign and noncancerous, even if they have abnormal cell shapes. Cancer of the uterus nearly always develops in the lining of the uterus (endometrial cancer). Only in rare cases (a less than 0.1% incidence) does cancer develop from a malignant change in a fibroid (called leiomyosarcoma). Nevertheless, rapidly enlarging fibroids in a premenopausal woman or even slowly enlarging fibroids in a postmenopausal woman require surgical evaluation to rule out cancer.
HOW ARE UTERINE FIBROIDS DIAGNOSED?
A physician will perform a pelvic examination to check for pregnancy-related conditions and for signs of fibroids or other abnormalities, such as ovarian cysts.
Medical and Personal History
The physician needs to have a complete history of any medical or personal conditions that might be causing heavy bleeding. He or she may need the following information: