The role of fibroid tumors in infertility
is controversial. Many of the studies examining the relationship
between these tumors and infertility are retrospective and non-
randomized. Current evidence suggests that submucosal and
intramural fibroid tumors that distort the uterine cavity can
impair in vitro fertilization attempts.21 The impact of
intramural and subserosal fibroid tumors that do not distort the
intrauterine cavity is unclear. Despite the lack of clear
evidence of their role in conception problems, submucosal fibroid
tumors, intramural fibroid tumors that distort the uterine
cavity, fibroid tumors larger than 5 cm, and multiple fibroid
tumors are often treated in patients with otherwise unexplained
infertility.22 The possible role of fibroid tumors in early
miscarriage is also controversial. Given the conflicting data and
potential observational bias and methodologic problems in studies
examining this association, a causal relationship should not be
assumed.23
Diagnosis
The bimanual examination is often the first
indication that a patient may have uterine fibroid tumors.
Several studies, including transvaginal ultrasonography, sono-
hysterography, hysteroscopy, and magnetic resonance imaging
(MRI), may be helpful in evaluating these tumors. Transvaginal
ultrasonography has the lowest sensitivity and specificity, but
it is the best initial test based on its noninvasive nature and
cost-efficiency. MRI is preferred when precise myoma mapping is
required (usually for surgical purposes), but it is the most
expensive modality for evaluating fibroid tumors. Sonohys-
terography and hysteroscopy can be used to evaluate the extent of
submucosal fibroid tumors, but these tests are relatively
invasive.24
Management
Knowing the full range of treatment options
enables family physicians to counsel patients about the optimal
management of symptomatic uterine fibroid tumors. The number of
treatment options is increasing and includes expectant
management, surgery, uterine artery embolization, ablative
techniques, and medical management
(Table 2). Clinical guidelines have been
created to assist patients and physicians in choosing appropriate
management options25 (Table 3). However, a systematic review by
the Agency for Healthcare Research and Quality emphasized the
paucity of evidence to support specific procedures and treatments
based on individual patient characteristics.26,27
Expectant Management
Expectant management with observation is
increas- ingly recognized as a reasonable course for women with
asymptomatic small and large fibroid tumors. Even rap- idly
growing tumors should not be removed routinely because the risk
of a malignant leiomyosarcoma is small percent in one
study).28,29
Surgical Treatments
Selected patients may benefit from surgery.
One of the biggest challenges is identifying malignant leio-
myosarcomas; rapid growth alone is not an adequate marker. There
is evidence that combining dynamic MRI (i.e., MRI enhanced by
gadopentetate dimeglumine) and measurement of serum lactate
dehydrogenase levels is useful in distinguishing leiomyosarcoma
from benign fibroid tumors.29 This approach may be useful in
evaluating selected patients, such as postmenopausal women with
enlarging tumors. Other patients who may benefit from surgery
include those with persistent abnormal uterine bleeding or
symptoms resulting from uterine bulk that do not respond to
conservative measures.26
Hysterectomy. The presence of uterine
fibroid tumors is the most common indication cited for
hysterectomy, accounting for more than 30 percent of these
procedures.26 Although most hysterectomies in women with fibroid
tumors are performed for symptomatic relief, the procedure is
sometimes recommended to asymptomatic women whose uterine size is
estimated to be greater than that at 12 weeks" gestation. Common
justifications for this recommendation include the risk that
tumors of this size could potentially mask other adnexal
pathology, increase operative morbidity rates, and become
malignant. Current evidence does not support the treatment of
fibroid tumors in asymptomatic women.25-27
The Maryland Women"s Health Study30 and the
Maine Women"s Health Study31 were large, prospective studies
designed to measure the outcomes and effectiveness of
hysterectomy for benign conditions. The most common indication
for surgery in both studies was uterine fibroid tumors (48.1 and
35 percent, respectively). These studies demonstrated that
hysterectomy substantially improves symptoms and quality of life
in women with multiple and severe symptoms associated with
gynecologic disorders. The Maine study enrolled a comparison
group of women who received nonsurgical medical treatment.31
Medical therapy for abnormal bleeding and chronic pelvic pain
produced significant improvements, but one quarter of the
nonsurgical group subsequently under- went hysterectomy. Women
with uterine fibroid tumors who continued with nonsurgical
treatment reported no significant changes in symptoms or quality
of life over the one year follow-up. Not all women who are
treated surgically report improvement. In the Maryland study,
almost 8 percent of women had more or the same number of symptoms
24 months after hysterectomy.30 Baseline depression, therapy for
emotional problems, annual income of less than $35,000, and
bilateral oophorectomy were significantly associated with poorer
out- comes. Some women in the Maine study reported new symptoms
after hysterectomy (e.g., hot flashes, weight gain,
depression).31 Most studies evaluating the effect of hysterectomy
on sexuality are poorly designed, but the available evidence
suggests that hysterectomy does not adversely affect
sexuality.32
Myomectomy. Myomectomy (i.e., surgical
removal of fibroid tumors while preserving the uterus)
traditionally has been performed by laparotomy. Endoscopic
myomectomy is now a treatment option for many women, and
hysteroscopic myomectomy may be considered in women with
symptomatic submucosal fibroid tumors. Ultimately, however, the
choice of surgical approach is largely dependent on the expertise
of the physician. Although elective cesarean delivery
traditionally has been recommended for women who become pregnant
after myomectomy (especially when the uterine cavity has been
entered), data to support this recommendation are
limited.33
Uterine Artery Embolization. Uterine artery
embolization is performed under intravenous sedation. Using a
femoral approach, a microcatheter is introduced into the uterine
artery. Polyvinyl alcohol foam particles or other occluding
agents are then injected. Complete occlusion of both uterine
arteries initially was the goal of this treatment, but recent
data suggest that incomplete embolization may produce effective
infarction of myomas with less severe pain.34 The Fibroid
Registry for Outcomes Data was formed in 1999 to collect
prospective data on more than 3,000 women undergoing embolization
for fibroid tumors. Short-term outcomes in women included in this
database have been encouraging. In the first 30 days after
treatment, the incidence of adverse effects was low, and major
complications in the hospital and 30 days postdischarge were
uncommon (0.66 and 4.8 percent, respectively).35 Future data will
address long-term out- comes of uterine artery
embolization.
Myolysis. Myolysis (i.e., delivering energy
to tumors to desiccate them directly or disrupt their blood
supply) is most often performed with the neodymium-doped yttrium
aluminum garnet (Nd:YAG) laser or bipolar needles. Combination
treatment with myolysis and endometrial ablation may reduce the
need for subsequent procedures in patients with persistent
bleeding.36
MEDICAl
TREATMENTS
Medical therapy is available for women with
symptomatic fibroid tumors who prefer conservative
management.
Gonadotropin-Releasing Hormone Agonists.
Gonado- tropin-releasing hormone (GnRH) agonists are the most
well-established therapy for medical management, causing
amenorrhea and a rapid reduction in the size of the tumor.
However, the benefits of GnRH agonists are tempered by
significant side effects resulting from hypoestrogenism (e.g.,
hot f lashes, vaginal dryness, bone demineralization). Because
GnRH agonists are not appropriate for long-term use, this therapy
is best suited for women in the perimenopausal or preoperative
periods.37
Hormone Therapy. Hormone therapy with
cyclic or noncyclic estrogen–progestin combinations appears
to be ineffective in alleviating the symptoms of fibroid tumors
and limiting tumor growth.26 Studies have found no evidence that
low-dose contraceptives cause the growth of uterine fibroid
tumors; thus, these tumors are not a contraindication to the use
of these contraceptives. A small study found significant
improvement in bleeding after treatment with depot medroxy-
progesterone acetate (Depo-Provera) in 20 African women with
menorrhagia attributed to uterine fibroid tumors.38 A review of
six clinical trials with a total of 166 women demonstrated that
treatment with mifepristone (Mifeprex) resulted in reduced tumor
size and improvement in symptoms.39 However, none of the studies
were placebo controlled or blinded, and a notable adverse effect
was the development of endometrial hyperplasia. Better-quality
clinical trials are needed before recommendations can be
made.
Other Therapies. The selective estrogen
receptor modulator raloxifene (Evista) has been shown in one
small study to decrease tumor size in postmenopausal women;
however, there was no effect on uterine bleeding.40 Small trials
have provided insufficient evidence to assess the effectiveness
of nonsteroidal anti-inflammatory drugs in the management of
uterine fibroid tumors.41 A noninvasive treatment using a
combination of MRI and ultrasonography (ExAblate 2000) has been
approved by the U.S. Food and Drug Administration.42 This
treatment focuses high-intensity sound waves on the tumor,
inducing coagulation necrosis. The main advantage is that it is
an out- patient procedure with a short recovery time. Long-term
follow-up and additional studies are needed to identify women who
will benefit most from this treatment.
The opinions and assertions contained
herein are the private views of the authors and are not to be
construed as official or as reflecting the views of the U.S. Navy
Medical Department or the U.S. Navy at large.
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PATRICIA EVANS, MD,
Georgetown University-Providence Hospital
Family Practice Residency Program, Colmar Manor,
Maryland
SUSAN BRUNSELL, MD,
National Naval Medical Center, Bethesda,
Maryland
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