Morning Topics/Gynecology/Myomas

CLINICAL GYNECOLOGIC SERIES: AN EXPERT’S VIEW
We have invited select authorities to present background information on challenging clinical problems and
practical information on diagnosis and treatment for use by practitioners
Uterine Myomas: An Overview of Development,
Clinical Features, and Management
Edward E. Wallach, MD, and Nikos F. Vlahos, MD
OBJECTIVE: To review the biology and the pathophysiology
of uterine myomas, focus on options for management, and
emphasize principles that will render the decision-making
process as logical as possible.
DESIGN: Literature review and synthesis of the authors’
experience and philosophy.
RESULTS: Uterine myomas are the most common solid
pelvic tumors in women. There is increasing evidence that
they have a genetic basis and that their growth is related to
genetic predisposition, hormonal influences, and various
growth factors. Treatment choices are wide and include
pharmacologic, surgical, and radiographically directed intervention. Most myomas can be followed serially with
surveillance for development of symptoms or progressive
growth.
CONCLUSION: The past century has witnessed development
of highly sophisticated diagnostic and therapeutic technology for myomas. The tools currently at our disposal permit
greater management flexibility with safe options, which
must be tailored to the individual clinical situation. (Obstet
Gynecol 2004;104:393– 406. © 2004 by The American College of Obstetricians and Gynecologists.)
Uterine leiomyomata are among the most frequent entities encountered in the practice of gynecology. The
management of patients with myomas has changed substantially during the last century and probably will continue to do so with the passage of time. The scope of this
article is to review the biology and pathophysiology of
myomas, focus on options for management, and emphasize principles that will render the decision-making proFrom the Department of Gynecology and Obstetrics, The Johns Hopkins Medical
Institutions, Baltimore, Maryland.
We thank the following individuals who, in addition to members of our Editorial
Board, will serve as referees for this series: Dwight P. Cruikshank, MD, Ronald
S. Gibbs, MD, Gary D. V. Hankins, MD, Phillip B. Mead, MD, Kenneth L.
Noller, MD, and Catherine Y. Spong, MD.
VOL. 104, NO. 2, AUGUST 2004
© 2004 by The American College of Obstetricians and Gynecologists.
Published by Lippincott Williams & Wilkins.
cess as logical as possible. In so doing, new information
and approaches will be emphasized, with the full realization that, during the careers of many of us, management
of myomas will continue to change. The purpose of this
article is to present the authors’ recommended approach
in the diagnosis and treatment of patients with myomas,
as developed from a combination of published evidence
and individual clinical experience. For this purpose a
MEDLINE search was conducted using a combination
of keywords, such as “myoma,” “leiomyoma,” “fibroids,” “myomectomy,” and “hysterectomy.” Randomized controlled studies were used when available;
otherwise literature that was the most relevant to the
topic was used at the authors’ discretion.
Uterine leiomyomata are referred to interchangeably
as myomas, fibroids, fibromyomas, leiomyofibromas,
and fibroleiomyomas. Because the tumor consists of
uterine smooth muscle tissue as well as fibrous tissue, the
term fibroid does not adequately capture the nature of the
lesion. For the sake of simplicity, this report will use the
term myoma.
The importance of this disorder can easily be appreciated from the following statistics: Myomas are the most
common solid pelvic tumors in women, occurring in
20 – 40% of women during their reproductive years.
Approximately 600,000 hysterectomies are performed
per year in the United States. A diagnosis of uterine
myoma is the most common indication for hysterectomy. Many surgical procedures other than hysterectomy are also commonly performed because of myomas.
Uterine myomas are benign tumors that originate
from smooth muscle cells of the uterus, although in some
cases the smooth muscle of uterine blood vessels may be
their source. Myomas range in size from seedlings to
large uterine tumors. They may be solitary or multiple
and can be found within the myometrium (intramural),
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doi:10.1097/01.AOG.0000136079.62513.39
393
externally extending to the serosa (subserous), or internally impinging on the uterine cavity (submucous). Myomas may also be pedunculated and extend through the
internal os of the cervix.1–5
Myomas are estrogen-dependent tumors. Their
growth is clearly associated with exposure to circulating
estrogen. Myomas predictably decrease in size during
menopause and under other hypoestrogenic conditions.
They exhibit maximum growth during a woman’s reproductive life when estrogen secretion is maximal, demonstrating a spurt in growth in the decade before menopause. This growth spurt may be a function of
anovulatory cycles with unopposed circulating estrogen.
Myomas occasionally grow during pregnancy,6 a phenomenon that may be caused by estrogens, but also by
increased blood flow and edema. Estrogen receptors are
present in higher concentration in uterine myomas than
in adjacent myometrium. They bind 20% more estradiol
(E2) per milligram of cytoplasmic protein than normal
adjacent myometrium.7 Growth patterns and locations
within the uterus appear to be the major determinants of
the clinical manifestations of myomas.
CLINICAL MANIFESTATIONS
Most patients with uterine myomas are symptom-free.5,8
When symptoms occur, they usually correlate with the
location of the myomas, their size, or concomitant degenerative changes.9,10 Excessive menstrual bleeding, attributed to vascular alterations of the endometrium, is often
the only symptom produced by myomas. The obstructive effect on uterine vasculature produced by intramural tumors leads to endometrial venule ectasia.11,12 As a
consequence, proximal congestion in the myometrium
and endometrium occurs, and this contributes to excessive bleeding during cyclic sloughing of the endometrium. The increased size of the uterine cavity and the
surface area of the endometrium also contribute to increasing the quantity of menstrual flow.13 Hypermenorrhea may be further aggravated by the presence of
endometritis, which is frequently observed histologically
in the endometrial tissue overlying submucous tumors.14
A dysregulation of local growth factors and aberrant
angiogenesis has also been implicated in the abnormal
bleeding patterns observed in women with myomas.15
Pain, as a symptom of myomas, is relatively infrequent. It is usually associated with torsion of the pedicle
of a pedunculated myoma, cervical dilatation by a submucous myoma protruding through the lower uterine
segment, or carneous degeneration associated with pregnancy. In each of these 3 conditions, pain is acute and
requires immediate attention. Adenomyosis is frequently found in patients with myomas, and diffuse
adenomyosis may be the cause of pain. This condition
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can be difficult to diagnose, especially in a uterus distorted by myomas, but magnetic resonance imaging
(MRI) may prove helpful in detecting adenomyosis and
differentiating it from myomas. Other pathologic conditions, including ectopic pregnancy, rupture or torsion of
an ovarian cyst, or acute pelvic inflammatory disease,
need to be considered in any woman with identifiable
myomas who experiences acute abdominal pain. It is a
mistake to automatically attribute pain experienced in
association with myoma to the myoma itself.
Pressure and increased abdominal girth are more
commonly encountered than pain. These symptoms develop insidiously, are often less apparent, and are usually
vaguely described. As myomas grow, pressure is exerted
on adjacent viscera with manifestations from the urinary
tract, such as frequency, outflow obstruction, and compression of the ureter(s).16 Gastrointestinal symptoms
such as constipation or tenesmus may be the result of a
posterior wall myoma that is exerting pressure on the
recto-sigmoid. Rectal pressure is rare unless the myomatous uterus is incarcerated in the cul-de-sac or contains a
solitary large posterior wall myoma.
Infertility is rarely caused by myomas, but when it is,
it is associated with a submucous myoma17,18 or a markedly distorted, enlarged endometrial cavity that interferes with normal implantation or with sperm transportation.19 Severe displacement of the cervix is also capable
of adversely affecting sperm deposition at the cervical os.
Likewise, intramural myomas may cause obstruction or
dysfunction of the tubal ostia or intramural portion of
the tubes. For patients undergoing in vitro fertilization,
distortion of the endometrial cavity by myomas is associated with decreased pregnancy rates and spontaneous
abortion rates in up to 50% of cases.20 Uterine myomas
have also been implicated in recurrent pregnancy
loss.21,22 Although there are no prospective studies to
compare expectant management with myomectomy in
otherwise asymptomatic women, most authors agree
that there is an improvement in reproductive outcome
after surgery.23–25
Malignant transformation of myomas is extremely
rare. It is felt that leiomyosarcomas arise de novo and
may be unrelated to benign leiomyomata.1 In a report of
presumed myomas examined in the pathology laboratory at The Johns Hopkins Hospital in 1965, 0.29% were
malignant,2 whereas, according to Corscaden and
Singh,3 malignancy occurred in less than 0.13%. Even
this figure appears high, considering that most myomas
are never removed, and not all those that are removed
undergo section and histologic study. More recently, in a
series of 1,332 women who underwent hysterectomy or
myomectomy for symptomatic myomas,4 uterine sarcoma (leiomyosarcoma, endometrial stromal sarcoma,
OBSTETRICS & GYNECOLOGY
and mixed mesodermal tumor) was found in 0.23%.
Taking into account that only a small percentage of
women with uterine myomas are symptomatic and may
require surgery, a more realistic figure for malignancy
with presumed uterine myomas is probably much
smaller than the rates cited above.
GROWTH PATTERNS
Because malignancy in association with myomas is rare,
careful consideration must be given to specific indications for performing surgery. A history of rapid growth,
for example, an increase in uterine size by 6 weeks in a
year,5 especially postmenopausal growth, should
prompt resection of the tumor(s), even in the absence of
associated symptoms. Rapid growth of myomas is common during pregnancy.26 Therefore, in younger patients
in whom pregnancy has been ruled out and in older
patients beyond menopause, rapid growth must raise the
suspicion of a malignancy. Nevertheless, the risk of
malignancy even with rapidly enlarging myomas remains very low, as mentioned above.4 Small asymptomatic myomas require only serial follow-up, initially at
3-month intervals to establish a growth pattern. If the
growth pattern is stationary, pelvic examinations can be
safely repeated at 4- to 6-month intervals. Myomas often
remain constant in size for many years. Because uterine
size tends to vary with phase of the menstrual cycle and
tissue response to hormonal stimulation, selection of a
uniform time in the cycle for each follow-up examination
is desirable. Myomas tend to exhibit precipitous growth
during the fifth decade of a woman’s life. With larger
asymptomatic tumors, expectant management may be
justified, provided the examiner is confident that the
pelvic mass consists exclusively of myomas and does not
either represent an ovarian neoplasm or obscure the
detection of such an extrauterine tumor. The expectant
approach is clearly applicable to women approaching
menopause.
Ultrasound examination also assists in documenting
growth of myomas with a finer level of discrimination
than that obtained by serial pelvic examination. The
presence of hydronephrosis can also be determined.
Intravenous pyelography may be occasionally necessary to define renal and ureteral characteristics when
ureteral distortion is strongly suspected. In specific cases,
computed tomography can supplement ultrasonography. However, it has been reported that 5% of patients
diagnosed with myomas by computed tomography were
subsequently found to have an ovarian tumor at the time
of surgery.27 Magnetic resonance imaging provides better discrimination of the source of a pelvic mass.28 Regardless of imaging procedures, in the event of diagnostic uncertainty, surgical exploration may be required.
VOL. 104, NO. 2, AUGUST 2004
Fig. 1. Hysterosalpingogram demonstrating a large filling
defect caused by a solitary submucous myoma before
hysteroscopic resection.
Wallach. Uterine Myomas. Obstet Gynecol 2004.
Hysterosalpingography (HSG) is especially effective
in evaluating the contour of the endometrial cavity and
the patency of the fallopian tubes in infertility patients
who have uterine myomas (Fig. 1) and in women before
having in vitro fertilization. Hysterosalpingography or
sonohysterography may further assist in delineating the
location, extent, and resectability of submucous myomas
when planning the route of surgery in noninfertile
women. Occasionally peritoneal distribution of the contrast media may outline the silhouette of a large pedunculated tumor (Fig. 2).
Careful observation is suitable management for most
myomas.29 Most myomas produce no symptoms, are
Fig. 2. Hysterosalpingogram provides the outline of a normal uterine cavity. Spillage of the contrast media through
the left fallopian tube outlines the circumference of a large
pedunculated myoma originating from the left lateral uterine wall.
Wallach. Uterine Myomas. Obstet Gynecol 2004.
Wallach and Vlahos
Uterine Myomas
395
confined to the pelvis, and are rarely malignant. Clinical
settings that may require aggressive management of
uterine myomas are shown in the Box.
•
•
•
•
•
•
•
•
Indications for Surgical Management of
Uterine Myomas
Abnormal uterine bleeding not responding to conservative treatments
High level of suspicion of pelvic malignancy
Growth after menopause
Infertility when there is distortion of the endometrial cavity or tubal obstruction
Recurrent pregnancy loss (with distortion of the
endometrial cavity)
Pain or pressure symptoms (that interfere with
quality of life)
Urinary tract symptoms (frequency and/or obstruction)
Iron deficiency anemia secondary to chronic blood
loss
THERAPY
Management of uterine myomas may involve one of the
following approaches or a combination thereof: expectant management, medical management (GnRH analogues, progestational compounds, antiprogestins), surgical management (myomectomy or hysterectomy),
uterine artery embolization, and other approaches, eg,
high frequency ultrasonography, laser treatment, cryotherapy, or thermoablation. The choice of approach
should be predicated upon careful consideration of
many factors, both medical and social, including age,
parity, childbearing aspirations, extent and severity of
symptoms, size and number of myomas, location
of myomas, associated medical condition(s), possibility
of malignancy, proximity to menopause, and desire for
uterine preservation.
For example, a woman with multiple myomas who
has completed her childbearing may benefit from hysterectomy, whereas myomectomy is appropriate for a nulliparous woman. A patient with submucosal myomas
may benefit from hysteroscopic resection, whereas a
patient with subserosal pedunculated symptomatic myomas may benefit from laparoscopic resection.
There was a time when hysterectomy was the standard of care in the management of uterine myomas,
whereas myomectomy was rarely invoked as the appropriate treatment. Expectancy and hormonal treatment
were infrequently used. The introduction of ultrasonography, hysteroscopy, and laparoscopy, computed to-
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Uterine Myomas
mography (CT) scan, and MRI and the development of
GnRH analogues have significantly altered our therapeutic approach to uterine myomas and are responsible
for providing a variety of means for their management.
The availability of diverse modes for managing uterine
myomas, therefore, currently enables the gynecologist to
individualize management by understanding each patient’s specific problems, needs, and goals and then to
apply sound principles based upon significant clinical
experience. No 2 patients are identical. A multitude of
factors must be considered before arriving at the best
course of management in any given individual.
HYSTERECTOMY
Hysterectomy is the second most frequent major surgical
procedure performed in women in the United States,
second only to cesarean delivery. Twenty percent of
women will have had a hysterectomy by the age of 40,
and one third by age 65. Indications for hysterectomy
include uterine myomas (33.5%), endometriosis
(18.2%), uterine prolapse (16.2%), and cancer (11.2%).
Removal of the uterus has been the usual procedure of
choice whenever surgery is indicated for uterine myomas and when childbearing considerations have been
fulfilled. Specific exceptions include a solitary subserous
or pedunculated myoma and a submucous myoma
readily accessible for hysteroscopic removal. Hysterectomy is also the procedure of choice whenever there is a
reasonable likelihood of malignancy within a myoma,
eg, as evidenced by suspicious features on MRI or CT
scan or when a myomectomy is not technically feasible,
such as in patients with extensive leiomyomatosis. Although this situation occurs infrequently, myomectomy
in such patients may be difficult, time-consuming, and
associated with a substantial complication rate. Therefore, to balance the risks of performing a difficult and
potentially complicated myomectomy, sufficient indication for uterine preservation should be evident. These
issues will be revisited during the discussion of myomectomy.30
Why do a hysterectomy? Many patients inquire, quite
logically, that if their problem is exclusively the presence
of leiomyomata, why remove the entire uterus? This
logical question, however, fails to take into consideration
whether the myomatous uterus will be morphologically
normal and capable of normal function following an
extensive myomectomy. Several factors should influence
the gynecologist’s judgment, including the age of the
woman with leiomyomata and her childbearing aspirations. If she is approaching menopause and is no longer
interested in pregnancy, the decision is less difficult than
when the woman with multiple myomas is in her third or
OBSTETRICS & GYNECOLOGY
fourth decade and/or wishes to be able to conceive. The
patient’s comfort level regarding hysterectomy represents a major consideration. For many women, hysterectomy conjures up the specter of loss of sexuality and
femininity. Before surgery, counseling and discussion
with other women who have undergone hysterectomy
can be very constructive. Several recent publications
report improvement in quality of life for most women
who have had hysterectomy and conclude that hysterectomy does not adversely influence sexuality.31 Weber et
al32 in a prospective study also reported a high rate of
satisfaction among women after abdominal hysterectomy for benign gynecologic conditions. Benefits include
relief from abnormal bleeding and menstrual pain. In
Weber’s study, sexual function was not adversely affected by hysterectomy. The data in this study also
provide evidence that the cervix and uterus are not
required for coital orgasm. Two thirds of the women in
the study experienced relief from urinary stress incontinence. In a prospective study33 of 1,299 women who
underwent hysterectomy for symptomatic myomas, follow-up at 3, 6, 12, 18, and 24 months thereafter showed
significant improvements in symptom severity, depression and anxiety levels, and overall quality of life. Along
these lines, an additional report34 suggests that standardized measurement of quality of life among women with
conditions leading to hysterectomy could help in establishing treatment guidelines. In this study, 61% of the
hysterectomies performed in 482 women were done for
uterine myomas.34 Surgery to relieve bleeding, pain,
pelvic pressure, and urinary tract symptoms may lead to
improvement in sexual satisfaction and quality of life.
Other factors that may prompt hysterectomy for uterine
myomas include associated conditions, such as pelvic
floor relaxation, abnormal endometrial or cervical cytology, or inability to tolerate hormonal treatment, each of
which may also be alleviated by a single curative surgical
procedure. Additional benefits for menopausal women
following hysterectomy for myomas include elimination
of the need for progestational agents, the ability to take
estrogen without experiencing bleeding, and relief from
concerns about myoma growth during estrogen replacement. The need for routine gynecologic follow-up commitment after hysterectomy is also simplified, compared
with the frequent visits previously required for assessment of myoma growth.
Hysterectomy for uterine myomas is not free of complications. Anatomic distortions of the uterus increase
the risk of damage to adjacent structures, including the
urinary tract and bowel. If hysterectomy is performed
for a woman who has had previous conservative uterine
surgery, the presence of adhesions may increase the
technical difficulty and heighten the chance of bowel
VOL. 104, NO. 2, AUGUST 2004
injury. Urinary tract injuries tend to occur when myomas extend into the broad ligament, compress the bladder, or extend deep into the pelvis. The incidence of
ureteral injury in one extensive report was 0.4 per 1,000
with total abdominal hysterectomy, and that of vesicovaginal fistula was 1.0 per 1,000.35 In all instances these
urinary tract injuries were most common after procedures that were described as technically difficult. Even in
Weber’s report,32 despite the documented high degree of
satisfaction after hysterectomy, 4 of 34 women developed stress incontinence after surgery. Additional longterm problems after hysterectomy for myomas include
development of vaginal vault prolapse. Conservation of
the cervix has been proposed for selected patients undergoing abdominal hysterectomy because of its presumed
significance in sexual function. In a recent study,36 however, there was no difference in the frequency of sexual
activity and orgasm between women who underwent
supracervical and those who had total hysterectomy.
Supracervical hysterectomy is also associated with a
decreased risk of urinary tract injury,35 requires less
operating time, and has been hypothesized to lessen the
risk of vault prolapse caused by preservation of the
uterosacral and cardinal ligament complex. Even if, in
the most recent prospective randomized study,37 there
was no difference in pelvic relaxation symptoms between the procedures after 2 years of follow-up, we
believe that this time interval may be too limited to
adequately address the question.
One might consider the inclination of the surgeon to
perform bilateral oophorectomy when performing an
abdominal hysterectomy equivalent to an additional risk
concomitant oophorectomy at the time of vaginal hysterectomy does not seem to increase morbidity.37– 40 In our
experience, this is true as well after abdominal hysterectomy for myomas. The Wilcox survey41 revealed that,
in 1.7 million hysterectomies performed in the United
States between 1988 to 1990, uterine myoma was the
primary diagnosis for 29% of white and 61% of black
women. The percentage of patients undergoing concomitant bilateral oophorectomy was 61.4% for women over
45 years of age, compared with 37% for younger women.
We do not automatically remove the ovaries at the time
of surgery for women less than 45 years of age unless
there is underlying pathology or at the patient’s request.
Hysterectomy is an acceptable choice for symptomatic
myomas in patients who have significant bleeding, pain,
pressure, or anemia that is refractory to therapy and for
whom fertility is not an issue. We always leave the
decision to our patients; nevertheless, we routinely recommend hysterectomy for these patients.
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Uterine Myomas
397
ABDOMINAL MYOMECTOMY
Myomectomy is the preferred treatment whenever preservation of the uterus is desired. It is also the procedure
of choice for a solitary pedunculated leiomyoma. Myomectomy should also be considered even if childbearing
is not a factor for the women with symptomatic myomas
who do not want a hysterectomy. Indications for myomectomy include interference with fertility or predisposition to repeated pregnancy loss because of the nature
and/or location of the myomas. Infertility is rarely a
consequence of myomas, but a causal relationship may
be suspected, particularly when other factors for infertility have been excluded or adequately treated and there is
significant distortion of the endometrial cavity. The location of myomas is the most significant element, because they can interfere with establishment or maintenance of pregnancy. Submucous leiomyomata are
clearly implicated in infertility and recurrent pregnancy
loss.19,42 Myomectomy, therefore, is recommended before gonadotropin stimulation required for in vitro fertilization. We also recommend myomectomy in patients
with large myomas that may interfere with the accessibility of the ovaries during oocyte retrieval.
Desire for uterine retention cannot be underestimated.
Technology today even enables the uterus of a woman
lacking ovaries to serve as a gestational vehicle by virtue
of in vitro fertilization, endometrial preparation with
exogenous hormone therapy, and embryo donation.
Furthermore, publicity regarding unnecessary hysterectomies has motivated women to become involved in the
decision-making process regarding uterine retention in
the presence of benign pathology. Wide dissemination of
such attitudes may render myomectomy an even more
prevalent procedure in the future than it is today.
Having arrived at a decision to perform myomectomy, the surgeon must carry out a thorough preoperative appraisal, selectively using the techniques described
earlier. Hypermenorrhea and other forms of abnormal
bleeding require endometrial evaluation before performing a myomectomy in a patient aged more than 35 years.
In women at risk for endometrial pathology, such as
those with a history of chronic anovulation or with perior postmenopausal bleeding, evaluation of the endometrium should be mandatory. This can be achieved either
by an office endometrial biopsy or, if there is concern
about the adequacy of the sample, by hysteroscopy and
dilation and curettage. A hysteroscopic examination will
establish the size, shape, and location of submucous
myomas, as well as determine the feasibility of hysteroscopic resection. At the time of hysteroscopy, a thorough
endometrial sampling can be performed. After hysteroscopy, definitive surgery should be deferred for 4 – 6
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Uterine Myomas
weeks to minimize the chance of disseminated infection
because of endometrial contamination.
Hematological status, especially when heavy or prolonged bleeding is present, should be appraised well in
advance of surgery. The patient with a normal hemoglobin should have 1 or 2 units of her own blood, obtained
2 weeks before myomectomy and stored, while she
undergoes treatment with supplemental iron. For the
anemic patient, pretreatment with GnRH analogues or
progestational agents combined with iron supplementation can produce an amenorrheic state during which iron
stores can be replenished and anemia corrected. At the
end of a hormonally induced 4- to 6-month interval of
amenorrhea, the hemoglobin level should return to normal and permit preparation for autologous blood collection. Even with stored autologous blood, typing and
cross matching additional units of blood prepares for the
possibility of significant intraoperative blood loss. Several approaches have been used to reduce blood loss,
including pharmacologic vasoconstricting agents and
mechanical vascular occlusion with similar success.43
Blood loss correlates with preoperative uterine size, total
weight of the myomas removed, and operating time. The
general principles for abdominal myomectomy involve
adequate exposure, hemostasis, careful handling of reproductive tissues, and adhesion prevention. No discussion of myomectomy is complete without paying tribute
to William Alexander,44 who described the first multiple
myomectomy, Victor Bonney,45 who felt that myomectomy is a preferable procedure, and I. C. Rubin,46 who
championed the procedure of multiple myomectomy.
The technical details and surgical strategies for abdominal myomectomy are well delineated in standard gynecologic surgical textbooks.
Multiple myomectomy is frequently a more difficult
and time-consuming procedure than hysterectomy. The
number and location of myomas within the uterus, as
well as the possibility of having had previous myomectomies and a history of recurrent myomas, also enter
into the equation.
Nevertheless, not everybody agrees that abdominal
myomectomy is a more morbid procedure than a hysterectomy. Several retrospective studies failed to show any
difference in operative morbidity between the 2 procedures.30,47–50 According to Iverson et al,30 morbidity
among patients undergoing abdominal myomectomy
was less than that after hysterectomy. In their series they
reported a decreased estimated blood loss and febrile
morbidity in patients undergoing abdominal myomectomy compared with those undergoing abdominal hysterectomy for myomas. Patients in the hysterectomy
group experienced ureteral, bladder, and bowel injuries,
OBSTETRICS & GYNECOLOGY
whereas no intraoperative visceral injuries were encountered in the myomectomy group.
When reviewing these reports, one should consider
that selection bias may have governed the choice of
procedure. The decision to perform hysterectomy is
often predicated upon the anticipated difficulty associated with myomectomy. Therefore women with large,
multiple myomas, as well as those with previous multiple
myomectomies, may have been preferably advised to
have hysterectomy. A well-designed prospective randomized study is necessary to provide a definite answer
to this question. In our experience, significant blood loss,
a greater need for blood replacement, a higher frequency
of postoperative anemia, paralytic ileus, and pain, as well
as a longer hospital stay, frequently accompany multiple
myomectomies. Long-term complications must also be
considered. The need for future uterine surgery to manage recurrence of myomas is high. Following abdominal
myomectomy, clinically significant recurrence rates have
been reported in the range of 10% after 5 years of
follow-up and one third of those patients will have a
hysterectomy.51 According to another study from the
University of Milan, the 10-year recurrence rate in 622
women who had undergone myomectomy was 27%,
with a steady increase in frequency throughout the
course of follow-up. Age was not a factor nor was the
location of the myomas, but women with a solitary
myoma experienced a slightly lower recurrence rate.52
Compared with women who had a single myoma removed, the relative risk of recurrence was 1.2 in those
with 2 or 3 myomas and 2.1 with removal of 4 myomas.53 The risk for recurrence following laparoscopic
myomectomy is higher,54 reaching up to 50% after 5
years in some reports.55
Cervical myomas can be surgically removed with a
vaginal approach in certain instances. The myoma can
be removed through an already dilated cervix by advancing the bladder and making an anterior midline
cervical incision. The myoma may be enucleated and the
cervical incision repaired with interrupted sutures. The
overlying vaginal epithelium may then be reapproximated. Preoperative and perioperative antibiotic therapy
is recommended in this approach because of the hazards
of ascending infection from the vagina.
When extensive dissection of the myometrium has
been necessary during myomectomy, cesarean delivery
is usually advisable following establishment of pregnancy. This rule of thumb should supersede the classic
dogma that cesarean delivery is indicated whenever the
endometrial cavity has been entered. When advising
patients who desire pregnancy, the possibility of pelvic
adhesions or the anatomic impairment of the interstitial
portion of the oviduct as a result of dissection in this
VOL. 104, NO. 2, AUGUST 2004
Fig. 3. Different stages of hysteroscopic resection with a
loop resectoscope of a submucosal leiomyoma in a woman
with infertility.
Wallach. Uterine Myomas. Obstet Gynecol 2004.
location after myomectomy should be discussed as an
additional cause of postoperative infertility.
HYSTEROSCOPIC MYOMECTOMY
Hysteroscopy has been used for resection of submucosal
myomas with very good results (Fig. 3). Indications for
hysteroscopic myomectomy include abnormal bleeding,
history of pregnancy loss, infertility, and pain. Contraindications include endometrial cancer, lower reproductive tract infection, inability to distend the uterine cavity,
inability to circumnavigate the lesion, and extension of
the tumor deep into the myometrium. Long-term follow-up studies have documented that approximately
20% of subjects will require additional treatment within 5
to 10 years after initial resection, a figure that approximates that following abdominal myomectomy. Recurrences may be explained by incomplete removal of myoma tissue or by new myoma growth.
The European Society of Hysteroscopy classifies submucous myomas according to level of myometrial penetration. Category T:O includes all pedunculated submucous myomas. Submucous myomas extending less
than 50% into the myometrium are classified as T:I,
while those with greater than 50% penetration are classified as T:II.56 Mapping the myomas enables the hysteroscopist to plan the surgical approach. Category T:O
and T:I myomas can be performed hysteroscopically by
a surgeon with modest previous experience. Category
T:II myomas should usually be resected abdominally,
and hysteroscopic resection should be reserved for
highly skilled hysteroscopic surgeons.
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399
Fig. 4. Laparoscopic resection, using a combination of
bipolar coagulation and endo-shears, of multiple subserous
myomas in an infertility patient.
Wallach. Uterine Myomas. Obstet Gynecol 2004.
LAPAROSCOPIC MYOMECTOMY
Laparoscopic myomectomy can be performed when myomas are easily accessible, as in superficial subserous or
pedunculated myomas (Fig. 4). These myomas can be
morcellated and removed through the laparoscopic cannula or placed in the cul-de-sac and removed via a
colpotomy incision. A morcellating instrument has been
developed which readily fragments segments of the myoma and grasps it for removal through the cannula (Fig.
5). Laparoscopic coagulation of a myoma, or myolysis,
was first performed in the late 1980s in Europe.57–59 The
procedure of myolysis was viewed as a conservative
alternative to myomectomy in women wishing to pre-
Fig. 5. Morcellation and extraction of the resected myomas
following laparoscopic myomectomy with a grasping forceps and an electrical morcellator.
Wallach. Uterine Myomas. Obstet Gynecol 2004.
400
Wallach and Vlahos
Uterine Myomas
Fig. 6. Cross section of a hysterectomy specimen obtained
from a 40-year-old woman who was a poor candidate for
myomectomy because of extensive leiomyomatosis.
Wallach. Uterine Myomas. Obstet Gynecol 2004.
serve fertility. The procedure has been carried out with
the energy of a neodymium:yttrium-aluminum-garnet
(Nd:YAG) laser via denaturation of protein and destruction of vascularity. Bipolar coagulation and cryomyolysis have also been described, but sufficient follow-up has
not been available to enable adequate evaluation of
safety and the impact on future fertility. Cowan et al60
reported on the outcome of 9 women who underwent
cryomyolysis under MRI guidance. A mean leiomyoma
volume reduction of 65% was documented in 8 patients
who were available for follow-up; however, 1 patient
required laparotomy and myomectomy because of the
laceration of a vessel, and another had a peroneal nerve
defect associated with foot drop that resolved 4 months
later.60 Uterine rupture during pregnancy following
laparoscopic resection of leiomyomata has been reported
and has been attributed to inadequate reconstruction of
the myometrium. Nevertheless, it is still unclear whether
the actual incidence of uterine rupture is higher than that
following abdominal myomectomy. Laparoscopic assisted myomectomy involves laparoscopic dissection of
the myomas from the uterine wall and their extraction
through a minilaparotomy incision, thus sparing a large
abdominal incision. Because these procedures have not
been standardized to the same extent as abdominal myomectomy, the surgeon who undertakes them should be
skilled in operative endoscopy.
OBSTETRICS & GYNECOLOGY
The patient contemplating myomectomy should be
aware of the risks involved in “conservative” surgery, as
well as those associated with hysterectomy for myomas.
She should also be advised of the possibility that hysterectomy may be required rather than the proposed myomectomy. This is a rare event, but a candid preoperative
discussion is critical for maintaining mutual trust between the patient and her physician. Unusual cases of
diffuse leiomyomatosis of the uterus discovered at the
time of planned myomectomy occasionally preclude removal of myomas and necessitate hysterectomy (Fig. 6).
Unfortunately, preoperatively the surgeon is not invariably able to predict the feasibility of uterine conservation
because of unforeseen technical factors. Most patients
who wish to retain their childbearing function will select
myomectomy over hysterectomy when given the option.
For those who wish to conceive, a delay of 4 to 6 months
before attempting pregnancy is recommended after the
surgical procedure, because the myometrium is significantly disrupted during myomectomy. For infertility
patients we recommend an HSG 4 months after the
procedure to evaluate the anatomy of the uterine cavity
and the fallopian tubes.
UTERINE ARTERY EMBOLIZATION
Uterine artery embolization for treatment of myomas
was first described in 1995, although this approach had
been used for many years to control pelvic hemorrhage.
The principle is simple. By limiting blood supply to the
myomas (infarction), their volume may be reduced. The
embolization material, usually polyvinyl alcohol particles, is passed through a fluoroscopically guided transarterial catheter inserted in the common femoral artery to
selectively occlude arteries supplying the myomas. The
procedure is performed under conscious sedation by an
interventional radiologist. Because of the shortened hospital stay, this minimally invasive procedure has become
an attractive new alternative to abdominal surgery (myomectomy, hysterectomy). It has been recommended for
patients with larger myomatous uteri who are symptomatic, women who do not want extirpative therapy, and
individuals who may be poor candidates for major surgery. Most patients require overnight hospitalization for
pain control. In a series of 80 patients with myomarelated hypermenorrhea, 90% reported complete cessation of symptoms after uterine artery embolization.61
The procedure is not free of side effects and complications. Pain may persist and last for more than 2 weeks
after the procedure.62 Postembolization fever, severe
postembolization syndrome, pyometra, failure of satisfactory regression of myomas, sepsis, hysterectomy, and
even deaths have been reported following uterine artery
VOL. 104, NO. 2, AUGUST 2004
embolization.62 Ovarian failure has also been reported in
1–2% of patients after the embolization procedure. The
effect of uterine artery embolization on future fertility is
still in question; however, Ravina et al63 recently reported a small series of 12 pregnancies in 9 women with
symptomatic uterine leiomyomata who underwent uterine artery embolization. Uterine artery embolization will
continue to attract women with uterine myomas because
it can provide symptomatic relief. Because of the newness of this approach, several questions remain to be
answered. These include questions about recurrence
rate, long-term effects on fertility, and overall safety
compared with conventional surgical treatment. Uterine
artery embolization must be included as an option in the
course of developing a management plan for symptomatic myomas, and this option should be discussed with
the patient.
HORMONE THERAPY
Progestins
Progestational agents alone have been reported to have a
salutary influence on myoma growth. Norethindrone,
medrogestone, and medroxyprogesterone acetate have
been successfully used to achieve diminution in aggregate size of the myomatous uterus.64 – 66 These compounds were thought to produce a hypoestrogenic effect
by inhibiting gonadotropin secretion and suppressing
ovarian function. Progestational compounds may also
exert a direct antiestrogenic effect at the cellular level.
However, evidence that the antiprogesterone mifepristone decreases myoma size sheds doubt on this theory.67–71
Gonadotropin-Releasing Hormone Analogues
Gonadotropin-releasing hormone analogues (GnRHa)
have been used successfully to achieve hypoestrogenism
in various estrogen-dependent conditions, eg, endometriosis, precocious puberty, and uterine myomas.72 This
approach offers great promise as a primary means of
conservative therapy for myomas or as an adjunct to
myomectomy.
The effects of either progestational therapy or GnRHa
treatment are transient, and within several cycles after
discontinuing administration, myomas tend to return to
their pretherapy size.73 Adjunctive therapy with a 3- to
4-month course of GnRHa should reduce myoma size
and render surgery easier, accompanied by less blood
loss. In the study by Andreyko et al,74 a daily dose of 800
mg of nafarelin for 6 months caused a mean decrease in
uterine volume of 57% in 10 patients followed by serial
MRI. Maheux et al75 reported a mean decrease of 71% in
myoma size following treatment with intranasal busere-
Wallach and Vlahos
Uterine Myomas
401
lin in 9 patients. Schlaff et al76 used leuprolide in a
double-blind, placebo-controlled study and demonstrated 42.7% and 30.4% declines in nonmyoma and
myoma volume, respectively, through serial MRI studies. This approach has special advantages in facilitating a
hysteroscopic resection of a submucous myoma, because
the time consumed in the hysteroscopic resection itself is
largely a function of tissue volume. In our experience,
the tissue plane separating the myoma from surrounding
myometrium tends to be more fibrotic and adherent
after GnRHa therapy; these observations, however,
have not been substantiated in a comparative study.
After a course of GnRHa, myomectomy is performed
through a hypovascular myometrium, theoretically reducing blood loss.77,78 Pretreatment with GnRHa, however, not only facilitates the myomectomy itself, but also
provides an amenorrheic interval before surgery during
which hemoglobin levels can be restored in the hypermenorrheic anemic patient, enabling presurgical blood
donation for subsequent autotransfusion. The concern
that presurgical shrinkage of small myomas by GnRHa
will render them undetectable at surgery and lead to
early recurrence was not borne out by a randomized,
double-blind study using placebo and leuprolide acetate.79 Despite their efficacy in reducing myoma size, the
use of GnRH agonists has been associated with significant short- and long-term side effects, such as postmenopausal symptoms and osteoporosis. Hormonal add-back
therapy may alleviate some of these symptoms; however, it may also negate their beneficial effects on myoma
size.80 Severe pelvic pain occasionally will accompany
shrinkage of myomas during treatment with a GnRH
analogue. Results of clinical studies of GnRHa therapy
for myomas are variable, and, at present, accurate prediction of responders to GnRHa appear to be impossible.
Long-term treatment of young patients is neither practical nor desirable because of the likelihood of bone loss
as a consequence of hypoestrogenism during prolonged
therapy with GnRHa. For perimenopausal women,
however, in whom reduction in myoma volume may
stabilize when menopause occurs, short-term GnRHa
therapy may eliminate the need for surgery.
OTHER APPROACHES
Davies et al81 reported a procedure in which myomas are
removed through a posterior or anterior colpotomy, or
both, depending on the position of the myomas. Each
leiomyoma is delivered into the colpotomy and the
tumor removed by enucleation or morcellation. The
uterine incisions are closed in layers, and then the colpotomy incisions are closed. The procedure was completed
vaginally in 32 (91.4%) of 35 patients. Pelvic hematomas
402
Wallach and Vlahos
Uterine Myomas
developed in 4 patients. One colpotomy required resuturing. Although this approach may be useful in selected
cases, it was associated with a prolonged hospital stay
and is limited to carefully selected groups of patients with
a small number of easily accessible leiomyomata.
Recently, an MRI-guided, high-frequency focused ultrasonography (HIFUS) has been reported to be capable
of destroying myoma cells.82– 84 This noninvasive procedure is still experimental and cannot be recommended
yet as a clinically effective modality for treating myomas.
The carbon dioxide laser has also been used as a
surgical adjunct to myomectomy. During laparotomy,
small myomas have been directly vaporized with the
laser, and both medium and large leiomyomas were
excised.85 In this limited-case series, improved hemostasis, greater precision enabling removal of only abnormal
tissue, and ability to remove myomas from previously
inaccessible areas were described as definite advantages
of laser vaporization. Nevertheless, wide acceptance of
this technique borne out by long-term results through
extended follow-up in a larger series of patients has not
yet occurred.
Baggish et al86 described treatment of submucous
myomas with the Nd:YAG laser. One approach involves
multiple passes with the clear fiber into the substance of
the myoma. This maneuver devascularizes the myoma,
thereby destroying its blood supply. Alternatively, the
base may be transected with the laser and the myoma
removed or left in the cavity to be expelled. Slicing the
lesion plane by plane reduces the size of the myoma.
Elements of the myoma can be removed with a sponge
or forceps or can be left to be passed spontaneously.
Concerns regarding incomplete removal of the leiomyoma and the fact that these approaches are limited to
selected groups of patients resulted in the limited spread
of these techniques.
CONCLUSION
A thorough understanding of the pathogenesis of uterine
myomas, clinical presentation, and the available diagnostic tools are the keys to selecting which course to follow
in treating any given patient with myomas. At the
present, we should use all modalities at our disposal
judiciously, with ample thought to the value and cost of
diagnostic tests and the risk/benefit ratios of therapies in
the management of uterine myomas. This report has
described a broad range of current approaches to therapy. The experience and skill of any individual surgeon
is paramount in selecting the form of treatment for
myomas. These concluding comments represent the authors’ assessment based upon their aggregate experience(s) in the care of patients with myomas. First, we feel
OBSTETRICS & GYNECOLOGY
that surgery for myomas is not always necessary and
should be performed only for appropriate indications,
such as uncontrollable pain or bleeding, progressive and
significant growth, and poor reproductive performance
once other potential causes have been eliminated or
treated. Second, myomectomy, rather than hysterectomy, should be performed whenever preservation of
childbearing function is a desired goal. The route for
myomectomy (hysteroscopic, laparoscopic, or via laparotomy) should be predicated on the location of the
myomas for removal, as well as on the individual surgeon’s preferred approach. Continued follow-up without surgery is advisable mostly for patients approaching
menopause. Our major indication for the use of GnRH
analogues is the achievement of amenorrhea to facilitate
correction of iron deficiency anemia before surgery. The
authors have found that preoperative treatment with
GnRH analogues before myomectomy renders the capsule surrounding the myoma more fibrous and the enclosed myomas more difficult to resect. We consider
uterine artery embolization to be most effective for patients with large symptomatic myomas who are poor
surgical candidates and at high risk for general anesthesia, as well as for those who are reluctant to undergo a
major surgical procedure. Experience with uterine artery
embolization is relatively brief, and it is premature to
know with assurance whether the procedure is curative
or temporizing. The effects of uterine artery embolization on future fertility need extensive further evaluation
before this approach can be recommended for women
who have childbearing aspirations. We determine our
surgical approach, endoscopic or by laparotomy, based
on size, number, extent, and location of myomas. Hysterectomy has its place in myoma management in its
definitiveness. By the same token, hysterectomy, our
usual recommendation for women at or near menopause, should never be imposed upon the woman who
simply wishes to retain her uterus for no reason other
than wanting uterine preservation. Fundamentally, all
therapeutic measures, and especially invasive techniques, should be reserved for patients with symptomatic myomas. For asymptomatic women, serial follow-up
for growth and/or development of symptoms is generally safe. Modalities such as myolysis and high frequency
ultrasound ablation are still experimental and should be
used primarily in centers where these procedures are
commonly performed under carefully controlled research protocols.
Howard Kelly led us into the 20th century describing
treatment approaches for myomas as “expectant, palliative, abortive, or radical.”87 Now, at the beginning of the
21st century, the approaches are still the same; however,
a century later we have sophisticated diagnostic and
VOL. 104, NO. 2, AUGUST 2004
therapeutic approaches which allow us the flexibility to
tailor our management according to the individual’s
needs.
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Address reprint requests to: Edward E. Wallach, MD, Department of Gynecology and Obstetrics, The Johns Hopkins Medical Institutions, 600 North Wolfe Street, Phipps Building
#201, Baltimore, MD 21287-1201; e-mail: jensam2@comcast.
net and [email protected].
Received February 11, 2004. Received in revised form May 19, 2004.
Accepted May 21, 2004.
OBSTETRICS & GYNECOLOGY