Available online at www.sciencedirect.com
Journal of the Chinese Medical Association 75 (2012) 487e493
www.jcma-online.com
Review Article
Typical and atypical clinical presentation of uterine myomas
Wen-Hsiang Su a,b,c,d, Wen-Ling Lee e,f,g, Ming-Huei Cheng f,h, Ming-Shyen Yen f,j,
Kuan-Chong Chao f,j, Peng-Hui Wang f,i,j,k,l,*
a
Department of Obstetrics and Gynecology, Da Chien General Hospital, Miaoli, Taiwan, ROC
Institute of Systems Biology and Bioinformatics, National Central University, Tao-Yuan, Taiwan, ROC
c
Institute of Statistics, National Central University, Tao-Yuan, Taiwan, ROC
d
Hsin Sheng College of Medical Care and Management, Tao-Yuan, Taiwan, ROC
e
Department of Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan, ROC
f
Institute of Clinical Medicine, and Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei, Taiwan, ROC
g
Department of Nursing, Oriental Institute of Technology, New Taipei City, Taiwan, ROC
h
Medical Division, Eli Lilly and Company (Taiwan), Inc, Taipei, Taiwan, ROC
i
Department of Obstetrics and Gynecology, National Yang-Ming University Hospital, Yilan, Taiwan, ROC
j
Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
k
Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
l
Infection and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan, ROC
b
Received April 12, 2012; accepted May 31, 2012
Abstract
Myoma is the most common benign neoplasm that can occur in the female reproductive system, most frequently seen in women in their 50s.
Although the majority of myomas are asymptomatic, some patients have symptoms and/or signs of varying degrees. Typical myoma-related
symptoms or signs include: (1) menstrual disturbances like menorrhagia, dysmenorrhea and intermenstrual bleeding, (2) pelvic pain unrelated to menstruation, (3) compression symptoms, similar to a sensation of bloatedness, urinary frequency and constipation, (4) subfertility status
such as recurrent abortion, preterm labor, dystocia with an increased incidence of Cesarean section, and postpartum hemorrhage, and
(5) cosmetic problems due to increased abdominal girth However, there are undoubtedly some clinical presentations secondary to uterine
myomas are not so specific, such as: (1) uncommon compression-related symptoms, (2) cardiac symptom and atypical symptoms secondary to
vascular involvement or dissemination, (3) abdominal symptoms mimicking pelvic carcinomatosis, (4) dyspnea, (5) pruritus, (6) hiccup or
internal bleeding, and (7) vaginal protruding mass or uterine inversion. Familiarization with these symptoms and awareness of other unusual or
atypical presentations of uterine myomas will remind clinical practitioners of their significance, and of the necessity of follow-up examinations
and individualized management to fit the needs and childbirth desires of the patients.
Copyright Ó 2012 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.
Keywords: fibroids; leiomyomas; myomas; symptomatic; uterus
1. Introduction
The incidence of myoma can vary from 20%e50% in
different study populations and surveys.1 The diagnosis of
* Corresponding author. Dr. Peng-Hui Wang, Department of Obstetrics and
Gynecology, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road,
Taipei 112, Taiwan, ROC.
E-mail address: [email protected] (P.-H. Wang).
uterine myoma is the most frequently seen reason for hospital
admission, and hysterectomy is performed on three-quarters of
those women hospitalized, approximately 30%e60% of
patients from different communities.2,3 Therefore, this
common disorder among women of reproductive age is
considered to be a major burden on the health care system.4e7
The correct assessment and diagnosis of a possible clinical
presentation of myoma relies on an understanding of the
etiology, risk factors and development of leiomyomas.8 For
1726-4901/$ - see front matter Copyright Ó 2012 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.
http://dx.doi.org/10.1016/j.jcma.2012.07.004
488
W.-H. Su et al. / Journal of the Chinese Medical Association 75 (2012) 487e493
example, due to the slow-growing characteristic of this
disease, affected women are most commonly asymptomatic.l
However, in around 20%e50% of patients, myoma induces
problems that affect quality of life. Although nearly all
myomas initial arise from the uterine myometrium layer, these
tumors develop into one of three categories, intramural, subserous, and submucous types, and the severity of symptoms
seems to correlate with the number, size, and location of the
tumors.9
When a female of reproductive age presents with symptoms
like menorrhagia, dysmenorrhea, fainting, pallor, dyspnea,
urinary frequency, and constipation, it may be common to
quickly assume a diagnosis of uterine fibroids. On the other
hand, some unusual or atypical symptoms like acute abdominal pain, and pain between periods or internal bleeding do
occur in patients with a well-established diagnosis of uterine
fibroids that may be ignored, leading to a misdiagnosis and
further delay in medical management. Here, we would like to
discuss these symptoms in detail.
2. Pathogenesis
3.1. Compression symptoms
The precise cause of myoma development and growth is not
fully understood, but molecular studies have revealed that each
tumor is unicellular in origin and about 40% have nonrandom
and tumor-specific chromosomal abnormalities that may affect
growth rates.10 In addition, women with a positive family
history of myomas have a 1.5- to 3.5-fold higher risk of
developing similar lesions than those women without a family
history.8 African-American women have a two- to 9-fold
greater likelihood of developing myomas than Caucasian
women.11 All evidence supports an ethnic or genetic predisposition for the occurrence of myomas.
The importance of steroid hormones in the pathogenesis of
myomas is supported by the observation that myomas are
never found in preadolescent girls, that the prevalence of
myomas increases throughout the reproductive years, peaking
in the fifth decade, and that their prevalence is markedly
reduced after menopause. In addition, early age at menarche
and obesity, which are associated with a greater exposure to
endogenous estrogens, contribute to a two-fold increased risk
of uterine myomas. By contrast, increased parity and cigarette
smoking, which might decrease endogenous estrogen levels,
showed a nearly 50% reduced risk compared with nulliparous
women and nonsmoking women, respectively.10 Myomas are
reported to show higher concentrations of estrogen receptors,
progesterone receptors, and aromatase, an enzyme important
for local estrogen production, than normal myometrium.12
However, the relationship between orally administered
hormones and the prevalence of uterine myomas is controversial. For example, the use of oral pills seems to be unrelated
to the development of uterine myomas, and low-dose pills do
not stimulate the growth of existing uterine myomas in most
women.10 However, the use of progestins, such as depot
medroxyprogesterone acetate, may reduce the risk of developing uterine myomas.13 On the other hand, agents which are
modified from the original form of progesterone, for example,
selective progesterone receptor modulators (SPRM), might
also be involved in the growth of uterine myomas,14,15 since
SPRM has been tested in recent clinical trials.16,17
3. Typical symptoms of uterine myomas
The symptoms of this disease are mainly related to the
physical changes in the pelvic organs arising from the onset of
this tumor and may present in women of any age but usually in
women between menarche and menopause.18,19
The symptoms related to myomas are primarily those of
physical changes to the pelvic organs due to the presence of an
enlarging mass.1,3,4 These symptoms, similar to those of an
enlarged pregnant uterus, may lead to a suspicion of conception
in some premenstrual victims. Pelvic heaviness or a dull aching
sensation, such as that experienced by women in early pregnancy, might be the only symptom of this slow-growing tumor.
Increased urinary frequency and urgency can also develop,
especially when these tumors arise from the anterior wall of the
uterus. In addition, these symptoms might worsen with the onset
of menses, thereby aggravating menses-related symptoms.3
3.2. Menses-related symptoms
Abnormal menstruation, including excess or prolonged
bleeding, is believed to be the most common symptom and is
experienced by about 30% of women with myomas.20
However, the most common menses-related symptom is
menorrhagia. Since the exact causeeeffect relationship
between myoma and excess menstrual bleeding is poorly
understood, women with this disease are more likely to report
gushing-type bleeding, even if the uterine myoma was small.
Controversy exists as to whether a submucous myoma is
associated with a higher incidence of heavy bleeding.21 In
women who do not seek gynecological care, leiomyomarelated menstruation problems are often neglected.22 Blood
vessels in uterine fibroids are abnormal in distribution and
appearance, suggesting that altered angiogenesis might be the
cause of menstrual disturbance.23 Nonetheless, the old theory
of an expanded surface area of the endometrium has been
disproven,22 and local compression of veins in the interior
uterine layers was proposed as a possible mechanism.24
Other symptoms of anemia, including pallor, fainting,
dyspnea, and fatigue might result from massive blood loss
whenever menses begins, and could worsen during menses. In
addition to the general discomfort caused by symptoms of
acute and colic pain during menses, these symptoms
substantially interfere with the health and life quality of
women, often leading to surgical intervention.
3.3. Pain-related symptoms
About one-third of women with myomas experience pelvic
pain. Dysmenorrhea seems less common in this group of
W.-H. Su et al. / Journal of the Chinese Medical Association 75 (2012) 487e493
patients than in those with adenomyosis.25e27 Secondary
dysmenorrhea is still one of the most frequently heard
complaints related to fibroids. However, in a noncare-seeking
population study, dyspareunia and noncyclic pelvic pain, but
not dysmenorrhea, increased in severity with the presence of
uterine fibroids.28
Pain-related symptom varies in degree, from dull pelvic
pain to severe and colic pain. However, intractable pelvic pain
noticed during the intermenstrual period is unusual. The
changed status of the uterine myomas with a compromised
blood supply often results in painful symptoms. For example,
cases of myoma degeneration or torsion of pedunculated
myomas can be found in the literature.29,30 Torsion of
a pedunculated uterine myoma represents a surgical emergency, with expedited intervention necessary to improve
symptoms and avoid consumptive coagulopathy.29 Severe pain
accompanied with fever is another warning sign of possible
red degeneration of myoma during pregnancy.30
3.4. Subfertility status
Since myomas have such a high incidence, they may
sometimes be the only identifiable abnormality after a detailed
infertility investigation. In these situations, the focus remains
on the position of the tumor. Evidence suggests that only
submucous myomas appear to interfere with fertility,31 and
only very rarely do myomas affect the pregnancy outcome,
such as by recurrent abortion or obstructed labor.19 Therefore,
surgical intervention should be the last option to be considered
for an infertile patient with a uterine myoma. Though full-term
pregnancy rates of 40%e50% have been reported following
a myomectomy, the success of such an operation depends on
a lot of other confounding factors that affect the couple’s
fertility.32,33
3.5. Cosmetic problem
Though the occurrence of uterine myoma seems correlated
with higher body mass index in premenstrual women, an
increase in abdominal girth without appreciable change in
body weight tends to bother slender patients more than others.
A protruding mass from an otherwise flat abdominal wall
compromises their body image and encourages these patients
to seek help, though no other symptoms are noticed.
4. Atypical symptoms of uterine myomas
Other atypical or unusual presentations of this disease
might be encountered in well-established or new cases, and
represent either the existence of a special form of leiomyomatosis or a changed status of this disease; immediate treatment may be necessary.34
4.1. Uncommon compression-related symptoms
Other atypical compression symptoms are also found in
women with uterine myomas. For example, the masses arising
489
from the posterior wall might cause rectal symptoms like
tenesmus, back pain or constipation, though they appear to be
less common. These symptoms might worsen when menses
comes and can aggravate the symptoms related to menses.3
Flank pain, especially on the right side, is an atypical
symptom of the uterine myoma, and is due to compression of
the ureter, although its incidence is far below our expectation.
Transient relief after lying on the opposite side might be
reliable evidence of the existence of this compression.35
4.2. Cardiac symptom and atypical symptoms secondary
to vascular involvement or dissemination
Cardiac symptoms like chest pain might occur in a rare
condition known as intravenous leiomyomatosis.36 Benign
smooth muscle fibers invade the venous channels of the pelvis
and, even though they grow slowly, they might grow into the
vena cava and right heart and cause these unusual symptoms.
Surgical intervention with primary excision and follow-up
antiestrogen therapy for prevention is recommended to treat
these cases. This mechanism might explain the occurrence of
distant myomas with more unusual symptoms like urination
difficulty and urethral obstruction from a leiomyoma of
the bladder, and visual impairment from an orbital
leiomyoma.37e40
4.3. Abdominal symptoms mimicking pelvic
carcinomatosis
Multiple pelvic growths with various compression symptoms with or without ascites will raise the suspicion of pelvic
carcinomatosis. However, another rare benign condition,
leiomyomatosis peritonealis disseminata (LPD), which is
caused by the direct seeding of myomatous cells on the surface
of the peritoneum, could be the possible diagnosis. It is
believed that LPD is associated with recent pregnancy or
previous operation for myoma using a mocellator.41,42
4.4. Dyspnea
Dyspnea with pleural effusion, pelvic mass and ascites
mimicking Meigs syndrome is another rare carcinoma-like
presentation of this disease. Leiomyoma arising from the
uterus,43 ovary,44 or fallopian tube45 might be the only
diagnosis.
4.5. Pruritus
Pruritus with multiple raised skin lesions on the limbs is
unusual and is the only symptom of piloleiomyoma.46
However, the coexistence of uterine myoma and cutaneous
leiomyoma nodules might be the initial symptom of piloleiomyoma. Renal evaluation should be done first in cases of
piloleiomyoma, before conservative follow-up is recommended, because piloleiomyoma is often accompanied with
renal carcinoma.
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W.-H. Su et al. / Journal of the Chinese Medical Association 75 (2012) 487e493
4.6. Hiccup or internal bleeding
Unusual symptoms like hiccup or internal bleeding might
result from a subserosal myoma with rapid growth. While the
former might be irritation of the vagus or phrenic nerve and
deserve a more thorough evaluation before operation,47,48 the
latter might be due to rupture of superficial vessels and
deserve prompt diagnosis and emergency management.49,50
4.7. Vaginal protruding mass or uterine inversion
Sometimes submucous myoma induces uterine inversion,
which results in hemorrhage.51 If this rapid growth occurs in
a menopausal woman, then malignant change must be highly
suspected,52 and imaging might help to distinguish benign and
malignant uterine masses.53,54
5. Symptoms and medical treatment
If menstruation symptoms are the only patient complaint,
medical treatment can be prescribed first. At present, many
effective drugs are available in routine clinical practice,
though some are still under investigation.8 Tranexamic acid,
nonsteroidal anti-inflammatory drugs, high-dose estrogen,
progestin, gonadotropin-releasing hormone agonists (GnRH
agonists),55,56 contraceptives or levonorgestrel-releasing
intrauterine system have all been proven to reduce menstrual
bleeding and restore the hemoglobin level.23 Spontaneous
expulsion of a submucosal myoma after GnRH agonist treatment has even been reported.57 Mifepristone, danazol, and
tamoxifen show modest overall benefit, but they need more
thorough evaluation.8,16,17,58 Therefore, medical therapy
seems a reasonable option for women with symptomatic
myomas who prefer non-surgical treatment, are concerned
about fertility preservation, or expect a less aggressive operation after shrinkage of the uterine volume.3
SPRMs have been developed since the late 70s when
mifepristone was first described.15 SPRMs act through nuclear
progesterone receptors (two isoforms, including progesterone
receptor A and progesterone receptor B) and can have agonist,
antagonist, or mixed agonist antagonist actions, depending on
the cell and tissue.59 However, the mechanisms underlying
some of these effects remain unknown, although they follow
the rule of nuclear receptors. Following the binding of the
ligand to the specific ligand-binding domain, nuclear receptors
interact with the transcriptional machinery through a large
molecular complex including coregulators, such as coactivators, and corepressors.59 SPRMs have been used, in
particular, for the inhibition of ovulation, the transformation of
endometrial morphology, and the apoptosis of myoma cells.59
Mifepristone has unique major antagonist properties which are
conducive to its use for pregnancy termination.60,61 Ulipristal
acetate has been marketed in 2009 for emergency contraception.14 The oral SPRM, ulipristal, proved highly effective as
a treatment for symptomatic uterine fibroids, according to two
randomized studies published in the New England Journal of
Medicine.16,17 In both studies, this universal SPRM rapidly
reduced excessive bleeding, and reduced the size of uterine
fibroids.
The Uterine Fibroid Symptoms and Quality of Life (UFSQOL) questionnaire, which consists of eight symptom questions and 29 health-related quality of life questions with six
subscales, was proposed as a useful tool in evaluating the
change in symptoms after follow-up,62 medical treatment,63 or
even after an operation.64 An electronic version of the questionnaire called the Fibroid Symptom Diary (FSD), containing
eight items that assess bleeding severity, menstrual cramping,
and fibroid-related fatigue, with three pain-specific items
(i.e., abdominal pain, low back pain, and pain during intercourse), is another option for assessing changes in symptoms
and treatment benefit.65
6. Symptoms and operation
Persistent symptoms like pain or menorrhagia after medical
treatment are classic indications that surgical intervention may
be necessary. The choice between a myomectomy and
hysterectomy is usually determined by the patient’s age,
parity, and, most important, future reproductive plans.
Hysterectomy addresses more than 90% of symptoms, and
might be an appropriate back-up plan for myomectomy, which
treats about 80% of symptoms. However, the fact that onefourth of patients suffered from recurring symptoms after
myomectomy and received a follow-up hysterectomy within
20 years makes the choice more difficult for a patient with
a complete family.5 Since the value of myomectomy for subfertile patients is not well-established, the possible damage
and adhesion related to the adverse reproductive outcome after
operation should be emphasized before operation and prevented during surgery. For this reason, a variety of options,
which further enhance the myomectomy procedure have been
proposed in recent years. Instead of laparotomy, laparoscopy
with careful multilayer closure and the use of antiadhesive
barriers has been recommended as the surgery of choice.66e69
Vaginal myomectomy is considered a feasible and safe
surgical procedure, with low morbidity and a short hospital
stay.70 A hysteroscopic myomectomy via the cervical canal is
a reasonable choice for a submucous myoma.71 Magnetic
resonance imaging-guided focused ultrasound surgery
(MRIgFUS) is another noninvasive treatment for symptomatic
uterine myomas.31 Sustained symptom relief after this operation relies on careful selection of patients.72 Uterine embolization is an option with substantial symptom improvement
noted for most patients, and with hysterectomy required in
only 2.9% of patients in the first 12 months after therapy.73,74
Uterine artery embolization (UAE) reduced fibroid volume
and provided significant relief of menorrhagia.75e77 However,
a smaller baseline leiomyoma size and a submucosal location
seemed more likely to result in a positive imaging outcome
and symptom relief after UAE.76 Combined with laparoscopic
myomectomy (LM), UAE demonstrated superiority in treating
recurrent symptomatic myomas with less blood loss and
recurrence rate.78e81 Therefore, uterine artery occlusion
(UAO) combined with myomectomy was considered a good
W.-H. Su et al. / Journal of the Chinese Medical Association 75 (2012) 487e493
option for treating pregnant women with uterine leiomyomas
who are undergoing Cesarean section, with increased operative time but similar surgical morbidity.82
Another similar option is laparoscopic uterine vessel
occlusion (LUVO), which was believed to be more effective in
treating symptomatic fibroids than UAO.83e86 In fact, the
uterine vessel occlusion (which some papers call uterine artery
occlusion) procedure can be further classified into two
different strategies, based on the literature.83e86 One is UAO
alone, without simultaneous blockage of the uterine vessels
and the anastomotic sites between the uterine vessels and the
ovarian vessels. The other is uterine artery occlusion with
simultaneous blockage of the uterine vessels and the anastomotic sites between the uterine vessels and the ovarian vessels
(UVO). However, women treated with UVO were associated
with a greater risk of a significant increase in the folliclestimulating hormone (FSH) level during the first month after
operation than those treated with UAO.85 Symptoms related to
the diminished ovarian function should be followed after
UVO.86 When combined with LM, UVO was more effective,
with a longer period of symptom control in most women with
symptomatic myomas and prevented reoperation in most
patients.78e81
Ultra minilaparotomy (UMLT), a new procedure, resulted
in a better recovery than conventional laparotomy when
treating uncomplicated uterine myomas, but with a similar rate
of symptom relief, especially for uterine fibroids less than
8 cm in size and fewer than five in number.6,32,33 When
compared to the laparoscopic approach for UVO procedure
(LUVO), the UMLT approach for UVO procedure is also an
acceptable option with similar therapeutic outcomes, although
LUVO might yield a faster recovery. Since LUVO and UMLT
myomectomy combination might require less operation time
and achieve a higher success rate, this approach might be
a more reasonable choice in the management of symptomatic
uterine fibroid than the combination of LUVO and LM.81
Because of its reduced impact on ovarian function,
combined LUAO and UMLT myomectomy seem to be
a feasible option for women who wish to preserve the uterus.
The best choice of operation for a subfertile woman or those
who want to maintain fertility remains a subject of debate and
requires further evaluation, although LM is suggested and
recommended in many studies.4
7. Symptoms and differential diagnosis
After an inquiry about symptoms, the diagnosis of uterine
myomas may be provisionally made by palpating an enlarged,
firm, irregular uterus during pelvic examination. However,
a distorted uterine cervix alignment that is difficult to expose
during speculum manipulation might also raise the suspicion
of a uterine mass. The establishment of the diagnosis of
uterine myomas requires the assistance of special tools. For
example, imaging studies, especially ultrasound through the
vaginal route (transvaginal ultrasound), will help physicians
make a differential diagnosis with other benign or malignant
uterine masses. Sometimes, a more powerful tool, such as
491
color Doppler ultrasound, computed tomography, magnetic
resonance imaging, or positron emission tomography, may
help to distinguish benign uterine masses from malignant
tumors.
In conclusion, familiarity with the typical and atypical
clinical presentations of women with uterine myomas aids the
discussion between the physician and the woman. Although
tumor size is regarded as an important factor in deciding the
treatment regimen, symptoms and signs might have a greater
effect on the choice of management. Because of the extremely
low incidence of malignant change, asymptomatic patients
require only routine follow-up between 6 months and
12 months regularly, although the recommended interval is
still inconclusive. To establish the best policy for the
management of women with uterine myomas, a detailed study
of symptoms and/or signs is encouraged.
Acknowledgments
This work was supported in part by grants from Veterans
General Hospitals University System of Taiwan Joint Research
Program (VGHUST99-G4), Taipei Veterans General Hospital
(V99C1-085, V100C-054, V101C1-128, V101E4-004,
V101E5-006), and the National Science Council (NSC 992314-B-010-009-MY3), Taiwan.
References
1. Gupta S, Jose J, Manyonda I. Clinical presentation of fibroids. Best Pract
Res Clin Obstet Gynaecol 2008;22:615e26.
2. Zhao SZ, Wong JM, Arguelles LM. Hospitalization costs associated with
leiomyoma. Clin Ther 1999;21:563e75.
3. Cheng MH, Chao HT, Wang PH. Medical treatment for uterine myomas.
Taiwan J Obstet Gynecol 2008;47:18e23.
4. Horng HC, Wen KC, Su WH, Chen CS, Wang PH. Review of myomectomy. Taiwan J Obstet Gynecol 2012;51:7e11.
5. Tsai HW, Chen YJ, Ho CM, Hseu SS, Chao KC, Tsai SK, et al. Maneuvers
to decrease laparoscopy-induced shoulder and upper abdominal pain:
a randomized controlled study. Arch Surgery 2011;146:1360e6.
6. Wen KC, Sung PL, Lee WL, Li YT, Su WH, Wang PH. Myomectomy for
uterine myomas through ultramini-laparotomy. J Obstet Gynaecol Res
2011;37:383e92.
7. Chen YJ, Wang PH, Ocampo EJ, Twu NF, Yen MS, Chao KC. Single-port
compared with conventional laparoscopic-assisted vaginal hysterectomy:
a randomized controlled trial. Obstet Gynecol 2011;117:906e12.
8. Cheng MH, Wang PH. Uterine myoma: a condition amenable to medical
therapy? Expert Opin Emerg Drugs 2008;13:119e33.
9. Lasmar RB, Xinmei Z, Indman PD, Celeste RK, Di Spiezio Sardo A.
Feasibility of a new system of classification of submucous myomas:
a multicenter study. Fertil Steril 2011;95:2073e7.
10. Van Voorhis B. A 41-year-old woman with menorrhagia, anemia, and
fibroids: review of treatment of uterine fibroids. J Am Med Assoc
2009;301:82e93.
11. Ligon A, Morton CC. Leiomyomata: heritability and cytogenetic studies.
Hum Reprod Update 2001;7:8e14.
12. Tsui KH, Wang PH, Chen CK, Chen YJ, Chiou SH, Sung YJ, et al. Nonclassical estrogen receptors action on human fibroblasts. Taiwan J Obstet
Gynecol 2011;50:474e8.
13. Lumbiganon P, Rugpao S, Phandhu-fung S, Laopaiboon M,
Vudhikamraksa N, Werawatakul Y. Protective effect of depotmedroxyprogesterone acetate on surgically treated uterine leiomyomas:
492
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
W.-H. Su et al. / Journal of the Chinese Medical Association 75 (2012) 487e493
a multicentre caseecontrol study. Br J Obstet Gynaecol 1996;103:
909e14.
Stewart EA. Uterine fibroids and evidence-based medicineenot an
oxymoron. N Engl J Med 2012;366:471e3.
Bouchard P, Chabbert-Buffet N, Fauser BC. Selective progesterone
receptor modulators in reproductive medicine: pharmacology, clinical
efficacy and safety. Fertil Steril 2011;96:1175e89.
Donnez J, Tomaszewski J, Vázquez F, Bouchard P, Lemieszczuk B,
Baró F, et al. PEARL II Study Group. Ulipristal acetate versus leuprolide
acetate for uterine fibroids. N Engl J Med 2012;366:421e32.
Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF,
Ivanova T, et al. PEARL I Study Group. Ulipristal acetate versus placebo
for fibroid treatment before surgery. N Engl J Med 2012;366:409e20.
Laughlin SK, Herring AH, Savitz DA, Olshan AF, Fielding JR,
Hartmmann KE, et al. Pregnancy-related fibroid reduction. Fertil Steril
2010;94:2421e3.
Shavell VI, Thakur M, Sawant A, Kruger ML, Jones TB, Singh M, et al.
Adverse obstetric outcomes associated with sonographically identified
large uterine fibroids. Fertil Steril 2012;97:107e10.
Yang JH, Chen MJ, Chen CD, Chen CL, Ho HN, Yang YS. Impact of submucous myoma on the severity of anemia. Fertil Steril 2011;95. 1769e72.e1.
Lee KC, Haung CY, Wang PH. Parasitic peritoneal leiomyomatosis
mimicking intra-abdominal abscess with hematoma. Taiwan J Obstet
Gynecol 2012;51:115e6.
Murat Naki M, Tekcan C, Ozcan N, Cebi M. Levonorgestrel-releasing
intrauterine device insertion ameliorates leiomyoma-dependent menorrhagia among women of reproductive age without a significant regression
in the uterine and leiomyoma volumes. Fertil Steril 2010;94:371e4.
Hickey M, Fraser IS. Clinical implications of disturbances of uterine
vascular morphology and function. Baillieres Best Pract Res Clin Obstet
Gynaecol 2000;14:937e51.
Cheng MH, Chao HT, Wang PH. Unusual clinical presentation of uterine
myomas. Taiwan J Obstet Gynecol 2007;46:323e4.
Wang PH, Liu WM, Fuh JL, Cheng MH, Chao HT. Comparison of surgery
alone and combined surgical-medical treatment in the management of
symptomatic uterine adenomyoma. Fertil Steril 2009;92:876e85.
Chen ML, Lee KC, Yang CT, Hung KH, Wu MH. Simultaneous laparoscopy for endometrioitic women undergoing in vitro fertilization.
Taiwan J Obstet Gynecol 2012;51:66e70.
Huang BS, Seio KM, Tsui KH, Huang CY, Lu YF, Wang PH. Fertility
outcome of infertile women with adenomyosis treated with the combination of a conservative microsurgical technique and GnRH-agonist: longterm follow-up in a series of 9 patients. Taiwan J Obstet Gynecol
2012;51:212e6.
Learman LA, Nakagawa S, Gregorich SE, Jackson RA, Jacoby A,
Kuppermann M. Success of uterus-preserving treatments for abnormal
uterine bleeding, chronic pelvic pain, and symptomatic fibroids: age and
bridges to menopause. Am J Obstet Gynecol 2011;204:272.e1e7.
Tsai YJ, Yeat SK, Jeng CJ, Chen SC. Torsion of a uterine leiomyoma.
Taiwan J Obstet Gynecol 2006;45:333e5.
Lee WL, Chiu LM, Wang PH, Chao HT, Yuan CC, Ng HT. Fever of
unknown origin in the puerperium. A case report. J Reprod Med
1998;43:149e52.
Bouwsma EV, Gorny KR, Hesley GK, Jensen JR, Peterson LG,
Stewart EA. Magnetic resonance-guided focused ultrasound surgery for
leiomyoma-associated infertility. Fertil Steril 2011;96:e9e12.
Wang PH, Liu WM, Fuh JL, Chao HT, Yuan CC, Chao KC. Comparison
of ultramini-laparotomy for myomectomy through midline vertical incision or modified Pfannenstiel incision–a prospective short-term follow-up.
Fertil Steril 2009;91:1945e50.
Wen KC, Sung PL, Chao KC, Lee WL, Liu WM, Wang PH. A prospective
short-term evaluation of uterine leiomyomas treated by myomectomy
through conventional laparotomy or ultramini-laparotomy. Fertil Steril
2008;90:2361e6.
Du J, Zhao X, Guo D, Li H, Sun B. Intravenous leiomyomatosis of the
uterus: a clinicopathologic study of 18 cases, with emphasis on early
diagnosis and appropriate treatment strategies. Hum Pathol 2011;42:
1240e6.
35. Wu KY, Yen CF, Huang KG. Obstructive uropathy with acute pyelonephritis induced by a voluminous postmenopausal uterine leiomyoma.
Taiwan J Obstet Gynecol 2009;48:82e3.
36. Lou YF, Shi XP, Song ZZ. Intravenous leiomyomatosis of the uterus with
extension to the right heart. Cardiovasc Ultrasound 2011;9:25.
37. Wang HS, Huang CH, Chen MT, Wu WJ. Bilateral ureteral leiomyoma
with bilateral ureteropelvic junction obstruction. Kaohsiung J Med Sci
2010;26:150e3.
38. Baumann BM, Jarecki J. Obstructed uterus and kidneys. J Emerg Med
2010;38:497e8.
39. Ding DC, Hwang KS. Female acute urinary retention caused by anterior
deflection of the cervix which was augmented by a uterine myoma.
Taiwan J Obstet Gynecol 2008;47:350e1.
40. Zhang CH. [Analysis of 24 cases of misdiagnosed orbital tumors with
visual impairment as the presenting symptom]. Zhonghua Yan Ke Za Zhi
1993;29:238e40.
41. Karas‚ahin KE, Gezginç K, Ulubay M, Bas‚er I. Disseminated peritoneal
leiomyomatosis. Taiwan J Obstet Gynecol 2008;47:123e5.
42. Cucinella G, Granese R, Calagna G, Somigliana E, Perino A. Parasitic
myomas after laparoscopic surgery: an emerging complication in the use
of morcellator? Description of four cases. Fertil Steril 2011;96:e90e6.
43. Hsu WCTP, Chow SN, Huang SC. Pseudo-Meigs’ syndrome with
degenerative uterine leiomyoma in pregnancy. Taiwan J Obstet Gynecol
2004;43:161e4.
44. Hsiao CH, Wang HC, Chang SL. Ovarian leiomyoma in a pregnant
woman. Taiwan J Obstet Gynecol 2007;46:311e3.
45. Yang CC, Wen KC, Chen P, Wang PH. Primary leiomyoma of the fallopian
tube: preoperative ultrasound findings. J Chin Med Assoc 2007;70:80e3.
46. Sadeghian G, Ziaei H. Pruritus as an unusual symptom in multiple piloleiomyoma. Skinmed 2011;9:129e30.
47. Cheng MH, Twu NF, Fuh JL, Wang PH. Intractable hiccups of as an
unusual presentation of a uterine leiomyoma: a case report. J Reprod Med
2005;50:954e6.
48. Wang PH, Fuh JL. Hiccups-functional or pathological? J Chin Med Assoc
2011;74:179.
49. Su WH, Cheung SM, Chang SP, Lee WL. Internal bleeding from
a ruptured serosal vein covering the myoma surface mimicking upper
gastrointestinal bleeding. Taiwan J Obstet Gynecol 2008;47:352e4.
50. Horowitz E, Dekel A, Feldberg D, Rabinerson D. Massive hemoperitoneum due to rupture of an artery overlying a uterine leiomyoma: a case
report. Acta Obstet Gynecol Scand 2005;84:408e9.
51. Chen YL, Chen CA, Cheng WF, Huang CY, Chang CY, Lee CN, et al.
Submucous myoma induces uterine inversion. Taiwan J Obstet Gynecol
2006;45:159e61.
52. Wang PH, Chao HT, Lee WL. Rationale of myomectomy for perimenopausal women. Maturitas 2007;58:406e7.
53. Lee WL, Yuan CC, Wang PH. Positron emission tomography and uterine
leiomyomas. Gyn Oncol 2007;107:593e4.
54. Sung PL, Chen YJ, Liu RS, Shieh HT, Wang PH, Yen MS, et al. Wholebody positron emission tomography with 18F-fluorodeoxyglucose is an
effective method to detect extra-pelvic recurrence in uterine sarcomas.
Eur J Gynaecol Oncol 2008;29:246e51.
55. Wang PH, Lee WL, Cheng MH, Yen MS, Chao KC, Chao HT. Use of
a gonadotropin-releasing hormone agonist to manage perimenopausal
women with symptomatic uterine myomas. Taiwan J Obstet Gynecol
2009;48:133e7.
56. Wang PH, Su WH, Sheu BC, Liu WM. Adenomyosis and its variance: adenomyoma and female fertility. Taiwan J Obstet Gynecol 2009;48:232e8.
57. Wen L, Tseng JY, Wang PH. Vaginal expulsion of a submucosal myoma
during treatment with long-acting gonadotropin-releasing hormone
agonist. Taiwan J Obstet Gynecol 2006;45:173e5.
58. Wang PH, Chao HT. Reconsideration of tamoxifen use for breast cancer.
Taiwan J Obstet Gynecol 2007;46:93e5.
59. Chabbert-Buffet N, Pintiaux A, Bouchard P. The immninent dawn of
SPRMs in obstetrics and gynecology. Mol Cell Endocrinol
2012;358:232e43.
60. Wang PH, Yang MJ. Medical abortion for an early pregnancy. Taiwan J
Obstet Gynecol 2011;50:1.
W.-H. Su et al. / Journal of the Chinese Medical Association 75 (2012) 487e493
61. Li YT, Hsieh CH, Hou GQ, Chen TH, Chu YC, Lin TC, et al. Simultaneous use of mifepristone and misoprostol for early pregnancy termination. Taiwan J Obstet Gynecol 2011;50:11e4.
62. Spies JB, Coyne K, Guaou Guaou N, Boyle D, Skyrnarz-Murphy K,
Gonzalves SM. The UFS-QOL, a new disease-specific symptom and
health-related quality of life questionnaire for leiomyomata. Obstet
Gynecol 2002;99:290e300.
63. Harding G, Coyne KS, Thompson CL, Spies JB. The responsiveness of the
uterine fibroid symptom and health-related quality of life questionnaire
(UFS-QOL). Health Qual Life Outcomes 2008;6:99.
64. de Melo FC, Diacoyannis L, Moll A, Tovar-Moll F. Reduction by 98% in
uterine myoma volume associated with significant symptom relief after
peripheral treatment with magnetic resonance imaging-guided focused
ultrasound surgery. J Minim Invasive Gynecol 2009;16:501e3.
65. Deal LS, Williams VS, Fehnel SE. Development of an electronic daily
uterine fibroid symptom diary. Patient 2011;4:31e44.
66. Su H, Han CM, Wang CJ, Lee CL, Soong YK. Comparison of the efficacy
of the pulsed bipolar system and conventional electrosurgery in laparoscopic myomectomy - a retrospective matched control study. Taiwan J
Obstet Gynecol 2011;50:25e8.
67. Yen MS, Chao KC, Wang PH. Laparoscopic myomectomy. Taiwan J
Obstet Gynecol 2010;49:392e3.
68. Wen KC, Chen YJ, Sung BL, Wang PH. Comparing uterine fibroids
treated by myomectomy through traditional laparotomy (LT) and two
modified approaches: ultraminilaparotomy (UMLT) and laparoscopicallyassisted ultraminilaparotomy (LA-UMLT). Am J Obstet Gynecol
2010;202:e1e8.
69. Fossum GT, Silverberg KM, Miller CE, Diamond MP, Holmdahl L.
Gynecologic use of Sepraspray Adhesion Barrier for reduction of adhesion development after laparoscopic myomectomy: a pilot study. Fertil
Steril 2011;96:487e91.
70. Parker WH. Uterine myomas: management. Fertil Steril 2007;88:255e71.
71. Casadio P, Youssef AM, Spagnolo E, Rizzo MA, Talamo MR, De
Angelis D, et al. Should the myometrial free margin still be considered
a limiting factor for hysteroscopic resection of submucous fibroids? A
possible answer to an old question. Fertil Steril 2011;95:1764e1768.e1.
72. Chen SY, Huang SC, Sheu BC, Chang DY, Chou LY, Hsu WC, et al.
Simultaneous enucleation and in situ morcellation of myomas in laparoscopic myomectomy. Taiwan J Obstet Gynecol 2010;49:279e84.
73. Homer H, Saridogan E. Uterine artery embolization for fibroids is associated with an increased risk of miscarriage. Fertil Steril 2010;94:324e30.
74. You JH, Sahota DS, Yuen PM. Uterine artery embolization, hysterectomy,
or myomectomy for symptomatic uterine fibroids: a cost-utility analysis.
Fertil Steril 2009;91:580e8.
493
75. Goodwin SC, Bradley LD, Lipman JC, Stewart EA, Nosher JL,
Sterling KM, et al. UAE versus Myomectomy Study Group. Uterine artery
embolization versus myomectomy: a multicenter comparative study. Fertil
Steril 2006;85:14e21.
76. Pron G, Bennett J, Common A, Wall J, Asch M, Sniderman KOntario
Uterine Fibroid Embolization Collaboration Group. The Ontario Uterine
Fibroid Embolization Trial. Part 2. Uterine fibroid reduction and symptom
relief after uterine artery embolization for fibroids. Fertil Steril
2003;79:120e7.
77. Pron G, Cohen M, Soucie J, Garvin G, Vanderburgh L, Bell SOntario
Uterine Fibroid Embolization Collaboration Group. The Ontario Uterine
Fibroid Embolization Trial. Part 1. Baseline patient characteristics, fibroid
burden, and impact on life. Fertil Steril 2003;79:112e9.
78. Liu L, Li Y, Xu H, Chen Y, Zhang G, Liang Z. Laparoscopic transient
uterine artery occlusion and myomectomy for symptomatic uterine
myoma. Fertil Steril 2011;95:254e8.
79. Bae JH, Chong GO, Seong WJ, Hong DG, Lee YS. Benefit of uterine
artery ligation in laparoscopic myomectomy. Fertil Steril 2011;95:775e8.
80. Wang PH, Liu WM, Fuh JL, Chao HT, Yuan CC, Chao KC. Symptomatic
myoma treated with laparoscopic uterine vessel occlusion and subsequent
immediate myomectomy: which is the optimal surgical approach? Fertil
Steril 2009;92:762e9.
81. Liu WM, Wang PH, Chou CS, Tang WL, Wang IT, Tzeng CR. Efficacy of
combined laparoscopic uterine artery occlusion and myomectomy via
minilaparotomy in the treatment of recurrent uterine myomas. Fertil Steril
2007;87:356e61.
82. Lin JY, Lee WL, Wang PH, Lai MJ, Chang WH, Liu WM. Uterine artery
occlusion and myomectomy for treatment of pregnant women with uterine
leiomyomas who are undergoing Cesarean section. J Obstet Gynaecol Res
2010;36:284e90.
83. Lee WL, Liu WM, Cheng MH, Chao HT, Fuh JL, Wang PH. Uterine
vascular occlusion for leiomyomas: laparoscopy versus laparotomy. J
Minim Invasive Gynecol 2009;16:562e8.
84. Wang PH, Liu WM, Fuh JL, Chao HT, Yuan CC, Chao KC. Laparoscopic
uterine vessel occlusion in the management of women with symptomatic
uterine myomas with and without adding laparoscopic myomectomy: 4year results. J Minimal Invasive Gynecol 2008;15:712e8.
85. Lee WL, Liu WM, Fuh JL, Tsai YC, Shih CC, Wang PH. Basal folliclestimulating hormone level changes after different types of uterine vessel
occlusion in the management of uterine fibroids. Fertil Steril
2010;94:2286e90.
86. Lee WL, Liu WM, Fuh JL, Tsai YC, Shih CC, Wang PH. Use of uterine
vessel occlusion in the management of uterine myomas: two different
approaches. Fertil Steril 2010;94:1875e81.