Review Article

Adenomyosis: A Clinical Review of a Challenging

Gynecologic Condition
Jennifer Struble, MD, Shannon Reid, MD, and Mohamed A. Bedaiwy, MD, PhD*
From the Department of Obstetrics and Gynecology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada (Dr. Struble), Division of Reproductive
Endocrinology and Infertility, University of British Columbia, Vancouver, British Columbia, Canada (Dr. Bedaiwy), and Department of Obstetrics and
Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada (Drs. Reid and Bedaiwy).

ABSTRACT Adenomyosis is a heterogenous gynecologic condition. Patients with adenomyosis can have a range of clinical presentations.
The most common presentation of adenomyosis is heavy menstrual bleeding and dysmenorrhea; however, patients can also be
asymptomatic. Currently, there are no standard diagnostic imaging criteria, and choosing the optimal treatment for patients is
challenging. Women with adenomyosis often have other associated gynecologic conditions such as endometriosis or leiomyo-
mas, therefore making the diagnosis and evaluating response to treatment challenging. The objective of this review was to
highlight current clinical information regarding the epidemiology, risk factors, pathogenesis, clinical manifestations, diag-
nosis, imaging findings, and treatment of adenomyosis. Several studies support the theory that adenomyosis results from
invasion of the endometrium into the myometrium, causing alterations in the junctional zone. These changes are commonly
seen on imaging studies such as transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI). The second most
common theory is that adenomyosis results from embryologic-misplaced pluripotent mullerian remnants. Traditionally,
adenomyosis was only diagnosed after hysterectomy; however, studies have shown that a diagnosis can be made with biopsies
at hysteroscopy and laparoscopy. Noninvasive imaging can be used to help guide the differential diagnosis. The most common
findings on 2-dimensional/3-dimensional TVUS and MRI are reviewed. Two-dimensional TVUS and MRI have a respectable
sensitivity and specificity; however, recent studies indicate that 3-dimensional TVUS is superior to 2-dimensional TVUS
for the diagnosis of adenomyosis and may allow for the diagnosis of early-stage disease. Management options for adenomyo-
sis, both medical and surgical, are reviewed. Currently, the only definitive management option for patients is hysterectomy.
Journal of Minimally Invasive Gynecology (2016) 23, 164–185 Ó 2016 Published by Elsevier Inc. on behalf of AAGL.
Keywords: Adenomyosis; Imaging diagnostic criteria
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Adenomyosis is identified by uterine enlargement
secondary to areas of the endometrium, both the endome-
trial glands and stroma, located deep within the myome-
trium. These areas cause hyperplasia and hypertrophy of
the surrounding myometrium and clinically result in an
The authors declare that they have no conflict of interest.
Corresponding author: Mohamed A. Bedaiwy, MD, PhD, Division of
Reproductive Endocrinology and Infertility, Department of Obstetrics and
Gynaecology, Faculty of Medicine, The University of British Columbia,
D415A 4500 Oak Street, Vancouver, BC V6H 3V4 Canada.
E-mail: bedaiwymmm@yahoo.com
Submitted July 31, 2015. Accepted for publication September 19, 2015.
Available at www.sciencedirect.com and www.jmig.org
1553-4650/$ - see front matter Ó 2016 Published by Elsevier Inc. on behalf of AAGL.
http://dx.doi.org/10.1016/j.jmig.2015.09.018
enlarged uterus. Ectopic areas of the endometrium can
be diffusely present throughout the myometrium or
focal, forming a circumscribed nodular collection, an
adenomyoma [1]. Frequently, it is found in the posterior
uterine wall, less commonly in the anterior wall of the
uterus, and infrequently in the cornua or by the cervical
os [1–3].
The degree of disease is determined by symptom severity,
the number of adenomyotic foci, and the distance of the
deepest focus of the ectopic endometrium from the lower
border of the endometrium. Levgur et al [4] created the
following grading system to describe the depth of adenomy-
otic foci: deep (.80%), intermediate (40%–80%), and
superficial (,40%).
Struble et al. Adenomyosis
Prevalence and Incidence
The true incidence of adenomyosis is unknown. Histori-
cally, a diagnosis of adenomyosis was made after hysterec-
tomy in women later in their reproductive years; however,
the use of preoperative imaging has shown that adenomyosis
may also occur in adolescents [5]. The prevalence has been
reported to range from 1% [6] to 70%; this large range is
likely reflective of the lack of standard diagnostic criteria
both by imaging modalities and pathological analyses. There
may also be variations in the literature because of factors such
as potential bias by the pathologist in making the diagnosis
because of knowledge of the patient’s history or differences
in the number of tissue samples examined [7]. The mean fre-
quency of adenomyosis at hysterectomy is between 20% and
30% [8,9]. Cystic adenomyosis may be present in up to 24%
of hysterectomy specimens [10] and is usually found in pa-
tients who are multiparous and over the age of 30 [11]. How-
ever, cystic adenomyosis can also occur in young girls; this
rare form of the disease is called juvenile cystic adenomyosis
[12,13]. Cases of juvenile cystic adenomyosis reported in the
literature are in women younger than 30, which is often used
as a cutoff age to differentiate juvenile cystic adenomyosis
from adult cystic adenomyosis [13]. Case reports describe
young girls presenting with lower abdominal pain and sever
dysmenorrhea refractory to medical treatment [12]. Surgical
management is required for management [12,13], and
complete resection of the cystic adenomyoma can be done
laparoscopically [13]. Juvenile cystic adenomyosis can be
misdiagnosed as a noncommunicating rudimentary horn [12].
Risk Factors
The etiology of adenomyosis is unknown, and various
theories have been proposed. Support for the various theories
comes from commonly identified risk factors such as expo-
sure to estrogen, parity, and prior uterine surgery as summa-
rized in Table 1.
It is thought that increased estrogen exposure may
contribute to the disease. Adenomyosis is most commonly
diagnosed in women during their 40s and 50s, which is in
keeping with clinical practice in which hysterectomies are
common in this age group and adenomyosis is then diagnosed
at histology. However, the increased rate of adenomyosis in
this age group may also be caused by prolonged exposure
to hormones over a woman’s lifetime [1]. A study by Temple-
man et al [15] compared 961 women with a surgically
confirmed diagnosis of adenomyosis with 79 329 women in
their base cohort to serve as the comparison group for adeno-
myosis analyses. They found that increasing parity, early
menarche (%10 years of age), short menstrual cycles (%
24 days in length), elevated body mass index, and oral contra-
ceptive (OCP) use were all statistically significant findings in
patients with adenomyosis, thus suggesting an association
between adenomyosis and estrogen exposure (Table 1)
[15]. It is not clear if contraceptive use is a risk factor for ad-
enomyosis or if women were prescribed an OCP to manage
165
symptoms of dysmenorrhea and heavy menstrual bleeding,
which are common symptoms in patients with adenomyosis
[15]. Parazzini et al [8] studied 707 women, 150 of whom had
adenomyosis, and found similar risk factors for adenomyo-
sis. The frequency of adenomyosis was greater in parous
women (odds ratio [OR] 5 3.1 for 2 or more births) and
women who had a previous spontaneous abortion
(OR 5 1.7); however, they did not find a relationship between
the risk of adenomyosis and the use of OCPs [8]. They also
found that women who smoked tended to be at a decreased
risk (OR 5 0.7 for current smokers) [8]. It is thought that
cigarette smoking alters hormonal metabolism, leading to a
reduced incidence of endometrial abnormalities [18,19].
Additionally, studies have shown increased rates of
adenomyosis in patients who have received tamoxifen
treatment. Tamoxifen binds to selective estrogen receptors
and can stimulate both normal and ectopic endometrial
tissue, fostering the development of adenomyosis [16,17,20].
Parity may be a risk factor because studies have shown an
increased frequency of adenomyosis in multiparous patients
[15]. This may be caused by the elevated levels of estrogen
as described previously or secondary to trophoblast invasion
into the myometrium at implantation [1].
A similar mechanism may occur because of trauma
during uterine surgery, which explains the higher prevalence
of adenomyosis in patients who have had prior uterine
surgery. Levgur et al [4] found that pregnancy termination
was more common in women with adenomyosis alone or
adenomyosis with leiomyomas than in women with leio-
myomas alone and women with neither (p , .01), thus
supporting the theory of endometrial trauma as a cause of
adenomyosis. Parazzini et al [8] also reported an increased
risk of adenomyosis in women who had a history of dilata-
tion and curettage (OR 5 2.2). In a case control study by
Riggs et al [21], they studied 189 women with adenomyosis
and 178 women without adenomyosis. In the group of
women with adenomyosis, they found that the rate of cesar-
ean delivery was 25% compared with 14% in the group
without adenomyosis. They concluded that there is a strong
association between adenomyosis and previous cesarean
section, with an OR of 2.08 [21].
Patients with adenomyosis may also have another disease
process such as leiomyomas or endometriosis. A study by
Taran et al [14] compared women who had pathologically
confirmed diagnoses of leiomyoma (n 5 152) with adeno-
myosis (n 5 76). In this study, women with adenomyosis
were more likely to be younger; have depression, infertility,
dysmenorrhea, dyspareunia, and pelvic pain; and have had
prior uterine surgery [14].
Pathogenesis
A diagnosis of adenomyosis is made when endometrial
glands and stroma are present within the musculature of
the uterus. Although the pathogenesis of adenomyosis is
not known, there are at least 4 proposed theories [1,22] as
166 Journal of Minimally Invasive Gynecology, Vol 23, No 2, February 2016

Table 1
Risk factors

Risk factor Statistical significance Study

Exposure to estrogen
- Age: 40s and 50s
- Average age of women diagnosed
- Early menarche (%10 years of age)
- Short menstrual cycles (%24 days
in length)
46.5 years; average age of women with
adenomyosis and adenomyosis plus
leiomyomas found at hysterectomy n 5 36 [4]
41.0 6 6.4 women with adenomyosis vs
44.4 6 4.8 women with leiomyoma p , .001
[14]
POR 5 1.59; 95% CI, 1.26–2.01
POR 5 1.46; 95% CI, 1.13–1.89
Levgur et al [4]: total n 5 111; adenomyosis
alone: n 5 17; adenomyosis 1 leiomyomas
n 5 19; leiomyomas alone n 5 39, neither
adenomyosis or leiomyomas n 5 36
Taran et al [14] compared women who had
pathologically confirmed diagnoses of
leiomyoma (n 5 152) to adenomyosis (n 5 76)
Templeman et al [15]: surgical diagnosis of
adenomyosis n 5 961 compared with disease-
free women in the same age range n 5 79 495

- Past oral contraceptive use POR 1.54; 95% CI, 1.28–1.85

- Elevated BMI B POR 1.30; 95% CI, 1.11–1.51

B
POR 1.35; 95% CI, 1.12–1.62
B 25–29.9
R30
B

- Tamoxifen [16,17] Adenomyosis was histologically diagnosed in
53.6% of tamoxifen treated patients and 18.2%
of patients who had not had tamoxifen
treatment (p 5 .019) [17]
Patients who had been treated with tamoxifen
were followed; of the patients who had a
hysterectomy for various reasons, 57.1% were
found to have adenomyosis [16]
Parity POR 5 1.80; 95% CI, 1.47–2.20 [15]
OR 5 3.1; 95% CI, 1.7–5.5 in women reporting 2
or more births (p , .01) [8]
- Pregnancy termination OR of women with adenomyosis vs women with
neither adenomyosis nor leiomyomas;
OR 5 4.35; CI, 1.19–15.99;
p 5 .03 [4]
R1 spontaneous abortions vs none; OR 5 1.7;
95% CI, 1.1–2.6 [8]
Prior uterine surgery 60.5% women with adenomyosis vs 26.1% of
women with leiomyoma (p 5 .039) [14]
OR 5 2.2; 95% CI, 1.4–4.0 in women who
reported dilatation and curettage compared
with those who did not [8]
Cohen et al [17] compared 28 postmenopausal
breast cancer patients with tamoxifen and 11
similar patients without tamoxifen treatment
Cohen et al [16]: 14 patients had an abdominal
hysterectomy and bilateral salpingo-
oophorectomy for various reasons; 8 of these
women had adenomyosis
Templeman et al [15]: surgical diagnosis of
adenomyosis n 5 961 compared with disease-
free women in the same age range n 5 79 495
Parazzini et al [8]: 707 women had a
hysterectomy; adenomyosis was identified in
150 subjects (21.2%)8
Levgur et al [4]: total n 5 111; adenomyosis
alone: n 5 17; adenomyosis 1 leiomyomas
n 5 19; leiomyomas alone n 5 39, neither
adenomyosis or leiomyomas n 5 36
Parazzini et al [8]: 707 women had a
hysterectomy; adenomyosis was identified in
150 subjects (21.2%)
Taran et al [14] compared women who had
pathologically confirmed diagnoses of
leiomyoma (n 5 152) with adenomyosis
(n 5 76)
Parazzini et al [8]: 707 women had a
hysterectomy; adenomyosis was identified in
150 subjects (21.2%)

CI 5 confidence interval; OR 5 odds ratio; POR 5 prevalence odds ratio.

summarized in Figure 1. The first theory is that adenomyosis Two other theories that are not as common are that adeno-
results from direct invasion of the endometrium into the my- myosis is caused by invagination of the basalis along the
ometrium. A second theory is that adenomyosis results from intramyometrial lymphatic system and that adenomyosis
embryologic-misplaced pluripotent mullerian remnants. results from bone marrow stem cells [1].
Struble et al. Adenomyosis
Fig. 1
Four identified potential theories of adenomyosis pathogenesis.
Invagination of the Endometrial Basalis
The first and most common theory of the pathogenesis of
adenomyosis is that it develops from the downward invagi-
nation of the endometrial basalis layer into the myometrium.
The mechanisms that stimulate deep myometrial invasion
are unknown but may be because of myometrial weakness
caused by prior pregnancy or surgery [22].
Invagination Caused by Myometrial Weakness
Pregnancy and trauma may cause a disruption of the
myometrial-endometrial border, which causes reactive
hyperplasia of the basalis and penetration into the injured
myometrium [22]. Ostrzenski [23] published a case report
of a patient who had a laparoscopic myomectomy. At the
time of surgery, the endometrium, myometrium, and uterine
serosa were not approximated, and the patient developed
iatrogenic adenomyosis 3 months postoperatively [23].
Invagination Caused by Altered Immunologic Activity
Another potential mechanism that results in invagination
of the basalis endometrium into the myometrium may be
caused by altered immunologic activity at the endometrial-
myometrial interface. It has been shown that macrophage-
activated T and B cells produce antibodies and stimulate
cytokines that alter the junction zone of the endomyome-
trium [24].
Although it is not clear what triggers the invagination
process, hormones likely play a role in initiating and main-
taining adenomyosis [22]. Clinically, women often develop
adenomyosis during their reproductive years, and the dis-
ease regresses after menopause. Some studies have shown
that adenomyotic tissue exhibits higher expression of estra-
diol receptors, and this increased response to estrogen
may enhance the invagination and growth of endometriotic
tissue into the myometrium [22,25]. Studies have shown
167
that compared with a normal adjacent myometrium, a
myometrium containing adenomyosis had higher levels
of estrogen sulfatase and aromatase activity, supporting
the theory that a hyperestrogenemia is required for the
development and maintenance of adenomyosis [22]. A
study by Green et al [20] found that mice exposed to estro-
gen by treatment with tamoxifen had increased rates of
adenomyosis and an abnormal myometrium [20].
Role of Hormones
Other hormones that may play a role include prolactin,
follicle-stimulating hormone (FSH), and progesterone. It is
thought that elevated prolactin levels promote myometrial
cell degeneration and invasion of endometrial stroma into
the myometrium and progression to adenomyosis [26].
Taran et al [14] completed a case control study of 76 women
undergoing hysterectomy with adenomyosis and 152 women
with uterine leiomyomas but no adenomyosis. They found
that adenomyosis was independently associated with a
history of depression. Depression and the subsequent eleva-
tion in prolactin from antidepressant treatment are consistent
with animal models of adenomyosis [14]. In animal models,
elevated FSH and prolactin appear to induce adenomyosis
[27,28]. In mice studies, it has been found that mice who
lack a fully functional FSH receptor developed uterine
vascular pathology and adenomyosis, which were not
observed in wild-type mice [28]. Further research using
FSH receptor–deficient mice might allow for further under-
standing of genes involved in tissue patterning under condi-
tions that produce hormonal, growth factor, and receptor
imbalances that lead to conditions such as adenomyosis [28].
Progesterone plays an important role in regulating the
function and receptivity of the endometrial lining throughout
the menstrual cycle. In women who have progesterone resis-
tance, their endometrium shows an impaired decidualization
response, and, therefore, they are unable to establish and
168
maintain a successful pregnancy [29]. The endometrium
responds to progesterone through its interaction with the pro-
gesterone receptor, which has 2 isoforms (i.e., PR-A and
PR-B). The relative concentration of these 2 isoforms deter-
mines the downstream effect of progesterone; PR-A promotes
a proinflammatory state, and PR-B promotes an anti-
inflammatory state. Bedaiwy et al [30] completed a case con-
trol study in women undergoing laparoscopic tubal ligation or
diagnostic laparoscopy and obtained samples of endometria
from all participants, 7 with histopathologically proven
adenomyosis and 14 controls. They found that PR-A was
the predominant isoform detected in patients with adenomyo-
sis. In eutopic endometria, levels of PR-A were significantly
higher in patients with adenomyosis (p 5 .001) [30].
De Novo from Embryologic-misplaced Pluripotent
Mullerian Remnants
Another common theory is that adenomyosis develops
de novo from mullerian rests. This metaplasia theory is
supported by findings of adenomyosis in locations outside
the myometrium such as the rectovaginal septum [1] by a
case report of histologically confirmed adenomyosis in a
patient with Rokitansky-Kuster-Hauser syndrome and there-
fore no functional endometrium [31] and in studies showing
that an ectopic endometrium in adenomyosis differs from a
eutopic endometrium in both its proliferative and biological
characteristics [1,30,32]. Matsumoto et al [33] examined 23
patients with adenomyosis and found that an ectopic endo-
metrium did not have the same secretory pattern as a eutopic
endometrium, and the induction of apoptotic cells and bcl-2
gene expression were different in an ectopic endometrium
compared with a eutopic endometrium. The adenomyotic
tissue did not have the same cyclic changes as a eutopic
endometrium and was rarely influenced by hormonal
change, which suggests that adenomyotic lesions do not
originate in the basal endometrium [33]. Growth factors
such as basic fibroblast growth factor and angiogenic growth
factor have been found to be different between an ectopic
and eutopic endometrium, which may contribute to the path-
ogenesis of abnormal uterine bleeding as seen in some
patients with adenomyosis [34].
Invagination Along the Intramyometrial Lymphatic
System and Displaced Bone Marrow Stem Cells
Two other less common theories are that adenomyosis
develops by invagination of the basalis endometrium along
the intramyometrial lymphatic system [1] or it develops
from displaced bone marrow stem cells [35,36]. It has
been proposed that adenomyosis may develop from
invagination of the deepest portion of the endometrial
mucosa along the intramyometrial lymphatic system
[25,32]. Adenomyosis can be found in hysterectomy
specimens within intramyometrial lymphatics [25,37].
Journal of Minimally Invasive Gynecology, Vol 23, No 2, February 2016
Research has shown that endometrial repopulation can be
driven by bone marrow–derived stem cells. Stem cells are
thought to have a role in the cyclic regeneration of the endo-
metrium during each menstrual cycle, and this has potential
implications for the etiology of both endometriosis and
adenomyosis. Supporters of this theory believe that the
stem cells foster the development of the endometrium within
the musculature of the uterus, leading to adenomyosis
[35,36].
Clinical Manifestations
Symptoms
The clinical presentation of adenomyosis is heteroge-
neous as summarized in Table 2. Abnormal uterine bleeding
and dysmenorrhea are 2 of the most commonly reported
symptoms in patients with adenomyosis, occurring in
approximately 65% of patients [22,43]. Symptom onset is
typically reported in women between the ages of 40 and 50.
Heavy menstrual bleeding occurs in approximately 40%
to 60% of patients. This may be secondary to the increased
endometrial surface of the enlarged uterus, or it may be
secondary to the increased vascularization of the endome-
trial lining [38]. Other proposed causes are improper uterine
contractions during menses and overproduction of prosta-
glandin and estrogen [44]. Levgur et al [4] studied 36
patients with adenomyosis and found that there was no sig-
nificant difference between median numbers of adenomyotic
foci in women with heavy menstrual bleeding compared
with women without heavy menstrual bleeding, but the
degree of myometrial invasion was statistically associated
with heavy menstrual bleeding. Heavy menstrual bleeding
occurred in 36.8% of patients with deep foci and 13.3%
with intermediate foci (p , .001). Heavy menstrual bleeding
was not associated with superficial foci [4].
Painful menstruation occurs in approximately 15% to
30% of patients with adenomyosis. This may be secondary
to bleeding and swelling of areas of endometrial tissue
within the myometrium, or it may be secondary to the
increased prostaglandin production in adenomyotic tissue
compared with normal myometrium [38]. Studies have
shown that there is increased production of prostaglandins
within adenomyotic tissue compared with a normal myome-
trium and that there is significantly more prostaglandin and
eicoisanoid production in patients with severe dysmenorrhea
compared with patients who reported no dysmenorrhea [45].
Levgur et al [4] found that dysmenorrhea was associated
with both the amount of adenomyotic foci and the depth of
invasion. The mean number of foci was 10 in women with
dysmenorrhea and 4.5 in women without (p , .003).
Dysmenorrhea was present in 77.8% of women with deep
foci and 12.5% of women with intermediate myometrial
foci (p , .001) and was not associated with superficial
foci [4]. This study was limited to uteri specimens less
than 280 g. They decided that in larger uteri the diagnosis
Struble et al. Adenomyosis 169

Table 2
Symptoms and signs of adenomyosis

Common presenting symptoms and signs % Affected Study (n 5 subjects)

Symptom
- Heavy menstrual bleeding 40–50 Huang et al [38]: Expert opinion
40–50 Levgur et al [4]: 111 uterine specimens; adenomyosis alone
n 5 17, adenomyosis and leiomyomas n 5 19,
leiomyomas alone n 5 39, neither n 5 36
- Deep foci* 36.8 Levgur et al [4]
- Intermediate foci* 13.3 Levgur et al [4]
- Dysmenorrhea 15–30 Huang et al [38]: expert opinion
15–30 Levgur et al [4]
- Deep foci* 77.8 Levgur et al [4]
- Intermediate foci* 12.5 Levgur et al [4]
- Chronic pelvic pain 76.9 Shrestha et al [39]: prospective case control n 5 78 women
with adenomyosis without fibroid
- Asymptomatic 33
- Dyspareunia 7 Huang et al [38]: expert opinion
Signs
- Uterine enlargement 30 [4] Levgur et al [4]
Slightly enlarged uterus in most Ozdegirmenci et al [40]: 75 women who had TVUS and MRI
cases [40] consistent with adenomyosis were treated with either
LNG-IUD or hysterectomy
- Tender uterus Significantly more tender uterus Huang et al [38]: expert opinion
was found in adenomyosis group Shrestha et al [39]: prospective case control
- Infertility 11–12 Huang et al [38]: expert opinion
- Associated uterine abnormalities McElin et al [41]
- Leiomyomas [41] 50
- Endometriosis [41] 11
- Endometrial polyp [41] 7
- Abnormalities at hysteroscopy: irregular These findings may be associated Molinas and Campo [42]: expert opinion
endometrium with endometrial defects, with adenomyosis
cystic hemorrhagic lesions, altered
vascularization [42]

LNG-IUD 5 levonorgestrel intrauterine system; MRI 5 magnetic resonance imaging; TVUS 5 transvaginal ultrasound.
* Adenomyosis was defined as endometrial glands or stroma within the myometrium at a depth of 2.5 mm or more. Adenomyosis foci within the myometrium, expressed as
percentage of myometrial thickness and graded as deep (exceeding 80%), intermediate (40–80%), and superficial (under 40%) [4].

of adenomyosis was not as common, possibly because of
atrophy of foci caused by large leiomyomas, and, therefore,
large specimens were not suitable for accurate evaluation
[4]. McCausland [46] also found a statistically significant
correlation between severity of heavy menstrual bleeding
and depth of adenomyosis.
Conversely, Sammour et al [47] found that the spread of
adenomyosis foci correlated significantly with both pelvic
pain (p 5 .02) and dysmenorrhea (p 5 .01) but not with
heavy menstrual bleeding or dyspareunia. Other reported
symptoms include dyspareunia, which can be present
in 7% to 10% of patients [38], and chronic pelvic pain [48].
Signs
Diffuse uterine enlargement is frequently described as
a globular uterus and is a common finding on physical
examination when a patient has adenomyosis. Often, the
uterus does not exceed the size of a 12-week gestational age
pregnant uterus [49]. The uterus enlarges globally
secondary to proliferation of the ectopic endometrial tissue,
which causes smooth muscle cell hyperplasia and hypertro-
phy [1]. Adenomyosis can also be present in the endometrial
cavity as a polypoid mass, or it can form adenomyomas,
which are focal areas of circumscribed nodular aggregates
of smooth muscle [1,25,44]. Some women may have a
tender uterus on physical examination. Shrestha and Sedai
[39] completed a prospective case control study comparing
women undergoing a hysterectomy with a histologic diag-
nosis of sole adenomyosis without fibroids (n 5 78), women
with both adenomyosis and fibroids (n 5 27), and women with
only a fibroid uterus (n 5 45). Women in the adenomyosis
group had significantly more uterine tenderness and chronic
pelvic pain [39]. Infertility is found in 11% to 12% of patients
[38]. Other associated uterine abnormalities are common in
women with adenomyosis such as leiomyomas (50%), endo-
metriosis (11%), and endometrial polyps (7%) [41].
170
Diagnosis
Histology: Hysterectomy
Historically, the diagnosis of adenomyosis has been made
by histologic findings after a hysterectomy. At hysterectomy,
often the uterus is enlarged globally, and the surface is
smooth. When cut in half, the cut surface often appears
spongy with areas of focal hemorrhage. On microscopic
examination, adenomyosis is identified when endometrial
tissue is found inside the myometrium. The minimal dis-
tance required for a diagnosis has been debated but ranges
from one half to 2 low-power fields from the endomyome-
trial junction [49] or a minimal depth of invasion ranging
from 1 to 4 mm [4,6,7,22,25]. Involvement of at least 25%
[25] to one third of myometrial thickness is another criteria
for diagnosis that has been used [44]. No one criterion is
universally accepted, and this variation in diagnostic criteria
has contributed to the variation in prevalence rates published
in the literature [50].
Histology: Hysteroscopic Biopsy
A histologic diagnosis of adenomyosis can also be
obtained from hysteroscopic or laparoscopic myometrial
biopsies [51]. Fernandez et al [51] published a case report
of a patient with a preoperative diagnosis of hypermenorrhea
secondary to adenomyosis and an endometrial polyp. The pa-
tient had a hysteroscopy, resectoscopy, and polypectomy.
During her procedure, 3 intramyometrial lacunae were iden-
tified, and blood came through the openings. These lacunae
were resected and sent for histology with the final diagnosis
being adenomyosis [51]. Adenomyosis does not have patho-
gnomonic signs at hysteroscopy. However, Molinas and
Campo [42] have shown that hysteroscopy is a useful tool
as part of a patient’s investigations because it allows for visu-
alization of the uterine cavity, it provides the ability to assess
for other potential abnormalities, and it offers the possibility
of obtaining endometrial or myometrial biopsies under direct
visualization. Some evidence suggests that an irregular endo-
metrium with endometrial defects, cystic hemorrhagic
lesions, and altered vascularization can be seen at hysterosco-
py and that these findings may be associated with adeno-
myosis [42]. Conversely, McCausland [46] completed
hysteroscopy and myometrial biopsies in 90 patients, 50 of
which had normal-appearing cavities defined by the absence
of polyps or submucous myomas, and identified significant
adenomyosis, greater than 1 mm, in 66% (n 5 33) of patients
compared with controls with a depth of only 0.8 mm. It must
be noted that a diagnosis of adenomyosis can be missed if the
adenomyosis is deeper than the biopsy samples taken or is
located at sites that are not biopsied [1].
Histology: Laparoscopic Biopsy
Studies have also looked at the role of myometrial
biopsies at laparoscopy for the diagnosis of adenomyosis.
Popp et al [52] found that the sensitivity of a single myome-
trial sample taken at laparoscopy was between 8% and
Journal of Minimally Invasive Gynecology, Vol 23, No 2, February 2016
18.7%. Brosens and Barker [53] also found that myometrial
needle biopsy has low sensitivity. They performed 8 needle
biopsies on 27 hysterectomy specimens with adenomyosis
and found that the sensitivity increased with the number of
biopsies and the depth of adenomyosis. The calculated sensi-
tivity of 2 random biopsies was between 2.3% and 56% [53].
As mentioned previously, often adenomatous tissue has an
immature proliferative pattern and is surrounded by a zone of
myometrial hypertrophy and hyperplasia. The adenomyosis
can be present diffusely throughout the myometrium or local-
ized to discrete areas called adenomyomas. Any area of the
uterus may be involved, but the most commonly affected
area is the posterior wall of the uterus [49]. These findings
can be seen on imaging as described later.
Imaging
Commonly, the diagnosis of adenomyosis is made histo-
logically; however, the use of imaging can help to guide the
differential diagnosis. The 2 most common modalities are
transvaginal ultrasound (TVUS) and magnetic resonance
imaging (MRI).
Currently, there are no standard diagnostic imaging criteria
for adenomyosis. This results in inconsistent preoperative
diagnosis, confusion among clinicians and patients, as well
as a lack of common language used between various studies,
making comparisons between published literature challenging
as illustrated in Supplemental Table 1 and Supplemental
Table 2 in the appendix. Although there is no general
consensus for the diagnosis of adenomyosis with imaging,
we provide commonly described findings seen on imaging.
TVUS
Two-dimensional TVUS. The most common 2-dimensional
(2D) TVUS findings for adenomyosis are heterogenous
myometrial echotexture (Fig. 2A), poorly defined foci of
abnormal myometrial echotexture, myometrial cysts [1],
and a globular and/or asymmetric uterus (Fig. 2B) [54].
Although uterine enlargement (described as up to 12 cm in
uterine length) has been reported as a sonographic
finding–associated adenomyosis [55], the majority of 2D
TVUS studies have not defined the criteria used for uterine
enlargement. In addition, the term ‘‘globular uterus’’ appears
to be a diagnostic feature, which is subjectively interpreted
by the ultrasound operator. Interestingly, a study by Exa-
coustos et al [56] found that a 2D TVUS volume measure-
ment [cm3], calculated by the ellipsoid formula (uterine
longitudinal diameter ! transverse diameter ! anteropos-
terior diameter ! 0.532), was higher for women without ad-
enomyosis than those with adenomyosis confirmed at
histology. Other less commonly reported findings include a
lack of contour abnormality, absence of mass effect, ill-
defined margins between a normal and abnormal myome-
trium (Figs. 2C and D), and an elliptic myometrial abnor-
mality [57]. When the ectopic endometrium extends into
Struble et al. Adenomyosis
Fig. 2
Common 2-D TVUS findings of adenomyosis.
the inner myometrium, this can give the appearance of echo-
genic linear striations, and when these are not well-defined,
they may give the appearance on ultrasound of poor defini-
tion of the endomyometrial junction or pseudowidening of
the endometrium [57]. The diffuse spread of small vessels
within the myometrium has also been described as a diag-
nostic feature of adenomyosis (Figs. 2C and D) [56]. An ad-
enomyoma is a focal circumscribed nodular collection of
ectopic endometrium commonly identified on the posterior
uterine wall (Fig. 2E) [1]. Reinhold et al [57] reported that
171
areas of decreased echogenicity or heterogeneity of the
myometrium are found in approximately 75% of patients
with adenomyosis. These findings represent areas of smooth
muscle hyperplasia or echogenic islands of heterotopic
endometrial tissue surrounded by smooth muscle, respec-
tively [57]. Myometrial cysts will be present in 50% of
patients. Cysts are dilated glands or hemorrhagic foci in
the heterotopic endometrium. Commonly, these are less
than 5 mm in diameter. However, in cystic adenomyosis,
these can be larger (greater than 5 mm in diameter). These
172
can appear as echogenic nodules on ultrasound because of
the increased amount of hemorrhage within the ectopic
endometrial glands [57].
3-dimensional TVUS. As described previously, alterations
in the junctional zone such as thickening or hyperplasia
have an important role in the pathogenesis, clinical presen-
tation, and diagnosis of adenomyosis. Three-dimensional
(3D) TVUS allows the junctional zone to be visualized
more clearly compared with 2D TVUS [58]. In supporting
the theory that adenomyosis arises from invasion of the
endometrium across the junctional zone and into the myo-
metrium, 3D TVUS may be advantageous in identifying
early adenomyosis because it allows for evaluation of the
junctional zone. On the coronal view, the junctional zone
can be identified as a hypoechoic area around the endome-
trium, and this junctional zone can be measured [58]. Find-
ings of adenomyosis are commonly described as a widened
junctional zone, an ill-defined junctional zone, and a distor-
tion or infiltration of the hypoechoic inner myometrium
[56,58].
MRI. On MRI, the most common described findings are a
large, regular, asymmetric uterus without leiomyomas
[54], abnormal myometrial signal intensity, thickening of
the junctional zone, and myometrial foci of high-signal
intensity on T1-weighted images [43,57].
Thickening of the junctional zone can be focal or diffuse,
representing the smooth muscle hyperplasia accompanying
the heterotopic endometrial tissue. Reinhold et al [59]
completed a prospective study of 119 patients in which 28
had adenomyosis confirmed by histopathology. They found
that patients with adenomyosis had a mean junctional zone
thickness of 15 mm, which was statistically different from
patients without adenomyosis of 7 mm (p , .0001). They
concluded that adenomyosis could be diagnosed with a
high degree of accuracy when the maximal junctional
zone thickness is 12 mm or greater [59] and that a maximal
junction zone thickness of 8 mm or less usually ruled out
adenomyosis [59]. Junctional zone thickness can be altered
secondary to hormone influences, and, therefore, some
MRI diagnoses, especially in postmenopausal women, are
made based on a ratio of the junctional zone to the myome-
trial wall thickness of 40% [60].
In approximately 50% of patients, bright foci can be
seen in areas of abnormal low-signal intensity within the
myometrium on T2-weighted images. These represent foci
of heterotopic endometrial tissue, cystic dilatation of hetero-
topic glands, or hemorrhagic foci [57]. Conversely, bright
foci on T1-weighted images correspond to areas of hemor-
rhage and are seen less commonly. Cystic adenomyosis
can result when the degree of hemorrhage is large. This
appears as well-circumscribed, cystic lesions in the
myometrium that show hemorrhage in varying stages of
organization. On T2-weighted images, these areas have a
low-signal intensity rim [57].
Journal of Minimally Invasive Gynecology, Vol 23, No 2, February 2016
Other findings that can be seen on MRI include linear stri-
ations of increased signal intensity radiating from the endo-
metrium into the myometrium on T2-weighted images.
These represent invasion of the basal endometrium into the
myometrium. Pseudowidening of the endometrium occurs
when these striations become less defined. Other signs of
adenomyosis on MRI include a lack of contour abnormality
or mass effect, ill-defined margins between normal and
abnormal myometrium, and an elliptic shape of a low-
signal-intensity myometrial abnormality [57].
Diagnostic Accuracy. Many studies have been performed
to determine the diagnostic accuracy of TVUS and MRI as
summarized in Table 3. Reinhold et al [61] completed a
prospective study by performing TVUS on 100 women
undergoing hysterectomy for a variety of conditions and corre-
lated imaging findings with histologic examination. TVUS
correctly identified 25 of 29 pathologically proven cases of ad-
enomyosis and ruled it out in 61 of 71 patients. They
concluded that TVUS could be used to accurately diagnose ad-
enomyosis [61]. In a prospective study, Brosens et al [62] per-
formed TVUS on 56 women with heavy menstrual bleeding
and dysmenorrhea and compared the sonographic diagnosis
of adenomyosis with histologic findings after hysterectomy
(n 5 34, 15 of whom had a diagnosis of adenomyosis) or
with the appearances on MRI (n 5 22, 13 of whom had a diag-
nosis of adenomyosis). TVUS showed sensitivity, specificity,
and positive and negative predictive values of 86%, 50%, 86%,
and 77% respectively. They concluded that TVUS had good
sensitivity but poor specificity [62].
Exacoustos et al [56] compared 2D TVUS with 3D TVUS
in 72 women before hysterectomy and correlated sonographic
findings of adenomyosis to histologic findings. The histologic
prevalence of adenomyosis was 44.4%, the overall accuracy
of 2D TVUS was 83%, sensitivity was 75%, specificity was
90%, the positive predictive value was 86%, and the negative
predictive value was 82%. They found the most specific
finding on 2D TVUS was the presence of myometrial cysts
with a specificity of 98% and accuracy of 78%. The most sen-
sitive finding was heterogeneous myometrium with a sensi-
tivity of 88% and an accuracy of 75% [56]. The overall
accuracy for 3D TVUS was higher than 2D TVUS at 89%
and was found to have a sensitivity of 91%, specificity of
88%, a positive predictive value of 85%, and a negative pred-
icative value of 92% [56]. Findings on 3D TVUS that had high
sensitivity and accuracy were when the difference between
the maximal junctional zone thickness and the minimal junc-
tional zone was greater than or equal to 4 mm and findings of
junctional zone infiltration and distortion [56]. Exacoustos
et al [56] concluded that when using 3D TVUS, the coronal
section of the uterus allows for accurate evaluation and mea-
surement of the junctional zone and has good diagnostic accu-
racy for adenomyosis.
Compared with MRI, Reinhold et al [59] concluded that
there was no statistically significant difference between the
sensitivities (p 5 .65) and specificities (p 5 .75) of TVUS
 Struble et al.
Table 3
Diagnostic accuracy of TVUS and MRI

Study Study design Sensitivity Specificity PPV NPV Notes

Adenomyosis
Ultrasound
Reinhold TVUS was completed on 100 86% 86% 71% 94% TVUS identified 25 of 29
et al [61] patients before pathologically proven cases
hysterectomy; 29 cases had of adenomyosis
adenomyosis
Brosens Performed TVUS on 56 86% 50% 86% 77%
et al [62] women with heavy
menstrual bleeding and
dysmenorrhea and
compared the sonographic
diagnosis of adenomyosis
to histologic findings after
hysterectomy (n 5 34, 15
of whom had a diagnosis of
adenomyosis) or to the
appearances on MRI
(n 5 22, 13 of whom had a
diagnosis of ademonyosis)
Levgur [49] Review article 50%–87%
Exacoustos Completed 2D TVUS and 3D 2D TVUS: 75% 2D TVUS: 90% 2D TVUS: 86% 2D TVUS: 82% The overall accuracy of 2D
et al [56] TVS on 72 women before 3D TVUS: 91% 3D TVUS: 88% 3D TVUS: 85% 3D TVUS: 92% TVUS was 83%; the overall
hysterectomy and accuracy for 3D TVUS was
correlated sonographic higher than 2D TVUS at
findings of adenomyosis to 89%
histologic findings
MRI
Togashi Correlated MRI findings with The cause of uterine
et al [63] surgical/pathological enlargement was correctly
findings in 93 patients who diagnosis by MRI in 92 of
had an enlarged uterus; the the 93 cases [63]
cause of the enlarged uterus
was due to leiomyoma
(n 5 71), ademonyosis
(n 5 16), and leiomyoma
and adenomyosis (n 5 6)
Ultrasound versus MRI
Reinhold Prospectively studied 119 TVUS: 89% TVUS: 98% TVUS: 71% TVUS: 96% No statistically significant
et al [59] patients undergoing MRI: 89% MRI: 89% MRI: 65% MRI: 95% difference between the
hysterectomy; imaging sensitivities (p 5 .65) and
(TVUS and MRI) findings

173
(Continued )
 174
Table 3
Continued

Study Study design Sensitivity Specificity PPV NPV Notes

were compared with those specificities (p 5 .75) of
at histopathologic TVUS and MRI
examination 28 patients
had histopathologic
diagnosis of adenomyosis
Bazot Prospectively studied 120 TVUS: 65% TVUS: 97.5% TVUS: 92.8% TVUS: 88.8%
et al [54] patients, 40 (33.0%) of MRI: 77.5% MRI: 92.5% MRI: 83.8% MRI: 89.2%
whom had adenomyosis, by
comparing transabdominal
ultrasounds, transvaginal
ultrasound, and MRI for the
diagnosis adenomyosis and
correlating these findings
with histologic findings
Dueholm 106 patients underwent TVUS: 0.68 (0.44–0.86) TVUS: 0.65 (0.50–0.77)
et al [64] hysterectomy; each patient MRI: 0.70 (0.46–0.87) MRI: 0.86 (0.76–0.93)
had a preoperative TVUS
and MRI. Each uterus had
pathologic analysis; 22
specimens had

Journal of Minimally Invasive Gynecology, Vol 23, No 2, February 2016

adenomyosis
Ascher 20 patients; 17 were found to TVUS: 53% TVUS: 66% MRI is significantly better
et al [65] have adenomyosis MRI: 88% MRI: 66% (p , .02) than TVUS in the
diagnosis of adenomyosis
Reinhold Review article TVUS: 80%–86% TVUS: 50%–96% The overall accuracy of
et al [57] MRI: 86%–100% MRI: 86%–100% TVUS: 68%–86%
The overall accuracy of MRI:
85%–90.5%
Outwater Review article Ultrasound: 53%–89% Ultrasound: 50%–89%
et al [107] MRI: 88%–93% MRI: 66%–91%
Champaneria Systematic review including TVUS: 72% (95% CI, TVUS: 81% (95% CI, TVUS: positive likelihood TVUS: negative
et al [66] 23 articles (2312 women) 65%–79%) 77%–85%) ratio of 3.7 (95% CI, 2.1–6.4) likelihood ratio of 0.3
MRI: 77% (95% CI, MRI: specificity of MRI: positive likelihood ratio (95% CI, 0.1–0.5)
67%–85%) 89% (95% CI, of 6.5 (95% CI, 4.5–9.3) MRI: negative likelihood ratio
84%–92%) of 0.2 (95% CI, 0.1–0.4)

2D 5 2-dimensional; 3D 5 3-dimensional; CI 5 confidence interval; MRI 5 magnetic resonance imaging; NPV 5 negative predictive value; PPV 5 positive predictive value; TVUS 5 transvaginal ultrasound.
Struble et al. Adenomyosis
and MRI after completing a prospective study on 119
patients who had TVUS and MRI before hysterectomy. Of
the 119 patients, 28 had confirmed adenomyosis [59]. Bazot
et al [54] also found that TVUS was just as accurate in
women with adenomyosis who did not have other uterine
pathology. They prospectively studied 120 patients, 40
(33.0%) of whom had adenomyosis, by comparing transab-
dominal ultrasound, TVUS, and MRI for the diagnosis of
adenomyosis and correlating these findings with histologic
findings. They found the sensitivity, specificity, and positive
and negative predictive values of TVUS and MRI to be
65.0% and 77.5%, 97.5% and 92.5%, 92.8% and 83.8%,
and 88.8% and 89.2%, respectively, and concluded that in
women who do not have a leiomyoma TVUS is as efficient
as MRI in diagnosing adenomyosis, whereas in women who
have an associated leiomyoma the sensitivity was lower in
TVUS and, therefore, MRI may be recommended in these
patients [54].
Conversely, Ascher et al [65] prospectively compared
TVUS and MRI for the diagnosis of adenomyosis in 20
women with a clinical suspicion of adenomyosis. All cases
were confirmed by pathology; 17 were found to have
adenomyosis. The sensitivity was 53% and 88%, and the
specificity was 66% and 66% for TVUS and MRI, respec-
tively. They concluded that MRI was significantly better
(p 5 .02) than TVUS in the diagnosis of adenomyosis
[65]. Dueholm et al [64] also found that MRI was superior
to TVUS in a study of 106 women who had TVUS and
MRI before hysterectomy, 22 of whom had adenomyosis.
MRI has been shown to be highly accurate in the diag-
nosis of adenomyosis. Togashi et al [63] correlated MRI
findings with surgical/pathological findings in 93 patients
who had an enlarged uterus. The cause of the enlarged uterus
was leiomyomas (n 5 71), ademonyosis (n 5 16), and leio-
myomas and adenomyosis (n 5 6). The cause of uterine
enlargement was correctly diagnosed by MRI in 92 of
the 93 cases [63]. More recently, Champaneria et al [66]
completed a systematic review to compare the diagnostic
accuracy of MRI and ultrasound. They included 23 articles
involving 2312 women and found that TVUS had a pooled
sensitivity of 72% (95% confidence interval [CI], 65%–
79%), specificity of 81% (95% CI, 77%–85%), a positive
likelihood ratio of 3.7 (95% CI, 2.1–6.4), and a negative like-
lihood ratio of 0.3 (95% CI, 0.1–0.5). MRI had a pooled
sensitivity of 77% (95% CI, 67%–85%), specificity of
89% (95% CI, 84%–92%), a positive likelihood ratio of
6.5 (95% CI, 4.5–9.3), and a negative likelihood ratio
of 0.2 (95% CI, 0.1–0.4). They concluded that both TVUS
and MRI had high levels of accuracy in diagnosing adeno-
myosis but that the correct diagnosis was reached more often
by MRI [66].
Treatment
Historically, the standard treatment for adenomyosis has
been hysterectomy. However, this is not always an option for
175
patients, especially those women who want to maintain
fertility options or who are not good surgical candidates
because of other comorbidities [1]. Treatment options for
adenomyosis include both medical and surgical manage-
ment. However, determining the optimal treatment for
patients can be difficult. As described previously, there are
no agreed upon diagnostic imaging criteria. Patients’ symp-
toms can be heterogeneous, adenomyosis can be associated
with other gynecologic conditions, and there are few high-
quality randomized controlled trials [67]. Much of the pub-
lished literature includes only case reports, retrospective
studies, or studies with small numbers of participants.
Because there are no agreed upon 2D/3D TVUS and MRI
diagnostic criteria, it is challenging to monitor the treatment
effect objectively after medical management or to compare
studies in which different imaging criteria has been used.
The accuracy of ultrasound is also dependent on the popula-
tion that is studied and if there is additional pathology pre-
sent such as endometriosis or leiomyomas, operator skill
and experience, quality of the ultrasound machine, and post-
image processing of 3D acquisition [67].
Determining the effect of treatment on patients’ symp-
toms is also challenging because concurrent benign gyneco-
logic pathology such as leiomyomas, endometriosis, or
polyps can lead to significant bias when studying the effect
of treatment on adenomyosis-related symptoms such as
heavy menstrual bleeding and dysmenorrhea [67]. Some
medical therapies have shown regression of disease in the
short-term [1]. Unfortunately, there are limited medical
options for patients who alleviate their symptoms but allow
for conception as summarized in Table 4.
Medical Management
Nonsteroidal Anti-inflammatory Drugs
Women with dysmenorrhea have elevated levels of pros-
taglandins, which can result in painful cramps. Women may
experience symptom improvement by taking nonsteroidal
anti-inflammatory drugs (NSAIDs), which inhibit cyclooxy-
genase, the enzyme involved in the production of prostaglan-
dins. Marjoribanks et al [68] completed a review comparing
all NSAIDs with placebo in the treatment of primary
dysmenorrhea. They concluded that NSAIDs are signifi-
cantly more effective for pain relief than placebo in
women with dysmenorrhea (OR 5 7.91; 95% CI, 5.65–
11.09). However, the overall adverse effect was also
increased (OR 5 1.52; 95% CI, 1.09–2.12). Women must
understand these potential adverse effects and if willing
may try treatment with NSAIDs as an option for symptoms
of dysmenorrhea [68].
Oral Contraceptive Pills and Progestins
Patients may show symptomatic improvement of
dysmenorrhea and heavy menstrual bleeding when taking
oral contraception continuously or from use of a high-dose

Table 4
Medical management options for adenomyosis
Medical therapies
NSAIDs
Combination oral
contraceptives and
progestin-only regimens
Levonorgestrel-releasing
intrauterine system
Danazol
GnRH agonist/analog
COX 5 cyclooxygenase; FSH 5 follicle-stimulating hormone; GnRH 5 gonadotropin-releasing hormone; LH 5 ; LNG 5 levonorgestrel.
Mechanisms
Reversible inhibition of COX-1 and COX-2
enzymes, which results in decreased
formation of prostaglandin precursors
Mechanism of estrogen-progestin
contraceptives: suppression of
hypothalamic GnRH and pituitary
gonadotropin secretion, suppression of
ovarian folliculogenesis, suppression of
ovarian steroid production
Mechanisms due to progestin: endometrial
decidualization and atrophy
Mechanisms [6,69]:
1 Decidualization of the endometrium
2 Downregulation of estrogen receptors on
adenomyotic foci causing:
i A reduction in foci size, thus allowing
the uterus to contract more efficiently
leading to a reduction in menstrual
blood loss
ii A reduction in prostaglandin produc-
tion and therefore an improvement in
dysmenorrhea
Suppression of pituitary release of FSH and
LH causing atrophy of both normal and
ectopic endometrial tissue
Decrease expression of aromatase
cytochrome P450 in disease eutopic
endometrium [70]
Decreases gonadotropin secretion leading to
ovarian quiescence and inducing a
pseudomenopausal, hypoestrogenic state
[38]
Dose
Various options (i.e., ibuprofen 400-600 mg
every 4-6 h or 800 mg every 8h to a
maximum dose of 2400mg/d) starting with
the onset of symptoms or menses, and
continue for 2 to 3 days
Take as directed
It releases 20 mg/d LNG into the uterine
cavity for up to a 5-year period
400 mg orally daily
Buserelin acetate nasal spray 600 mg/d in
divided doses [38]
Buserelin acetate 450 mg/d nasally
176
Duration Possible effect
Prostaglandins are known to cause cramping
abdominal pain [68]
May use continuously Reduced menstrual flow and improvement
and dysmenorrhea
Can be left in place for 1 Reduced menstrual flow
5 years 2 Improvement in heavy menstrual bleeding
Benefit may be limited to and dysmenorrhea
2 years post insertion71
Journal of Minimally Invasive Gynecology, Vol 23, No 2, February 2016
Improvement of symptoms and reduction of
uterine size
3 months [38] Reduces the size of adenomyosis;
improvement in dysmenorrhea and heavy
menstrual bleeding long course
(.6 months) is limited because of side
effects including hot flashes, vaginal
atrophy, accelerated bone demineralization
2 years Case report n 5 1 [71]: anemia, leg
numbness, and chronic pelvic pain
resolved; no estrogen deficiency symptoms
for more than 2 years on treatment
Struble et al. Adenomyosis
progestin such as continuous oral norethindrone acetate or
subcutaneous depot medroxyprogesterone. These medica-
tions help improve symptoms by inducing amenorrhea and
for a short period of time may also induce regression of
adenomyosis [1]; however, randomized control trials are
lacking, and some experts believe that these therapies are
ineffective in treating adenomyosis [22].
Levonorgestrel Intrauterine Device
The levonorgestrel intrauterine device (LNG-IUD)
(Mirena; Bayer HealthCare Pharmaceuticals Inc., Toronto,
ON, Canada) is an effective treatment for adenomyosis. It
acts by releasing 20 mg levonorgestrel per day for up to
5 years. Symptomatic improvement is thought to occur sec-
ondary to 2 mechanisms. First, it causes decidualization of
the endometrium, resulting in decreased menstrual flow. Sec-
ond, it is thought to act on adenomyotic foci by causing a
downregulation of the estrogen receptors. This causes the
ectopic foci of endometrium to reduce in size, allowing the
uterus to contract more efficiently, reducing menstrual blood
loss, and resulting in decreased prostaglandin production and
improving dysmenorrhea [6,69]. Various studies have been
published reporting improvements in symptoms of heavy
menstrual bleeding and dysmenorrhea as well as radiologic
changes after the insertion of the LNG-IUD [43,69,72,73].
Fedele et al [72] studied 25 women who had TVUS-
diagnosed adenomyosis and recurrent heavy menstrual
bleeding. Each patient had a 20-mg/d LNG-IUD inserted
and completed a pictorial blood loss assessment chart
each month; patients had TVUS examinations at 3, 6, and
12 months after insertion. One patient requested the IUD
be removed after 4 months because of persistent irregular
bleeding, and another patient had expulsion of the IUD after
2 months. Of the remaining 23 women, they found a reduced
uterine volume; decreased blood loss; and a significant
increase in hemoglobin, hematocrit, and serum ferritin
1 year after insertion [72].
Bragheto et al [43] studied 29 women who suffered from
heavy menstrual bleeding and dysmenorrhea secondary to
adenomyosis diagnosed by MRI. Women were evaluated
at baseline and then at 3 and 6 months after LNG-IUD inser-
tion. They found a significant reduction in junctional zone
thickness (24.2%, p , .0001); however, there was no reduc-
tion in uterine volume. There was also a significant decrease
in pain scores, and the most common pattern of bleeding was
oligomenorrhea [43].
Sheng et al [73] studied the efficacy of the LNG-IUD in
94 women with moderate or severe dysmenorrhea associated
with adenomyosis diagnosed by TVUS. They followed
women for 3 years and found a significant improvement in
scores of dysmenorrhea; the mean baseline score of 77.9
decreased to 11.8 36 months after insertion (p , .001).
They also found a decrease in uterine volume and serum
CA 125 levels. Overall, patient satisfaction rate was 72.5%
[73]. Cho et al [74] also studied the long-term clinical effects
of LNG-IUD in 47 women diagnosed with adenomyosis.
177
They found that pain scores and pictorial blood loss assess-
ment chart scores decreased in 6 months and showed signif-
icant decreases after 36 months. However, there was a
significant increase in uterine volume, pain scores, and
pictorial blood loss assessment chart scores at 36 months
compared with 12 months after insertion. They concluded
that LNG-IUD is effective at reducing uterine volume with
an improvement of vascularity and patients’ symptoms;
however, this benefit may be limited to 2 years after insertion
[74].
Ozdegirmenci et al [40] completed a randomized study in
75 women with a clinical suspicion of adenomyosis com-
plaining of heavy menstrual bleeding and/or dysmenorrhea.
Women who had TVUS and MRI findings consistent with
adenomyosis were randomized to either LNG-IUD or
hysterectomy. In addition to monitoring blood loss and
hemoglobin levels, the authors also studied the impact of
treatment on the participants’ quality of life. For quality of
life evaluation, they used the World Health Organization
Quality of Life-Short Form, Turkish Version. This question-
naire has 26 questions that relate to 4 domains: physical
health, psychological health, social relationships, and envi-
ronment. The version they used included a national environ-
ment item (environmental-TR), which contributes to the
environmental domain of the scale to calculate a national-
environmental domain score. National environment items
supplement the core World Health Organization Quality of
Life questionnaire and reflect special aspects of quality of
life not included in the core World Health Organization
Quality of Life questionnaire because they are not univer-
sally valued. The participants scored each item, illustrating
how they felt in the past 2 weeks; a higher score indicated
a better quality of life. They found that hemoglobin levels
were significantly increased in both treatment groups at
6 months and 1 year after treatment, and there was no statis-
tical difference between the 2 groups. When pretreatment
and post-treatment quality of life scores were compared,
they found women who had a hysterectomy showed
improvement in 3 domains (environmental, environmental-
TR, and physical), whereas women who had the LNG-IUD
showed improvement in all 5 domains (environmental,
environmental-TR, physical, physiological, and social)
[40]. They concluded that LNG-IUD may be a promising
therapy for adenomyosis with results similar to hysterec-
tomy in terms of managing heavy menstrual bleeding and
hemoglobin levels and superior to hysterectomy with respect
to physiologic, social well-being, and quality of life at a
1-year follow-up [40].
Generally, women experience significant symptom
improvement with the LNG-IUD, and this may provide a
medical treatment that allows them to retain future fertility
options. The most frequent problem with the LNG-IUD is
irregular spotting during the initial months postinsertion;
however, this usually resolves within 3 months [6]. Other
potential side effects that Sheng et al [73] found were weight
gain (28.7%), simple ovarian cyst formation (22.3%), and
178
lower abdominal pain (12.8%) [73]. Headache, breast
tenderness, acne [72], and transient depressive episodes
have also been reported [40].
Danazol
Danazol acts by suppressing pituitary release of FSH and
luteinizing hormone and therefore causes atrophy of both
normal and ectopic endometrial tissue. Systemic treatment
with danazol has been shown to decrease the expression of
aromatase cytochrome P450 in diseased eutopic endometria;
this may contribute to the improvement of symptoms and
reduced uterine size in patients treated with danazol [70].
However, it is not well tolerated by many patients because
of its side effect profile, which can include acne, depression,
deepening of the voice, hirsutism, hot flashes, decreased
high-density lipoprotein levels, increased liver enzyme con-
centrations, oily skin, muscle cramps, reduced breast size,
and weight gain [1].
Novel ways of treating adenomyosis with danazol are
being studied such as intracervical injections and IUDs.
These methods allow local delivery of hormones in an
attempt to minimize systemic side effects. Takebayashi
et al [75] studied patients receiving cervical danazol suspen-
sion injections and reported that all women had subjective
improvement of symptoms by the 24th week. Igarashi et al
[76] studied 14 women with dysmenorrhea, heavy menstrual
bleeding, or infertility diagnosed with adenomyosis
confirmed by bimanual examination, transvaginal ultraso-
nography, and MRI. Each patient had a danazol-loaded
IUD inserted. They found that serum danazol levels re-
mained below the level of detection during the study, unlike
in patients receiving oral danazol, and, therefore, the danazol
IUD did not cause any of the side effects typically observed
with oral therapy. During their study, 9 patients had complete
remission of dysmenorrhea, a reduction of symptoms was
reported in 4 patients, and 1 patient reported no change in
symptoms. Heavy menstrual bleeding resolved in 12
patients, and there was no change in 2 patients. There was
a reduction of the maximal thickness of the myometrium
in 9 patients. Additionally, after the danazol IUD was
removed, 3 of the 4 infertile patients successfully conceived
[76].
Shawki [77] prospectively studied 21 women with heavy
menstrual bleeding, dysmenorrhea, and adenomyosis diag-
nosed by TVUS and hysteroscopic-guided endomyometrial
biopsies. All women had a 400-mg loaded danazol IUD
placed for 6 months. They found that menstrual-related
pains and dysmenorrhea resolved in 17 women (80.9%).
Improvement in bleeding and regular menstrual blood flow
occurred in 16 women (76%), and there was a significant
increase in hemoglobin levels during treatment. Two women
achieved spontaneous pregnancy within 6 months after
removal of the IUD out of 9 infertile women. There was
only 1 case of spontaneous expulsion, and no systemic
side effects known with danazol were reported during the
study. In keeping with other studies, serum levels of danazol
Journal of Minimally Invasive Gynecology, Vol 23, No 2, February 2016
were undetectable [77]. This remains an experimental treat-
ment and is not readily available for patient use.
Gonadotropin-releasing Hormone Agonists
Gonadotropin-releasing hormone (GnRH) agonists cause
a suppression of pituitary gonadotropins and thus induce
ovarian quiescence, resulting in a medical menopausal,
hypoestrogenic state [38]. The first report of using a
GnRH analog in the management of adenomyosis was pub-
lished by Grow and Filer [78] in 1991. They reported a 65%
reduction in uterine volume after 4 months of treatment as
well as amenorrhea and improvement in severe dysmenor-
rhea [78]. Huang et al [38] reported 2 cases of women
with infertility suspected to be secondary to adenomyosis.
Both women had biopsy-proven adenomyosis and had
3-month treatment of buserelin acetate nasal spray
600 mg/d in divided doses. In the first case, the patient’s
symptoms of heavy menstrual bleeding and dysmenorrhea
completely resolved, and her uterine volume decreased
from 344 to 180 cm3. The second patient also had improve-
ment in her symptoms and a decrease in uterine volume from
330 to 178 cm3 after a 3-month treatment. Both patients went
on to conceive within 6 months of stopping treatment. This
study showed that GnRH analogs can be effective for
patients with heavy menstrual bleeding and dysmenorrhea
secondary to adenomyosis and can result in a reduction in
uterine size. However, treatment is often limited to a short
duration because of undesirable side effects that occur
with long course treatment, such as hot flashes, vaginal atro-
phy, and accelerated bone demineralization [38]. Addition-
ally, after discontinuation of therapy, symptoms may
return, and uterine volumes may increase to pretreatment
size [1]. Further research is required to determine the
duration of GnRH analog treatment, which will result in
symptomatic improvement while minimizing the risk of
long-term side effects and delay in patients wanting to
conceive [38].
More recently, Akira et al [71] published a case report of a
patient on low-dose buserelin acetate treatment for 2 years
without side effects of low estrogen. The patient had adeno-
myosis complicated by deep vein thrombosis. The deep vein
thrombosis was confirmed by leg venography and treated
with thrombolytic therapy. The patient wanted to conserve
her uterus, and it was decided to treat her adenomyosis,
which was causing chronic pelvic pain, dysmenorrhea, and
anemia caused by hypermenorrhea with a low-dose GnRH
agonist. She was started on 450 m/d buserelin acetate nasally.
Her anemia, leg numbness, and chronic pelvic pain resolved,
and she did not have symptoms of estrogen deficiency for
more than 2 years on treatment [71].
Aromatase Inhibitors
Aromatase cytochrome P450 converts androgens to estro-
gens, and its expression has been observed in both eutopic
and ectopic endometria in patients with endometriosis. It
is thought that aromatase P450 expression in the
Struble et al. Adenomyosis
endometrium is limited to women with proliferative repro-
ductive tract disorders such as adenomyosis, endometriosis,
and leiomyomata [79,80]. Studies have shown an
improvement in mean pain scores, lesion size, and quality
of life scores in patients with endometriosis treated with
aromatase inhibitors [81], and, therefore, patients with ad-
enomyosis may similarly benefit from treatment with aroma-
tase inhibitors [6]. Further research is required to determine
the role of aromatase inhibitors for the treatment of adeno-
myosis [1].
Surgical
Endometrial Ablation and Hysteroscopic Resection
Endometrial ablation can be used as a treatment option
in patients who have completed childbearing. Typically,
ablation procedures are classified as being either nonresecto-
scopic such as bipolar radiofrequency, cryotherapy, circu-
lating hot water, microwave, and thermal balloon or as
resectoscopic including wire loop resection, laser, or roller
ball ablation. A common concern with ablation and resection
procedures is that the depth of the adenomyotic lesions
limits the success of the treatment. Deep ectopic endome-
trium can become trapped behind the ablated edge, resulting
in pain and bleeding [1]. Resection is often limited to super-
ficial lesions because there is risk of causing significant
bleeding from arteries present approximately 5 mm below
the myometrial surface [82].
McCausland and McCausland [83] examined 50 patients
diagnosed with adenomyosis up to 3.5 years after endome-
trial ablation and found that patients with superficial adeno-
myosis (,2 mm) had good results, whereas patients with
deep adenomyosis (.2 mm) had poor outcomes after
ablation. They reported that the rollerball electrode has a
coagulation effect approximately 2 to 3 mm into the myome-
trium and can therefore destroy the endometrium and sur-
rounding hypertrophic dysfunctional smooth muscle.
However, as the ectopic endometrium penetrates further
into the myometrium, there is less complete destruction of
the tissue [83]. They also found that patients with postabla-
tion bleeding responded well to treatment with progesterone
if they had superficial adenomyosis; however, progesterone
therapy was often ineffective in patients with deep adeno-
myosis [83].
El-Nashar et al [84] completed a retrospective study of
816 women who had a global endometrial procedure with
either a thermal balloon ablation or radiofrequency ablation.
They found that 16% of patients had treatment failure
requiring hysterectomy or reablation because of bleeding
or pain. The overall amenorrhea rate, defined as cessation
of bleeding for at least 12 months after the procedure, was
23%. Predictors of amenorrhea were age greater than 45,
uterine length less than 9 cm, endometrial thickness less
than 4 mm, and the use of radiofrequency ablation instead
of thermal balloon ablation [84]. Predictors of treatment
179
failure included age younger than 45 years, parity of 5 or
greater, prior tubal ligation, and history of dysmenorrhea
[84]. These factors should be considered because many
women with adenomyosis are multiparous and suffer from
dysmenorrhea and therefore may be more likely to fail this
treatment option. A repeat procedure can be considered in
patients who do not have a satisfactory result after their
initial surgery [85].
More recently, Gordts et al [86] published an article on
2 patients with cystic adenomyosis and illustrated the role
of hysteroscopy in both the diagnosis and excision of myo-
metrial cystic adenomyosis by using mechanical dissection
and ablative bipolar current. They explained that at hysteros-
copy the cystic adenomyosis may appear as a bulge into the
cavity, or one may see abnormal vascularization or fibrosis in
the endometrium overlying the cyst [86]. Visualization of
the cystic structures is improved by lowering the intrauterine
pressure. In addition to being able to visualize the cavity
directly, another benefit of this approach is that it allows
for biopsies under direct visualization and/or ultrasound
guidance. In their first case, the patient was found to have
a bulging area of abnormal vascularization at hysteroscopy.
This area was opened using hysteroscopic scissors, and a
brownish fluid came from the area. On inspection of this
cyst, the authors noted a fibrotic wall and areas of
endometrial-like tissue. The lesion was resected, and the
histologic findings were in keeping with cystic adenomyosis
[86]. In the second case, Gordts et al [86] described a patient
known to have an intramural cyst diagnosed on MRI. At
hysteroscopy, the cavity appeared normal; however, using
ultrasound guidance, the cystic lesion was localized, and
they used a spirotome (Medivents Corporation, Hasselt,
Belgium) to create a channel into the cyst. The inner cystic
wall was coagulated, and follow-up hysteroscopy 10 weeks
later revealed a slightly inflamed endometrial cavity and a
normal uterine cavity with no adhesions. The patient went
on to have GnRH agonist therapy and in vitro fertilization
therapy that was unsuccessful and had recurrence of heavy
menstrual bleeding. Follow-up MRI illustrated a focal
enlargement of the junctional zone present at the midthird
of the uterine corpus. They concluded that hysteroscopy al-
lowed for direct visualization of the cavity and the ability to
treat cystic adenomyosis by mechanical dissection or bipolar
ablative surgery while causing minimal tissue damage, leav-
ing the outer myometrium intact, preserving fertility, and
avoiding an abdominal scar [86]. However, it is noted that
this approach is not an option for diffuse adenomyosis, and
when patients have larger cystic adenomyotic structures
localized in the outer intramural third, a laparoscopic
approach is better [86].
Uterine Artery Embolization
Uterine artery embolization (UAE) is another method for
managing symptoms secondary to dysmenorrhea. Patients
report an improvement in symptoms after UAE [87] with a
significant improvement in symptoms of heavy menstrual
180
bleeding and dysmenorrhea (p , .001) [88]. In a review
article by Popovic et al [89], they found that in 511 women
from 15 studies in which long-term data were available,
improvements were reported by 387 patients (75.7%).
They concluded that UAE for adenomyosis had significant
clinical and symptomatic improvements at both a short-
term and long-term follow-up. The median follow-up from
these studies was 26.9 months [89]. However, commonly
reported side effects include pelvic pain, nausea, and fever
because of ischemic necrosis [90]. Nearly 5% of patients
suffer a major complication such as infection, hemorrhage,
or unplanned surgical procedure [91]. Additionally, there
are reports of decreased ovarian function after UAE [90].
Jha et al [87] studied 30 patients with adenomyosis diag-
nosed by MRI before UAE. Follow-up MRI 1 year after
UAE showed changes such as areas of devascularization of
adenomyosis. The 3 patients with pure adenomyosis and 6
patients with adenomyosis and uterine fibroids but in
whom adenomyosis was the dominant disease reported an
improvement in symptoms [87]. Kim et al [88] completed
a retrospective study on women who underwent UAE for
adenomyosis, excluding patients with fibroids. Of the 66
patients, 54 patients had a follow-up period of 3 years or
longer and were enrolled in the study. Thirty-one (57.4%)
of these women had long-term success [88]. They concluded
that UAE was an option for patients; however, women
should be informed of the risks of treatment failure
(7.4%), recurrence (35%), and the potential need for hyster-
ectomy (26%) [88].
Myometrium or Adenomyoma Excision
Excision of adenomyotic foci can be completed if the
ectopic endometrium is well identified. However, the lesions
often are not clearly defined, and adenomyosis is present
diffusely throughout the myometrium. Subsequently, the
success after excisional treatment is low at 50% [82].
Wang et al [92] prospectively studied 165 women who had
conservative adenomyomectomy and compared outcomes
of patients who had surgery alone (n 5 51) versus women
who had surgery and then had a postoperative 6-course treat-
ment of GnRH agonist (n 5 114). After treatment, there was
a significant decrease in dysmenorrhea scores and heavy
menstrual bleeding for both treatment groups. Women who
were more likely to have symptom relapse after the 2-year
follow-up were those with a higher preoperative serum
CA125 as well as higher baseline heavy menstrual bleeding
and dysmenorrhea compared with those women who did not
have symptom relapse [92]. Additionally, this study showed
promising reproductive outcomes after treatment; 71 women
were sexually active and did not use contraception, and 55 of
these women became pregnant. The clinical pregnancy
rate was 77.5%, and 49 women (69.0%) had a successful de-
livery. There was no statistical difference between the 2
groups [92].
Fedele et al [93] also evaluated reproductive outcomes in
28 women who had conservative surgery for uterine adeno-
Journal of Minimally Invasive Gynecology, Vol 23, No 2, February 2016
myoma. Patients (n 5 18) wanting children were followed
for a mean of 53.2 months. Thirteen (72.2%) women
conceived, and there were 18 pregnancies. Of these, there
were 9 (50%) term deliveries, 7 (38.8%) spontaneous abor-
tions, 1 (5.6%) ectopic pregnancy, and 1 (5.6%) preterm
delivery with neonatal death. Although excision may pro-
vide an option for symptomatic patients wanting to become
pregnant, it should be noted that this rate of spontaneous
abortion is higher than the general population possibly
because of scar tissue formation, and, therefore, patients
should be counseled appropriately [93].
Myometrial Electrocoagulation
Myometrial electrocoagulation by laparoscopy or hys-
teroscopy can cause a decrease in adenomyosis secondary
to necrosis. This method has been used in both diffuse
and localized disease and may be an option in symptomatic
patients with extensive adenomyosis who have failed med-
ical therapy in which excision is not possible and they want
to preserve their uterus but do not wish to conceive. Wood
[82] reported 2 cases that had improvement in dysmenor-
rhea and bleeding 2 years after treatment. The procedure
is completed by using unipolar or bipolar needles at 50-
W coagulation, and the extent of treatment is controlled
by current strength and duration of time the needles are
in place. The depth of coagulation is predetermined by
the thickness of disease found on preoperative MRI. Lim-
itations to myometrial electrocoagulation are that this
approach may be less accurate than surgical excision
because the extent of abnormal tissue being treated cannot
be confirmed during the time of surgery. Second, the
treated areas form scar tissue, and this may decrease the
strength of the uterus. Patients may be at risk of uterine
rupture, and, therefore, permanent contraception should
be offered. Wood [82] reported a case of uterine rupture
at 12 weeks gestational age in a patient treated with myo-
metrial electrocoagulation and therefore felt that this pro-
cedure should be offered to women over the age of
40 who have completed childbearing and who want to
avoid a larger surgery such as excision or hysterectomy.
The published reports of myometrial electrocoagulation
are limited, and the success of treatment ranges from 55%
to 70% [1]. Wood et al [94] reported 7 patients treated by
myometrial electrocoagulation. Four (57.1%) of these
patients were considered cured, meaning they had relief of
heavy menstrual bleeding and dysmenorrhea requiring no
further treatment [94]. Phillips et al [95] studied 10 patients
with symptomatic adenomyosis diagnosed by MRI and had
laparoscopic bipolar coagulation for management. Twelve
months after surgery, 7 (70.0%) patients had either resolu-
tion or significant reduction of dysmenorrhea and heavy
menstrual bleeding. One patient had unresolved symptoms
requiring hysterectomy, and 2 patients with recurrent heavy
menstrual bleeding required endomyometrium resection.
Another patient had continued heavy menstrual bleeding
but refused further treatment [95].
Struble et al. Adenomyosis
Myometrial Reduction
Myometrial reduction is an approach to treating patients
with diffuse adenomyosis by removing the abnormal tissue
and then completing metroplasty during laparoscopy or
laparotomy [1]. Three approaches have been described. A
classic reduction method is when the uterus is dissected
longitudinally in the midline and there is resection of
the anterior and posterior portions of the myometrium [1].
Nishida et al [96] described covering the remaining part of
the uterus with the myometrium. They found this method
was not very successful because women developed adeno-
myosis and required hysterectomy within 1 year [96].
Fujishita et al [97] described a second method; in their
modified method, a transverse H incision is completed.
They compared 2 methods in 11 women (classic reduction,
n 5 5; transverse H incision, n 5 6). Between the 2 methods,
there was no difference in operation time, blood loss, and
volume of specimen removed. The modified group had a
greater improvement in pain, and there was 1 successful
pregnancy in this treatment group. No patients became preg-
nant in the classic group. A major complication of this
method is perforation during surgery, which occurred in 2 pa-
tients (40%) by the classic method and in only 1 patient
(17%) by the H incision technique [97].
Nishida et al [96] describe a third method of conservative
surgical management for diffuse uterine adenomyosis. They
preformed this in 44 patients with diffuse adenomyosis.
After surgery, menstruation resumed in all women within
3 months, and there was an improvement in dysmenorrhea,
menstrual blood loss, and anemia. Additionally, 2 women
became pregnant after surgery; 1 had an interstitial preg-
nancy, and the other was still pregnant after in vitro fertiliza-
tion/embryo transfer during the time of publication [96].
Removing diffuse adenomyosis is problematic in patients
who want to become pregnant because excision of the dis-
ease results in a reduced uterine volume. This is a concern
for future pregnancies because the reduction of myometrium
may predispose to spontaneous abortion or premature labor.
Additionally, this method causes uterine scarring, which
may contain small areas of adenomyosis leading to
decreased uterine wall strength and increased risk of uterine
rupture [82,85,96]. Although pregnancy rates after
these procedures have been low, these small studies have
shown an improvement in dysmenorrhea and heavy
menstrual bleeding, and, therefore, these conservative
surgeries may be an option for patients with symptomatic
diffuse adenomyosis who want to preserve their uterus [96].
MRI-guided Focused Ultrasound Surgery for Adenomyosis
Removing areas of adenomyosis in patients wanting
to maintain their fertility is challenging. As described
previously, conservative surgery can cause scarring and
negatively affect fertility. Therefore, magnetic resonance–
guided focused ultrasound surgery may provide an alterna-
tive treatment for patients with adenomyosis wanting to
preserve fertility. The treatment causes cell death and necro-
181
sis of the targeted adenomyotic tissue, preserving the
surrounding myometrium and uterine walls [98]. The ultra-
sound beams are focused on the target and cause thermal
coagulation and consequent necrosis. With the use of
MRI-guided ultrasound surgery, there is excellent anatomic
resolution and high thermal imaging sensitivity [90]. Com-
plications of this procedure include the risk of skin burn,
nausea and vomiting, and sciatic nerve palsy [1].
Most of the published data are only of small case series
and reports. Fukunishi et al [99] looked at 20 cases and found
after treatment patients had a significantly smaller mean
uterine volume and lower scores related to heavy menstrual
bleeding and bulk during a period of 3 to 6 months after
treatment. In another study, dysmenorrhea was assessed
3 months after treatment in 78 patients; complete relief
was reported in 39.1% of patients, significant relief in
37.7%, and partial relief in 13.0% [100]. Exacerbation of
pain did not occur [100].
Hysterectomy
Hysterectomy provides definitive treatment for patients
with adenomyosis and historically was the primary diag-
nostic and therapeutic option for patients. Commonly, it
is the treatment of choice for patients with significant symp-
toms who have completed childbearing. This procedure can
be completed laparoscopically, vaginally, or abdominally.
Among these options, vaginal hysterectomy is preferable
to an abdominal hysterectomy because of faster recovery and
lower morbidity [101]. However, Furuhashi et al [102] found
that patients with adenomyosis undergoing vaginal hysterec-
tomy had an increased risk of bladder injury. They reviewed
1246 vaginal hysterectomies and compared complication
rates between patients with leiomyomas (n 5 893) and
women with adenomyosis (n 5 535). They found there was
no significant difference between operative time and esti-
mated blood loss when analyzed by uterine weight between
the 2 groups. However, adenomyosis was associated with
an increased risk of bladder injury, which occurred in 0.7%
of patients in the leiomyoma group and 2.3% of patients in
the adenomyosis group. They thought this may be caused
by difficulty in identifying the supravaginal septum and the
vesicovaginal or vesicocervical planes [102].
The role of laparoscopy-assisted vaginal hysterectomy
was studied to see if this approach could decrease the risk
of bladder injury. However, in a study by Meikle et al [103],
there was no significant difference in the rate of bladder injury
or bowel and ureteral injuries between laparoscopy-assisted
vaginal hysterectomy and vaginal hysterectomy.
Further to this, laparoscopic hysterectomy is thought to
allow better dissection of anatomic planes and therefore pre-
vent injury [1]. It also has been shown to have other benefits
compared with vaginal hysterectomy. Candiani et al [104]
prospectively studied 60 patients randomized to either vaginal
hysterectomy or laparoscopic hysterectomy and then fol-
lowed for 12 months. Patients who had a laparoscopic hyster-
ectomy had a shorter hospital stay (2.7 days vs 3.2 days,
182
p % .001), less blood loss (83 mL vs 178 mL, p 5 .004), and
less postoperative pain (p 5 .023) [104]. Decreased postoper-
ative pain after laparoscopic hysterectomy compared with
vaginal hysterectomy was also found by Ghezzi et al [105]
in a prospective randomized trial comparing laparoscopic
and vaginal hysterectomy in 82 patients.
As mentioned previously, hysterectomy is commonly
offered to patients as definitive treatment in women with
significant symptoms who have completed childbearing.
However, it should be noted that there is a possibility that
patients may still experience pelvic pain after hysterectomy.
In a study by Stovall et al [106], they looked at the long-term
outcomes of 99 women who had hysterectomy (vaginal or
abdominal) for pelvic pain of at least 6 months’ duration.
Patients were excluded from the study if they had symptoms,
signs, previously documented findings, or findings at the
time of surgery of extrauterine disease. Histopathologic
studies found adenomyosis in 20.2%, leiomyomata in
12.1%, and both leiomyomata and adenomyosis in 2.02%
[106]. Patients were followed for an average of 21.6 months
after surgery, and 77.8% showed significant improvement.
However, 22.2% had persistent pelvic pain. Of those patients
with adenomyosis, 22.2% had persistent pelvic pain after the
hysterectomy [106].
Fig. 3
Summary of the various modalities used to identify adenomyosis.
Journal of Minimally Invasive Gynecology, Vol 23, No 2, February 2016
Conclusion
Adenomyosis is present when endometrial tissue is
abnormally located within the myometrium. The true inci-
dence of this disease is not known, but advancements in
imaging are allowing women to be identified more
frequently. Risk factors for the disease include exposure to
estrogen, parity, and prior uterine surgery. There are
numerous proposed theories of pathogenesis, but the 2
most commonly described theories are that adenomyosis
develops from invagination of the endometrial basalis
secondary to either myometrial weakness (because of preg-
nancy or surgery) or altered immunologic activity at the
endometrial-myometrial interface. The second commonly
proposed theory is that adenomyosis occurs from mullerian
rests; this theory is supported by studies that show ectopic
endometrium has different proliferative and biological
characteristics compared with a eutopic endometrium.
The 2 most common symptoms of adenomyosis are
heavy menstrual bleeding and dysmenorrhea. Other re-
ported symptoms include dyspareunia and chronic pelvic
pain. On examination, patients often have an enlarged
uterus that may be tender to palpation. Traditionally, a
diagnosis was only made histologically after hysterectomy.
Struble et al. Adenomyosis
Fig. 4
Summary of surgical options for adenomyosis.
However, studies have shown that a diagnosis can be made
with biopsies obtained during hysteroscopy and laparos-
copy. Noninvasive imaging can also be used to help guide
in the differential diagnosis. The 2 most commonly studied
imaging modalities are TVUS and MRI. Many studies have
shown that TVUS and MRI have respectable sensitivities
and specificities for adenomyosis; however, there is a
lack of common diagnostic language in the literature.
The most commonly reported findings on TVUS are heter-
ogenous myometrial echotexture; ill-defined foci of
abnormal myometrial echotexture; myometrial cysts; and
a globular, asymmetric uterus. Recent studies indicate
that the use of 3D TVUS is superior to 2D TVUS for the
diagnosis of adenomyosis and may allow for the diagnosis
of early-stage disease. The most common findings on
MRI include a large, regular, asymmetric uterus without
leiomyomas; abnormal myometrial signal intensity; junc-
tional zone thickening; and myometrial foci of high-
signal intensity on T1-weighted images as summarized in
Figure 3.
Management for patients can include medical options
such as NSAIDs, oral contraceptive pills, progestins, levo-
norgestrel IUD, danazol, GnRH agonists, and aromatase
inhibitors or surgical options such as endometrial ablation
and resection, UAE, myometrium or adenomyoma excision,
myometrial electrocoagulation, myometrial reduction,
MRI-guided focused ultrasound surgery, and for definitive
management, hysterectomy as summarized in Figure 4.
The lack of properly randomized trials accounts for the
insufficient evidence to support one treatment over another.
Factors that should be considered while making treatment
decisions include age, severity of symptoms, desire of future
fertility, and associated comorbidities such as endometriosis
and fibroids.
Supplementary Data
Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.jmig.2015.09.018.
183
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