Review Article

A Systematic Review of Adenomyosis: It Is Time to Reassess What

We Thought We Knew about the Disease
Megan Loring, MD, Tammy Y. Chen, MPH, and Keith B. Isaacson, MD
From the Center for Minimally Invasive Gynecologic Surgery, Newton-Wellesley Hospital, Newton, Massachusetts (all authors)

ABSTRACT Objective: To summarize and update our current knowledge regarding adenomyosis diagnosis, prevalence, and symptoms.
Data Sources: Systematic review of PubMed between January 1972 and April 2020. Search strategy included:
“adenomyosis [MeSH Terms] AND (endometriosis[MeSH Term OR prevalence study [MeSH Terms] OR dysmenorrhea
[text word] OR prevalence[Text Word] OR young adults [Text Word] OR adolesce* [Text Word] OR symptoms[Text
Word] OR imaging diagnosis [Text Word] OR pathology[Text Word].
Methods of Study Selection: Articles published in English that addressed adenomyosis and discussed prevalence, diagno-
sis, and symptoms were included. The included articles described pathology diagnosis, imaging, biopsy diagnosis, preva-
lence and age of onset, symptoms, and concomitant endometriosis.
Tabulation, Integration, and Results: Sixteen articles were included in the qualitative analysis. The studies are heteroge-
neous when diagnosing adenomyosis with differing criteria, protocols, and patient populations. The prevalence estimates
range from 20% to 88.8% in women who are symptomatic (average 30%−35%), with most diagnosed between the ages of
32 years and 38 years. The correlation between imaging and pathology continues to evolve. As imaging advances, newer
studies report that younger women who are symptomatic are being diagnosed with adenomyosis on the basis of both mag-
netic resonance imaging and/or transvaginal ultrasound. High rates of concomitant endometriosis create challenges when
discerning the etiology of pelvic pain. Symptoms that are historically attributed to endometriosis may actually be caused by
adenomyosis.
Conclusion: Adenomyosis remains a challenge to identify, assess, and research because of the lack of standardized diagnos-
tic criteria, especially in women who wish to retain their uterus. As noninvasive diagnostics such as imaging and myometrial
biopsies continue to improve, younger women with variable symptoms will likely create criteria for diagnosis with adeno-
myosis. The priority should be to create standardized histopathologic and imaging diagnoses to gain a deeper understanding
of adenomyosis. Journal of Minimally Invasive Gynecology (2020) 00, 1−12. © 2020 AAGL. All rights reserved.
Keywords: Abnormal uterine bleeding; Dysmenorrhea; Radiologic and pathologic diagnostic criteria; Pelvic pain; Endometriosis

Adenomyosis is a gynecologic condition defined as the
presence of endometrial glands and stroma deep within the
myometrium, causing myometrial hypertrophy, hyperpla-
sia, and fibrosis [1−5]. The most common symptoms are
heavy menstrual bleeding and severe dysmenorrhea.
Patients with adenomyosis often have concomitant endome-
triosis, making it difficult to distinguish the etiology of pel-
vic pain and other menstrual symptoms [2]. Currently, the
Dr. Isaacson is a consultant for Karl Storz and Medtronic. The other
authors declare that they have no conflict of interest.
Corresponding author: Megan Loring, MD, Center for Minimally Invasive
Gynecologic Surgery, Newton-Wellesley Hospital, 2014 Washington St,
2nd floor, MIGS/Women’s Health, Newton, MA 02462.
E-mail: mloring@partners.org
Submitted June 29, 2020, Revised October 19, 2020, Accepted for publication
October 20, 2020.
Available at www.sciencedirect.com and www.jmig.org
pathogenesis of the disease remains unclear because of the
varying phenotypic expressions. Studies have reported that
key pathogenic mediators of adenomyosis symptoms
include sex steroid hormones, inflammation, neoangiogenic
growth factors, extracellular matrix enzymes, and neuro-
genic factors [3].
Traditionally, adenomyosis has been histologically diag-
nosed at the time of hysterectomy, resulting in more diag-
noses in patients in their late reproductive years or in
women who are perimenopausal [2]. Owing to a lack of
standardized histologic diagnostic criteria, the diagnosis
can be somewhat subjective and influenced by awareness of
the patients’ history and the number and site of the myome-
trial sections [4]. However, recent advances have created
the opportunity to diagnose adenomyosis with less-invasive
methods such as transvaginal ultrasound (TVUS), magnetic
resonance imaging (MRI), and analysis of hysteroscopic

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https://doi.org/10.1016/j.jmig.2020.10.012

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2 Journal of Minimally Invasive Gynecology. Vol 00, No 00, 00 2020
biopsies [2]. As imaging diagnostics improve, more patients
who are symptomatic, including women undergoing fertil-
ity evaluations and even adolescents, are being diagnosed
earlier. This shift in diagnosis suggests that adenomyosis is
not a condition affecting only women who are older and
multiparous [2,6,7]. Despite these improvements in imag-
ing, radiologic diagnostic criteria still remain unstandard-
ized among institutions [2]. Inconsistent diagnostic
methods and definitions make estimating an accurate preva-
lence nearly impossible, which results in wide discrepan-
cies. The reported prevalence of adenomyosis ranges from
5% to 70%, whereas the mean frequency at hysterectomy is
approximately 20% to 30% [2].
Adenomyosis is a complex, poorly understood disease
with varying symptoms that often coexists with endometri-
osis. Although histopathologic diagnosis of adenomyosis at
the time of hysterectomy is the historic “gold standard,” we
now have the ability to detect the disease in younger women
with advanced imaging techniques. The accuracy of these
imaging findings, especially when compared with biopsy
data, is still being refined and standardized [8,9]. Being
able to accurately diagnose younger patients with less-inva-
sive methods will allow us to better estimate true preva-
lence and to learn about the natural history of the disease.
Moreover, women in their peak fertility years will be able
to have more knowledge of their condition, thus potentially
guiding reproductive choices. The aim of this review was to
summarize and update our current knowledge regarding
adenomyosis diagnosis, prevalence, and symptoms.
Methods
Search Strategy
A systematic literature review was conducted following
the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses guidelines by searching PubMed from Janu-
ary 1972 to April 2020 (Fig. 1) [10]. The search string
included “adenomyosis [MeSH Terms] AND (endometri-
osis[MeSH Term OR prevalence study [MeSH Terms] OR
dysmenorrhea[Text Word] OR prevalence[Text Word] OR
young adults [Text Word] OR adolesce* [Text Word] OR
symptoms[Text Word] OR imaging diagnosis [Text Word]
OR pathology[Text Word].
The inclusion criteria were as follows: articles published
in English, articles with the primary topic being adenomyo-
sis, randomized controlled trials, and observational studies.
The exclusion criteria were as follows: articles discussed
only treatment, articles that did not mention adenomyosis,
review articles, and animal studies. The studies were ini-
tially screened by 2 authors (M.L. and T.C.) through title
and abstract review, and duplicates were removed. During
full-text review, the included articles were limited to those
that specifically addressed adenomyosis; met the inclusion
criteria; and discussed prevalence, diagnosis, and symptoms
(Fig. 1).
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Grading of Recommendations, Assessment, and
Evaluation Quality Assessment
The quality of the included studies was assessed using
the Grading of Recommendations, Assessment, and Evalua-
tion methodology, which is a method to assess certainty in
evidence and quality of evidence (Table 1) [11]. Two
authors (M.L. and T.C.) independently assessed the quality
of the studies on the basis of the Grading of Recommenda-
tions, Assessment, and Evaluation criteria and definitions
for the type of study or evidence as well as the 4 areas of
study limitations, consistency, directness, and precision.
Randomized controlled studies were given more weight
than observational studies. For study limitations, risk of
bias was evaluated on the basis of study design, methodol-
ogy, and analysis. Consistency was based on the degree of
consistency of results within and across different studies.
Directness was based on the generalizability of study popu-
lation and evidence to the population of interest. Precision
was based on the reported effect size and the precision of
effect size. Scores for each category were calculated and
were summed to assign a score from 0 to 4, with 4 repre-
senting the highest quality.
Results
A total of 78 articles were found through a search on
PubMed. After reviewing the titles and abstracts, 42 were
included in the full-text review; of these, 16 articles met the
inclusion criteria and were selected for analysis (Table 1).
In our review, we encountered several different definitions
and diagnostic criteria; therefore, we separated the defini-
tions into pathologic, imaging, and biopsy diagnosis
(Table 2). The other articles were categorized into themes
of prevalence and age of onset, symptoms, and concomitant
endometriosis.
Pathologic Diagnosis
Pathologists worldwide still struggle to define adeno-
myosis in a consistent and reproducible way, stressing the
importance of a standard pathologic definition. Definitions
for adenomyosis vary widely at the institutional level,
regionally, and worldwide. Luciano and Tellum [8,9]
describe adenomyosis as endometrial glands and stroma in
the myometrium >2.5 mm from the endomyometrial bor-
der. The diagnosis is then graded according to the depth of
the myometrial involvement: grade 1, 2, or 3 corresponding
to the inner third, two-thirds, or entire myometrium
[8,9,12]. Others use high-power fields to define adenomyo-
sis instead of distance. Pervez and Javed [13] define the dis-
ease as endometrial glands and stroma found in the
myometrium at a distance of at least 1 low-power field
from the endometrial−myometrial junction. Others use
both approaches in their definition. For instance, either
ectopic endometrium present ≥2 mm deep in the myome-
trium or ectopic endometrium visible ≥1 microscopic field
Loring et al. A Systematic Review of Adenomyosis 3

Fig. 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram.

at 10-fold magnification from the endomyometrial junction
merit an adenomyosis diagnosis. Adenomyosis foci are
often circumferentially surrounded by bundles of hypertro-
phic smooth muscle cells or stromal fibroblasts [14].
Although only a few articles define the surrounding changes
of hypertrophy and reactive fibrosis as adenomyosis, these
changes may be as important in the pathogenesis of the dis-
ease as the actual presence of ectopic endometrial glands
[15−17].
Not only do pathologic definitions differ; the protocols
for histologic sectioning also vary among institutions.
Some protocols specify a minimum of 3 sections, whereas
others only specify the thickness of the tissue slices [13].
The required thickness ranges from 5 mm to 10 mm or even
from 7 mm to 12 mm [9,12,14]. The lack of a standard path-
ologic protocol makes it impossible to diagnose and discuss
adenomyosis in a rigorous, reproducible manner.
In summary, it is not surprising that we lack a clear, stan-
dard pathologic definition of adenomyosis. In fact, histori-
cally there has been such little interest in adenomyosis
among pathologists that a recently published gynecologic
pathology textbook dedicated just 1 page to the topic of
adenomyosis [18]. Most current literature supports the diag-
nosis of adenomyosis on the basis of the presence of

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 4
Table 1
Summary of studies included in systematic review including patient age, diagnostic method used for adenomyosis, estimated prevalence of adenomyosis (if calculated in the paper), and GRADE score
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Author (year) Study design Total Participants Age (years) Diagnostic method or Estimated prevalence of GRADE
sample criteria adenomyosis score
Lucianio [8] (2013) Prospective 54 Symptomatic premenopausal Mean age 42.1 Histology (ultrasound 66.6% (n = 36) 3
patients guided targeted biopsy)
Tellum [9] Prospective 81 Premenopausal patients Mean: 42.4 § 4.5 Histology (ultrasound 57% (n = 46) 1
For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.

(2019) undergoing hysterectomies guided targeted biopsy)

Tellum [12] Retrospective 93 Premenopausal patients -Adenomyosis: 43.5§ 4.9 Pathology 61% (n = 57) 1
(2019) undergoing hysterectomies -No adenomyosis:
41.2§ 4.2
Pervez [13] (2013) Retrospective 861 Symptomatic patients under- Pathology 34.4% (n = 296) 0
going hysterectomies
Stamatopoulus [14] Prospective 135 Patients undergoing Mean: 46.7 § 11.20 Pathology 17.8% (n = 24) 2
(2012) hysterectomy
Chapron [20] (2017) Cross-sectional 292 Non-pregnant patients under- -Range: 18 to 42 MRI Total study population: 1
going surgery for benign -Endometriosis (31.2 § 59.9% (n = 175)
gynecological conditions 5.3) - Endometriosis group:
-Endometriosis-free 64.6%
(32.9§6.2) (n = 153)
- Endometriosis-free:
40.0%
(n = 22)
Leyendecker [21] Cross-sectional 143 Patients indicated for MRI Range: 22-42 MRI Total study population: 2
(2015) (mean = 32.3) 88.8% (n = 127)
- Prevalence of adeno-

Journal of Minimally Invasive Gynecology. Vol 00, No 00, 00 2020

myosis in
endometriosis: 91.1%
Marcellin [22] Cross-sectional 39 Patients with histologically -Study group (with MRI 33.3% (n = 39) 1
(2018) proven bladder deep infil- aFOAM): 31.3§ 3.5
trating endometriosis -Control group (without
aFOAM): 33.3§5.5
Kissler [23] (2007) Prospective 70 Patients with severe Range: 21-41 MRI Patients with dysmenor- 1
dysmenorrhea (mean = 31.1) rhea for 1-10 years:
52.5% (n = 21)

Patients with dysmenor-

rhea for 11-25 years:
87% (n = 26)
Parker [24] (2006) Clinical Trial 53 Symptomatic patients - JZ <8 mm: 30.9§ 1.1 MRI 15% (n = 6) 3
-JZ 8 to <11mm:
33.8§6.4
- JZ 11 mm: 39.8.§ 3.5
Naftalin [26] (2012) Prospective 985 Symptomatic patients Median: 40 TVUS 20.9% (n = 206) 1
(IQR 32-48)
Loring et al. A Systematic Review of Adenomyosis 5

endometrial glands and/or stroma 2.5 mm from the endo-

aFOAM = anterior focal adenomyosis of the outer myometrium; GRADE = Grading of Recommendations, Assessment, and Evaluation; IQR = interquartile range; JZ = junctional zone; MRI = magnetic resonance imaging;
GRADE
metrial−myometrial border. Many publications suggest
score
that the more in-depth the samples are assessed (i.e., the

-1
2

1
more tissue slices examined by pathology), the more often
adenomyosis is found within a hysterectomy specimen
Estimated prevalence of

[8,19].
Diffuse adenomyosis:
34.0% (n = 53)

22.0% (n = 157)
22% (n = 157)
adenomyosis

Imaging Diagnosis
The imaging definition of adenomyosis continues to
evolve as technologies and techniques improve. Practi-
tioners are relying more on the noninvasive methods of
TVUS and MRI to recognize the imaging characteristics of
adenomyosis. This review will demonstrate that there are
Diagnostic method or

still limitations in imaging accuracy and standardization,

especially when correlating imaging to tissue biopsy diag-
nosis of the disease.
criteria

TVUS

TVUS

TVUS
MRI

MRI

MRI
MRI is used to distinguish adenomyosis from other uterine
diseases and assess the abnormal thickening of the junctional
zone (JZ) or the endomyometrial border, a sign of adenomyo-
sis. Despite increased use of MRI to assess for adenomyosis,
IV: 38.6 § 4.0
(mean = 32.5)

III: 34.3§ 4.7

II: 36.9 § 6.1
(IQR 23-27)

(IQR 30-43)

(IQR 30-43)

the cutoff of JZ thickness needed for diagnosis is not stan-

Range: 17-46

I: 38.7 § 5.6
Age (years)

Median: 24

Median: 38

Median: 38

dardized. Numerous studies used JZ maximum (JZmax) thick-

ness of 12 mm to signify adenomyosis [12,20−22], whereas
others used lower cutoffs of 9 mm [23] and 11 mm [24].
What makes the JZ thickness even more controversial is that
no one clearly understands why the JZ enhances differently
Patients surgically treated for
Symptomatic premenopausal

Symptomatic premenopausal

on MRI than the outer myometrium despite both tissues

Patients with regular men-

appearing identical on hematoxylin and eosin stains. In addi-

Symptomatic patients

tion, the JZ has estrogen and progesterone receptors that lead

to a variation in thickness throughout the menstrual cycle
adenomyosis
strual cycles

[25]. It is unclear why a thickened JZ would correlate patho-

Participants

patients

patients

physiologically to the presence of endometrial glands and

stroma deep in the myometrium.
JZ uniformity and the presence of high-intensity spots
within the myometrium on MRI are viewed as potential
sample

signs of an increased likelihood of adenomyosis [6,15]. In

Total

156

227

718

714

152

particular, Tellum et al [12] found that a JZmax on preopera-

tive MRIs among women who were symptomatic was not
associated with the histologic diagnosis of adenomyosis
Cross-sectional

Retrospective

(area under the curve 0.57; p = .26). JZ thickness also did

Study design

Prospective

Prospective

Prospective

not differ significantly between those with adenomyosis

and those without [12]. However, the presence of an irregu-
lar JZ did show a strong association with a histologic diag-
TVUS = transvaginal ultrasound.

nosis of adenomyosis, with sensitivity of 74% and

specificity of 83% among women who were symptomatic
Pinzauti [27] (2015)

Naftalin [29] (2016)

Naftalin [30] (2014)

[12]. Stamatopoulos et al [14] demonstrated MRI sensitivity

Kunz [28] (2007)

Kishi [41] (2012)

of 46.1% and specificity of 99.1% among women with

Author (year)
Continued

heavy bleeding and/or a bulky uterus. Although largely con-

Table 1

sidered the most accurate diagnostic imaging method for

adenomyosis, MRI still has limitations, with inconsistent
specificity and sensitivity among studies.

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6 Journal of Minimally Invasive Gynecology. Vol 00, No 00, 00 2020

Table 2
Type of diagnostic method used (histology, MRI, or TVUS) to define adenomyosis along with the exact definition used in each study

Author Diagnosis method Definition/criteria

Luciano et al, (2013) [8] Histology Presence of endometrial glands and stroma in the myometrium >2.5 mm from the
endometrial border
Tellum et al, (2019) [9] Histology Presence of ectopic endometrial glands and stroma at 2.5 mm below the endometrial-
myometrial junction
Tellum et al, (2019) [12] MRI JZ cutoff of 12 mm
Presence of one or more JZmax ≥12 mm, myometrial cysts, or adenomyoma
Pervez et al, (2013) [13] Histology Endometrial glands and stroma were found in the myometrium at a distance of one
low power field from the endometrial-myometrial junction
Chapron et al, (2017) [20] MRI JZ cutoff of 12 mm
Leyendecker et al, (2015) [21] MRI JZ cutoff of 12 mm
Marcellin et al, (2018) [22] MRI JZ cutoff of 12 mm
Kissler et al, (2007) [23] MRI JZ cutoff of 9 mm
Pinzauti et al, (2015) [27] TVUS Asymmetrical myometrial thickening
Hypoechoic striation
Parallel anechoic lacunae or cysts
Heterogeneous myometrium
Naftalin et al, (2016) [29] TVUS Asymmetrical myometrial thickening
Linear striations
Parallel shadowing
Myometrial cysts
Hyperechoic striations
Adenomyoma
Irregular endometrial-myometrial junction
Kishi et al, (2012) [41] MRI Four discrete subtypes:
I: Intrinsic- Adenomyosis had developed in connection to the thickened JZ and
healthy muscular structures were preserved outside the adenomyosis
II: Extrinsic- Adenomyosis was located in the outer shell of the uterus, JZ was kept
intact without aberrancy, and healthy muscular structures were preserved in
between the adenomyosis and the JZ
III: Intramural- Adenomyosis residing solitarily without any geographic relationship
to the JZ or the serosa
IV: Indeterminant- Adenomyosis that did not meet any of the other categorization
criteria

JZ = junctional zone; MRI = magnetic resonance imaging; TVUS = transvaginal ultrasound.

TVUS
Previously, the JZ was only visible on MRI, but with 3-
dimensional (3D) TVUS, we can now assess the JZ alongside
the presence or absence of other key features of adenomyosis
on 2-dimensional (2D) TVUS. Naftalin et al [26] looked at
the prevalence of adenomyosis at a general gynecology clinic
in both women who were symptomatic and those who were
asymptomatic. An adenomyosis diagnosis was likely based
on the presence of any 1 of the features listed in Table 3. In
the small proportion of the women who underwent hysterec-
tomies, TVUS diagnoses were corroborated with histology
[26]. The sensitivity and specificity of TVUS-diagnosed
adenomyosis were 81.8% (95% confidence interval [CI],
52.3%−94.9%) and 81.3% (95% CI, 57.0%−93.4%),
respectively [26]. The positive predictive value was 75%,
and the negative predictive value was 86.7% [26].
Pinzauti et al [27] looked at TVUS features only in a
cohort of both women who were symptomatic and those
who were asymptomatic, aged 18 years to 30 years, and
seeking contraception [27]. Adenomyosis was suggested
when at least 1 of the TVUS features was present (Table 3).
Diffuse adenomyosis was found in 34% of all women. The
most common sonographic feature observed was asymmet-
rical myometrial thickening of the uterine walls (56.6%).
At 3D-TVUS assessment, women with 2D-TVUS features
of diffuse adenomyosis had significantly higher measure-
ments of JZmax, JZmin, and JZdiff than women without 2D-
TVUS features. Given the young age of the subjects, no
pathologic correlations were made [27].
Biopsy Studies
To advance our understanding of the mechanisms of
adenomyosis, imaging findings need to be corroborated
with histopathologic findings. Luciano et al [8] conducted
targeted myometrial biopsies on areas identified on preoper-
ative 2D- and 3D-TVUS as markers of possible adenomyo-
sis during laparoscopic hysterectomy. Of the 32 patients
who were not on hormonal therapy at the time of surgery
and did not have a history of endometrial ablation, targeted

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Loring et al. A Systematic Review of Adenomyosis
Table 3
Specific TVUS features used to define adenomyosis. In each study, adenomyosis was suggested for the patient if 1 or more features were present
Imaging features
Naftalin [29] (2016)
TVUS features Asymmetrical myometrial thickening
Linear striations
Parallel shadowing
Myometrial cysts
Hyperechoic islands
Adenomyoma
Irregular endometrial−myometrial junction
TVUS = transvaginal ultrasound.
biopsy specimens demonstrated adenomyosis in 26 patients.
The overall prevalence of adenomyosis in hysterectomy
specimens was 66.6% [8].
In a study by Tellum et al [9], core biopsy specimens
were obtained in the operating room before hysterectomy in
81 women. Ultrasound guidance was used to biopsy any
possible direct sign of adenomyosis, such as anechoic intra-
myometrial cysts or hyperechoic islets. If no adenomyosis
was visible, random biopsies were taken. Of the 46 women
with adenomyosis found in their hysterectomy specimen,
only 10 (22%) had adenomyosis in their biopsy specimen
[25]. Despite the demonstrated safety of the biopsies, a low
rate of confirmation of adenomyosis questions the diagnos-
tic utility of this method. These biopsy studies also under-
score the need to corroborate histopathology with not only
imaging findings but also with a patient’s symptoms.
Prevalence
Kissler et al [23] analyzed the prevalence of MRI-sus-
pected adenomyosis in patients with severe dysmenorrhea
and compared it with the duration of dysmenorrhea. The
patients were grouped into 2 groups by duration of dysme-
norrhea: group 1 included patients with a history of dysme-
norrhea between 1 year and 10 years (mean age: 30.07 §
4.37 years), and group 2 included patients with a history of
dysmenorrhea for more than 11 years (mean age: 33.31 §
4.58 years) [10]. Adenomyosis was detected in 52.5% of
the patients in group 1 and in 97% of the patients in group
2. The study concluded that the duration of dysmenorrhea
strongly influences the development of adenomyosis [10].
In Kunz et al [28], patients (mean age: 32.5 years) with a
history of infertility and regular menstrual cycles underwent
MRI for evaluation. Regardless of an endometriosis diagno-
sis, the diameter of the JZ increases with age, and at the age
of 34 years both study groups had parallel and sharp increases
in the diameter of the JZ, suggesting adenomyosis [28].
Leyendecker et al [21] examined the association of
adenomyosis and endometriosis using the measurement of
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7
Author
Pinzauti [27] (2015)
Asymmetrical myometrial thickening
Hypoechoic striations
Parallel shadowing
Myometrial anechoic lacunae or cysts
Heterogeneous myometrium
the diameter of the JZ together with the presence of other
features of adenomyosis on MRI, such as cystic structures
within the myometrium, focal thickening of the JZ, or JZ
irregularity. Using this method, the prevalence of adeno-
myosis was 88.8% in patients who were symptomatic and
premenopausal [21].
In a cohort of women who were premenopausal and who
received both ultrasound and hysterectomy, the prevalence of
histologically suspected adenomyosis was 66.6% [8]. The
ultrasounds were found to have strong specificity and positive
predictive value [8]. Pinzauti et al [27] used both 2D- and
3D-TVUS to evaluate the prevalence of diffuse adenomyosis
in women aged 18 years to 30 years who were nulligravid
and without a history of endometriosis or other gynecologic
pathologies [27]. Of the 156 women in the study, 34.0%
showed ultrasound features of diffuse adenomyosis on 2D-
TVUS [27]. Having the features on 2D-TVUS was associated
with an increased incidence of both dysmenorrhea and heavy
menstrual bleeding and the likelihood of having 3D-TVUS
features of adenomyosis. Another ultrasound study of both
patients who were symptomatic and those who were asymp-
tomatic at the gynecology clinic had a lower prevalence of
adenomyosis of 21.9% [26].
Each of the studies mentioned has different diagnos-
tic criteria and inconsistent prevalence estimates.
Another limitation in comparing prevalence among the
studies is the diversity of patient populations. Without
consistent diagnostic criteria for MRI and TVUS, it
remains difficult to conduct epidemiologic studies on
adenomyosis.
w?>In summary, the older data on the prevalence of
adenomyosis suggesting that it is more likely present in
women who are multigravid and aged between 40 years and
50 years was most likely a reflection on those at risk for a
hysterectomy. These older studies did not look at the likeli-
hood of finding the disease in women who wished to pre-
serve their uterus. Of note, the accuracy of ultrasound and
MRI is not yet at a stage where it reflects the true preva-
lence of the disease.
8 Journal of Minimally Invasive Gynecology. Vol 00, No 00, 00 2020
Symptoms
Discerning the etiology of dysmenorrhea and heavy
menstrual bleeding remains a challenge. Although most
women with sonographic features of adenomyosis have 1
or both of these symptoms, many are asymptomatic.
Eighty-three percent of the women who had sonographic
features of diffuse adenomyosis were symptomatic [24],
whereas in another study 6% of the women with ultrasound
features of adenomyosis had no dysmenorrhea [21]. In a
large prospective study, the severity of menstrual pain was
associated with the number of ultrasound features of adeno-
myosis [29]. In addition, a 22% increase in menstrual blood
loss was seen for each additional feature of adenomyosis
seen on TVUS [30]. In some patients, infertility may be the
only sign of uterine disease, which often leads to an imag-
ing diagnosis [28,31].
Concomitant Endometriosis
Many women with adenomyosis also have concomitant
gynecologic conditions such as endometriosis, thus making
a “pure” diagnosis of adenomyosis nearly impossible.
Therefore, it is important to consider how much of a wom-
an’s dysmenorrhea is truly attributable to endometriosis
without concurrently assessing for adenomyosis. Chapron
et al [20] evaluated the relationship between MRI appear-
ance of adenomyosis and endometriosis in patients who
were symptomatic. Among patients with histologically
diagnosed endometriosis, the prevalence of adenomyosis
was 64.6% [20]. In 55 women who were symptomatic and
without surgical evidence of endometriosis, diffuse adeno-
myosis on the basis of MRI was found in 34.6% [20].
Similarly, after surgical excision of endometriosis,
chronic pelvic pain was significantly more likely to persist
with JZ >11 mm on preoperative MRI, leading the authors
to conclude that adenomyosis contributes to chronic pelvic
pain in women with endometriosis [24]. In the same study,
increased JZ thickness was not associated with any particu-
lar American Society for Reproductive Medicine endome-
triosis stage; a total of 6 subjects had JZ >11 mm: three
with American Society for Reproductive Medicine stage I
endometriosis, 2 with stage II, and 1 with stage III [24].
Conversely, there was no relationship between endometri-
osis phenotypes and MRI appearance of adenomyosis [24].
Focal adenomyosis in the outer myometrium was signifi-
cantly increased in women with endometriosis compared
with the control subjects [24]. If only endometriosis is being
addressed surgically in patients, a significant portion will
continue to have symptoms because adenomyosis is not
being treated. In Leyendecker et al [21], the prevalence of
endometriosis was 80.6% in women diagnosed with adeno-
myosis using MRI and a JZ cutoff of 9 mm. In patients with
endometriosis, the prevalence of “visualized” adenomyosis
was 91.1% [21]. The prevalence of adenomyosis in patients
with endometriosis and with dysmenorrhea of more than 11
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years’ duration was 87% [23]. These data show that long-
standing dysmenorrhea, previously attributed to endometri-
osis, is perhaps more likely due to adenomyosis [23].
In summary, many symptoms we had attributed to endo-
metriosis are likely due to adenomyosis. This is because we
did not know we could use ultrasound or MRI to assist with
the diagnosis. We only saw “symptomatic” atypical lesions
in the peritoneum at the time of laparoscopy and assumed
that these noninfiltrating lesions were responsible for symp-
toms such as dysmenorrhea and dyspareunia.
Discussion
Adenomyosis remains a poorly understood gyneco-
logic disorder. Widely held beliefs that adenomyosis
only affects women who are multiparous and aged
between 40 years and 60 years—the “perimenopausal
years”—are erroneous [6]. These epidemiologic data are
historically accepted as “fact” because histopathologic
evaluation at the time of hysterectomy used to be the
only diagnostic option. Previously, diagnoses of adeno-
myosis were not considered for women with dysmenor-
rhea and/or heavy menstrual bleeding who chose not to
undergo hysterectomy during gynecologic consultations.
Advances in imaging techniques and technology allow a
better glimpse into the myometrium and, specifically,
the JZ. Visual changes consistent with adenomyosis on
MRI such as JZ thickening and JZ irregularity allow for
presumptive diagnoses of adenomyosis at a sensitivity
of 70% to 88% and specificity of 91% [6]. Similarly,
TVUS has an accuracy of approximately 89% [8]; how-
ever, the weights of different ultrasound features and the
number of features needed to establish a reliable diagno-
sis remain unclear [5]. Regardless, with at least 1 TVUS
feature, many women receive a noninvasive diagnosis of
adenomyosis to explain their debilitating menstrual
symptoms. Simply having an explanation for symptoms
is empowering and can allow for improved treatment
recommendations and fertility considerations.
When presumptive diagnoses of adenomyosis that are
based on imaging are correlated with histopathology, the
accuracy of TVUS decreases [8,9]. This can be attributed to
nonstandard pathologic diagnoses or even pathologist bias,
in addition to the previously mentioned subjectivity in
imaging and lack of standardization. Several studies have
shown that the incidence of adenomyosis increases with
increased sectioning of uteri at the time of hysterectomy.
Bird et al [32] reported adenomyosis in 31% of the 200 con-
secutive hysterectomies examined; when 6 additional
blocks were examined, and sub-basal lesions were included,
the prevalence increased to 61.5% [33].
In a similar vein, unpublished data from our institu-
tion show persistent discrepancies between the imaging
and histopathologic diagnoses of adenomyosis (Table 4).
Retrospective analysis of 130 consecutive patients who
were premenopausal and who had a preoperative TVUS
Loring et al. A Systematic Review of Adenomyosis 9

at our clinic before undergoing total laparoscopic hyster- Table 4

ectomy for possible adenomyosis symptoms such as
abnormal uterine bleeding, dysmenorrhea, dyspareunia, Unpublished data from our clinic at the Center for Minimally Inva-
chronic pelvic pain, and endometriosis showed signifi- sive Gynecologic Surgery at Newton-Wellesley Hospital, 2018 to
2019
cant false-negative and false-positive TVUS results com-
pared with the pathologic findings when using the Total patients undergoing hysterectomy Number %
published Morphological Uterus Sonographic Assess-
ment criteria [34]. Our false-positive rate of 14.6% and 130 100
TVUS diagnosis of adenomyosis 37 28.5
false-negative rate of 23.8% are very similar to those in Pathology diagnosis of adenomyosis 49 37.7
Champaneria et al [35]. True positive 18 13.8
The role of hysteroscopy as a diagnostic tool can also be False positive 19 14.6
considered in the evaluation of possible adenomyosis. The True negative 62 47.7
visual changes of the endometrium suggestive of adeno- False negative 31 23.8
Sensitivity — 36.7
myosis can be seen, such as hypervascularization, straw- Specificity — 76.5
berry pattern, endometrial defects, and submucosal Positive predictive value — 48.6
hemorrhagic cysts [36,37]. Moreover, hysteroscopy pro- Negative predictive value — 66.7
vides a means for collecting histologic biopsy samples
TVUS = transvaginal ultrasound.
under direct visualization by using a hysteroscopic biopsy
tool and ultrasound guidance. Endomyometrial biopsy had
a specificity of 78.46% but a sensitivity of only 54.32%,
which was attributed to a high number of false-negative In several studies, the average age of women showing
results in cases of deep endometriosis [38]. When hysteros- symptoms of adenomyosis and visual changes consistent
copy is indicated in the evaluation of abnormal uterine with the disease on TVUS or MRI ranged from 32 years to
bleeding or subfertility, practitioners should be aware of the 38 years, demonstrating that this disease is present in youn-
visual changes consistent with adenomyosis. ger women [21,23,26]. Gynecologists are failing to recog-
The prevalence estimates of adenomyosis range from nize adenomyosis as a potential common cause of
5% to 70%, further confirming the inability to determine dysmenorrhea and heavy menstrual bleeding in women
the true prevalence [39]. These discrepancies are attributed who are aged between 20 years and 30 years. Besides
to varied imaging diagnostic criteria, nonstandardized his- being a significant cause of dysmenorrhea and heavy
tologic definitions, and heterogeneous patient populations menstrual bleeding, adenomyosis adversely affects fertil-
[2,39]. Historically, most prospective studies have shown ity. With many women opting to delay childbearing, it is
the prevalence to be approximately 20% [39], whereas we not surprising that this disease is now emerging as a major
estimate the prevalence to be closer to 30% [13,20,21,27]. contributor to infertility. Women with adenomyosis have

Table 5
Quick-reference summary of the salient symptoms and diagnostic features from the studies included in our review

Diagnosis
MRI MRI findings Sensitivity (%) Specificity (%) Reference
JZmax >12 mm plus focal not well- 46.1 99.1 Stamatopoulos et al, 2012 [14]
demarcated areas present in
myometrium
Irregular JZ (not correlated with spe- 74 83 Tellum et al, 2019 [12]
cific thickness, specifically not
JZmax >11 mm)
US US features, see Table 3 Sensitivity (%) Specificity (%) Reference
Presence of 1+ feature 71.4 88.9 Naftalin et al, 2016 [29]
Presence of 2+ features 92 83 Luciano et al, 2013 [8]
Biopsy % Notes Reference
Adenomyosis identified histopatho- 22 — Tellum et al, 2019 [9]
logically in both the biopsy and
final hysterectomy specimen
81 *Excluded women with previous Luciano et al, 2013 [8]
uterine treatments

JZ = junctional zone; MRI = magnetic resonance imaging; TVUS = transvaginal ultrasound; US = ultrasound.
* Special note.

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10 Journal of Minimally Invasive Gynecology. Vol 00, No 00, 00 2020

lower implantation rates and higher miscarriage rates than
those without adenomyosis [5]. Clinical pregnancy rates
are significantly lower in women with adenomyosis diag-
nosed with TVUS than in those in a nonadenomyosis
group, 23.6% vs 44.6%, respectively, even after normali-
zation of the groups for age using regression analysis
[16]. Various mechanisms are proposed for infertility in
adenomyosis, including impaired uterotubal transport and
aberrant endometrial function as well as receptivity and
dyssynchronous uterine contractions.
Concomitant endometriosis and adenomyosis certainly
exist, although the rates of coexistence vary. The rates of
endometriosis in adenomyosis, and vice versa, could be as
high as 80.6% and 91.1%, respectively [21]. As such, it is
plausible that we are diagnosing and treating early-stage
endometriosis, but missing a diagnosis of adenomyosis as a
major cause of dysmenorrhea, especially among younger
women. This helps explain why up to 20% of the women
with surgically treated endometriosis do not have improve-
ment in their pain symptoms after 6 months postsurgery [40].
It can be challenging to ascertain an accurate diagnosis
of adenomyosis in a young woman with bothersome gyne-
cologic symptoms. However, it is important to recognize
and treat the clinical implications of adenomyosis and to
educate patients, especially when considering future fertil-
ity desires. We propose the use of Table 5 as a quick-refer-
ence summary of the salient diagnostic features from the
studies included in our review. Moreover, we have created
a diagnostic flow chart (Fig. 2) for practitioners to use as a
clinical tool to evaluate women with menstrual complaints,
including subfertility. It is our hope that these clinical tools
will increase the ability of young women to be properly
diagnosed and educated about their disease.
Conclusion
Adenomyosis continues to mystify scientists, gynecolo-
gists, and patients alike. A lack of standard histopathologic
and imaging diagnoses makes this disease challenging to
study. As we learn more about adenomyosis, we have come

Fig. 2
Diagnostic flow chart for practitioners to use as a clinical tool to evaluate women with menstrual complaints, including subfertility. Follow instructions
on the flow chart to evaluate symptoms and assign points. Number of points plus clinical evaluation are used together to assess “how likely” a diagnosis
of adenomyosis may be.

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Loring et al. A Systematic Review of Adenomyosis
to realize that it is not only a disease of women who are mul-
tiparous and perimenopausal. Instead, it is potentially present
in 30% to 35% of the women and can start when women are
aged between 20 years and 30 years. Although dysmenorrhea
and heavy menses are common symptoms, sometimes subfer-
tility is the only sign of uterine disease. Moreover, young
women are being diagnosed and treated for endometriosis
only, thus likely failing to recognize and treat their real dis-
ease in their uterus. We must shift our thinking to considering
adenomyosis as a potential diagnosis in all women. Standardi-
zation of imaging and histopathologic diagnoses is a priority.
With standardization, research efforts will be more robust,
and hopefully our understanding of this debilitating condition
will evolve more quickly.
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