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The Obstetrician & Gynaecologist 10.1576/toag.11.1.41.27467 www.rcog.org.uk/togonline 2009;11:41–47 Review

Review Adenomyosis uteri:

an update
Authors Mohamed K Mehasseb / Marwan A Habiba

Key content:
• Adenomyosis uteri is defined by the presence of endometrium in the
myometrium.
• The prevalence in asymptomatic women remains unknown.
• It is commonly associated with other pathologies.
• Hysterectomy remains the main surgical option for women whose families
are complete.

Learning objectives:
• To understand the theories regarding the aetiology.
• To appreciate the clinical picture and complications.
• To learn about current treatment modalities.

Ethical issues:
• Counselling women with adenomyosis uteri is challenging when the clinical
significance of the condition is uncertain.
• Are more expensive diagnostic tests, such as magnetic resonance imaging,
justifiable?
• Is the risk–benefit weighted against invasive investigation?
Keywords endometrial–myometrial interface / endomyometrial ablation /
hysterectomy / magnetic resonance imaging (MRI)
Please cite this article as: Mehasseb MK and Habiba MA. Adenomyosis uteri: an update. The Obstetrician & Gynaecologist 2009;11:41–47.

Author details
Mohamed K Mehasseb MSC MD MRCOG
Clinical Research Fellow and Specialist
Registrar in Obstetrics and Gynaecology
Reproductive Sciences Section — Department
of Cancer Studies and Molecular Medicine,
University of Leicester, Leicester LE2 7LX, UK
Email: mkm7@le.ac.uk (corresponding author)
Marwan A Habiba MSC PHD FRCOG
Senior Lecturer and Consultant in
Obstetrics and Gynaecology
Reproductive Sciences Section — Department
of Cancer Studies and Molecular Medicine,
University of Leicester, UK

© 2009 Royal College of Obstetricians and Gynaecologists 41

TOG11_1_41-47-Mehasseb 24/12/08
Review
Figure 1
Histological section of uterine
adenomyosis showing endometrial
glands and stroma deep in the
myometrium and separate from the
overlying endometrium
(magnification 5)
Table 1
Incidence of concomitant
pathology in hysterectomy
specimens containing
adenomyosis4,5
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04:21 PM Page 42
2009;11:41–47
Introduction
Adenomyosis uteri is defined by the presence of
endometrium within the myometrium.
Microscopically, uterine adenomyosis is defined by
ectopic, non-neoplastic endometrial glands and
stroma, surrounded by hypertrophic and
hyperplastic myometrium (Figure 1). The first
descriptions of the condition were made by
Rokitansky in 18601 and von Recklinghausen in
1896.2
Definition
There is no consensus on the depth of endometrial
penetration diagnostic of adenomyosis uteri
(opinions range from one high power field to
25% of the myometrial thickness), which makes
comparisons between different studies difficult. A
cut-off point of 2.5 mm for glandular extension
below the endometrial–myometrial interface is
advocated.3 A characteristic feature of the
endometrial–myometrial interface is the lack of
submucosa. As a result, the endometrial glands
and stroma lie in direct contact with the
myometrium. In addition, the
endometrial–myometrial interface is irregular
over its entire surface. The term ‘adenomyosis
sub-basalis’ is suggested for more superficial
disease.
Adenomyosis uteri can involve the whole muscle
thickness down to the serosa and can be either
‘focal’ or ‘diffuse’. In diffuse adenomyosis uteri,
the uterus becomes enlarged and globular.
Glandular foci may contain brown haemosiderin
deposits. Focal lesions can resemble leiomyomas:
Disease %
Leiomyomas 20.5–70
Pelvic endometriosis 6.3–24
Salpingitis isthmica nodosa 1.4–19.8
Endometrial polyps 2.3–14.7
Endometrial hyperplasia 7.3–13.6
Endometrial hyperplasia with atypia 3.5
Adenocarcinoma 2.2–5.3
The Obstetrician & Gynaecologist
hence the older term ‘adenomyoma’. Adenomyosis
uteri has poorly defined margins and cannot be
enucleated. Endometrial glands and stroma in
adenomyosis uteri resemble the basalis
endometrium and show limited changes
throughout the menstrual cycle but secretory
changes, including stromal decidualisation, may
be seen during pregnancy and in women
receiving exogenous progestogens.
The precise reason for myometrial
hyperplasia/hypertrophy around deep, focal
adenomyotic lesions is unknown but it may be an
attempt at controlling endometrial invagination or
it may represent smooth muscle bundles pushed
aside by the ingrowing endometrium. Myometrial
hypertrophy is often absent in postmenopausal
women.
Associated pathology
Up to 80% of women with adenomyosis also have
other lesions, the most frequent being leiomyomas.
Endometrial polyps, hyperplasia (with and without
atypia) and adenocarcinoma are more frequent in
women with adenomyosis (Table 1).4 Pelvic
endometriosis is observed in 6–24% of women
with adenomyosis uteri. Women with endometrial
carcinoma have also been reported to have a higher
incidence (60%) of adenomyosis uteri compared
with woman without cancer (39%) but
adenomyosis has no adverse effect on cancer
survival.5 Adenocarcinoma may, rarely, involve foci
of adenomyosis. Whether adenocarcinomas located
in both the overlying endometrium and foci of
adenomyosis represent separate entities, or the
extension of the former into adenomyotic foci, is
unknown. When carcinoma is limited to
adenomyotic foci, it should be considered
intramucosal, since it does not make the prognosis
worse than if the carcinoma is confined to the
endometrium proper.5
Pathogenesis
Adenomyosis uteri is believed to result from
abnormal ingrowth and invagination of the basal
endometrium into the subendometrial
myometrium at the endometrial–myometrial
interface. During periods of regeneration, healing
and re-epithelialisation, the endometrium can
invade a predisposed myometrium or a
traumatised endometrial–myometrial interface.
Hormonal, genetic, immunological and growth
factors possibly play a role in this sequence of
events. In one series,6 seven cases were reported in
which mothers and daughters were affected.
Tamoxifen treatment is also associated with a
higher incidence.
Local, but not systemic, hyperestrogenism may be
involved and may also account for the
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The Obstetrician & Gynaecologist 2009;11:41–47 Review

hypertrophy/hyperplasia in the surrounding

myometrium and overlying endometrium. Several Investigators Sensitivity (%) Specificity (%) Table 2
Accuracy of transvaginal
studies in animal models support a role for Transvaginal ultrasound
ultrasound and MRI in the diagnosis
Fedele et al. (1992)9 87 99
hyperprolactinaemia (either induced by pituitary Ascher et al. (1994)10 53 75
of adenomyosis9–18
transplantation or drug therapy) in the pathogenesis Brosens et al. (1995)12 86 50
Reinhold et al. (1995)13 86 86
of adenomyosis uteri but it is unclear if a similar Kocak et al. (1998)14 89 88
mechanism is involved in humans. Other studies in Bromley et al. (2000)15 84 84
Bazot et al. (2001)16 65 98
rodent models have described in utero or neonatal Dueholm et al. (2002)17 68 65
dosing with tamoxifen or diethylstilbestrol to induce MRI
Mark et al. (1987)18 61 100
adenomyosis uteri and all showed marked Ascher et al. (1994)10 88 66
myometrial disruption and pathology. These models Reinhold et al. (1996)11 89 89
Bazot et al. (2001)16 78 93
raise the possibility of in utero developmental events Dueholm et al. (2002)17 70 86
leading to uterine adenomyosis.
with adenomyosis uteri was 6–6.4%.24,25 Older
Prevalence women tend to be more symptomatic, whilst
The majority of cases are diagnosed following symptoms in younger women are relatively mild or
histological examination of hysterectomy absent. The relative importance of parity and age
specimens but this introduces selection bias when remains unanswered, as parous women also tend to
estimating the prevalence of the disease. The be older. No association is seen with age at
percentage of hysterectomy specimens containing menarche, menopausal status, or age at
adenomyosis varies from 5–70%.7 This wide hysterectomy or its indication.
variation may be partly explained by the
histological criteria used and/or by the number of Spontaneous miscarriage has been observed more
tissue blocks examined. The exact prevalence in the frequently in women with adenomyosis uteri. Sharp
‘normal’ population is unknown. The specificity of curettage during termination of pregnancy or
preoperative diagnosis based on the clinical picture following early pregnancy loss increases the risk
is poor, ranging from 2.6–26%.8 The sensitivity and possibly by disrupting the endometrial–myometrial
specificity of magnetic resonance imaging (MRI) interface and facilitating embedding of the
and ultrasound is highlighted in Table 2.9–18 endometrium within the myometrium.23,24 This
practice has largely been superseded by suction
Using MRI criteria, Hauth et al.19 identified uterine curettage. Interestingly, sharp curettage of the
adenomyosis in 12 out of 100 healthy women. In nonpregnant uterus does not increase the risk of
another study,20 the diagnosis was suggested by uterine adenomyosis. This differential effect may be
MRI in 19 of 204 (9.1%) women following term related to disruption of the endometrial–
deliveries and in 16 of 104 (15.4%) women myometrial interface by invading trophoblasts.
following preterm delivery; the overall incidence Women who smoke tend to be at reduced risk of
was 11.3%. In 1931, Lewinski21 reported an adenomyosis uteri. Oral contraceptives, intrauterine
incidence of 54% in 54 autopsies. contraceptive devices and tubal sterilisation do not
appear to be associated with increased risk.
Clinical correlates Adenomyosis has been reported in 60% of
Despite lack of agreement on the histological postmenopausal women on long-term tamoxifen
criteria, adenomyosis uteri is frequently reported therapy, perhaps because tamoxifen reactivates pre-
following hysterectomy. As the incidence of the existing adenomyosis. Kunz et al.26 found a high
disease in the general population remains unclear, incidence in their cohort of infertile women with
and because of its common association with other endometriosis (28%). A summary of clinical
pathologies such as fibroids, the clinical correlates is presented in Table 3.22–32
significance remains uncertain.
Menstrual disorders
The majority of cases are reported in women aged About 35% of women with adenomyosis uteri are
40–50 years and there is a positive association with asymptomatic. Symptomatic women mostly
parity. Adenomyosis occurs relatively frequently in
pregnancy. It has been reported in 27 out of 151 Increased risk Decreased risk No risk Table 3
(17%) caesarean hysterectomy specimens7 and was Parity Smoking Age at menarche
Summary of risk factors and
symptoms of adenomyosis22–32
diagnosed using MRI in 11.3% of women Spontaneous miscarriage Menopausal status
Endometriosis Age at first childbirth
postpartum.20 There is no relation to age at first Menorrhagia Oral contraceptives,
childbirth and prior caesarean section does not Infertility intrauterine contraceptive
Surgical termination/ devices, tubal sterilisation
seem to be a predisposing factor. Four large curettage in pregnancy Indication for and age
studies4,22–24 failed to demonstrate an increased Endometrial hyperplasia at surgery
Preterm birth Endometrial carcinoma
incidence with caesarean delivery. The average Caesarean section
incidence of caesarean section delivery in women Dilatation and curettage

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Box 1
Transvaginal ultrasound criteria
used to diagnose adenomyosis
(most often diagnosed in the
presence of three or more
sonographic criteria)10–13,39–42
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present with menorrhagia (40–50%),
dysmenorrhoea (10–30%) and metrorrhagia
(10–12%) and, occasionally, dyspareunia or
dyschesia.28,31 Menorrhagia may be due to
dysfunctional contractility of the myometrium.
Mefenamic acid administration can reduce blood
loss, suggesting that prostaglandins may be
involved.7 Other factors that may be involved are
anovulation or endometrial hyperplasia. The extent
and spread of adenomyosis uteri may correlate with
pelvic pain and dysmenorrhea and, to a lesser
degree, with menorrhagia and dyspareunia.33
Endometriosis
Pelvic endometriosis coexists with adenomyosis
uteri in 2–24% of cases, suggesting that the two
conditions may be linked. Using MRI in a cohort of
infertile women, 126 out of 160 (79%) women with
endometriosis and 19 out of 67 (28%) women
without endometriosis had adenomyosis.26
Kunz et al.34 hypothesise that pelvic endometriosis
and uterine adenomyosis are variants of the same
disease, involving dislocation of the basal
endometrium both in the underlying myometrium
and the peritoneal cavity. They postulate that
chronic uterine dysfunctional peristalsis and
hyperperistalsis are important causal factors.
Women with endometriosis displayed a marked
uterine hyperperistalsis that differed significantly
from the peristalsis of the controls during the early-
and mid-follicular and midluteal phases. During
the late follicular phase of the cycle, uterine
peristalsis in women with endometriosis became
dysperistaltic, arrhythmic and convulsive in
character while, in controls, peristalsis continued to
show long and regular cervicofundal contractions.
Infertility
Because of its association with multiparity, scant
attention has been paid in the past to a possible
relationship between adenomyosis uteri and
infertility.Adenomyosis uteri is linked to lifelong
infertility in baboons.35 Advances in imaging and
delayed pregnancy may contribute to the condition
being encountered more frequently in fertility clinics.
Reported studies26 include a cohort of infertile
women with poorly defined demographics and a
high incidence of endometriosis. The authors suggest
that adenomyosis impairs uterine sperm transport,
an effect that could not be confirmed in the absence
of endometriosis.
Transvaginal criteria (used separately or in combination)
• Uterine enlargement in the absence of leiomyomas
• Asymmetric enlargement of the anterior or posterior
myometrial wall
• Lack of contour abnormality or mass effects
• Heterogeneous, poorly circumscribed areas within the
myometrium
• Hyperechoic islands or nodules, finger-like projections or
linear striations, indistinct endometrial stripe
• Anechoic lacunae or cysts of varying size
The Obstetrician & Gynaecologist
It has been proposed that the abnormal structure
of the endometrial–myometrial interface and
myometrium in adenomyosis uteri, especially at
the fundus, could interfere with normal
fertilisation and implantation. One putative
mechanism is the production of excess nitric oxide
by the enzyme endothelial nitric oxide synthase,
which could affect human sperm function,
fertilisation, implantation and embryo
development. Overexpression of endothelial nitric
oxide synthase in adenomyosis uteri may be
triggered by an immune response stimulating
macrophages to attack endothelial cells or by
endometrial cells.36 Evidence37 from recipients of
sibling oocytes via in vitro fertilisation (IVF),
however, suggests that adenomyosis uteri, as
diagnosed by ultrasound, has no impact on
implantation rate.
Imaging and diagnosis
Management of adenomyosis uteri is hindered by
the lack of a reliable, noninvasive diagnostic test.
No serum markers are currently available. The role
of invasive hysteroscopic or laparoscopic biopsy
remains limited, with only small series reported.
The small number and size of biopsies obtained
may be insufficient to rule out the disease,
especially given that the diagnosis may be
influenced by the numbers of uterine sections
examined.
Hysterosalpingography
Hysterosalpingography was an early imaging
modality used for the diagnosis of adenomyosis
uteri but it has low sensitivity and specificity.
Features suggestive of adenomyosis include
multiple, small (14 mm) spicules extending from
the endometrium into the myometrium, with
saccular endings. A local accumulation of contrast
material in the myometrium may produce a
honeycomb appearance.38
Pelvic ultrasonography
Transvaginal ultrasound (TVS) is superior to
transabdominal ultrasound in demonstrating the
subtle features suggestive of adenomyosis uteri. The
normal myometrium has three distinct
sonographic layers. The middle layer is the most
echogenic and is separated from the thin outer layer
by the arcuate venous and arterial plexuses. The
inner layer is hypo-echoic relative to the middle and
outer layers (the subendometrial or myometrial
halo). The presence of adenomyosis uteri can alter
or distort the sonographic appearance of these
zones (Box 1).10–13,39–42
Studies on the accuracy of TVS reported variable
accuracy indices, with sensitivity and specificity
varying between 53–89% and 50–99%,
respectively (Table 2). The reported studies were
conducted on selected women prior to surgery
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The Obstetrician & Gynaecologist
and caution is needed when TVS is used for other
groups with a lower prevalence of uterine
adenomyosis.
Three-dimensional ultrasonography offers
advantages in determining organ volume and
uterine pathology, including endometrial
tumours. There are some reports on the use of 3D-
TVS and 3D power Doppler in adenomyosis,
including vessel distribution and branching, and
differences in perfusion patterns in affected
areas.43,44
Magnetic resonance imaging
In women of reproductive age, three different
zones can be identified within the uterus by MRI.
The normal endometrium and endometrial
secretions appear as a high signal intensity-type
stripe on T2-weighted sagittal images.
Immediately underneath this is a band of low
signal intensity, which represents the innermost
layer of the myometrium: the junctional zone.45
The outer layer of the myometrium is of
intermediate signal intensity. There is considerable
variation in the normal junctional zone thickness,
ranging from 2–8 mm.19,46 The appearance of
diffuse or focal widening of the junctional zone on
MRI is suggestive of adenomyosis uteri. Areas of
low signal intensity corresponding to smooth
muscle hyperplasia can also be seen, together with
high signal intensity foci or linear striations
representing the ectopic endometrial tissue
(Box 2).
There is growing evidence to support the role of
MRI in the diagnosis of adenomyosis uteri. The
high cost and limited availability, however,
hinder its routine use. Several studies have
compared the accuracy of TVS and MRI (Table 2).
Although the sensitivities and specificities of
both techniques were comparable, MRI proved to
be superior to TVS in women where associated
leiomyomas or additional pathologies were
suspected.16
Treatment
Advances in treatment have been limited by the
difficulties in determining a clinical diagnosis and
the lack of a specific intervention. Different surgical
and medical modalities of treatment have been
addressed in the literature but many of these have
not been tested specifically for adenomyosis uteri.
In the absence of treatments directed at the disease
itself, management is often directed at the
symptoms. It could be argued that further
diagnostic tests using MRI, TVS or invasive biopsies
would be beneficial in only a few cases; for instance,
as part of planned conservative management of
women with clinically significant symptoms or for
localisation prior to excision.
© 2009 Royal College of Obstetricians and Gynaecologists
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2009;11:41–47 Review
• Focal or diffuse thickening of the junctional zone
Box 2
MRI criteria suggestive of
• Low signal intensity uterine mass with ill-defined border adenomyosis19,45,46
• Junctional zone thickness 12 mm
• Poor definition of junctional zone border
• Localised high signal foci within an area of low signal
intensity
• Linear striations of increased signal radiating out from the
endometrium into the myometrium
• Bright foci in endometrium of similar intensity to the
myometrium (T1-weighted)
• Ratio of maximal junctional zone thickness to myometrium
thickness (ratiomax) 40%
Medical
Nonhormonal therapy, including mefenamic and
tranexamic acid, may be effective for the
symptomatic relief of menorrhagia associated with
uterine adenomyosis7 but there are no studies
specific to adenomyosis uteri. Hormonal
treatments for symptomatic relief include
progestogens, the combined oral contraceptive pill
and gonadotrophin-releasing hormone (GnRH)
analogues. The aim of medical therapy is to
suppress the cyclical changes of ovarian steroids,
inhibiting pituitary gonadotrophins or preventing
the mid-cycle estrogen surge. Overall, the effect of
these treatments is limited to a variable and
unpredictable degree of symptomatic relief, usually
restricted to the duration of treatment.
Low-dose, continuous combined oral
contraceptives with withdrawal bleeds every
4–6 months may be effective in relieving
menorrhagia and dysmenorrhoea47 but, again, there
are no specific studies on adenomyosis uteri.
GnRH analogues have also been used in the
treatment of adenomyosis uteri.48 They reduce
uterine volume and result in symptomatic relief but
their use is limited because of skeletal and general
side-effects.
The use of danazol has largely been superseded
because of its side-effects. A more recently-
developed danazol-loaded intrauterine device was
used to treat 12 women with adenomyosis uteri.49
Three pregnancies were reported following
discontinuation of the treatment. Danazol serum
levels were undetectable and both menstrual and
ovulatory functions were preserved.49 In another
study,50 there was a significant decrease in
dysmenorrhea.
Reports have been published on the use of the
levonorgestrel-releasing intrauterine system
(Mirena®: Schering Health, Berks, UK) in women
with adenomyosis uteri outside the context of
infertility. Menorrhagia disappeared in all cases,
leading to improvement of anaemia. Reduction in
uterine size was, however, modest (9.8%). Other
studies42,51 reported an improvement in
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dysmenorrhea. The levonorgestrel-releasing
intrauterine system has also been successfully used
for adenomyosis-associated menorrhagia when
inserted immediately after endometrial ablation.52
Mifepristone (RU486) has been used for the
treatment of endometriosis. Long-term, low-dose
mifepristone causes anovulation, a reduction in
painful symptoms and improved endometriosis
scores.53 When given for up to 30 days, mifepristone
has been shown to suppress markedly the
development of adenomyosis uteri in mice54 but it
has not been used in humans. There is a case report55
on the concomitant use of the aromatase inhibitor
anastrozole with a GnRH agonist in a woman with
severe symptomatic uterine adenomyosis.
Surgical
Laparoscopic myometrial electrocoagulation
induces localised coagulation and necrosis of
adenomyosis uteri. Needle punctures are made at
1–2 cm intervals to deliver a unipolar or bipolar
coagulation current. Electrocoagulation can be
difficult to apply with precision and can reduce the
strength of the remaining myometrial tissue.
Furthermore, there is a risk of emergency
hysterectomy for uncontrollable bleeding during
the procedure, as well as a high incidence of
adhesion formation following the procedure.
Although not recommended, this technique may be
best suited for women 40 years of age who have
completed their families but who wish to avoid
hysterectomy.56
Localised excision of affected myometrium can be
performed in localised adenomyosis uteri if the
extent of the disease can be accurately defined.
The approach is similar to myomectomy and may
be useful for women seeking to preserve their
fertility, provided the remaining myometrium is
sufficient to allow uterine expansion. Complete
microsurgical resection of the visible
adenomyotic areas, followed by GnRH agonists,
has been suggested to improve symptom control
and fertility. Published series are small, with
limited success. The surgical and obstetric
complications of myometrial excision must be
considered. Excision of a large part of the
myometrium, as may be needed to remove all
affected areas, may lead to difficulty in wound
apposition, decreased expansive capacity of the
uterus and weakening, leading ultimately to
uterine rupture.57
Reduction of the uterine blood flow by uterine
artery embolisation has been shown to reduce the
symptoms associated with adenomyosis uteri and
to improve the quality of life. Many women,
however, had concurrent fibroids, for which
uterine artery embolisation is a recognised
46
The Obstetrician & Gynaecologist
treatment option.58 The chances of a subsequent
successful pregnancy are unclear. Laparoscopic
uterine artery ligation has been studied in 20
women with symptomatic uterine adenomyosis.59
Only 15% of women, however, rated the
treatment as satisfactory at 6-month follow-up,
suggesting that this approach may not be
effective.
Endomyometrial ablation or resection may be an
option for women with superficial disease
complaining of menorrhagia but, clearly, desire for
a future pregnancy is a contraindication.60 In
addition, it should be considered that deep
adenomyosis uteri has been associated with an
increased failure rate of endometrial ablation,
proportionate to the depth of endometrial
penetration. Hysterectomy remains the main
surgical option for women not wishing to preserve
their fertility.
Conclusion
Adenomyosis uteri remains one of the most
common pathological findings in hysterectomy
specimens. This clearly argues for better diagnosis
and specific therapy aimed at reducing
hysterectomy rates. With better imaging modalities,
such as MRI and modern ultrasound, accurate
diagnosis is becoming increasingly possible.
Preoperative diagnosis raises the possibility of
specific therapy and can be useful for counselling
prior to interventions such as endometrial ablation.
Wider use of imaging will enable better recognition
of the impact of adenomyosis uteri. There remains
a need for specific therapy based on a better
understanding of the pathophysiology of the
disease.
References
1 Von Rokitansky C. Ueber uterusdru¨sen – neubildung in uterus- und
ovarial-sarcomen. [Article in German] Ztsch K K Gesellsch der Aerzte zu
Wien 1860;37:577–81.
2 von Recklinghausen F. Die Adenomyomata und Cystadenomata der
Uterus und Tubenwandung: Ihre Abkunft von Resten des Wolff’schen
Koerpers. [Article in German.] Berlin: August Hirschwald Verlag; 1896.
3 Uduwela AS, Perera MA, Aiqing L, Fraser IS. Endometrial–myometrial
interface: relationship to adenomyosis and changes in pregnancy. Obstet
Gynecol Surv 2000;55:390–400. doi:10.1097/00006254-200006000-
00025
4 Bergholt T, Eriksen L, Berendt N, Jacobsen M, Hertz JB. Prevalence and
risk factors of adenomyosis at hysterectomy. Hum Reprod
2001;16:2418–21.
5 Hall JB, Young RH, Nelson JH, Jr. The prognostic significance of
adenomyosis in endometrial carcinoma. Gynecol Oncol 1984;17:32–40.
doi:10.1016/0090-8258(84)90057-X
6 Emge LA. The elusive adenomyosis of the uterus. Its historical past and
its present state of recognition. Am J Obstet Gynecol 1962;83:1541–63.
7 Azziz R. Adenomyosis: current perspectives. Obstet Gynecol Clin North
Am 1989;16:221–35.
8 Reinhold C, Tafazoli F, Wang L. Imaging features of adenomyosis. Hum
Reprod Update 1998;4:337–49. doi:10.1093/humupd/4.4.337
9 Fedele L, Bianchi S, Dorta M, Arcaini L, Zanotti F, Carinelli S. Transvaginal
ultrasonography in the diagnosis of diffuse adenomyosis. Fertil Steril
1992;58:94–7.
10 Ascher SM, Arnold LL, Patt RH, Schruefer JJ, Bagley AS, Semelka RC,
et al. Adenomyosis: prospective comparison of MR imaging and
transvaginal sonography. Radiology 1994;190:803–6.
11 Reinhold C, McCarthy S, Bret PM, Mehio A, Atri M, Zakarian R, et al.
Diffuse adenomyosis: comparison of endovaginal US and MR imaging
with histopathologic correlation. Radiology 1996;199:151–8.
© 2009 Royal College of Obstetricians and Gynaecologists
TOG11_1_41-47-Mehasseb 24/12/08 04:21 PM Page 47
The Obstetrician & Gynaecologist
12 Brosens JJ, de Souza NM, Barker FG, Paraschos T, Winston RM.
Endovaginal ultrasonography in the diagnosis of adenomyosis uteri:
identifying the predictive characteristics. Br J Obstet Gynaecol
1995;102:471–4.
13 Reinhold C, Atri M, Mehio A, Zakarian R, Aldis AE, Bret PM. Diffuse uterine
adenomyosis: morphologic criteria and diagnostic accuracy of
endovaginal sonography. Radiology 1995;197:609–14.
14 Kocak I, Yanik F, Ustun C. Transvaginal ultrasound in the diagnosis of
diffuse adenomyosis. Int J Gynaecol Obstet 1998;62:293–94.
15 Bromley B, Shipp TD, Benacerraf B. Adenomyosis: sonographic findings
and diagnostic accuracy. J Ultrasound Med 2000;19:529–34.
16 Bazot M, Cortez A, Darai E, Rouger J, Chopier J, Antoine JM, et al.
Ultrasonography compared with magnetic resonance imaging for the
diagnosis of adenomyosis: correlation with histopathology. Hum Reprod
2001;16:2427–33.
17 Dueholm M, Lundorf E, Sorensen JS, Ledertoug S, Olesen F, Laursen H.
Reproducibility of evaluation of the uterus by transvaginal sonography,
hysterosonographic examination, hysteroscopy and magnetic resonance
imaging. Hum Reprod 2002;17:195–200.
18 Mark AS, Hricak H, Heinrichs LW, Hendrickson MR, Winkler ML, Bachica
JA, et al. Adenomyosis and leiomyoma: differential diagnosis with MR
imaging. Radiology 1987;163:527–9.
19 Hauth EA, Jaeger HJ, Libera H, Lange S, Forsting M. MR imaging of the
uterus and cervix in healthy women: determination of normal values. Eur
Radiol 2007;17:734–42. doi:10.1007/s00330-006-0313-3
20 Juang CM, Chou P, Yen MS, Twu NF, Horng HC, Hsu WL. Adenomyosis
and risk of preterm delivery. BJOG 2007;114:165–9.
doi:10.1111/j.1471-0528.2006.01186.x
21 Lewinski H. Beitrag zur Frage der Adenomyosis. [Article in German.]
Zentralbl Gynakol 1931;55:2163.
22 Panganamamula UR, Harmanli OH, Isik-Akbay EF, Grotegut CA, Dandolu
V, Gaughan JP. Is prior uterine surgery a risk factor for adenomyosis?
Obstet Gynecol 2004;104:1034–8.
23 Curtis KM, Hillis SD, Marchbanks PA, Peterson HB. Disruption of the
endometrial-myometrial border during pregnancy as a risk factor for
adenomyosis. Am J Obstet Gynecol 2002;187:543–4.
doi:10.1067/mob.2002.124285
24 Levgur M, Abadi MA, Tucker A. Adenomyosis: symptoms, histology, and
pregnancy terminations. Obstet Gynecol 2000;95:688–91.
doi:10.1016/S0029-7844(99)00659-6
25 Harris WJ, Daniell JF, Baxter JW. Prior cesarean section. A risk factor for
adenomyosis? J Reprod Med 1985;30:173–5.
26 Kunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G.
Adenomyosis in endometriosis – prevalence and impact on fertility.
Evidence from magnetic resonance imaging. Hum Reprod
2005;20:2309–16. doi:10.1093/humrep/dei021
27 Vercellini P, Parazzini F, Oldani S, Panazza S, Bramante T, Crosignani PG.
Adenomyosis at hysterectomy: a study on frequency distribution and
patient characteristics. Hum Reprod 1995;10:1160–2.
28 Parazzini F, Vercellini P, Panazza S, Chatenoud L, Oldani S, Crosignani PG.
Risk factors for adenomyosis. Hum Reprod 1997;12:1275–9.
doi:10.1093/humrep/12.6.1275
29 Devlieger R, D’Hooghe T, Timmerman D. Uterine adenomyosis in the
infertility clinic. Hum Reprod Update 2003;9:139–47.
30 Chrysostomou M, Akalestos G, Kallistros S, Papadimitriou V, Nazar S,
Chronis G. Incidence of adenomyosis uteri in a Greek population. Acta
Obstet Gynecol Scand 1991;70:441–4.
31 Vavilis D, Agorastos T, Tzafetas J, Loufopoulos A, Vakiani M, Constantinidis
T, et al. Adenomyosis at hysterectomy: prevalence and relationship to
operative findings and reproductive and menstrual factors. Clin Exp
Obstet Gynecol 1997;24:36–8.
32 Nikkanen V, Punnonen R. Clinical significance of adenomyosis. Ann Chir
Gynaecol 1980;69:278–80.
33 Sammour A, Pirwany I, Usubutun A, Arseneau J, Tulandi T. Correlations
between extent and spread of adenomyosis and clinical symptoms.
Gynecol Obstet Invest 2002;54:213–6. doi:10.1159/000068385
34 Kunz G, Beil D, Huppert P, Leyendecker G. Structural abnormalities of the
uterine wall in women with endometriosis and infertility visualized by
vaginal sonography and magnetic resonance imaging. Hum Reprod
2000;15:76–82. doi:10.1093/humrep/15.1.76
35 Barrier BF, Malinowski MJ, Dick EJ Jr, Hubbard GB, Bates GW.
Adenomyosis in the baboon is associated with primary infertility. Fertil
Steril 2004;82 Suppl 3:1091–4. doi:10.1016/j.fertnstert.2003.11.065
36 Ota H, Igarashi S, Hatazawa J, Tanaka T. Is adenomyosis an immune
disease? Hum Reprod Update 1998;4:360–7.
doi:10.1093/humupd/4.4.360
© 2009 Royal College of Obstetricians and Gynaecologists
2009;11:41–47 Review
37 Camargo F, Gaytan J, Caligara C, Simón C, Pellicer A, Remohí J. Impact of
ultrasound diagnosis of adenomyosis on recipients of sibling oocytes.
Fertil Steril 2001;76 Suppl 13:150. doi:10.1016/S0015-0282(01)02439–6
38 Wolf DM, Spataro RF. The current state of hysterosalpingography.
Radiographics 1988;8:1041–58.
39 Fedele L, Bianchi S, Dorta M, Zanotti F, Brioschi D, Carinelli S. Transvaginal
ultrasonography in the differential diagnosis of adenomyoma versus
leiomyoma. Am J Obstet Gynecol 1992;167:603–6.
40 Hirai M, Shibata K, Sagai H, Sekiya S, Goldberg BB. Transvaginal pulsed
and color Doppler sonography for the evaluation of adenomyosis. J
Ultrasound Med 1995;14:529–32.
41 Atri M, Reinhold C, Mehio AR, Chapman WB, Bret PM. Adenomyosis: US
features with histologic correlation in an in-vitro study. Radiology
2000;215:783–90.
42 Fedele L, Bianchi S, Raffaelli R, Portuese A, Dorta M. Treatment of
adenomyosis-associated menorrhagia with a levonorgestrel-releasing
intrauterine device. Fertil Steril 1997;68:426–9. doi:10.1016/S0015-
0282(97)00245-8
43 Lee SL, Busmanis I, Tan A. 3D-angio of adenomyotic uteri. Second World
Congress on 3D Ultrasound in Obstetrics and Gynecology, October 1999,
Las Vegas.
44 Ahmed AI, Mahmoud AE, Fadiel AA, Frederick N. Comparison of 2-, 3D
and doppler ultrasound with histological findings in adenomyosis. Fertil
Steril 2007;88 Suppl 1:S82. doi:10.1016/j.fertnstert.2007.07.272
45 Brown HK, Stoll BS, Nicosia SV, Fiorica JV, Hambley PS, Clarke LP, et al.
Uterine junctional zone: correlation between histologic findings and MR
imaging. Radiology 1991;179:409–13.
46 Lee JK, Gersell DJ, Balfe DM, Worthington JL, Picus D, Gapp G. The
uterus: in vitro MR-anatomic correlation of normal and abnormal
specimens. Radiology 1985;157:175–9.
47 Moghissi KS. Treatment of endometriosis with estrogen-progestin
combination and progestogens alone. Clin Obstet Gynecol
1988;31:823–8. doi:10.1097/00003081-198812000-00008
48 Grow DR, Filer RB. Treatment of adenomyosis with long-term GnRH
analogues: a case report. Obstet Gynecol 1991;78:538–9.
49 Igarashi M, Abe Y, Fukuda M, Ando A, Miyasaka M, Yoshida M, et al. Novel
conservative medical therapy for uterine adenomyosis with a danazol-
loaded intrauterine device. Fertil Steril 2000;74:412–3.
doi:10.1016/S0015-0282(00)00624-5
50 Tamaoka Y, Orikasa H, Sakakura K, Kamei K, Nagatani M, Ezawa S. Direct
effect of danazol on endometrial hyperplasia in adenomyotic women:
treatment with danazol containing intrauterine device. Hum Cell
2000;13:127–33.
51 Fong YF, Singh K. Medical treatment of a grossly enlarged adenomyotic
uterus with the levonorgestrel-releasing intrauterine system.
Contraception 1999;60:173–5. doi:10.1016/S0010-7824(99)00075-X
52 Maia H, Jr., Maltez A, Coelho G, Athayde C, Coutinho EM. Insertion of
mirena after endometrial resection in patients with adenomyosis. J Am
Assoc Gynecol Laparosc 2003;10:512–6.
doi:10.1016/S1074-3804(05)60158-2
53 Kettel LM, Murphy AA, Morales AJ, Yen SS. Preliminary report on the
treatment of endometriosis with low-dose mifepristone (RU 486). Am J
Obstet Gynecol 1998;178:1151–6. doi:10.1016/S0002-9378(98)70316-3
54 Nagasawa H, Aoki M, Mori T, Yamamoto K, Inaba T, Mori J. Stimulation of
mammary tumourigenesis and inhibition of uterine adenomyosis by
suppressed progesterone effects in SHN mice. Anticancer Res
1989;9:827–32.
55 Kimura F, Takahashi K, Takebayashi K, Fujiwara M, Kita N, Noda Y, et al.
Concomitant treatment of severe uterine adenomyosis in a
premenopausal woman with an aromatase inhibitor and a gonadotropin-
releasing hormone agonist. Fertil Steril 2007;87:1468 e9–12.
56 Wood C. Surgical and medical treatment of adenomyosis. Hum Reprod
Update 1998;4:323–36. doi:10.1093/humupd/4.4.323
57 Wang PH, Yang TS, Lee WL, Chao HT, Chang SP, Yuan CC. Treatment of
infertile women with adenomyosis with a conservative microsurgical
technique and a gonadotropin-releasing hormone agonist. Fertil Steril
2000;73:1061–2. doi:10.1016/S0015-0282(00)00411-8
58 Siskin GP, Tublin ME, Stainken BF, Dowling K, Dolen EG. Uterine artery
embolization for the treatment of adenomyosis: clinical response and
evaluation with MR imaging. AJR Am J Roentgenol 2001;177:297–302.
59 Wang CJ, Yen CF, Lee CL, Soong YK. Laparoscopic uterine artery ligation
for treatment of symptomatic adenomyosis. J Am Assoc Gynecol
Laparosc 2002;9:293–6. doi:10.1016/S1074-3804(05)60407-0
60 McCausland AM, McCausland VM. Depth of endometrial penetration in
adenomyosis helps determine outcome of rollerball ablation. Am J
Obstet Gynecol 1996;174:1786–93; 1793–4.
47