Key words
adenomyosis - hysterectomy - endometrial ablation - uterine artery embolization -
magnetic resonance guided focused ultrasound
Schlüsselwörter
Adenomyosis - Hysterektomie - Endometriumsablation - Uterusarterienembolisation -
Magnetresonanztomografie-gesteuerte fokussierte Ultraschalltherapie
Introduction
The first description of the condition initially referred to as “adenomyoma” was
provided in 1860 by the German pathologist Carl von Rokitansky, who found
endometrial glands in the myometrium and subsequently referred to this finding as
“cystosarcoma adenoids uterinum” [1], [2]. The modern definition of adenomyosis was provided in 1972 by Bird who
stated: “Adenomyosis may be defined as the benign invasion of endometrium into the
myometrium, producing a diffusely enlarged uterus which microscopically exhibits
ectopic non-neoplastic, endometrial glands and stroma surrounded by the hypertrophic
and hyperplastic myometrium” [1].
Because of the widespread use of hysterectomy as the primary therapeutic option,
starting in the 19th century, adenomyosis has never been fully characterized.
Currently the designation of benign uterine diseases including adenomyosis and
uterine fibroids resembles the 19th century designation of “cancer” before the
importance of histological and molecular factors affecting therapeutic response and
prognosis was highlighted.
The development of high-resolution imaging techniques, particularly magnetic
resonance (MR) imaging, has improved the preoperative diagnosis of adenomyosis. On
T2-weighted MR images of the uterus, the junctional zone myometrium can be clearly
distinguished from the endometrium and outer myometrium, and diffuse or focal
thickening of this zone is now recognized as one hallmark of adenomyosis [3]. Furthermore, both MR and transvaginal ultrasound (TVU)
are valuable in characterizing adenomyosis as they can identify myometrial cysts,
distorted and heterogeneous myometrial echotexture and poorly defined foci of
abnormal myometrial echotexture. However, the most predictive TVU finding for
adenomyosis is the presence of ill-defined myometrial heterogeneity [4]. MR imaging offers sensitivity rates of up to 88 % and
specificity rates of up to 93 %. Studies comparing MR and TVU offer inconclusive
data, with some studies reporting equivalent results, and others report the
superiority of MR imaging [5].
Medications such as non-steroidal anti-inflammatory drugs and/or hormonal therapy
(oral contraceptive pills, high-dose progestins, a levonorgestrel-releasing
intrauterine device, danazol, gonadotropin-releasing hormone agonists) are often
used to manage the symptoms of adenomyosis and to temporarily induce regression of
the adenomyosis. However, many women require more aggressive forms of treatment
[6].
Historically, the most common treatment for symptomatic adenomyosis has been
hysterectomy. Thus, an important factor driving innovation in adenomyosis therapies
is perioperative and postoperative morbidity as well as the potentially lower
quality-of-life outcome associated with hysterectomy. Moreover, hysterectomy is also
not appropriate in women who wish to have children.
A different area driving innovation in adenomyosis therapies is the high healthcare
costs. Recent reports have suggested that healthcare costs are higher for women with
leiomyomas than for unaffected women, and the costs of disability are substantial,
in all probability because surgical therapy in the form of hysterectomy procedures
is the major treatment option. Hysterectomies account for most of the costs,
recently estimated to exceed $2.1 billion annually in the United States and almost
200 million € in Germany [7], [8]. Nevertheless, despite the clinical importance of adenomyosis, there
is little evidence on which to base treatment decisions. The objective of this
review was to summarize the epidemiology, risk factors, clinical phenotype and to
evaluate the accrued experience with surgical and interventional alternatives to
hysterectomy.
Epidemiology
In the past, the diagnosis of adenomyosis was made solely based on histological
analysis. An accurate determination of its incidence or prevalence has therefore not
been carried out [4]. Thus, estimates of the prevalence of
adenomyosis vary widely, from 5 to 70 %, with the mean frequency of adenomyosis at
hysterectomy given as approximately 20 to 30 % [9], [10], [11], [12], [13], [14]. In a large series of consecutive laparoscopic
supracervical hysterectomies performed in the Gynecological University Clinic in
Tübingen, adenomyosis was diagnosed histologically in 8 % of cases (149 women out
of
1955 women), and concomitant adenomyosis and leiomyomas was diagnosed histologically
in 20 % of the women (398 women out of 1955 women); 70 % of the women with a
diagnosis of adenomyosis were premenopausal [15].
There appear to be wide variations in the incidence of adenomyosis between racial
and
ethnic groups and different geographic regions [13]. It
is not clear whether this is due to patient factors or differences in diagnosis
[13]. In addition, with an increasing number of
hysterectomies performed as laparoscopic supracervical interventions, resulting
consequently in morcellated uterine specimens, the spatial arrangement of the tissue
is modified, leading to a different reference to the surface and making the
histological diagnosis of adenomyosis more challenging. Finally, the likelihood of
establishing the presence of adenomyosis is directly proportional to the number of
tissue samples taken, with the diagnosis rate ranging from 31 to 62 % in the same
uterus [16].
Risk Factors
Age
70 to 80 % of women undergoing hysterectomy for adenomyosis are in their fourth
and fifth decade of life and are multiparous; several studies have reported a
mean age over 50 years for women undergoing hysterectomy for adenomyosis [4], [9], [13], [14], [17], [18], [19], [20], [21], [22]. However, newer
reports using MRI criteria for diagnosis suggest that the disease may cause
dysmenorrhea and chronic pelvic pain in adolescents and women of younger
reproductive age than previously appreciated [23], [24]. These reports suggest that the
clinical age at presentation of adenomyosis may be significantly earlier than
previously thought and that early-stage adenomyosis might present a different
clinical phenotype compared to late-stage disease.
Multiparity
A high percentage of women with adenomyosis are multiparous [17], [18], [19], [25], [26]. Pregnancy might facilitate the formation of adenomyosis by allowing
adenomyotic foci to be included in the myometrium due to the invasive nature of
the trophoblast on the extension of the myometrial fibers [25], [26]. In addition, adenomyotic tissue
may have a higher ratio of estrogen receptors and the hormonal milieu of
pregnancy may favor the development of islands of ectopic endometrium [4], [13]. Alternatively,
there may be an increased acceptance of hysterectomy in multiparous women.
Prior uterine surgery
Evidence regarding a significantly increased risk of prior uterine surgery in
women with adenomyosis is inconsistent. Clinical data have supported the
hypothesis that adenomyosis results when endometrial glands invade the
myometrial layer, with surgical disruptions of the endometrial-myometrial border
increasing the risk of adenomyosis in some studies [27], [28].
Levgur et al. and Parazzini et al. reported that patients who had undergone
pregnancy termination via dilation and curettage demonstrated higher rates of
adenomyosis than women without pregnancy terminations [14], [27]. Furthermore, Parazzini et al.
and Taran et al. also observed higher rates of adenomyosis in non-pregnant
patients who had undergone dilation and curettage [11], [17]. Whitted et al. observed an
increased prevalence of adenomyosis in subjects who had had prior cesarean
section [29]. However, other studies reported no
increased rates of cesarean section or any other uterine surgical procedure in
women with adenomyosis [12], [18], [19], [30].
Thus, it is unclear whether a history of previous uterine surgery is a risk
factor for adenomyosis [4]. Moreover, positing a
relationship between surgical history and the incidence of adenomyosis is risky
when considering the selection of surgical patients. The patients included in
the overwhelming majority of studies were treated in an era when laparotomy was
commonly performed; the results from these studies may well be different if they
were conducted today [19].
Smoking
Evidence regarding an association between smoking and adenomyosis is
controversial. On the one hand, in comparison with women who never smoked,
smokers appear less likely to have adenomyosis [11].
This finding can be explained by hormonally induced mechanisms: decreased serum
levels of estrogen have been reported in smokers, and adenomyosis has been
suggested to be an estrogen-dependent disorder [31], [32].
Alternatively, there is also evidence that there is no association between
adenomyosis and smoking [14]. Moreover, two studies
even reported a higher rate of a history of smoking in women with adenomyosis
than in controls [19], [33]. Thus, the association between adenomyosis and smoking deserves
further investigation.
Ectopic pregnancy
Implantation in a focus of adenomyosis could result in a pregnancy developing
within the myometrium [34], [35]. In addition, cigarette smoking has been shown to be an
independent, dose-related risk factor for ectopic pregnancy [36]. Thus, it has been hypothesized that women with
adenomyosis are more likely to have a history of ectopic pregnancy, since
adenomyosis may be a risk factor for the development of intramural ectopic
pregnancy [19], [34], [35]. Another possible explanation
for the higher rate of ectopic pregnancies in women with adenomyosis is thus the
higher rate of women with a history of smoking [19].
Nevertheless, assumptions regarding an increased likelihood of a history of
smoking and ectopic pregnancy in association with adenomyosis are hypotheses
that require additional evidence.
Depression and antidepressant use
Novel associations with adenomyosis found in both human and animal studies
include an increased risk of depression, and higher antidepressant use [17], [39], [40], [41]. This association
may be due to abnormalities in prolactin dynamics. Exposure of the murine uterus
to increased prolactin appears to be sufficient to cause histological
adenomyosis and is associated with up-regulation of the uterine prolactin
receptor messenger RNA [37], [38].
In vitro studies have demonstrated that prolactin is produced by human uterine
tissues including the endometrium, myometrium and leiomyomas and that a
functional prolactin receptor is present in the uterus and capable of acting as
a smooth muscle cell mitogen [17], [42], [43], [44]. However, in the study by Taran et al., too few of
the women with adenomyosis had serum prolactin results to permit direct analysis
of this relationship. Furthermore, it is possible that depression may have a
common pathogenic factor with adenomyosis (i.e., inflammation) [17]. Studies have showed that the growth and
progression of endometriosis and adenomyosis continues even in ovariectomized
animals. This indicates that, in addition to ovarian steroid hormones, the
growth of endometriosis may be regulated by the innate immune system in the
pelvic environment [45].
Tamoxifen treatment
Adenomyosis is relatively rare in postmenopausal women but a higher incidence of
adenomyosis has been reported in women treated with tamoxifen for breast cancer
[46], [47], [48], [49]. Tamoxifen is an
antagonist of the estrogen receptor in breast tissue via its active metabolite,
hydroxytamoxifen. In tissues, including the endometrium, it behaves like an
agonist, and adenomyosis can develop or be reactivated [50]. Thus, adenomyosis may be more common than is generally realized
in women taking tamoxifen and may account for postmenopausal bleeding in these
patients [49].
Clinical Phenotype
Symptoms of adenomyosis typically include menorrhagia, chronic pelvic pain and
dysmenorrhea. Until recently, the diagnosis of adenomyosis was rarely established
prior to hysterectomy and therefore, it is unsurprising that preoperative diagnosis
rates of adenomyosis based on clinical findings are poor, ranging from 3 to 26 %
[13]. The presenting symptoms of adenomyosis are
non-specific and can also be observed for disorders such as dysfunctional uterine
bleeding, leiomyomas and endometriosis, among others. Thus, certain findings on the
relationship between adenomyosis, menorrhagia, dysmenorrhea and pelvic pain are
controversial [12], [13].
Owolabi and Strickler stated in 1977 that “the common association of adenomyosis with
more obvious pelvic disease has diminished its significance as a cause of
gynaecologic symptoms. Adenomyosis is the addendum to textbook chapters on ectopic
endometrium; it is the forgotten process and a neglected diagnosis” [51]. Weiss et al. concluded more than three decades later
that “adenomyosis is an incidental finding and not the source of symptomatology for
women that undergo hysterectomy” [26]. However, most of
the data that led to these conclusions was from retrospective studies and, in the
case of the Weiss study, from studies of women late in the perimenopausal transition
when symptoms are likely to be on the wane. In contrast to leiomyomas, no published
and validated symptom questionnaire specific to adenomyosis is available.
Adenomyosis and leiomyomas commonly coexist in the same uterus. The incidence of
concomitant adenomyosis in hysterectomy specimens of women with leiomyomas is
reported to range between 15 and 57 % [10], [11], [14], [26], [52], [53]. Thus, differentiating the symptoms for each
pathological process can be problematic. Furthermore, the accurate preoperative
differentiation of both conditions in the same uterus remains poor, even with the
addition of imaging techniques including ultrasound and magnetic resonance imaging
[6].
However, recent studies suggest that there are ways in which women undergoing
hysterectomy with adenomyosis differ from women who have only leiomyomas. Women with
adenomyosis have been shown to have lower uterine weights, more dysmenorrhea,
dyspareunia, pelvic pain and more disease-specific symptoms compared to women with
leiomyomas alone [18], [19].
Furthermore, a number of features have been outlined that distinguish women with
adenomyosis and leiomyomas from women with only leiomyomas at the time of
hysterectomy. Women with adenomyosis and leiomyomas reported more dysmenorrhea and
had an increased risk of dyspareunia and pelvic pain compared to women with
leiomyomas alone [18]. The finding that women with
adenomyosis and leiomyomas undergoing hysterectomy have fewer and smaller leiomyomas
suggests that adenomyosis may contribute to or synergize with leiomyomas to increase
symptomatology, which in turn will be treated by hysterectomy [18]. Consequently, in women with symptoms that seem disproportionate to
the level of leiomyoma disease, clinicians should consider the presence of
adenomyosis in the differential diagnosis [18].
Major limitations of these studies included their retrospective design which
precluded an objective measurement of symptom severity. Furthermore, racial
diversity was underrepresented in all studies. While the incidence and prevalence
of
leiomyomas in black women has been shown to be increased and the disease more
severe, there is no data on racial differences for adenomyosis [54], [55].
Surgical and Interventional Alternatives to Hysterectomy
Surgical and Interventional Alternatives to Hysterectomy
Hysteroscopic procedures
Endometrial ablation/resection
Hysteroscopy has become a major diagnostic and therapeutic tool for uterine
disorders [56]. Hysteroscopic endometrial
ablation/resection has been used to treat patients with menorrhagia,
including patients with adenomyosis. Endometrial ablation/resection can be
performed using an yttrium aluminum garnet (YAG) laser, rollerball
resection, or global ablation techniques (thermal balloon ablation,
cryoablation, circulated hot fluid ablation, microwave ablation, and bipolar
radiofrequency ablation).
Levgur summarized the experience with more than 2000 patients treated by YAG
laser for abnormal bleeding in his recent review [56]. All analyzed publications underlined the risk of failure in
patients with adenomyosis and in several cases, particularly if foci
penetration exceeded 2.5 mm, hysterectomy was considered to be unavoidable
[56]. Wallwiener et al. performed endometrial
ablation combining YAG laser and an electrosurgical loop in a series of 34
symptomatic, “high-risk” patients with contraindications for hysterectomy
[57]. Endometrial ablation was successful in
28 of 34 cases; in this series of patients, hysterectomy, with the risk of
major or even lethal complications, could thus be avoided. However
hysterectomy had to be performed in 2 women with extensive adenomyosis [57].
Wood et al. analyzed the therapeutic efficacy of endometrial resection in a
series of 22 patients [58], [59]. In this series, a marked improvement occurred in 4 of 7
patients with adenomyosis after endometrial resection [58]. In the second series, endometrial resection cured
menorrhagia in 12 of 15 patients but dysmenorrhea in only 3 of 8 [59]. However, endometrial resection reduced the
need for hysterectomy to 30 % in this group of patients [59].
Hysteroscopic ablation by rollerball was first described in 1989 using a
modified urological resectoscope [60]. The
initial case series included 15 patients treated for dysfunctional uterine
bleeding [60]. After at least 6 months of
follow-up, 10 patients had amenorrhea or hypomenorrhea. There was one
failure; the patient underwent vaginal hysterectomy 4 months after the
procedure and was found to have adenomyosis [60].
This pattern of failure for rollerball ablation for patients with
adenomyosis has been confirmed in several studies [61], [62].
A large retrospective cohort study from the Mayo Clinic, Rochester, MN, USA,
analyzed the long-term outcomes and predictors of outcome for women
undergoing global endometrial ablation (either thermal balloon ablation or
radiofrequency ablation) to treat menorrhagia [63]. Univariate analysis (HR 1.5) showed that women with a
diagnosis of adenomyosis on ultrasound who underwent global endometrial
ablation had an increased risk of failure and required subsequent
hysterectomy or repeat ablation. However, adenomyosis was not identified as
an independent predictor of treatment failure in the final multivariable
model [63].
Excisional procedures
Myometrial/adenoymoma excision and myometrial reduction
Focal excision of adenomyosis can be performed if the location of foci can be
determined. However, unlike myomectomy, it is difficult to expose the
lesions, define margins and determine the extent of disease and thus, the
efficacy of excision remains low at 50 % [4].
Myometrial reduction to treat symptomatic adenomyosis refers to the removal
of diseased tissue from the uterus. A large proportion of the myometrium is
removed and the created wedge defect is repaired by metroplasty. The
procedure can be performed by laparoscopy, mini-laparotomy or laparotomy
[56], [64]. A
classic incision is made, with dissection of the uterus longitudinally in
the midline and resection of the anterior and posterior portions of the
myometrium [4].
Fedele et al. evaluated reproductive performance after adenomyoma excision in
a prospective, observational study of 28 women who wished to maintain
fertility [65]. Thirteen (72.2 %) women
conceived; however, seven women (38.8 %) had spontaneous abortions. The
cumulative pregnancy rate at 36 months of follow-up was 74.7 % with a total
of 18 pregnancies, of which nine (50 %) ended in term deliveries [65]. The high rate of spontaneous abortions in
this study is likely due to the large excisions needed which could have
reduced the gestational capability of uterus or due to residual
adenomyomatous growths that could have interfered with the course of
pregnancy [65].
The largest study on adenomyomectomy to date included 165 women treated with
surgery alone or with combined surgical-medical treatment (surgery followed
by six monthsʼ administration of a gonadotropin-releasing hormone agonist)
[66]. Adenomyomectomy was performed by
mini-laparotomy, ultramini-laparotomy, or laparoscopy. Women in both groups
experienced statistically significant symptom relief, and all symptom scores
declined from a mean at the end of the 2-year follow-up period; the
symptom-recurrence rates in the surgical-medical group were statistically
significantly lower than those in the surgery-alone group [66]. Additionally, fifty-five women became
pregnant, with a clinical pregnancy rate of 77.5 %, and 49 women (69.0 %)
had a successful delivery [66].
Fujishita et al. reported a modified method of reduction surgery of lesions
in a small series of women with imaging diagnosis of adenomyosis [67]. A transverse H-incision method for reduction
surgery was used in 6 women, and conventional reduction surgery was
performed in 5 women with adenomyosis. The subjective relief of pain was
more evident in the H-incision group. There was no case of pregnancy in the
conventional surgery group; however, 1 patient conceived spontaneously 4
months after surgery using the H-incision approach [67].
Osada et al. reported a new method of adenomyomectomy, whereby adenomyotic
tissues were excised and the uterine wall was reconstructed using a
triple-flap method [68]. The reported procedure
resulted in a reduction in symptoms and a low recurrence rate and allowed
over half of the women who wished to conceive to carry their pregnancy to
term without uterine rupture [68].
Other surgical procedures
Uterine artery ligation
Only one study investigated the effect of laparoscopic uterine artery
ligation in 20 women with symptomatic adenomyosis [69]. Both uterine arteries were laparoscopically ligated with
hemoclips, and electrocoagulation of both uterine ovarian vessels was
performed. Six months postoperatively, mean uterine volume had decreased
between 0.4 and 74.0 %. Two of nine women achieved remission of the mass
effect of an enlarged uterus. Thirteen of 16 patients achieved bleeding
control and 5 reported eumenorrhea or hypomenorrhea. Twelve of 16 patients
achieved control of dysmenorrhea and 6 were analgesia-free. However, nine
women experienced non-menstrual pain after surgery, three of whom later
underwent hysterectomy. Treatment outcome was rated as satisfactory by only
15 % of patients, and 45 % were dissatisfied. Seventeen women would have
refused the procedure if they could make the decision again. The authors
concluded that the poor satisfaction rate suggests that symptomatic
adenomyosis may not be effectively treated by laparoscopic uterine artery
ligation [69].
Myometrial electrocoagulation
Electrocoagulation has the capacity to shrink adenomyosis by causing
necrosis. The technique can be carried out laparoscopically to treat
localized or extensive disease [70]. Myometrial
electrocoagulation of adenomyosis is a laparoscopic procedure that can be
carried out using unipolar or bipolar needles and a coagulation current of
50 watts. However, the procedure is considered to be less accurate than
surgical excision because electrical conduction in abnormal tissue may be
incomplete and this cannot be evaluated during surgery [70].
Other interventions
Uterine artery embolization
Uterine artery embolization (UAE) for women with symptomatic leiomyomas was
first reported in 1995 [71]. UAE is a minimally
invasive procedure and represents an alternative to surgery. UAE has been
reported to be effective in women with leiomyomas and is associated with
high patient satisfaction rates [5]. Additionally,
UAE is more cost-effective and has shorter recovery periods and less pain
compared to surgical techniques [5]. Commonly
reported side effects of UAE are pelvic pain, nausea and fever due to
ischemic necrosis [6]. In addition, approximately
5 % of patients experience major complications including hemorrhage,
unplanned surgical procedures and infection. Moreover, there are reports of
an age-related impairment of ovarian function following UAE [6].
Adenomyosis and leiomyomas often coexist in the same uterus and their
symptoms are often similar. Thus, performing UAE in women with leioymomas
will also include patients with adenomyosis [6].
At the outset of UAE for women with symptomatic leiomyomas, several authors
attributed unsatisfactory clinical results to the presence of concurrent
adenomyosis [72], [73]. These observations reinforced the importance of a correct
diagnosis before UAE and the need to evaluate a possible negative impact of
adenomyosis on the clinical outcome of UAE [6].
There are, however, a number of encouraging reports in the last 14 years on
the use of UAE for the treatment of adenomyosis ([Table
1]). Kim et al. reported the largest study of patients who
underwent UAE for adenomyosis without leiomyomas; the study included 54
patients with a follow-up period of at least 3 years [80]. Thirty-one (57.4 %) of the 54 women who were followed up
demonstrated long-term success; 4 patients had immediate failure of
treatment, and 19 patients had recurrence. Changes in menorrhagia and
dysmenorrhea scores at follow-up showed a significant relief of symptoms
[80]. The time between UAE and the recurrence
of symptoms ranged from 4 to 48 months (mean, 17.3 months). Five patients
underwent hysterectomy because of symptom recurrence. Mean reduction in
volume of the uterus was 26.3 % at short-term follow-up and 27.4 % at
long-term follow-up [80]. Thus, the study by Kim
et al. was the first to show that UAE has an acceptable long-term success
rate in the management of symptomatic adenomyosis.
Table 1 Studies on the outcome of uterine artery
embolization in the treatment of adenomyosis.
|
Study, year [reference]
|
Patients (n)
|
Symptoms improved
n (%)
|
Follow-up (months)
|
|
1 at 12 months follow-up; 2 at 36
months follow-up
|
|
Goodwin et al., 1999 [72]
|
6
|
3 (50)
|
10.2
|
|
Siskin et al., 2001 [74]
|
13
|
12 (92)
|
8.2
|
|
Jha et al., 2003 [75]
|
9
|
9 (100)
|
12.0
|
|
Toh et al., 2003 [76]
|
12
|
3 (25)
|
10.9
|
|
Kim et al., 2004 [77]
|
43
|
40 (93)
|
3.5
|
|
Pelage et al., 2005 [78]
|
9
|
5 (55)
|
24.0
|
|
Kitamura et al., 2006 [79]
|
11
|
10 (91)
|
12.0
|
|
Kim et al., 2007 [80]
|
54
|
31 (57)
|
58.8
|
|
Bratby and Walker, 2009 [81]
|
161; 112
|
13 (79)1; 6 (56)2
|
36.0
|
|
Liang et al., 2012 [82]
|
17
|
17 (100)
|
6.0
|
|
Smeets et al., 2012 [83]
|
40
|
29 (73)
|
65.0
|
Bratby and Walker analyzed 27 women with symptomatic adenomyosis diagnosed on
MRI who underwent UAE [81]. There was an initial
favorable clinical response, with improvement of menorrhagia in 79 % (13/16)
of patients at 12 months. Follow-up data was available for a total of 14
patients at 2 and 3 years after embolization; 45.5 % reported a
deterioration in menorrhagia symptoms at 3 years. The authors concluded that
UAE for symptomatic adenomyosis is effective in the short-term but there is
a high recurrence rate of clinical symptoms 2 years following treatment
[81].
The study with the longest follow-up (mean clinical follow-up: 65 months)
evaluated UAE in 40 consecutive women with adenomyosis, of whom 22 women had
a concomitant diagnosis of leiomyomas [83].
Changes in junction zone thickness were assessed with magnetic resonance
imaging (MRI) at baseline and again at 3 months. During follow-up, 7 of 40
women (18 %) underwent hysterectomy; of the 33 women with preserved uterus,
29 were asymptomatic [83]. There was no
association between clinical outcome and the initial presence of leiomyomas
in addition to adenomyosis. Furthermore, UAE resulted in long-term
preservation of the uterus in the majority of patients and the only
predictor for hysterectomy during follow-up was the initial thickness of the
junction zone [83].
Several studies conducted on the efficacy of UAE in symptomatic adenomyosis
have shown sustained clinical and symptomatic improvements. However, none of
the studies were controlled or randomized. Thus, the efficacy of UAE in
adenomyosis remains unclear, primarily because of a lack of high-quality
data [84]. Larger-scale, randomized controlled
studies with longer follow-up times are mandatory to determine the efficacy
of UAE in the treatment of adenomyosis.
Magnetic resonance-guided focused ultrasound
Magnetic resonance-guided focused ultrasound (MRgFUS) surgery was approved by
the United States Food and Drug Administration (FDA) as a noninvasive
treatment for uterine leiomyomas [85]. Focused
ultrasound surgery delivers a concentrated quantity of ultrasound energy to
deep tissue areas without thermal effects to surrounding tissue [86].
The underlying process in adenomyosis is smooth muscle hyperplasia and thus,
MRgFUS treatment is ideal to target such lesions [86]. The distinction between leiomyomas and adenomyosis is made
using MR imaging to show diffuse or focal thickening of the junctional zone
of the uterus in the presence of adenomyosis [86].
Initial experience with MRgFUS to treat symptomatic adenomyosis has shown
promising results [87], [88], [89], [90]. The first patient treated with MRgFUS for symptomatic
adenomyosis completed the treatment with no complications, had improvement
of menorrhagia and shrinkage of the adenomyomatous mass [87]. The patient conceived spontaneously after the
procedure, and pregnancy and delivery were not affected by MRgFUS treatment
[87]. Fukunishi et al. reported early results
that indicated the safe and effective ablation of adenomyosis tissue by
MRgFUS. The procedure also resulted in an improvement of clinical symptoms
during the 6 months of follow-up [89].
Kim et al. evaluated the degree of symptom relief obtained after treatment
with MRgFUS in patients with adenomyosis [91].
Quality-of-life and pain assessment questionnaires from 35 women, collected
on the day of treatment and up to 6 months after treatment, indicated that
the treatment was safe and that there was a significant reduction in
symptoms [91]. Nevertheless, although these
reports show encouraging results for the use of MRgfUS to treat adenomyosis,
additional studies into the safety and efficacy of MRgFUS for women with
adenomyosis are necessary.
Conclusions
Adenomyosis is an important clinical challenge in gynecology and healthcare
economics; in its fully developed form hysterectomy is often used to treat it in
pre-menopausal and perimenopausal women. Although it has been recognized for over
a
century, reliable epidemiological studies on this condition are limited, probably
because in the past diagnosis was only possible postoperatively [13]. Symptomatic women receiving treatment for adenomyosis
are mostly in their fourth or fifth decade and multiparous. However, the diagnosis
is increasingly being made in younger women who wish to maintain their fertility.
Thus, the evolution of minimally invasive and uterine-conserving therapies and the
demand for these therapies requires a better understanding of the disease.
Additionally, there are no evidence-based guidelines to treat adenomyosis using
minimally invasive methods [6].
Minimally invasive surgical interventions (endometrial ablation/resection, myometrial
excision/reduction, myometrial electrocoagulation, uterine artery ligation) were
primarily introduced to treat symptomatic women with adenomyosis but have had
limited success in the treatment of adenomyosis. Moreover, all reported data are
from case reports or small case series with short follow-up times. Thus, although
some studies have reported follow-up data including pregnancy and delivery rates,
these procedures are not generally recommended for women who wish to maintain
fertility.
On the other hand, uterine artery embolization and magnetic resonance imaging guided
focused ultrasound therapy have shown encouraging results in the treatment of
adenomyosis. The studies on uterine artery embolization showed the most promising
results and were carried out in the largest patient cohorts. However, none of the
UAE studies were randomized or controlled. Thus, the efficacy of UAE in adenomyosis
remains unclear, primarily because of a lack of high-quality data. Furthermore, at
present the American College of Obstetrics and Gynecology and the Society of
Interventional Radiology list the desire for future fertility as a relative
contraindication to UAE [92]. In spite of all these
shortcomings, the emergence of various surgical and interventional therapeutic
modalities for a condition that, for decades, could only be solved by hysterectomy
is most gratifying [52].
The ontogeny of adenomyosis is clearly important for the development of new
alternatives to hysterectomy. Prospective randomized and controlled studies with
larger cohorts, validated and disease-specific symptom questionnaires, noninvasive
diagnostic modalities as well as new surgical and interventional alternatives to
hysterectomy are required to better understand adenomyosis and to avoid
hysterectomy.
For some women with adenomyosis who have completed their family planning,
hysterectomy still remains the best option. Understanding the diversity of the
disease, both with regards to pathology and symptomatology, will lead to targeted
therapies in the short term and prevention strategies in the longer term. Our goal
as researchers of benign myometrial lesions is to understand the biology of these
lesions and provide evidence to guide individualized treatment (surgery vs.
lifestyle modification vs. novel therapies based on research insights) in the
future.
