adenomyosis is a benign condition of the uterus , defined by the presence of endometrial glands and stroma within the myometrium . it is known as a histological diagnosis but it has a clinical dignity showing symptoms ( dysmenorrhea , dyspareunia , abnormal uterine bleeding , and infertility ) and sharing some pathogenic mechanisms with endometriosis . most of the major authors of the first half of the past century dealing with the disease considered pelvic endometriosis and uterine adenomyosis as variants of the same disease process [ 2 , 3 ] . also , sampson ( 1927 ) , although focusing mainly on the aetiology of the pelvic dissemination of the disease , mentioned uterine adenomyosis and referred to it as  primary endometriosis  . moreover , a 42.76% prevalence of adenomyosis in patients with endometriosis has been recently identified in patients reporting severe or incapacitating dysmenorrhea and deep dyspareunia and in patients with endometriosis of the rectosigmoid . a common pathogenesis for adenomyosis and endometriosis has been hypothesized [ 79 ] and it was argued that endometrial stroma being in direct contact with the underlying myometrium allows communication and interaction , thus facilitating endometrial invagination or invasion of a structurally weakened myometrium during periods of regeneration , healing , and reepithelization . mechanical damage   to and/or physical disruption of the endometrial - myometrial interface may be due to dysfunctional uterine hyperperistalsis and/or dysfunctional contractility of the subendometrial myometrium . finally , considering adenomyosis as consequence of infiltration of basal endometrium into the underlying myometrium [ 8 , 12 ] , a correlation between the stage of endometriosis and the depth of adenomyotic infiltration has been reported . up to the present , in literature there is a lack of studies evaluating specifically demographic characteristics and symptoms in patients with adenomyosis and different type of endometriosis . in this view , we considered in our paper women with diagnosis of adenomyosis and endometriosis undergoing surgery and we recorded their demographic and clinical characteristics . for this observational study , ethical approval was obtained from the local ethics committee ( 198/2013/o / ossn ) . from january 2010 to december 2012 , in the minimally invasive gynecological surgery unit of the department of gynecology , s. orsola - malpighi hospital , university of bologna , women with ultrasound diagnosis of adenomyosis and endometriosis undergoing surgery for endometriosis and patients with ultrasound diagnosis of adenomyosis undergoing surgery for infertility were enrolled . patients were divided according to the type of endometriosis ( superficial , ovarian , and deep infiltrating endometriosis ) . this anatomic classification based on depth of infiltration of endometriotic nodules has been largely accepted by many authors [ 14 , 15 ] . deep infiltrating endometriosis was considered as a particular form of endometriosis that penetrates > 5 mm under the peritoneal surface . in case more than one condition was found , we considered the more advanced disease to classify women in the three different types of endometriosis . in endometriosis groups , histological confirmation of endometriosis was considered as an inclusion criterion . we excluded women who had previously undergone a hysterectomy , those who were pregnant women , those with malignant gynaecological disease , and those who received hormonal therapy ( gonadotropin - releasing hormone agonist , levonorgestrel intrauterine system ) in the preceding 3 months before surgery . the following demographic data and symptoms were recorded : age , body mass index ( bmi ) , history of previous surgery , dysmenorrhea , dyspareunia , dyschezia , dysuria , and abnormal uterine bleeding . the level of patient 's discomfort and pain was evaluated by the visual analog scale ( vas ) system , utilizing a 10  cm line with the extreme points 0 and 10 corresponding to  no pain  and  maximum pain ,  respectively . menstrual bleeding was assessed with the use of the pictorial blood loss assessment chart ( pbac ) ,   a validated method used to objectively estimate blood loss ; monthly scores range from 0 to more than 500 , with higher numbers indicating more bleeding , and menorrhagia was defined as a pbac > 100 during 1 menstrual period , which corresponds to a blood loss of more than 80  ml . a transvaginal ultrasound scan was then done before surgery by a single operator ( g.m . ) and other diagnostic tests , such as magnetic resonance imaging ( mri ) and computed tomography ( ct ) , were performed when indicated to evaluate the presence , the localization , and the extension of endometriosis lesions . sonographic examinations were performed in a systematic manner by a single sonographer , using high - quality ultrasound machine ( voluson s8 , ge milwaukee , wi , usa ) equipped with a transvaginal wide - band 5.09.0  mhz transducer , which ensured a consistent approach to data collection and ultrasound examination . the probe was then rotated 90 anticlockwise and cervical canal and the uterine cavity were visualized in the transverse plane . the myometrium was systematically examined for the sonographic features associated with adenomyosis . diagnosis of adenomyosis was made when 3 or more of the following sonographic features were present : heterogeneous myometrial echotexture ( presence of an indistinctly myometrial area with decreased or increased echogenicity ) , globular - appearing uterus ( regular enlarged uterus ) , asymmetrical thickness of anteroposterior wall of the myometrium , subendometrial myometrial cysts ( round anechoic areas of 17  mm diameter ) , subendometrial echogenic linear striations ( radiate pattern of thin acoustic shadowing not arising from echogenic foci ) , or poor definition of the endometrial - myometrial junction , according to previous studies [ 1719 ] . moreover , ovarian cysts were classified as endometriomas when they appeared as well - circumscribed thick - walled cysts that contained homogeneous low - level internal echoes (  ground glass  ) . endometriotic nodules were typically visualized as stellate hypoechoic or isoechogenic solid masses with irregular outer margins which were tender on palpation and fixed to the surrounding pelvic structures , as previously described [ 2023 ] . the diagnosis of die was made if at least 1 structure in the anterior or posterior compartment showed the presence of retroperitoneal abnormal hypoechoic linear or nodular thickening with irregular contours and no vascular doppler signals , as described previously and validated ultrasonographic criteria [ 24 , 25 ] . locations for die in the anterior ( bladder ) or posterolateral compartment ( vagina , rectovaginal septum , torus and uterosacral ligaments , parametria and ureteral involvement , rectum , and rectosigmoid junction ) were examined . concerning ultrasound adenomyosis evaluation , we described and recorded an additional finding which has been observed in our clinical practice . in adenomyosis cases , we identified a particular endometrial shape named question mark sign (  ?  ) . sign was considered positive when the endometrium of the uterine fundus was deviated versus the pelvis posterior compartment ( figures 1 and 2 ) . we reported means , standard deviations and medians for continuous variables , and frequency counts and percentages for nominal or categorical variables . to assess differences between groups of women , fisher 's exact test generalized for more than two groups was performed for nominal and categorical variables . continuous data were analyzed with one - way anova and tukey 's post hoc pair wise comparisons for continuous variables . all the analysis was performed with the software spss 11.0 software ( spss inc . , demographic and clinical characteristics of women included in the study are summarized in table 1 . 51 were excluded from the data analysis as 21 patients had no histological diagnosis of endometriosis , 26 had intolerance to transvaginal ultrasound examination , and 4 had previously undergone a hysterectomy . from 217 patients included in the study with ultrasound diagnosis of adenomyosis , we found 66 with ovarian histological confirmation of endometriosis , 92 with die , and 52 patients who underwent surgery for infertility . only seven women were found with superficial endometriosis alone . for the analysis of data , we considered them together with the ovarian group . women with adenomyosis alone represented the oldest group of patients ( 37.8  5.18 years , p = 0.02 ) ; instead , bmi did not differ between groups . concerning the characteristics recorded , we found that patients with die were nulliparous more frequently than other groups ( p < 0.0001 ) and comparing to endometriosis patients ( 87/92 , 94.6% die ; 54/73 , 73.9% ovarian endometriosis ) , only 27 ( 27/52 51.9% ) women with adenomyosis alone were nulliparous . moreover , in women with one or more births adenomyosis alone was significantly more frequent than in the others ( p < 0.0001 ) . we evaluated the history of previous surgical procedures and we found that women with adenomyosis and die had more frequently a history of previous surgery ( p = 0.004 ) . regarding symptoms , die group complained of more intense pain symptoms ( dysmenorrhea , chronic pelvic pain , dyspareunia , dysuria , and dyschezia ) than other groups . moreover , patients with only adenomyosis were more likely to have abnormal uterine bleeding ( p < 0.0001 ) ( table 2 ) . describing the particular endometrial shape mentioned above , we found a strong relationship between this sonographic sign and adenomyosis associated deep infiltrating endometriosis . it was significantly ( p < 0.0001 ) more present in die group ( 34/92 [ 37% ] ) than in the others ( ovarian 7/73 [ 9.6% ] and adenomyosis alone 4/52 [ 7.7% ] ) . specifically , evaluating the different localizations of die ( anterior and posterior ) , we reported that it was significantly ( p = 0.01 ) associated with posterior deep nodule ( 23/46 [ 50% ] posterior die versus 11/46 [ 23.9% ] anterior die ) . today , several authors have described the association between adenomyosis and endometriosis , particularly die [ 2628 ] . in a prospective study kissler et al . found that severe dysmenorrhea of long duration in patients with endometriosis is significantly related to uterine adenomyosis . moreover , larsen et al . found a correlation between the severity of endometriosis and the degree of uterine adenomyosis and gonzalez et al . found again a correlation between uterine adenomyosis and deep endometriosis with poor prognosis , particularly endometriosis of the rectosigmoid . in our study , we evaluated clinical and demographic characteristics related to adenomyosis in patients undergoing surgery for different type of endometriosis . we identified a particular endometrial shape associated with adenomyosis and we named this specific endometrial finding  question mark sign .  the endometrium was deviated versus the pelvis posterior compartment from the fundus to the cervix . moreover , we reported that the question mark sign was strongly related to the presence of posterior deep infiltrating endometriosis . therefore , it is interesting to look for this endometrial sign during the preoperative ultrasound evaluation in the way to facilitate the diagnosis of both posterior deep infiltrating endometriosis and adenomyosis . probably , the uterus is deviated by the nodule in the posterior compartment of the pelvis changing the normal endometrial shape . moreover , from literature , the posterior wall of the uterus was predominantly affected by adenomyosis [ 29 , 30 ] . however , no data are available that show an increased mechanical stress of the posterior uterine wall due to chronic uterine peristalsis and hyperperistalsis and a relationship of the site of predilection of adenomyosis with ante- or retroflection of the uterus [ 29 , 30 ] . there is indirect evidence of an archimetral hyperestrogenism in women with endometriosis that interferes with the ovarian control of uterine peristaltic activity resulting in uterine hyperperistalsis [ 31 , 32 ] . moreover , it was argued that endometrial stroma being in direct contact with the underlying myometrium allows communication and interaction , thus facilitating endometrial invagination or invasion of a structurally weakened myometrium during periods of regeneration , healing , and reepithelization [ 10 , 11 ] . from our results , we found that patients with die and adenomyosis were nulliparous more frequently and complained of more intense pain symptoms ( dysmenorrhea , chronic pelvic pain , dyspareunia , dysuria , and dyschezia ) than other groups with the exception of abnormal uterine bleeding which was complained by the majority of women with only adenomyosis . heavy bleeding may be positively related to the depth of penetration of individual adenomyotic glands into the myometrium and to the density of deep endometrial glands within the myometrium . in concordance with previous clinical evidence , we found that a high percentage of women with adenomyosis were multiparous [ 11 , 18 , 34 , 35 ] . instead , patients affected by endometriosis are frequently associated with infertility because of anatomical and immunological alterations caused by endometriosis . generally , endometriosis is common in women with subfertility and can affect fertility at different level , from the induction of a local inflammation and decrease in endometrial receptivity to mechanical obstruction and altered sexual function . first , pregnancy might facilitate 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 myometrial fibers . second , the possibility of cesarean section may lead to iatrogenic adenomyosis [ 11 , 37 ] . third , the hormonal milieu of pregnancy may favour the development of islands of ectopic endometrium . a recent review in 2013 defined a number of factors that encourage the development of adenomyosis ( spontaneous miscarriage , curettage , hysteroscopic resection of the endometrium , uterine myomectomy , caesarean section , and taking tamoxifen ) and underlined that the main factor is having had more than one pregnancy . in agreement with our data , shrestha found that the frequency of adenomyosis was higher in parous women in comparison with nulliparous . moreover , vercellini and colleagues suggested that parity may be associated with an increased frequency of adenomyosis . other studies reported the same relationship between parity and adenomyosis [ 34 , 41 ] . concerning symptoms , die is the most severe form of endometriosis , associated with infertility or pain symptoms , including chronic pelvic pain , dysmenorrhea , dyspareunia , dysuria , and dyschezia . nowadays , it is clarified that there is an overlap in the symptom complexes of both endometriosis and adenomyosis . in endometriosis , the presence of adenomyosis is found to be a risk factor for dysmenorrhea severity . as described before , dysmenorrhea increases with greater depth of penetration of the adenomyotic process and to the density of deep endometrial glands into myometrium ; instead dyspareunia and chronic pain are not considered constant symptoms in patients with adenomyosis [ 5 , 44 ] . lazzeri and colleagues showed a persistence of dyspareunia in women after surgery for die when adenomyosis was present . consequently , a correct counselling about pain recurrence is required in case of coexistence of both pathological entities . surgery for posterior die with coexistence of adenomyosis could be not resolved for postoperative pain relief because of adenomyosis persistence . this information allows the chance of a correct counselling before surgery and should help to develop more effective treatment strategies in women affected by die and adenomyosis . the strength of our study is the large number of women with endometriosis histologically confirmed and that it was conducted in a tertiary care university hospital , by clinicians highly skilled in endometriosis management . moreover , sonographic examinations were performed in a systematic manner by a single sonographer , using high - quality ultrasound machine . first , the lack of histological confirmation of adenomyosis for the majority of patients included . however , recently transvaginal ultrasound has reached a high level of accuracy and many authors have reported the high agreement between ultrasound diagnosis of adenomyosis and histological findings [ 17 , 47 ] . a recent review   reported that transvaginal ultrasound should be the primary tool for the diagnosis of adenomyosis , with mri being used when transvaginal ultrasound is inconclusive or when large fibroids are present . secondly , being patients included in the study with a mean age of 35 years old , it can be a possible bias for evaluation of the natural history of adenomyosis pathology . since the adenomyotic nodules communicate with the uterine cavity , pathophysiologically a continuous process from initial to deep infiltration must exist . authors reported that endometriosis - associated adenomyosis progresses with age [ 13 , 49 ] . in conclusion , our data confirmed the strong relationship between adenomyosis and endometriosis and evaluated demographic aspects and symptoms in patients affected by different type of endometriosis . our findings suggest that adenomyosis and endometriosis share same symptoms with important difference linked to the type of endometriosis and help to better understand the endometriosis - adenomyosis relationship and their associated factors .
objective . 
 the aim of the study is to evaluate adenomyosis in patients undergoing surgery for different type of endometriosis . 
 it is an observational study including women with preoperative ultrasound diagnosis of adenomyosis . 
 demographic data and symptoms were recorded ( age , body mass index , parity , history of previous surgery , dysmenorrhea , dyspareunia , dyschezia , dysuria , and abnormal uterine bleeding ) . moreover a particular endometrial shape  question mark sign  linked to the presence of adenomyosis was assessed . 
 results . from 217 patients with ultrasound diagnosis of adenomyosis 
 , we found 73 with ovarian histological confirmation of endometriosis , 92 with deep infiltrating endometriosis , and 52 patients who underwent surgery for infertility . 
 women with adenomyosis alone represented the oldest group of patients ( 37.8  5.18 years , p = 0.02 ) . 
 deep endometriosis patients were nulliparous more frequently ( p < 0.0001 ) , had history of previous surgery ( p = 0.004 ) , and complained of more intense pain symptoms than other groups . 
 adenomyosis alone was significantly associated with abnormal uterine bleeding ( p < 0.0001 ) . 
 the question mark sign was found to be strongly related to posterior deep infiltrating endometriosis ( p = 0.01 ) . conclusion . 
 our study confirmed the strong relationship between adenomyosis and endometriosis and evaluated demographic aspects and symptoms in patients affected by different type of endometriosis .