adenomyosis adenomyosis adenomyosis is a medical condition characterized by the growth of cells that proliferate on the inside of the uterus (endometrium) atypically located among the cells of the uterine wall (myometrium), as a result, thickening of the uterus occurs. as well as being misplaced in patients with this condition, endometrial tissue is completely functional. the tissue thickens, sheds and bleeds during every menstrual cycle. adenomyosisadenomyosis uteri seen during laparoscopy: soft and enlarged uterus; the blue spots represent subserous endometriosis.specialtygynecologyfrequency20 to 35%. the condition is typically found in women between the ages of 35 and 50, but also affects younger women. patients with adenomyosis often present with painful menses (dysmenorrhea), profuse menses (menorrhagia), or both. other possible symptoms are pain during sexual intercourse, chronic pelvic pain and irritation of the urinary bladder. in adenomyosis, basal endometrium penetrates into hyperplastic myometrial fibers. unlike the functional layer, the basal layer does not undergo typical cyclic changes with the menstrual cycle. adenomyosis may involve the uterus focally, creating an adenomyoma. with diffuse involvement, the uterus becomes bulky and heavier. adenomyosis can be found together with endometriosis; it differs in that patients with endometriosis present endometrial-like tissue located entirely outside the uterus. in endometriosis, the tissue is similar to, but not the same as, the endometrium. the two conditions are found together in many cases yet often occur separately. before being recognized as a distinct condition, adenomyosis was called endometriosis interna. the less-commonly-used term adenomyometritis is a more specific name for the condition, specifying involvement of the uterus. signs and symptoms adenomyosis can vary widely in the type and severity of symptoms that it causes, ranging from being entirely asymptomatic 33% of the time to being a severe and debilitating condition in some cases. women with adenomyosis typically first report symptoms when they are between 40 and 50, but symptoms can occur in younger women. symptoms (viz., heavy bleeding and pain) and the estimated percent affected may include: heavy menstrual bleeding (40-60%), which is more common in women with deeper adenomyosis. blood loss may be significant enough to cause anemia, with associated symptoms of fatigue, dizziness, and moodiness. abnormal uterine bleeding chronic pelvic pain (77%) painful cramping menstruation (15-30%) painful vaginal intercourse, uncommon (7%) a 'bearing' down feeling pressure on bladder dragging sensation down thighs and legs clinical signs of adenomyosis may include: uterine enlargement (30%), which in turn can lead to symptoms of pelvic fullness. tender uterus infertility or sub-fertility (11-12%) - in addition, adenomyosis is associated with an increased incidence of preterm labour and premature rupture of membranes. women with adenomyosis are also more likely to have other uterine conditions, including: uterine fibroids (50%) endometriosis (11%) endometrial polyp (7%) causes the cause of adenomyosis is unknown, although it has been associated with any sort of uterine trauma that may break the barrier between the endometrium and myometrium, known as the junctional zone, such as a caesarean section, surgical pregnancy termination, and any pregnancy. it can be linked with endometriosis, but studies looking into similarities and differences between these two conditions have conflicting results. the pathogenesis of adenomyosis still remains unclear, but the functioning of the inner myometrium, also called the junction zone (jz), is believed to play a major role in the development of adenomyosis. it is also a matter of discussion whether the link between reproductive disorders and major obstetrical disorders also lies here. parity, age, and previous uterine abrasion increase the risk of adenomyosis. hormonal factors such as local hyperestrogenism and elevated levels of s-prolactin as well as autoimmune factors have also been identified as possible risk factors. as both the myometrium and stroma in an adenomyosis affected uterus show significant differences from those of a non-affected uterus, a complex origin that includes multifactorial changes on both genetic and biochemical levels is likely. the tissue injury and repair (tiar) theory is now widely accepted and suggests that uterine hyperperistalsis (i.e., increased peristalsis), during early periods of reproductive life will induce micro-injury at the endometrial-myometrial interface (emi) region. that again leads to elevation of local estrogen in order to heal the damage. at the same time, estrogen treatment will increase uterine peristalsis again, leading to a vicious circle and a chain of biological alterations essential for the development of adenomyosis. iatrogenic injury of the junctional zone or physical damage due to placental implantation most likely results in the same pathological cascade. this also explains that adenomyosis often becomes more severe after each pregnancy and childbirth, while endometriosis will ameliorate. mechanism pathophysiology cross section through the wall of a hysterectomy specimen of a 30-year-old woman who reported chronic pelvic pain and abnormal uterine bleeding. the endometrial surface is at the top of the image, and the serosa is at the bottom.misplaced endometrial tissue proliferation in the myometrium causes symptoms through different mechanisms. uterine menstrual contractions are caused by prostaglandin, which is produced by normal endometrial tissue. dysmenorrhea is the main characteristic for this disease which are the result for high prostaglandin levels. endometrial proliferation is also led by estrogen; some treatments try to reduce its levels in order to decrease symptoms. adenomyosis patients present with heavy menstrual bleeding due to the increase of endometrial tissue, greater degree of vascularization, atypical uterine contractions and increased levels of prostaglandins, estrogen and eicosanoids. histopathology the diagnosis of adenomyosis is through a pathologist microscopically examining small tissue samples of the uterus. these tissue samples can come from a uterine biopsy or directly following a hysterectomy. uterine biopsies can be obtained by either a laparoscopic procedure through the abdomen or hysteroscopy through the vagina and cervix. the diagnosis is established when the pathologist finds invading clusters of endometrial tissue within the myometrium. several diagnostic criterion can be used, but typically they require either the endometrial tissue to have invaded greater than 2% of the myometrium, or a minimum invasion depth between 2.5 and 8mm.histopathological image of uterine adenomyosis observed in hysterectomy specimen. hematoxylin & eosin stain. gross findings: enlarged uterus thickened uterine wall with trabeculated appearance hemorrhagic pinpoint or cystic spaces throughout wall microscopic findings: endometrial glands and stroma haphazardly distributed throughout myometrium concentric myometrial hyperplasia frequent around adenomyotic foci variants: gland-poor, stroma-poor, intravascular differential diagnosis: adenomyoma myo-invasive endometrial endometrioid carcinoma (vs. stroma-poor adenomyosis) low-grade endometrial stromal sarcoma (vs. gland-poor and intravascular adenomyosis) diagnosis imaging adenomyosis can vary widely in the extent and location of its invasion within the uterus. as a result, there are no established pathognomonic features to allow for a definitive diagnosis of adenomyosis through non-invasive imaging. nevertheless, non-invasive imaging techniques such as transvaginal ultrasonography (tvus) and magnetic resonance imaging (mri) can both be used to strongly suggest the diagnosis of adenomyosis, guide treatment options, and monitor response to treatment. indeed, tvus and mri are the only two practical means available to establish a pre-surgical diagnosis. transvaginal ultrasonography transvaginal ultrasound of the uterus, showing the endometrium as a hyperechoic (brighter) area in the middle, with linear striations extending upwards from ittransvaginal ultrasonography is a cheap and readily available imaging test that is typically used early during the evaluation of gynecologic symptoms. ultrasound imaging, like mri, does not use radiation and is safe for examination of the pelvis and female reproductive organs. overall, it is estimated that transvaginal ultrasonography has a sensitivity of 79% and specificity of 85% for the detection of adenomyosis. common transvaginal ultrasound findings in patients with adenomyosis include the following: globular, enlarged, and/or asymmetric uterus abnormally dense or especially varied density within the myometrium myometrial cysts - pockets of fluid within the smooth muscle of the uterus linear, acoustic shadowing without presence of a uterine fibroid echogenic linear striations - bright lines or stripes anterior/posterior wall asymmetry diffuse spread of small vessels within the myometrium less common findings: lack of contour abnormality absence of mass effect ill-defined margins between a normal and abnormal myometrium the power doppler or doppler ultrasonography function can be used during transvaginal ultrasonography to help differentiate adenomyomas from uterine fibroids. this is because uterine fibroids typically have blood vessels circling the fibroid's capsule. in contrast, adenomyomas are characterized by widespread blood vessels within the lesion. doppler ultrasonography also serves to differentiate the static fluid within myometrial cysts from flowing blood within vessels. the junction zone (jz), or a small distinct hormone-dependent region at the endometrial-myometrial interface, may be assessed by three-dimensional transvaginal ultrasound (3d tvus) and mri. features of adenomyosis are disruption, thickening, enlargement or invasion of the junctional zone. sagittal mri of a woman's pelvis showing a uterus with adenomyosis in the posterior wall. gross enlargement of the posterior wall is noted, with many foci of hyperintensity. magnetic resonance imaging magnetic resonance imaging (mri) provides slightly better diagnostic capability compared to tvus, due to the increased ability of mri to differentiate objectively between different types of soft tissue. this is possible with mri's higher spatial and contrast resolution. overall, it is estimated that mri has a sensitivity of 74% and specificity of 91% for the detection of adenomyosis. diagnosis through mri focuses predominately upon investigating the junctional zone. the uterus will have a thickened junctional zone with darker/diminished signal on both t1 and t2 weighted sequences. three objective measures of the junctional zone can be used to diagnose adenomyosis. a thickness of the junctional zone greater than 8–12 mm. less than 8 mm is normal. a junctional zone width being greater than 40% of the width of the myometrium. variability in the width of the junctional zone being greater than 5 mm. interspersed within the thickened, darker signal of the junctional zone, one will often see foci of hyperintensity (bright spots) on the t2 weighted scans representing small cystically dilatated glands or more acute sites of microhemorrhage. mri is limited by other factors, but not by calcified uterine fibroids (as is ultrasound). in particular, mri is better able to differentiate adenomyosis from multiple small uterine fibroids. treatment adenomyosis can only be cured definitively with surgical removal of the uterus. as adenomyosis is responsive to reproductive hormones, it reasonably abates following menopause when these hormones decrease. for women in their reproductive years, adenomyosis can typically be managed with the goals to provide pain relief, to restrict progression of the process, and to reduce significant menstrual bleeding. medications nsaids: nonsterioidal anti-inflammatory drugs, such as ibuprofen and naproxen, are commonly used in conjunction with other therapies for pain relief. nsaids inhibit the production of prostaglandins by decreasing the activity of the enzyme cyclooxygenase. prostaglandins have been shown to be primarily responsible for dysmenorrhea or the cramping pelvic pain associated with menses. hormones and hormone modulators levonorgestrel-releasing intrauterine devices or hormonal iuds, such as the mirena, are an effective treatment for adenomyosis. they reduce symptoms by causing decidualization of the endometrium, reducing or eliminating menstrual flow. additionally, by helping downregulate estrogen receptors, hormonal iuds shrink the clusters of endometrial tissue within the myometrium. this leads to reduced menstrual blood flow, helps the uterus contract more properly, and helps to reduce the menstrual pain. the use of hormonal iuds in patients with adenomyosis have been proven to reduce menstrual bleeding, improve anemia and iron levels, reduce pain, and even result in an improvement of adenomyosis with a smaller uterus on medical imaging. at least in the short term, patients who can tolerate hormonal iuds for the treatment of adenomyosis result in equivalent improvement of symptoms and better quality-of-life and social well-being as compared to women who undergo a hysterectomy. hormonal iuds are particularly well suited for individuals needing effective treatment of their adenomyosis while still maintaining future fertility potential. the most common negative side-effect of hormonal iuds is irregular menstrual bleeding or spotting. oral contraceptives reduce the menstrual pain and bleeding associated with adenomyosis. this may require taking continuous hormone therapy to reducing or eliminating menstrual flow. oral contraceptives may even lead to short-term regression of adenomyosis. progesterone or progestins: progesterone counteracts estrogen and inhibits the growth of endometrial tissue. such therapy can reduce or eliminate menstruation in a controlled and reversible fashion. progestins are chemical variants of natural progesterone. gonadotropin-releasing hormone (gnrh) agonists and danazol have been tried in order to relieve adenomyosis related symptoms and show some effect, but the studies are few, mainly with a retrospective study design and have small sample sizes. long-time use of gnrh-analogues is often associated with heavy side effects, loss of