Adenomyosis | |
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Adenomyosis uteri seen during laparoscopy: soft and enlarged uterus; the blue spots represent subserous endometriosis. | |
Specialty | Gynecology |
Frequency | 20 to 35%. [1] |
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), [2] 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. [2]
The condition is typically found in women between the ages of 35 and 50, but also affects younger women. [3] 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. [4] [5] Adenomyosis may involve the uterus focally, creating an adenomyoma. With diffuse involvement, the uterus becomes bulky and heavier. [6]
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. [7] [4] 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. [8] [9]
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. [3] [6]
Symptoms (viz., heavy bleeding and pain) and the estimated percent affected may include: [6]
Clinical signs of adenomyosis may include:
Women with adenomyosis are also more likely to have other uterine conditions, including:
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, [12] but studies looking into similarities and differences between these two conditions have conflicting results. [13]
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. [14] 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. [15] [16] [17] 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. [18] [19]
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. [20] 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. [21]
Misplaced endometrial tissue proliferation in the myometrium causes symptoms through different mechanisms. [6]
Uterine menstrual contractions are caused by prostaglandin, which is produced by normal endometrial tissue. [6] 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. [6] 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. [22]
The diagnosis of adenomyosis is through a pathologist microscopically examining small tissue samples of the uterus. [4] 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. [6]
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. [6]
Gross Findings:
Microscopic Findings:
Differential Diagnosis:
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. [6] Indeed, TVUS and MRI are the only two practical means available to establish a pre-surgical diagnosis. [24]
Transvaginal ultrasonography is a cheap and readily available imaging test that is typically used early during the evaluation of gynecologic symptoms. [24] Ultrasound imaging, like MRI, does not use radiation and is safe for examination of the pelvis and female reproductive organs. [25] Overall, it is estimated that transvaginal ultrasonography has a sensitivity of 79% and specificity of 85% for the detection of adenomyosis. [11]
Common transvaginal ultrasound findings are defined by the European MUSA group in 2015 [26] and are defined in 2022 by the MUSA group. [27] The ultrasound characteristics can be divided in direct and indirect features.
Direct features:
Indirect features:
The power Doppler or Doppler ultrasonography function can be used during transvaginal ultrasonography to help differentiate adenomyomas from uterine fibroids. [24] [28] [29] 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. [24] Doppler ultrasonography also serves to differentiate the static fluid within myometrial cysts from flowing blood within vessels. [24]
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. [21] There is no consensus about the actual histology of the junctional zone and a recent review showed that the ultrasound, MRI and histology all define and describe the junctional zone differently. [30]
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. [24] 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. [11] 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. [24]
Three objective measures of the junctional zone can be used to diagnose adenomyosis. [24]
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. [24]
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.
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.
Broadly speaking, surgical management of adenomyosis is split into two categories: uterine-sparing and non-uterine-sparing procedures. Uterine-sparing procedures are surgical operations that do not include surgical removal of the uterus. Some uterine-sparing procedures have the benefit of improving fertility or retaining the ability to carry a pregnancy to term. In contrast, some uterine-sparing procedures worsen fertility or even result in complete sterility. The impact of each procedure on a woman's fertility is of particular concern and typically guides the selection. Non-uterine-sparing procedures, by definition, include surgical removal of the uterus and consequently they will all result in complete sterility. [6]
Hysterectomy, or surgical removal of the uterus, has historically been the primary method of diagnosing and treating adenomyosis. [6] It was especially popular in women who had completed their childbearing or in cases where fertility was not desired. Today, there are many more medical and surgical interventions available. These treatments, such as hormonal therapy and endometrial ablation, have significantly reduced the number of women who require a hysterectomy. That being said, hysterectomies remain as the final treatment option for women in whom the other treatments have failed. [34] Typically viewed as definitive treatment for the bleeding and pelvic pain associated with adenomyosis, a hysterectomy will always result in sterility and cessation of menstrual bleeding. Pelvic pain, on the other hand, can persist after a hysterectomy in as many as 22% of women. [6]
There are many different types of hysterectomy, with varying options existing to removal the fallopian tubes, ovaries, and cervix. Also, the varying types of hysterectomy can be performed by many different surgical techniques.
A hysterectomy can be performed:
Variants also exist which combine several of these techniques and surgeries can even change during the operation from one technique to another in response to unforeseen obstacles or individual anatomy considerations. For example, adenomyosis can increase the size of the uterus to such an extent that it physically cannot be removed through the vagina without first being cut into smaller pieces.
Recent data suggest a prevalence of 20 to 35%. [1]
Adenomyosis is an often progressing condition. It is advocated that adenomyosis poses no increased risk for cancer development. However, both entities could coexist and the endometrial tissue within the myometrium could harbor endometrioid adenocarcinoma, with potentially deep myometrial invasion. [35]
Preterm labour and premature rupture of membranes both occur more frequently in women with adenomyosis. [10] [11]
In sub-fertile women who received in-vitro fertilization (IVF), women with adenomyosis were less likely to become pregnant and subsequently more likely to experience a miscarriage. [36] Given this, it is encouraged to screen women for adenomyosis by TVUS or MRI before starting assisted reproduction treatments (ART). [36]
The term adenomyosis is derived from the Greek terms adeno- (meaning gland ), myo- (meaning muscle ), and -osis (meaning condition). [37] [38]
The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer thickens and then is shed during menstruation in humans and some other mammals, including other apes, Old World monkeys, some species of bat, the elephant shrew and the Cairo spiny mouse. In most other mammals, the endometrium is reabsorbed in the estrous cycle. During pregnancy, the glands and blood vessels in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo and fetus. The speculated presence of an endometrial microbiota has been argued against.
The uterus or womb is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more embryos until birth. The uterus is a hormone-responsive sex organ that contains glands in its lining that secrete uterine milk for embryonic nourishment.
Hysterectomy is the surgical removal of the uterus and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes (salpingectomy), and other surrounding structures. The term “partial” or “total” hysterectomy are lay-terms that incorrectly describe the addition or omission of oophorectomy at the time of hysterectomy. These procedures are usually performed by a gynecologist. Removal of the uterus renders the patient unable to bear children and has surgical risks as well as long-term effects, so the surgery is normally recommended only when other treatment options are not available or have failed. It is the second most commonly performed gynecological surgical procedure, after cesarean section, in the United States. Nearly 68 percent were performed for conditions such as endometriosis, irregular bleeding, and uterine fibroids. It is expected that the frequency of hysterectomies for non-malignant indications will continue to fall given the development of alternative treatment options.
Uterine cancer, also known as womb cancer, includes two types of cancer that develop from the tissues of the uterus. Endometrial cancer forms from the lining of the uterus, and uterine sarcoma forms from the muscles or support tissue of the uterus. Endometrial cancer accounts for approximately 90% of all uterine cancers in the United States. Symptoms of endometrial cancer include changes in vaginal bleeding or pain in the pelvis. Symptoms of uterine sarcoma include unusual vaginal bleeding or a mass in the vagina.
Endometrial cancer is a cancer that arises from the endometrium. It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most often vaginal bleeding not associated with a menstrual period. Other symptoms include pain with urination, pain during sexual intercourse, or pelvic pain. Endometrial cancer occurs most commonly after menopause.
Heavy menstrual bleeding (HMB), previously known as menorrhagia or hematomunia, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding (AUB).
Abnormal uterine bleeding (AUB), also known as atypical vaginal bleeding (AVB), is vaginal bleeding from the uterus that is abnormally frequent, lasts excessively long, is heavier than normal, or is irregular. The term dysfunctional uterine bleeding was used when no underlying cause was present. Vaginal bleeding during pregnancy is excluded. Iron deficiency anemia may occur and quality of life may be negatively affected.
Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reproductive system, such as abnormal uterine bleeding.
An endometrial polyp or uterine polyp is a mass in the inner lining of the uterus. They may have a large flat base (sessile) or be attached to the uterus by an elongated pedicle (pedunculated). Pedunculated polyps are more common than sessile ones. They range in size from a few millimeters to several centimeters. If pedunculated, they can protrude through the cervix into the vagina. Small blood vessels may be present, particularly in large polyps.
Uterine fibroids, also known as uterine leiomyomas or fibroids, are benign smooth muscle tumors of the uterus, part of the female reproductive system. Some women with fibroids have no symptoms while others may have painful or heavy periods. If large enough, they may push on the bladder, causing a frequent need to urinate. They may also cause pain during penetrative sex or lower back pain. A woman can have one uterine fibroid or many. It is uncommon but possible that fibroids may make it difficult to become pregnant.
Uterine artery embolization is a procedure in which an interventional radiologist uses a catheter to deliver small particles that block the blood supply to the uterine body. The procedure is primarily done for the treatment of uterine fibroids and adenomyosis. Since uterine fibroids are the most common indication, it is also often referred to as uterine fibroid embolization. Compared to surgical treatment for fibroids such as a hysterectomy, in which a woman's uterus is removed, uterine artery embolization may be beneficial in women who wish to retain their uterus. Other reasons for uterine artery embolization are postpartum hemorrhage and uterine arteriovenous malformations.
Intermenstrual bleeding (IMB) is vaginal bleeding at irregular intervals between expected menstrual periods. It may be associated with bleeding with sexual intercourse.
Adenomyoma is a tumor (-oma) including components derived from glands (adeno-) and muscle (-my-). It is a type of complex and mixed tumor, and several variants have been described in the medical literature. Uterine adenomyoma, the localized form of uterine adenomyosis, is a tumor composed of endometrial gland tissue and smooth muscle in the myometrium. Adenomyomas containing endometrial glands are also found outside of the uterus, most commonly on the uterine adnexa but can also develop at distant sites outside of the pelvis. Gallbladder adenomyoma, the localized form of adenomyomatosis, is a polypoid tumor in the gallbladder composed of hyperplastic mucosal epithelium and muscularis propria.
Endometrial ablation is a surgical procedure that is used to remove (ablate) or destroy the endometrial lining of the uterus. The goal of the procedure is to decrease the amount of blood loss during menstrual periods. Endometrial ablation is most often employed in people with excessive menstrual bleeding, who do not wish to undergo a hysterectomy, following unsuccessful medical therapy.
A menstrual disorder is characterized as any abnormal condition with regards to a woman's menstrual cycle. There are many different types of menstrual disorders that vary with signs and symptoms, including pain during menstruation, heavy bleeding, or absence of menstruation. Normal variations can occur in menstrual patterns but generally menstrual disorders can also include periods that come sooner than 21 days apart, more than 3 months apart, or last more than 10 days in duration. Variations of the menstrual cycle are mainly caused by the immaturity of the hypothalamic-pituitary-ovarian (HPO) axis, and early detection and management is required in order to minimize the possibility of complications regarding future reproductive ability.
The uterine sarcomas form a group of malignant tumors that arises from the smooth muscle or connective tissue of the uterus. They can be difficult to detect, as symptoms are common to other uterine conditions and no specific screening test has been developed. This presents an issue for treatment, as the cancer spreads quickly.
Uterine clear-cell carcinoma (CC) is a rare form of endometrial cancer with distinct morphological features on pathology; it is aggressive and has high recurrence rate. Like uterine papillary serous carcinoma CC does not develop from endometrial hyperplasia and is not hormone sensitive, rather it arises from an atrophic endometrium. Such lesions belong to the type II endometrial cancers.
An interstitial pregnancy is a uterine but ectopic pregnancy; the pregnancy is located outside the uterine cavity in that part of the fallopian tube that penetrates the muscular layer of the uterus. The term cornual pregnancy is sometimes used as a synonym, but remains ambiguous as it is also applied to indicate the presence of a pregnancy located within the cavity in one of the two upper "horns" of a bicornuate uterus. Interstitial pregnancies have a higher mortality than ectopics in general.
The uterus-like mass (ULM) is a tumorlike anatomical entity originally described in the ovary in 1981 and thereafter reported in several locations of the pelvis and abdominal cavity including broad ligament, greater omentum, cervix, small intestine, mesentery and conus medullaris. Basically, it is represented by a miniature uterus comprising a smooth muscle wall lined by endometrium thus outlining a uterus anatomical structure. Some of the reported cases have been associated to urinary tract and internal genitalia malformations whereas others appeared as a solitary finding. The term endomyometriosis has also been applied to this lesion.
Thoracic endometriosis is a rare form of endometriosis where endometrial-like tissue is found in the lung parenchyma and/or the pleura. It can be classified as either pulmonary, or pleural, respectively. Endometriosis is characterized by the presence of tissue similar to the lining of the uterus forming abnormal growths elsewhere in the body. Usually these growths are found in the pelvis, between the rectum and the uterus, the ligaments of the pelvis, the bladder, the ovaries, and the sigmoid colon. The cause is not known. The most common symptom of thoracic endometriosis is chest pain occurring right before or during menstruation. Diagnosis is based on clinical history and examination, augmented with X-ray, CT scan, and magnetic resonance imaging of the chest. Treatment options include surgery and hormones.