Abstract

Adenomyosis is a gynecologic medical condition characterized by the abnormal presence of endometrial tissue (the inner lining of the uterus) within the myometrium (the thick, muscular layer of the uterus). In contrast, when endometrial tissue is present entirely outside the uterus, it represents a similar but distinct medical condition called endometriosis. The two conditions are found together in many cases, but often occur independently. Before being recognized as its own condition, adenomyosis used to be called "endometriosis interna". Additionally, the less-commonly used term "adenomyometritis" is a more specific name for the condition, specifying involvement of the uterus.

The condition is typically found in women between the ages of 35 and 50 but can also be present in younger women. Patients with adenomyosis often present with painful and/or profuse menses (dysmenorrhea & menorrhagia, respectively). 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. Therefore, unlike functional layer, basal layer does not undergo typical cyclic changes with menstrual cycle.

Adenomyosis may involve the uterus focally, creating an adenomyoma. With diffuse involvement, the uterus becomes bulky and heavier.

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 and the estimated percent affected may include:

- Chronic pelvic pain (77%)

- Heavy menstrual bleeding (40-60%), which is more common with 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

- Painful cramping menstruation (15-30%)

- Painful vaginal intercourse (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 physiological damages due to placental implantation most likely results in the same pathological cascade. This also explains that adenomyosis often gets more severe after each pregnancy and childbirth, while endometriosis will ameliorate.

Diagnosis | Pathology

The diagnose 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 (surgery to remove the uterus). 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 can find 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 depth of invasion such as 1–4 mm.

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.

Diagnosis | Imaging | Transvaginal ultrasonography

Transvaginal 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.

Diagnosis | Imaging | 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.

1. A thickness of the junctional zone greater than 8–12 mm. Less than 8 mm is normal.

2. A junctional zone width being greater than 40% of the width of the myometrium.

3. 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. In 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.

Treatment | Surgery

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.

Treatment | Surgery | Non-uterine-sparing procedures

Hysterectomy, or surgical removal of the uterus, has historically been the primary method of diagnosing and treating adenomyosis. 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. 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.

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:

- laparoscopically through small holes in the abdomen

- robotically in a manner similar to the laparoscopic procedure

- entirely by route of the vagina with no abdominal incisions

- through a larger abdominal incision

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.

Prognosis

Adenomyosis is a benign but 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. As the condition is estrogen-dependent, menopause presents a natural cure. Ultrasound features of adenomyosis will still be present after menopause. People with adenomyosis are also more likely to have uterine fibroids or endometriosis.

Prognosis | Fertility

Adenomyosis itself can cause infertility issues, however, fertility can be improved if the adenomyosis has resolved following hormone therapies like levonorgestrel therapy. The discontinuation of medication or removal of IUD can be timed to be coordinated with fertility treatments. There has also been one report of a successful pregnancy and healthy birth following high-frequency ultrasound ablation of adenomyosis.

Preterm labour and premature rupture of membranes both occur more frequently in women with adenomyosis.

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. Given this, it is encouraged to screen women for adenomyosis by TVUS or MRI before starting assisted reproduction treatments (ART).

Etymology

The term "adenomyosis" is derived from the Greek terms "adeno-" (meaning "gland"), "myo-" (meaning "muscle"), and "-osis" (meaning "condition").