Adenomyosis: Classification, Diagnosis, Symptoms, Treatment

Adenomyosis is a benign condition of the uterus that has been historically diagnosed via histological examination after hysterectomy (removal of the uterus). During the examination, ectopic endometrial glands and stroma are studied at a minimum depth of 2.5 mm below the endomyometrial junction (EMJ), accompanied by hypertrophic and hyperplastic myometrium. This condition is typically visualized using modalities such as ultrasound or MRI.

The reported prevalence of adenomyosis ranges from 5 % to 70 %. Before age 40, the condition affects 2 out of 10 women, whereas between ages 40 and 50 the prevalence increases to 8 out of 10 women. However, the true prevalence of adenomyosis is difficult to determine due to the absence of a unified definition and noninvasive diagnostic criteria. There are still no pathognomonic clinical features of adenomyosis, nor are there laparoscopic criteria that can be used to diagnose this condition.

Adenomyosis may coexist with other estrogen‑dependent benign disorders, such as endometriosis (70 % of cases), uterine fibroids (50 %), and endometrial hyperplasia (35 %).

The pathogenesis of adenomyosis remains unclear, although several theories have been proposed:

• Spontaneous or induced EMJ microtrauma;
• Enhanced pathological invasion of the endometrium into the myometrium;
• Stem cell metaplasia within the myometrium;
• Infiltration of endometrial cells into the uterine wall from the perimetrium via retrograde menstrual flow;
• Induction of adenomyotic lesions by aberrant local steroid and pituitary hormones;
• Abnormal uterine development in response to genetic and epigenetic modifications.

A new area of research focuses on expression of messenger RNA (mRNA) and long non‑coding RNA (lncRNA) in adenomyotic lesions.

Classification of Adenomyosis

Attempts have been made to classify adenomyosis into subtypes based on histologic findings and imaging results, but none of the proposed systems have been adopted in clinical practice. According to the simplest classification, adenomyosis is divided into diffuse and focal types depending on its distribution within the myometrium.

Diffuse adenomyosis is defined by multiple foci within the myometrium (with less than 25 % of the affected area surrounded by normal myometrium), whereas focal adenomyosis appears as isolated nodules of hypertrophic myometrium and ectopic endometrium.

However, the pathogenesis of adenomyosis remains uncertain, and the relationship between disease severity and clinical manifestations has not been established, , making it difficult to determine standardized treatment approaches.

In Russian‑language literature, a classification of adenomyosis based on depth of invasion is commonly used:

• Grade 1: the lesion is confined to the submucosal layer;
• Grade 2: the pathological process involves less than half of the myometrial thickness;
• Grade 3: the entire myometrial layer is involved;
• Grade 4: the lesion extends beyond the uterus.

3D Models of Adenomyosis:

Adenomyosis, Grade 1

Adenomyosis, Grade 2

Adenomyosis, Grade 3

Adenomyosis, Grade 4

According to Bird’s classification, adenomyotic lesions are subdivided based on the depth of penetration, determined by the affected uterine layer, and the degree of involvement, measured by the number of endometrial glands per low‑power field.

• Class I: subbasal/subendometrial adenomyosis (adenomyosis within one low‑power field beneath the basal endometrium, without further penetration).
• Class II: penetration of adenomyosis into the mid‑myometrium.
• Class III: penetration of adenomyosis beyond the mid‑myometrium.

The authors also demonstrated a direct correlation between the severity of dysmenorrhea and the depth of penetration. Thus, 4.3 % of women with Grade 1 adenomyosis reported dysmenorrhea, compared with 42.4 % of Grade 2 patients and 83.3% of Grade 3 patients.

Another histopathologic feature described in patients with deep adenomyosis is hemosiderin deposition around adenomyotic lesions. This results from bleeding within ectopic endometrial foci and suggests that hemosiderin deposition may reflect the extent and severity of adenomyosis; however, the clinical significance of this finding remains unclear.

Levghur et al. described the depth of adenomyosis as the percentage of myometrial thickness involved and distinguished:

• Superficial adenomyosis: less than 40 % of myometrial thickness;
• Intermediate adenomyosis: 40–80 % of thickness involved;
• Deep adenomyosis: more than 80 % of thickness involved.

The authors also noted dysmenorrhea in 77.8 % of patients with deep adenomyosis compared with 12.5 % in the intermediate group. Superficial myometrial foci were not associated with dysmenorrhea or menorrhagia.

Hulka et al. introduced a new category of focal adenomyosis and added the term “adenomyoma” to previous classifications.

Rasmussen et al. proposed a histologic classification based on endomyometrial biopsies obtained via transcervical resection of endometrium (TCRE). The procedure requires biopsy samples at least 5 mm deep.

• Internal adenomyosis: myometrial invasion ≥ 2 mm without contact with the basal endometrium.
• Serrated junctional zone (JZ): myometrial invasion > 3 mm with contact against the basal endometrium
• Linear JZ: absence of invasion or involvement ≤ 3 mm in contact with the basal endometrium.

Classification of Adenomyosis

Diagnosis of Adenomyosis

For clinical diagnosis, the criteria proposed by the MUSA consensus (Morphological Uterus Sonographic Assessment) based on transvaginal ultrasound findings are used. Although the MUSA group provided unified guidance for recognizing and identifying sonographic features of adenomyotic lesions, it did not lead to the development of a classification system for adenomyosis. Given that ultrasound is a subjective assessment method, standardization and classification remain challenging.

According to the MUSA classification, the sonographic features of adenomyosis can be divided into direct and indirect signs.

• Direct signs indicate the presence of ectopic endometrial tissue within the myometrium.
• Indirect signs are alterations secondary to the presence of endometrial tissue in the myometrium, such as muscular hypertrophy (globular uterine enlargement) or artifacts (e.g., shadowing).

Direct Signs of Adenomyosis

1. Myometrial Cysts

According to MUSA, myometrial cysts are defined as round structures within the myometrium. Their contents may be anechoic, low‑echogenic, have a “ground‑glass” appearance, or show mixed echogenicity. Cysts may be surrounded by a hyperechoic rim. There is no size requirement for myometrial cysts, and the hyperechoic rim is not mandatory. Experts recommend using color Doppler imaging to identify blood vessels, which assists in differentiating adenomyotic cysts from other myometrial cystic lesions.

2. Hyperechoic Islands

Hyperechoic islands are defined as hyperechoic areas within the myometrium. They may be regular, irregular, or poorly defined. However, hyperechoic islands must not be connected to the endometrium. The minimum distance from the endometrium is not precisely defined, as it may vary individually. No minimum diameter or number of hyperechoic islands has been established.

3. Echogenic Subendometrial Lines and Buds

Experts note that evaluating these features is difficult due to the lack of 3D ultrasound imaging, challenges in identifying the endometrial–myometrial interface, and the limited JZ visibility. The MUSA consensus defined this feature as follows: “Hyperechoic subendometrial lines or buds may be observed disrupting the JZ. Hyperechoic subendometrial lines are (almost) perpendicular to the endometrial cavity and are connected to the endometrium. However, experts note that any form of endometrial tissue invasion into the myometrium may be a sign of adenomyosis, even if it does not appear as lines or buds.”

Indirect Signs of Adenomyosis

1. Globular Uterus

A globular uterus is diagnosed when the perimetrium contour diverges from the cervix in at least two directions (anterior, posterior, or lateral), rather than following a trajectory parallel to the endometrium. The uterine diameters (length, width, depth) are approximately equal, producing a characteristic spherical shape. Consensus was reached that this sign may be falsely positive in cases of uterine fibroids or intracavitary anomalies.

2. Asymmetric Myometrial Thickening

This parameter is assessed by comparing the thickness of the anterior and posterior uterine walls. A ratio close to 1 indicates symmetry, whereas a ratio above or below 1 indicates asymmetry, although this assessment is subjective. A difference of more than 5 mm between the walls is considered an indirect sign. Note that uterine asymmetry may also be associated with transient uterine contractions or uterine fibroids.

3. Fan‑Shaped Shadowing

This type of shadowing is characterized by hyperechoic linear bands, sometimes alternating with hypoechoic ones. Fan‑shaped shadowing is best evaluated in grayscale mode. Diagnostic difficulties may arise due to other lesions that produce shadowing, such as uterine fibroids or cesarean‑section scar fibrosis.

4. Translesional Vascularity

Translesional vascularity is defined as blood vessels running perpendicular to the uterine cavity/perimetrium and traversing the lesion. This pattern is likely present in diffuse adenomyosis. Circular vascularity, typically seen around uterine fibroids, may also occur in adenomyosis. Although intralesional vessels may be seen in uterine fibroids, translesional vascularity (vessels crossing the lesion) is an atypical feature. This sign helps differentiate adenomyosis from uterine fibroids.

5. Irregular JZ

Several challenges exist in defining this criterion. First, the JZ is difficult to evaluate without 3D imaging. According to the MUSA group, the JZ may appear irregular due to cystic areas, hyperechoic spots, or hyperechoic lines. The degree of irregularity is expressed as the difference between the maximal and minimal JZ thickness.

Second, the extent of irregularity is subjectively assessed as the percentage of the JZ that appears irregular (less than 50 % or more than 50 %). The JZ should be evaluated using 3D ultrasound in sagittal, transverse, and coronal planes. Measuring the JZ thickness is not a mandatory diagnostic criterion.

6. Interrupted JZ

An interrupted JZ is diagnosed when a JZ portion cannot be visualized on either 2D or 3D ultrasound in any scanning plane. A continuous JZ means that it is clearly visible in all planes on 2D or 3D ultrasound.

Magnetic Resonance Imaging of Pelvis

A pooled analysis of studies showed that MRI has a sensitivity of approximately 78 % and a specificity of 93 % for diagnosing adenomyosis. Although transvaginal ultrasound is reported to have similar sensitivity and specificity, ultrasound results are too heterogeneous to combine. Thus, MRI‑based systems provide greater objectivity and consistency in the classification of adenomyosis. MRI allows visualization of the zonal anatomy of the uterus and clear JZ depiction, enabling diagnosis of lesions in any part of the endometrium and myometrium. The most comprehensive recent classification is the system proposed by Kobayashi, which includes five components and evaluates them accordingly.

MRI‑Based Classification of Adenomyosis (Kobayashi System, 2020)

The final score is then reported as a four‑letter code with corresponding numbers based on MRI findings.

Hysteroscopy

In patients with abnormal uterine bleeding, hysteroscopy can be a valuable diagnostic method that provides direct visualization of the uterine cavity and allows tissue sampling for histological examination. Although the diagnosis cannot be based on visual inspection alone, several features have been identified that may suggest adenomyosis: marked hypervascularization on the endometrial surface, irregular endometrium with small openings (the so‑called “strawberry pattern”), and fibrotic and/or hemorrhagic cystic lesions. More detailed information can be obtained during histological evaluation of biopsy samples taken using a resectoscope with a diathermic loop.

Clinical Manifestations

Adenomyosis is asymptomatic in approximately 30 % of cases. The most common clinical symptoms include menorrhagia (up to 50 % of patients), dysmenorrhea, metrorrhagia, abnormal uterine bleeding, chronic pelvic pain, dyspareunia, and infertility. The exact mechanism linking adenomyosis and infertility remains unclear. Several contributing factors have been proposed and can be grouped into four potential pathways:

1. Intrauterine abnormality and increased uterine peristalsis lead to abnormal sperm migration. Intrauterine anatomic distortions caused by uterine hyperperistalsis and inflammation may alter the axis of the uterine cavity and potentially impair sperm migration and embryo transport. Abnormal myometrial contractile waves result in abnormal sperm transport through the uterine cavity and may also increase intrauterine pressure.
2. Abnormal metabolism of endometrial steroids, enhanced inflammatory response and increased intrauterine oxidative environment lead to altered endometrial function and receptivity.
3. Impaired implantation may result from inflammation, inadequate expression of adhesion molecules (integrins), and reduced expression of implantation markers.
4. Chronic endometritis due to intrauterine microbial infection may negatively affect fertility in women with adenomyosis.

Note that endometriosis occurs in 54–90 % of patients with adenomyosis. Therefore, infertility cannot be attributed solely to adenomyosis, as coexisting endometriosis — well known to impair fertility — may be the primary cause.

Treatment of Adenomyosis

Medical Therapy

• Nonsteroidal anti‑inflammatory drugs (NSAIDs) are widely used to treat pain associated with endometriosis, but only a few randomized trials support their effectiveness in endometriosis and none in adenomyosis. NSAIDs may negatively affect fertility, particularly by suppressing ovulation. However, some evidence suggests that NSAIDs may be used as adjunctive therapy during IVF procedures.
• Combined oral contraceptives (COCs) are used in adenomyosis to reduce menstrual bleeding through decidualization and subsequent atrophy of the endometrium. In patients with dysmenorrhea and menorrhagia, COCs reduce the risk of symptom recurrence. Long‑term COC therapy provides satisfactory pain control in two‑thirds of women with symptomatic endometriosis or adenomyosis. However, no published data exist regarding the effect of COC therapy on subsequent fertility improvement.
• Gonadotropin‑releasing hormone (GnRH) analogs are used to induce a sustained hypoestrogenic state in women with histologically confirmed adenomyosis. However, limited data exist regarding their impact on future fertility. Published studies show no improvement in fertility after treatment with GnRH analogs combined with conservative microsurgery.
• Progestins in adenomyosis exert antiproliferative and anti‑inflammatory effects. They have been found to be partially effective in controlling pain symptoms associated with adenomyosis. Progestins reduce uterine volume and decrease the risk of abnormal uterine bleeding, but their effect on fertility remains understudied.

Find more scientifically accurate content on our social media

Subscribe and don’t miss out the latest resources

Surgical Therapy

• Endomyometrial resection is effective and indicated for patients with lesions confined to the EMJ and is used to treat recurrent abnormal uterine bleeding. However, endomyometrial resection is contraindicated in patients who wish to conceive. Destruction of the endometrium along with the JZ may cause serious complications such as pregnancy loss, preterm birth, and placentation abnormalities.
• Uterine artery embolization (UAE) has been described as an effective method for treating symptoms caused by adenomyosis. A serious complication is premature ovarian insufficiency. It may affect hormone production and ovarian reserve, leading to premature and iatrogenic amenorrhea and infertility. Endometrial receptivity decreases after this procedure; therefore, embolization is contraindicated in women planning pregnancy but is effective in perimenopausal women.
• High‑intensity focused ultrasound (HIFU) uses the thermal effect of focused ultrasound to induce coagulative necrosis within the targeted adenomyotic lesion. The lesion must be clearly visible on ultrasound or MRI for accurate targeting. This means the method is not effective for diffuse adenomyosis. Recovery time is shorter, which may be advantageous for pregnancy planning, although optimal timing has not been established.
• Conventional surgical excision of a significant portion of the myometrium containing adenomyotic tissue may reduce uterine contractile capacity and lead to scar formation.
• Electrocoagulation can be applied to focal or diffuse lesions. Its main disadvantages are reduced precision compared with surgical excision and lack of full control over the procedure.
• Hysterectomy is the definitive treatment for patients who have no reproductive plans.