Adenomyosis

Etiology

Although the histopathologic features of adenomyosis are well described, its etiology remains incompletely understood. Several mechanisms have been proposed. The most widely accepted theory suggests that adenomyosis results from the disruption of the interface between the endometrium basalis and the underlying myometrium. This disruption permits endometrial glands and stroma to invaginate into the myometrium, leading to cyclic proliferation, small-vessel angiogenesis, and adjacent smooth muscle hypertrophy and hyperplasia. The increased prevalence of adenomyosis following uterine instrumentation, eg, dilation and curettage or cesarean delivery, supports this mechanism.

A second theory proposes an embryologic origin in which pluripotent Müllerian stem cells undergo aberrant differentiation, giving rise to ectopic endometrial tissue. Evidence for this mechanism includes altered expression of specific genetic markers and case reports of endometrial tissue in individuals with Rokitansky–Küster–Hauser syndrome (Müllerian agenesis). Additionally, less widely supported theories of the underlying etiologies of adenomyosis include altered lymphatic drainage pathways and the potential contribution of displaced bone marrow–derived stem cells to the development of ectopic endometrial tissue.[2]

Adenomyosis Risk Factors

Risk factors for adenomyosis include conditions associated with increased estrogen exposure, eg, early menarche, short menstrual cycles, elevated body mass index, increased parity, oral contraceptive use, and tamoxifen therapy, as well as prior uterine surgery, including dilation and curettage, cesarean delivery, and myomectomy.[3]

Epidemiology

Accurate estimates of adenomyosis prevalence remain challenging due to historical underreporting and underdiagnosis. Reported rates of adenomyosis range widely from 5% to 70%, although more recent data suggest a prevalence of approximately 20% to 35%. Adenomyosis has traditionally been described as a condition affecting premenopausal, multiparous individuals in their 30s and 40s; however, this characterization largely reflects sampling bias from hysterectomy-based studies. Advances in transvaginal ultrasound and MRI have improved the accuracy of noninvasive diagnosis, providing greater insight into the broader population affected.

A rare variant of adenomyosis, juvenile cystic adenomyosis, is characterized by hemorrhagic myometrial cysts and typically presents in individuals younger than 30. Symptoms of juvenile cystic adenomyosis are often refractory to medical therapy and may require surgical management, including myomectomy or, less commonly, hysterectomy.

Pathophysiology

Ectopic endometrial tissue within the myometrium contributes to the clinical manifestations of adenomyosis through multiple interrelated mechanisms. Normal endometrial tissue produces prostaglandins that regulate uterine contractions during menstruation. When endometrial glands and stroma become embedded within the myometrium, these ectopic foci produce increased prostaglandin levels, resulting in exaggerated uterine contractility and dysmenorrhea. Estrogen-dependent proliferation of both eutopic and ectopic endometrial tissue further amplifies symptom severity and serves as a central target for medical therapy.

Heavy menstrual bleeding develops through a multifactorial process involving increased endometrial surface area, heightened vascularity, abnormal myometrial contractility, and elevated levels of signaling mediators, including prostaglandins, eicosanoids, and estrogen. These combined physiologic alterations contribute to the severity and persistence of bleeding symptoms associated with adenomyosis.[4][1]

Histopathology

The histologic diagnosis of adenomyosis is defined by the presence of endometrial glands and stroma within the smooth muscle of the myometrium. Criteria for the depth of myometrial invasion vary across definitions, with some approaches using an absolute measurement, typically ranging from 2.5 to 8 mm. In contrast, others apply a proportional threshold based on overall myometrial thickness. Multiple histologic grading systems have also been proposed to further characterize disease extent and burden.

Despite these frameworks, histopathologic diagnosis remains incompletely standardized and highly dependent on the quality, depth, and representativeness of tissue sampling.[5] Variability in specimen acquisition and interpretation continues to influence diagnostic consistency across clinical settings.

History and Physical

Clinical Features of Adenomyosis

Patients with adenomyosis may present with a broad spectrum of symptoms, although dysmenorrhea and heavy menstrual bleeding represent the most frequently reported clinical manifestations. Some individuals experience chronic pelvic pain, dyspareunia, or symptoms that closely resemble other gynecologic disorders, eg, endometriosis or uterine fibroids. A subset of patients remains asymptomatic, with adenomyosis identified incidentally during imaging performed for unrelated indications.

Physical examination findings tend to be nonspecific. Bimanual examination may reveal a uniformly enlarged, globular, or tender uterus, and in some cases, the uterus may feel boggy or softened. However, many patients have a completely normal pelvic examination, and reliance on physical findings alone is insufficient for diagnostic accuracy.

Given the substantial overlap of symptoms with other causes of abnormal uterine bleeding and pelvic pain, comprehensive history taking and physical examination remain essential components of evaluation. These steps guide the appropriate selection of imaging studies and further diagnostic evaluation.[6][7]

Evaluation

Imaging Studies

The evaluation of suspected adenomyosis begins with a thorough history and physical examination; however, clinical findings alone are insufficient for diagnosis due to significant overlap with other causes of abnormal uterine bleeding and pelvic pain. As a result, imaging plays a central role in the diagnostic workup. A comprehensive evaluation integrates clinical presentation with imaging findings to differentiate adenomyosis from other gynecologic conditions and guide appropriate management (see Table. Imaging Studies for Adenomyosis).[8][9]

Transvaginal ultrasound

Transvaginal ultrasound is typically the preferred initial imaging modality because of its accessibility, low cost, and ability to identify characteristic features, eg, a heterogeneous myometrium, myometrial cysts, asymmetrical myometrial thickening, or a poorly defined endometrial–myometrial junction. A 3-dimensional ultrasound may further improve visualization of the junctional zone.

Magnetic resonance imaging

MRI offers higher diagnostic accuracy and is particularly useful when ultrasound findings are inconclusive or when coexisting pathology, eg, leiomyomas or endometriosis, complicates interpretation. MRI features suggestive of adenomyosis include thickening of the junctional zone, high-signal myometrial foci on T2-weighted images, and diffuse or focal myometrial infiltration (see Image. Adenomyosis Imaging Findings).

Laboratory Studies

Laboratory testing is generally nonspecific. Hemoglobin levels may be assessed in patients with heavy menstrual bleeding, and pregnancy testing is appropriate when indicated, but no serum biomarkers reliably diagnose adenomyosis.

Table. Imaging Studies for Adenomyosis 

Treatment / Management

Management of adenomyosis is guided primarily by the patient’s desire for future fertility and individualized symptom burden. Hysterectomy remains the definitive cure, while medical and minimally invasive approaches focus on reducing heavy menstrual bleeding and dysmenorrhea while preserving uterine function.

Medical Therapies

Nonhormonal medical therapies include nonsteroidal anti-inflammatory drugs (NSAIDs), which provide symptom relief by inhibiting cyclooxygenase and reducing prostaglandin production, thereby decreasing menstrual cramping and dysmenorrhea. Hormonal therapies aim to suppress estrogen-driven endometrial proliferation and include combined oral contraceptive pills, the levonorgestrel-releasing intrauterine device (LNG-IUD), danazol, and aromatase inhibitors. Although high-quality randomized controlled trial data remain limited, the LNG-IUD is generally regarded as the most effective first-line hormonal option due to its favorable adverse effect profile and strong clinical efficacy.

Minimally Invasive and Surgical Therapies

Minimally invasive and surgical options include high-intensity focused ultrasound (HIFU), which uses MRI-guided or ultrasound-guided energy delivery to target focal adenomyotic lesions and may benefit patients who fail medical therapy while preserving fertility. Uterine artery embolization (UAE) reduces uterine blood flow, leading to ischemic necrosis and decreased uterine volume. However, long-term outcomes and comparative effectiveness require further study, and fertility preservation cannot be guaranteed.[8][9][10](A1)

Endometrial ablation may be considered for patients who do not desire future fertility; however, limited treatment depth reduces effectiveness for deeper disease. Excision of deeper adenomyotic tissue while preserving the uterus is an additional surgical approach, but disruption of the endometrial–myometrial interface increases recurrence risk and may contribute to adverse pregnancy outcomes, including uterine rupture, premature rupture of membranes, preterm labor, and spontaneous abortion.

However, hysterectomy remains the only definitive cure for adenomyosis and is appropriate for patients who have completed childbearing or who experience refractory symptoms despite conservative medical and procedural management.[10][11][12][13](A1)

Differential Diagnosis

The symptoms of adenomyosis, particularly dysmenorrhea, chronic pelvic pain, and heavy menstrual bleeding, overlap significantly with several other gynecologic conditions. Accurate diagnosis, therefore, requires careful correlation of clinical presentation with imaging findings. Conditions commonly considered in the differential diagnosis of adenomyosis include:

• Uterine leiomyomas (fibroids): Fibroids may cause uterine enlargement, abnormal bleeding, and pelvic pain similar to adenomyosis. Unlike adenomyosis, leiomyomas typically appear as well-circumscribed masses on ultrasound or MRI, whereas adenomyosis produces diffuse myometrial heterogeneity or ill-defined focal thickening.

• Endometriosis: Both conditions are estrogen-responsive and associated with dysmenorrhea, dyspareunia, and chronic pelvic pain. Endometriosis is characterized by ectopic endometrial tissue outside the uterus, whereas adenomyosis involves invasion into the myometrium. Furthermore, the 2 conditions frequently coexist. Please see StatPearls' companion resource, "Endometriosis," for further information. 

• Abnormal uterine bleeding due to ovulatory dysfunction (AUB-O): Anovulatory cycles can cause heavy or irregular bleeding but typically lack the uterine enlargement or imaging features seen in adenomyosis. Please see StatPearls' companion resource, "Abnormal Uterine Bleeding," for further information.

• Endometrial polyps: Polyps may cause intermenstrual or heavy bleeding. Polyps are usually focal and intracavitary, distinguishable on ultrasound or hysteroscopy.

• Adenomyoma: Adenomyomas are focal, well-circumscribed forms of adenomyosis that can mimic fibroids. MRI is often required to differentiate them.

• Chronic endometritis: May present with abnormal bleeding and pelvic discomfort, but is associated with endometrial inflammation rather than myometrial invasion.

• Malignancy (rare but important): Endometrial carcinoma or uterine sarcoma may present with abnormal bleeding or uterine enlargement. Suspicious imaging features or postmenopausal bleeding warrant further evaluation.

Therefore, a structured diagnostic approach that integrates history, physical examination, and targeted imaging helps distinguish adenomyosis from these overlapping conditions and guides appropriate management.[14][15]

Prognosis

The prognosis of adenomyosis varies widely and depends on multiple clinical factors, including the patient’s fertility goals, confidence in the diagnosis, tolerance of medical therapies, and willingness to pursue invasive procedures. Increasing recognition of adenomyosis in younger and asymptomatic individuals suggests a broader disease spectrum that remains incompletely understood. Symptom severity appears to correlate with both the number of adenomyotic foci and the depth of myometrial invasion.

A stepwise approach to management is generally recommended, beginning with medical therapy, typically NSAIDs and hormonal agents, and progressing to minimally invasive procedures, eg, endometrial ablation, excision of adenomyosis, or uterine artery embolization when symptoms persist. While these interventions may provide significant relief, hysterectomy remains the only definitive cure.[16][2]

Complications

The association between adenomyosis and infertility remains unclear. Some studies report an infertility rate of approximately 11% to 12%, but contradictory data exist, and no definitive causal relationship has been established. Numerous confounders, including coexisting gynecologic conditions, heterogeneous diagnostic criteria, and historical reliance on postoperative histopathology, limit interpretation. As imaging criteria, particularly transvaginal ultrasound and MRI, continue to be standardized and validated, future research will be better positioned to clarify the true relationship between adenomyosis and reproductive outcomes.[11][8]