A unified disease spectrum: Adenomyosis and Endometriosis – Insights from Advanced Transvaginal Ultrasound Imaging

Abstract

Adenomyosis and endometriosis are estrogen-dependent gynecologic disorders characterized by the ectopic presence of endometrial glands and stroma. Traditionally viewed as distinct entities, accumulating evidence supports their conceptualization as interconnected manifestations of a single disease spectrum rooted in uterine endometrial dysfunction. Both conditions share core pathophysiologic mechanisms—including junctional zone (JZ) disruption, tissue injury and repair (TIAR) processes, chronic inflammation, estrogen dependence, progesterone resistance, neuroangiogenesis, and fibrotic remodeling—and frequently coexist, particularly in women with deep infiltrating endometriosis (DIE). This coexistence is associated with earlier symptom onset, greater symptom severity (dysmenorrhea, dyspareunia, chronic pelvic pain), higher infertility rates, and poorer response to isolated treatments.

Recent advances in expert-level transvaginal ultrasound (TVUS), standardized by the Morphological Uterus Sonographic Assessment (MUSA) consensus, have revolutionized non-invasive diagnosis. When performed by trained operators using direct and indirect sonographic features, TVUS achieves diagnostic accuracy comparable to magnetic resonance imaging (MRI), enabling simultaneous mapping of internal (adenomyosis) and external (endometriosis) disease in a single examination. This integrated approach overcomes historical diagnostic limitations, facilitates precise phenotyping, optimizes surgical planning and fertility counseling, and explains persistent symptoms after endometriosis-directed therapy. Recognition of adenomyosis and endometriosis as a unified spectrum is essential for comprehensive management, symptom control, and long-term disease modification. Future research should focus on molecular validation, standardized classification systems, and prospective outcome studies evaluating integrated imaging-guided strategies.

Keywords: adenomyosis, endometriosis, unified disease spectrum, transvaginal ultrasound, MUSA criteria, junctional zone, tissue injury and repair (TIAR), deep infiltrating endometriosis

Introduction

Adenomyosis and endometriosis represent chronic, estrogen-dependent disorders that impose a substantial burden through chronic pelvic pain, abnormal uterine bleeding (AUB), infertility, and impaired quality of life. Historically classified as separate entities—adenomyosis as an intramural uterine condition and endometriosis as an extrauterine phenomenon—contemporary evidence increasingly frames them as phenotypic variants within a continuum of endometrial-myometrial dysfunction. This paradigm shift is driven by overlapping clinical presentations, histopathologic features, molecular signatures, and epidemiologic associations. Delayed diagnosis remains common due to nonspecific symptoms and reliance on invasive or resource-limited modalities. Expert-level TVUS has emerged as a transformative tool, enabling accurate, accessible, real-time evaluation of both conditions and supporting the unified-spectrum hypothesis.

Definition and pathophysiology of adenomyosis

Adenomyosis is histologically defined by the presence of endometrial glands and stroma within the myometrium, accompanied by reactive smooth-muscle hyperplasia and fibrosis. Unlike endometriosis, which involves ectopic endometrial tissue outside the uterus, adenomyosis reflects direct invasion from the basal endometrium into the inner myometrium (archimetra).

Prevailing pathogenic models emphasize JZ disruption as the initiating event. The JZ— the inner third of the myometrium—normally maintains structural integrity and coordinated peristalsis. Microtrauma from uterine hyperperistalsis or iatrogenic injury (e.g., curettage) activates the tissue injury and repair (TIAR) cascade. This process involves local upregulation of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), steroidogenic acute regulatory protein (STAR), and aromatase, leading to paracrine estrogen production independent of ovarian control. Estrogen further amplifies peristalsis and inflammation, perpetuating a vicious cycle of invasion, hypertrophy, and fibrosis. Additional contributors include neuroangiogenesis (nerve fiber ingrowth and vascular proliferation contributing to pain), altered immune surveillance, and epigenetic reprogramming of endometrial and myometrial cells.

Emerging evidence also implicates stem-cell metaplasia and genetic alterations (e.g., KRAS mutations) that may unify phenotypes across the spectrum.

Adenomyosis as a chronic and progressive disease.

Adenomyosis is no longer regarded as a static lesion but as a progressive inflammatory disorder that often begins in early reproductive life and worsens with cumulative menstrual cycles. Progressive myometrial fibrosis impairs uterine peristalsis, disrupts endometrial receptivity, and contributes to implantation failure. Clinical features include progressive dysmenorrhea, heavy/prolonged menstrual bleeding, chronic pelvic pain, deep dyspareunia, and subfertility/recurrent pregnancy loss. Disease burden escalates in the presence of coexisting endometriosis, with additive effects on symptom severity and reproductive outcomes.

Relationship between adenomyosis and endometriosis

Epidemiologic and clinical association

Coexistence rates range from 30% to >60% in imaging and surgical cohorts, rising to 55–79% in women with DIE. Patients with both conditions exhibit earlier symptom onset, more severe pain phenotypes, higher infertility rates, and reduced therapeutic responses compared with isolated disease.

Shared pathophysiologic mechanisms

Both disorders share fundamental drivers:

-Estrogen dependence and local hyperestrogenism via aromatase overexpression.

-Progesterone resistance.

-Chronic low-grade inflammation with cytokine dysregulation.

-Neuroangiogenesis and sensory nerve proliferation.

-Fibrotic remodeling and extracellular matrix dysregulation.

-Immune alterations (e.g., impaired natural killer cell activity).

The JZ serves as the critical interface: its hyperplasia and dysfunction permit inward myometrial invasion (adenomyosis) while facilitating outward dissemination of basal endometrial fragments via retrograde menstruation or transtubal migration (endometriosis). This supports the TIAR model, wherein uterine hyperperistalsis acts as the primum movens, generating microtrauma at the fundo-cornual raphe and activating self-perpetuating repair mechanisms. While some authors propose adenomyosis and endometriosis as distinct phenotypes of a single disease, others note that molecular and histopathologic differences warrant cautious interpretation pending further genomic and single-cell data.

Clinical implications of coexisting disease

Undiagnosed adenomyosis in endometriosis patients leads to persistent postoperative pain, incomplete symptom relief, suboptimal fertility outcomes, and inappropriate surgical or medical strategies. Comprehensive phenotyping is therefore mandatory for individualized care.

Role of advanced ultrasound in diagnosis

Limitations of traditional approaches

Historically, definitive adenomyosis diagnosis required hysterectomy. MRI, while accurate (sensitivity ~77%, specificity ~89%), is limited by cost, availability, and protocol variability. Routine pelvic ultrasound frequently misses subtle JZ changes.

Expert-Level Transvaginal ultrasound and MUSA criteria

Standardized expert TVUS, guided by the 2022 revised MUSA consensus, has achieved diagnostic performance comparable to MRI and histology. Features are classified as:

Direct features (ectopic endometrial tissue):

-Myometrial cysts

-Hyperechogenic islands

-Echogenic subendometrial lines and buds

Indirect features (secondary myometrial changes):

-Globular uterus

-Asymmetrical myometrial thickening

-Fan-shaped acoustic shadowing

-Translesional vascularity (color Doppler)

-Irregular or interrupted JZ (optimized with 3D imaging)

When ≥2–3 direct or composite features are present, TVUS sensitivity reaches 80–100% and specificity 60–85% in validation studies, with high inter-observer agreement among experts. Advantages include real-time dynamic assessment, accessibility, and cost-effectiveness.

Integrated Ultrasound Mapping: Adenomyosis and endometriosis together

The International Deep Endometriosis Analysis (IDEA) consensus incorporates systematic uterine evaluation using MUSA criteria as the first step of pelvic mapping. This single-examination protocol delineates:

-Internal disease extent and phenotype (focal vs. diffuse adenomyosis; internal vs. external).

-External pelvic lesions (peritoneal, ovarian, DIE).

Benefits include complete disease phenotyping, improved symptom-lesion correlation, precise preoperative planning (e.g., risk of complications in DIE with coexisting adenomyosis), fertility prognosis, and triage between medical and surgical pathways. Adenomyosis detection often explains “failed” endometriosis surgery.

Therapeutic and fertility implications

Recognition of the unified spectrum guides multimodal therapy: hormonal suppression targeting estrogen-driven inflammation, uterine-sparing surgery for focal lesions, or assisted reproduction with adenomyosis-specific protocols. Coexistence independently predicts poorer IVF outcomes and higher obstetric risks, underscoring the need for preconception imaging.

Future directions

Prospective multicenter studies should validate integrated TVUS protocols against long-term outcomes, incorporate artificial intelligence for feature detection, and explore molecular imaging or biomarkers. Standardized classification systems (e.g., for adenomyosis phenotypes) will facilitate research comparability.

Conclusion

Adenomyosis and endometriosis represent interconnected phenotypes within a unified spectrum of endomyometrial dysfunction. Expert-level TVUS, leveraging MUSA criteria and IDEA mapping, now enables accurate, non-invasive, comprehensive diagnosis in routine practice. Adoption of this imaging paradigm is poised to improve diagnostic timeliness, therapeutic precision, fertility optimization, and quality of life for millions of women worldwide. As evidence evolves, integrated ultrasound will remain central to personalized, evidence-based care.

References (selected):

1. Leyendecker G, et al. The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Reprod Biomed Online. 2009.

2. Harmsen MJ, et al. Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis. Ultrasound Obstet Gynecol. 2022.

3. Ottolina J, et al. Endometriosis and adenomyosis: modern concepts... J Clin Med. 2024.

4. Additional sources from meta-analyses on diagnostic accuracy, coexistence studies, and TIAR reviews.