The etiology differs regards to the locations of the lesion: a clinical experience of 1350 patients with adenomyosis confirmed by postoperative pathology

Abstract

By stratifying adenomyosis into diffuse/focal and anterior/posterior subtypes, we identified distinct clinical-pathological profiles: (1) Diffuse adenomyosis was independently associated with older age, higher gravidity, and severe dysmenorrhea, suggesting a progressive phenotype driven by tissue injury mechanisms; (2) Posterior lesions exhibited a 3.24-fold risk of concurrent endometriosis and increased surgical complexity, implicating shared pathways with deep infiltrating endometriosis. These findings redefine adenomyosis as a heterogeneous disorder with subtype-specific pathophysiology, advocating for tailored therapeutic strategies.

Introduction

Adenomyosis, characterized by the presence of endometrial glands and stroma within the myometrium, remains a significant challenge in gynecology due to its debilitating symptoms and debated etiology. Traditionally treated as a monolithic condition, its clinical heterogeneity—ranging from localized focal lesions to widespread diffuse thickening—suggests that different "topographies" may stem from distinct biological mechanisms. This study aims to bridge the diagnostic gap by analyzing a large-scale, pathologically confirmed cohort to determine if lesion location correlates with specific clinical profiles and underlying causes.

Methodology

This retrospective cohort study analyzed 1,350 patients who underwent surgery at the First Affiliated Hospital of Anhui Medical University between 2017 and 2022.

• Pathological Confirmation: All cases were confirmed via postoperative histopathology, ensuring diagnostic accuracy beyond imaging alone.
• Stratification: Patients were categorized using transvaginal pelvic ultrasonography (TVUS) into two main comparative frameworks: Diffuse vs. Focal and Anterior vs. Posterior.
• Statistical Analysis: Multivariate logistic regression was employed to identify independent risk factors, adjusting for variables like age, Body Mass Index (BMI), and reproductive history.

Clinical Characteristics

The study population comprised 1,350 patients with a mean age of approximately 46.7 years. A significant portion of the cohort presented with comorbid conditions, such as uterine leiomyomas (49.3%) and endometriosis (16.6%).

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Notably, 15.8% of patients were asymptomatic, with the condition discovered incidentally during surgery for other gynecological issues. Preoperative sonography failed to identify definitive signs in approximately 20% of pathologically confirmed cases, highlighting a persistent diagnostic gap.

Comparative Analysis of Subtypes

The analysis revealed stark differences between diffuse and focal adenomyosis. Diffuse disease was significantly associated with older age, higher BMI, and a higher number of pregnancies (gravidity).

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Patients with diffuse adenomyosis faced a significantly higher risk of moderate-to-severe dysmenorrhea (OR 1.88). Furthermore, lesion location played a critical role: posterior wall lesions were independently associated with severe dysmenorrhea (OR 1.58) and a 3.24-fold increased risk of concurrent endometriosis. This suggests that posterior adenomyosis might share an "extrinsic" origin with deep infiltrating endometriosis (DIE), potentially caused by cells migrating from outside the uterus.

Discussion: Etiological Implications

The findings support two primary etiological hypotheses:

1. Tissue Injury and Repair (TIAR): The strong correlation between diffuse disease, older age, and higher gravidity suggests that repeated uterine trauma (e.g., childbirth or medical procedures) may disrupt the endometrial-myometrial interface, allowing for invasive growth.
2. Extrinsic Origin: The link between posterior lesions and endometriosis suggests a shared pathway with DIE. The increased surgical complexity and blood loss associated with posterior lesions further underscore the inflammatory nature of this subtype, likely due to extensive pelvic adhesions.

Conclusion and Future Directions

Adenomyosis is a heterogeneous disorder with subtype-specific pathophysiology. While this study provides robust clinical evidence for distinct etiologies based on lesion location, it is limited by its focus on surgical cases, which may represent more severe phenotypes. Future research should integrate molecular and genetic profiling to confirm these etiological theories and develop personalized, subtype-specific therapeutic interventions.