Symptom Burden in Adenomyosis: A Comparative Analysis With Peritoneal and Deep Infiltrating Endometriosis

Discussion

In this study, we observed that over half of the patients experienced the onset of EM-related symptoms at a very early age, often during adolescence. Primary dysmenorrhea was highly prevalent (present in well over 50% of cases) across all patient groups, and many of these young patients were later confirmed to have EM. We also found that dyspareunia and chronic pelvic pain (CPP) were reported more frequently in patients with AM and peritoneal endometriosis (Groups 1 and 2) than in those with DIE (Group 3). Additionally, patients with advanced disease (Group 3) exhibited a greater involvement of the ovaries and tubo-ovarian adhesions (O and T #ENZIAN compartments), reflecting the extensive spread of EM in this group. These findings underscore the importance of early recognition of EM in adolescents and highlight how symptom profiles may vary with disease localization. More than half of the women in our cohort developed EM-related symptoms during their teenage years. This aligns with large surveys reporting that nearly two-thirds of adult patients with EM recall their first pelvic pain symptoms before age 20 (with about one in three even reporting onset before age 15) (15). Our findings reinforce that EM often begins in adolescence, a period when gynecologic complaints such as dysmenorrhea are too easily dismissed as “normal pains.” Indeed, EM is now recognized as a leading cause of secondary dysmenorrhea and chronic pelvic pain in adolescents (16). This has critical implications: clinicians should maintain a high index of suspicion for EM in young patients who present with severe menstrual pain or other persistent gynecologic symptoms. Early symptom onset also contributes to the notorious diagnostic delay of EM. Many patients in our study likely endured symptoms for years before a definitive diagnosis was made, echoing the need for improved awareness and early intervention in adolescent cases.

We found dysmenorrhea to be nearly ubiquitous in all groups (reported by ~95-100% of patients, depending on group) and primary dysmenorrhea was the case in more than the half of patients in each group (Table I). Far from being “just painful periods,” such significant dysmenorrhea in young women is often the earliest clinical manifestation of EM. The American College of Obstetricians and Gynecologists (ACOG) emphasizes that adolescents with dysmenorrhea unrelieved by first-line therapy should be evaluated for EM (17). Our results strongly support this guidance. Too often, primary dysmenorrhea is written off as idiopathic or functional; however, the most commonly identified cause of severe dysmenorrhea in adolescents is EM itself (18). In other words, the diagnosis of “primary” (idiopathic) dysmenorrhea should be made cautiously, if at all, in a teenager with intense menstrual pain. Instead, empiric treatment for presumptive EM or further diagnostic work-up is warranted to avoid prolonged suffering (18). In this context, progestins should be preferred, as treatment with combined oral contraceptives has been associated with a markedly increased prevalence of DIE in observational studies (19). Importantly, recent longitudinal evidence shows that even when an initial evaluation is unrevealing, many adolescents with refractory dysmenorrhea will later be found to have EM. Nocita et al. (2025) followed young women (≤25 years) with severe dysmenorrhea and no ultrasound signs of disease; remarkably, 20% of these initially “normal” cases developed sonographically visible EM lesions within only 1-3 years (20). This prospective finding confirms that an unremarkable early exam does not rule out evolving EM. In Nocita’s study, those patients were eventually diagnosed after serial ultrasound follow-up (20). Taken together with our findings, this underscores that severe adolescent dysmenorrhea should not be dismissed as benign or “primary”, because underlying EM or AM could be in an incipient stage. Early clinical suspicion and appropriate management (e.g., empiric hormonal suppression) may mitigate disease progression and improve long-term outcomes (20).

Another key finding of our analysis was the differential pattern of dyspareunia and chronic pelvic pain across EM phenotypes. Women with isolated AM (Group 1) or predominantly peritoneal/ovarian endometriosis (Group 2) reported dyspareunia and non-cyclical pelvic pain more frequently than those with DIE (Group 3). This somewhat counterintuitive pattern may reflect the contribution of AM and superficial peritoneal endometriosis to diffuse pelvic pain. AM, in particular, can induce a globally sensitized, enlarged uterus and a chronic inflammatory milieu, predisposing patients to persistent pain and painful intercourse (21). AM and peritoneal endometriosis can provoke a more diffuse peritoneal inflammation and uterine hypercontractility, which might explain the greater burden of chronic pain and deep dyspareunia in Groups 1 and 2. In sum, our results dispel the notion that AM is a relatively mild condition; on the contrary, women with AM (even without deep lesions) suffered levels of pain comparable to or exceeding those with extensive DIE, underscoring that AM can be a severely symptomatic disease (21). This insight reinforces the need to take symptoms like “primary” dysmenorrhea or deep dyspareunia seriously in all patients, including those suspected to have AM.

This study demonstrates that AM can manifest with a symptom profile equal in breadth and severity to both superficial peritoneal endometriosis and DIE, underscoring that its clinical burden is not less substantial than that of other EM phenotypes.

We also observed significant differences in the anatomical distribution of disease, with Group 3 (advanced DIE) exhibiting far more ovarian endometriomas and adnexal adhesions (ENZIAN O and T compartments) than Group 2 (Table II). This finding is in line with the progressive nature of EM: as the disease becomes deeply infiltrative, it often does not remain localized. Advanced EM cases commonly encompass multiple compartments – for example, our recent study demonstrated that ovarian endometriomas often coexist with DIE (22). Extensive adhesive pathology tends to accompany long-standing, widespread EM. Group 3 patients’ high rate of tubo-ovarian adhesions reflects this tendency; adhesions are a well-known hallmark of advanced-stage EM, resulting from chronic inflammation and repeated bleeding in the pelvis. Taken together, the predominance of O and T findings in Group 3 underscores that by the time EM becomes deeply invasive, it typically involves the ovaries and adhesive disease as well – a pattern that has important surgical implications. Surgeons managing patients with known DIE should anticipate and conduct a thorough evaluation for coexisting endometriomas and adhesions to ensure comprehensive treatment of the disease (22). Conversely, the presence of an endometrioma on imaging should raise suspicion for occult deep lesions, as multiple studies now highlight the frequent concurrence of these lesion types.

Strengths and limitations. Major strengths of this study include the use of a standardized preoperative symptom questionnaire, and the systematic intraoperative application of the #ENZIAN classification, which enabled a detailed comparison of symptom patterns across distinct disease subtypes. Although retrospective, the study is based on prospectively collected clinical and surgical data, reflecting routine standardized documentation at our center.

Several limitations should be acknowledged. As a single-center retrospective analysis from a tertiary referral unit, selection bias is possible, and the findings may not be fully generalizable. Only surgically treated patients were included, potentially underrepresenting milder cases managed conservatively. Symptom data were self-reported and cross-sectional, introducing potential recall bias. Another limitation of this study is that patients with peritoneal and deep infiltrating EM could also have concomitant adenomyosis. Given the frequent coexistence of these conditions, identifying patients with exclusively superficial peritoneal or deep disease is challenging. Nevertheless, the central aim was to demonstrate that isolated adenomyosis should not be underestimated, as it may represent a clinically significant cause of symptoms even in the absence of other EM lesions. Despite these limitations, the study provides meaningful insights into the symptom burden of isolated adenomyosis compared with superficial peritoneal and deep infiltrating endometriosis, an area that remains insufficiently characterized.