TOPLINE

Various risk factors and comorbidities displayed distinct patterns of association with endometriosis lesion subtypes. Chronic overlapping pain conditions were positively associated with superficial peritoneal endometriosis (SPE) and deep lesions, whereas depression was inversely associated with endometriomas.

METHODOLOGY

• Researchers conducted a pooled, cross-sectional analysis including 1244 participants with surgically confirmed endometriosis and 1271 control individuals without endometriosis from three population-based studies — two in the US and one in the UK (A2A, ENDO, and ENDOX).
• Endometriosis cases were classified based on the surgically visualized lesion macrophenotype as SPE only (71%), at least one endometrioma (8%), at least one deep lesion (11%), or both deep lesions and endometriomas (10%).
• Participants completed standardized questionnaires capturing menstrual and reproductive history, early-life factors, and co-existing comorbidities such as chronic overlapping pain conditions and immune-related conditions.
• Researchers assessed the association between various factors, including menstrual and reproductive characteristics and demographic characteristics, and surgically confirmed endometriosis.

TAKEAWAY

• A younger age at menarche (≤11 years vs 12 years) was associated with higher odds of endometriosis (odds ratio [OR], 1.35; 95% CI, 1.08-1.68), particularly SPE only (OR, 1.29; 95% CI, 1.01-1.65) and deep lesions plus endometriomas (OR, 2.07; 95% CI, 1.11-3.86).
• The presence of at least one chronic overlapping pain condition was linked to increased odds of endometriosis overall (OR, 1.66; 95% CI, 1.49-1.85 per condition), SPE only (OR, 1.80; 95% CI, 1.59-2.04 per condition), and deep lesions (OR, 1.76; 95% CI, 1.44-2.15 per condition).
• Immune-related conditions were positively associated with SPE only (OR, 1.21; 95% CI, 1.08-1.35 per condition).
• Depression or mood disorders were inversely associated with endometriomas (OR, 0.49; 95% CI, 0.27-0.87), an association that persisted after adjusting for concurrent life-impacting pelvic pain (OR, 0.39; 95% CI, 0.22-0.71).

IN PRACTICE

"[The study] findings provide novel evidence that endometriosis macrophenotypes may have distinct risk factor profiles, suggesting differences in etiology or pathophysiology. The patterns of co-existing conditions also differ by endometriosis macrophenotype, suggesting that clinical manifestation and presentation may differ by macrophenotypes," the authors wrote.

SOURCE

The study was led by Naoko Sasamoto, MD, PhD, of the Public Health Sciences Division at the Fred Hutchinson Cancer Center in Seattle, and Amy L. Shafrir of the School of Nursing and Health Sciences at Merrimack College in Andover, Massachusetts. It was published online on August 25, 2026, in the American Journal of Obstetrics and Gynecology.

LIMITATIONS

The study design prevented determination of temporality between some risk factors and diagnosis of endometriosis. The control groups might have included undiagnosed endometriosis cases.

DISCLOSURES

This study was supported by funding in whole or in part by the National Institutes of Health and from the National Institute of Child Health and Human Development. One author reported receiving support from the National Institute of Child Health and Human Development. Financial support for establishment of and data collection within the A2A cohort was provided by the J. Willard and Alice S. Marriott Foundation. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.