Supplementary Material for: The #Enzian Classification as a Predictor of Hormonal Therapy Response in Endometriosis-Associated Pain: A Retrospective Cohort Study in a Referral Center

Objectives:
To evaluate whether ultrasound-based #Enzian classification predicts pain profiles and response to hormonal therapy in patients with endometriosis. Endometriosis is a chronic inflammatory disease affecting 10% of reproductive-age women, often causing debilitating pelvic pain. Although #Enzian is validated for surgical planning, its predictive role in medical therapy remains unexplored.
Design:
Retrospective cohort study including 89 premenopausal patients referred between 2018–2023. Hormonal therapies included progestin-only pills (Dienogest – POP-D or other progestins – POP-O), combined estrogen-progestin pills (Dienogest – EP-D or other EP-O), or norethisterone acetate (NETA). Pain assessed via 0–10 VAS at baseline, ≥3 months, and ≥6 months.
Participants/Materials, Setting, Methods:
Patients had ultrasound-confirmed endometriosis and were hormone therapy-naïve for ≥6 months. Baseline evaluation included demographic data, reproductive history, prior surgeries, and six pain domains. #Enzian classification mapped lesion location and size (A: rectovaginal/vagina; B: uterosacral/parametria; C: rectum; FA: adenomyosis; FB: bladder; FU: ureter; FI: intestine above rectum; FO: extra-pelvic; O: ovary; P: peritoneum; T: fallopian tubes/adhesions). Linear regression and linear mixed-effects models assessed associations between #Enzian compartments and pain trajectories.
Results:
Dysmenorrhea occurred in 86.5%, dyspareunia in 56.2%. Ovarian endometriomas (O) were present in 76.4%, DIE (A, B, C) in 51.7%, adenomyosis (FA) in 66.3%. POP-D was most effective in reducing ovulatory pain in ovarian (O), uterosacral/parametria (B), rectal (C), and tubal/adhesion (T) involvement, while EP-D was superior for dyspareunia in T. Chronic pelvic pain remained refractory. Higher total #Enzian scores correlated with reduced therapy efficacy.
Limitations:
Retrospective design, single-center, small sample, use of aggregated pain scores, and incomplete follow-up may limit generalizability.
Conclusions:
Ultrasound-based #Enzian classification correlates with lesion distribution and predicts hormonal therapy efficacy. POP-D therapy is superior at lower #Enzian scores; chronic pelvic pain remains challenging. Findings support individualized medical management and warrant prospective validation including multidimensional pain and quality-of-life assessments.