Omega-3 polyunsaturated fatty acid intake and pain, inflammatory cytokines, and quality of life in endometriosis

Abstract

Background: Endometriosis is a chronic inflammatory gynecologic disorder associated with pelvic pain and impaired health-related quality of life (HRQoL). Omega-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory potential and may confer adjunctive benefit when combined with conventional therapy. This study evaluated the association between adjunctive omega-3 PUFA intake and pain, inflammatory biomarkers, and HRQoL in endometriosis. Methods: This retrospective, time-period–based cohort study included patients with confirmed endometriosis treated at a single center between January 2021 and December 2024. Conventional therapy during 2021–2022 served as the control period, whereas conventional therapy plus omega-3 PUFA supplementation during 2023–2024 constituted the exposure period. Outcomes included pain assessed by the visual analog scale (VAS), inflammatory biomarkers [interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP)], and HRQoL measured using the 36-Item Short Form Health Survey (SF-36), including the Physical Component Summary (PCS) and Mental Component Summary (MCS). Multivariable logistic regression and inverse probability of treatment weighting (IPTW) were applied, with pre-specified subgroup and sensitivity analyses. Results: Among 302 screened patients, 289 were analyzed (control n = 138; omega-3 n = 151), with comparable baseline characteristics. Median exposure to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) was 900 mg/day (interquartile range [IQR] 600–1,200) for 12 weeks (IQR 10–12). Compared with controls, the omega-3 group experienced greater reductions in overall pain (VAS Δ 3.0 ± 1.0 vs. 1.5 ± 0.9; p < 0.001), larger decreases in IL-6, TNF-α, and CRP (all p < 0.001), and greater improvements in SF-36 PCS (Δ 12.1 ± 5.2 vs. 5.3 ± 4.8) and MCS (Δ 10.3 ± 5.0 vs. 4.8 ± 4.6; both p < 0.001). Omega-3 PUFA intake was independently associated with clinically meaningful improvement, including VAS ≥2-point reduction (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.85–5.06), PCS ≥5-point increase (OR 2.74, 95% CI 1.67–4.50), and MCS ≥5-point increase (OR 2.41, 95% CI 1.50–3.88), with consistent findings across subgroup, sensitivity, and IPTW analyses. Conclusions: Adjunctive omega-3 PUFA intake was associated with improved pain, reduced inflammatory biomarkers, and better HRQoL in endometriosis, warranting confirmation in future prospective randomized studies.