Endometriosis Pathogenesis and Immune Function
Endometriosis occurs when endometrial tissue implants and grows outside the uterus — most commonly on the peritoneum, ovaries, and fallopian tubes. Retrograde menstruation deposits endometrial cells in the peritoneal cavity in most women, but normally the immune system clears this ectopic tissue. In endometriosis, this immune clearance fails, allowing ectopic tissue to establish, implant, and grow into lesions.
PFAS impair peritoneal macrophage function — the immune cells primarily responsible for clearing ectopic endometrial cells. Reduced macrophage phagocytic activity and altered cytokine production in PFAS-exposed macrophages could allow retrograde endometrial cells to escape immune clearance, increasing endometriosis risk.
Research Evidence
Case-control studies have found higher serum PFAS levels in women with laparoscopically confirmed endometriosis compared to women without the condition. A study from the ENDO Study — a multicenter U.S. investigation of endometriosis — found that specific PFAS compounds were associated with endometriosis diagnosis independent of age, BMI, and other covariates.
PFAS also promote the pro-inflammatory peritoneal environment that supports endometriotic lesion growth: elevated peritoneal fluid TNF-α, IL-6, and VEGF facilitate endometrial cell attachment, angiogenesis for lesion vascularization, and local immune suppression that prevents lesion clearance. PFAS-exposed women may have peritoneal fluid cytokine profiles that favor endometriotic lesion establishment.
Clinical and Fertility Implications
Gynecologists evaluating women for chronic pelvic pain, dysmenorrhea, or infertility — common endometriosis presentations — should include environmental PFAS exposure history in their assessment. In PFAS-contaminated communities, endometriosis rates may be elevated, and diagnosis may occur at younger ages than in unexposed populations.
Women with endometriosis seeking pregnancy benefit from minimizing additional PFAS-related immune challenges. Water filtration to reduce ongoing PFAS exposure may support immune function and reduce the peritoneal inflammatory burden that impairs fertility in endometriosis. This aligns with the general principle of environmental optimization during fertility treatment.