Immune mysteries of endometriosis

Endometriosis affects around one in ten people who menstruate, nearly 200 million globally, yet remains one of the most underdiagnosed and misunderstood conditions in medicine. For centuries, debilitating pelvic pain has been normalised or dismissed as an inevitable part of menstruation, allowing the disease to persist in silence. Endometriosis occurs when tissue resembling the uterine lining grows outside the uterus, forming lesions that respond to hormones, become infiltrated by blood vessels, nerves and immune cells, and cause chronic inflammation, pain and infertility. The long-held theory of retrograde menstruation (backward flow of menstrual tissue into the pelvic cavity) explains how endometrial cells reach the peritoneum, but not why only some individuals develop disease. Evidence points to a central role for the immune system. In endometriosis, immune cells fail to clear refluxed tissue and instead create an environment that supports its growth. Macrophages, normally the body’s housekeepers, become disease-modified, promoting lesion survival and nerve growth that amplifies pain. Recognising endometriosis as an immune disorder opens new therapeutic frontiers. In the future, immune-based strategies will aim to re-educate the immune system rather than suppress hormones, with patient-reported outcomes guiding the design of personalised care. The same immunological insights are also transforming diagnostics: menstrual fluid, once dismissed as waste, is now being explored as a rich and accessible source of biomarkers. Together, these advances are redefining endometriosis as a systemic, immune-mediated condition and offering hope for earlier diagnosis, targeted treatments, and meaningful improvement in patients’ lives.