Endometriosis is a chronic systemic disease: clinical challenges and novel innovations.

Endometriosis is a common disease affecting 5-10% of women of reproductive age globally. However, despite its prevalence, diagnosis is typically delayed by years, misdiagnosis is common, and delivery of effective therapy is prolonged. Identification and prompt treatment of endometriosis are essential and facilitated by accurate clinical diagnosis. Endometriosis is classically defined as a chronic, gynaecological disease characterised by endometrial-like tissue present outside of the uterus and is thought to arise by retrograde menstruation. However, this description is outdated and no longer reflects the true scope and manifestations of the disease. The clinical presentation is varied, the presence of pelvic lesions is heterogeneous, and the manifestations of the disease outside of the female reproductive tract remain poorly understood. Endometriosis is now considered a systemic disease rather than a disease predominantly affecting the pelvis. Endometriosis affects metabolism in liver and adipose tissue, leads to systemic inflammation, and alters gene expression in the brain that causes pain sensitisation and mood disorders. The full effect of the disease is not fully recognised and goes far beyond the pelvis. Recognition of the full scope of the disease will facilitate clinical diagnosis and allow for more comprehensive treatment than currently available. Progestins and low-dose oral contraceptives are unsuccessful in a third of symptomatic women globally, probably as a result of progesterone resistance. Oral gonadotropin-releasing hormone (GnRH) antagonists constitute an effective and tolerable therapeutic alternative when first-line medications do not work. The development of GnRH antagonists has resulted in oral drugs that have fewer side-effects than other therapies and has allowed for rapid movement between treatments to optimise and personalise endometriosis care. In this Review, we discuss the latest understanding of endometriosis as a systemic disease with multiple manifestations outside the parameters of classic gynaecological disease.