THE NEUROBIOLOGICAL AND IMMUNOLOGICAL BASIS OF THE CO-OCCURRENCE OF ENDOMETRIOSIS WITH DEPRESSION AND ANXIETY: A SYSTEMATIC REVIEW
Abstract
Introduction: Endometriosis is a chronic, oestrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age worldwide. In addition to its well-documented gynaecological symptoms, endometriosis is increasingly associated with psychiatric disorders, particularly depression and anxiety disorders. The neurobiological and immunological mechanisms underpinning this comorbidity remain poorly understood. Objective: This systematic review aims to synthesise current data on the neurobiological, neuroendocrine and immunological mechanisms linking endometriosis to depression and anxiety disorders, taking into account additional psychiatric symptoms such as sleep disorders, post-traumatic stress disorder (PTSD) and sexual dysfunction. Methods: A systematic search of the PubMed/MEDLINE database was conducted to identify articles published between January 2008 and March 2026, using predefined search terms relating to endometriosis, mental health, neuroinflammation and immune dysregulation. Study selection was carried out in accordance with the PRISMA 2020 guidelines. Studies analysing the association between endometriosis and psychiatric outcomes, or investigating the underlying biological mechanisms, were included. Results: Thirty studies met the inclusion criteria. The data consistently indicate elevated rates of depression (prevalence 9.8-98.5 per cent) and anxiety (11.5-87.5 per cent) in women with endometriosis compared with the general population. Key mechanisms identified include: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis; systemic and central neuroinflammation mediated by pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha), oestrogen-induced neurotransmitter imbalances, central sensitisation, oxidative stress and gut-brain axis dysfunction. Conclusions: The relationship between endometriosis and psychiatric disorders is bidirectional and mediated by combined neuroendocrine-immunological pathways. These findings highlight the need for integrated, multidisciplinary management strategies that take into account both the somatic and psychological dimensions of endometriosis.