From Mice to Primates: Assessing Hormone-Based Endometriosis Models for Preclinical and Therapeutic Insights

Endometriosis, a complex gynecological disorder characterized by ectopic endometrial-like tissue, affects over 10% of women, causing chronic pain and infertility. Despite extensive research, its pathophysiology remains incompletely understood, with proposed mechanisms including inflammation, hormonal dysregulation, and retrograde menstruation. Given ethical and practical challenges in human studies, animal models are essential for investigating endometriosis pathogenesis and evaluating therapeutic interventions. This review examines hormone-related animal models of endometriosis, comparing induction methods (autotransplantation, xenotransplantation, and spontaneous models) and their applications in studying sex steroid hormones (SSH) and the hypothalamic-pituitary-gonadal (HPG) axis. We analyzed 158 studies (2010-2024) from PubMed Central/Medline, focusing on SSH and HPG axis involvement. A novel scoring system was developed to assess the model's suitability based on species, induction method, pharmacological effects, hormonal/genetic evaluations, histological confirmation, feasibility, ethics, and cost. Non-human primate models, particularly spontaneous and hormone-induced baboon models, scored highest due to their physiological resemblance to humans. However, rodent models remain widely used due to practicality. Our findings highlight the need for improved preclinical models to enhance translational research, ultimately aiding in the development of targeted therapies for endometriosis. This comprehensive analysis provides a framework for selecting optimal animal models in future endometriosis research.