Comprehensive Review of Genetic and Epigenetic Dimensions of Endometriosis, New Treatment Strategies

Abstract

Background: Endometriosis is a benign condition with an unidentified genetic cause, and conventional therapeutic methods are ineffective. Methods: Articles pertaining to the genetic and epigenetic dimensions of endometriosis were extracted. Theories concerning the etiology of endometriosis were examined. Therapeutic prospects were evaluated considering both genetic and epigenetic factors of endometriosis. Findings: Retrograde menstruation, coelomic metaplasia, embryonic rest, metastatic endometriosis, and endometrial stem cell recruitment are regarded as etiological factors of endometriosis. Genome-wide investigations have found variables linked to an elevated incidence of endometriosis. Epigenetic modifications, such as diminished COX2 promoter methylation, can influence the quantity and functionality of neutrophils by elevating estrogen synthesis, hence contributing to the onset of endometriosis. Two critical factors in the onset and advancement of endometriosis are the evasion of endometriotic lesions from the immune response and elevated concentrations of inflammatory cytokines. Novel therapeutic alternatives for endometriosis encompass aromatase inhibitors, and their combination with gestagens, oral contraceptives, or gonadotropin-releasing hormone agonists not only demonstrates efficacy but also alleviates pain, diminishes the size of ectopic lesions, and enhances patients' quality of life. Histone deacetylase inhibitors limit the growth of endometriotic stromal cells while exhibiting little negative effects on normal stromal cells. Conclusion: Genetics and epigenetics significantly influence the development of endometriosis, and therapeutic approaches utilizing epigenome-modulating agents present promising new options, demonstrating superior efficacy compared to conventional treatments. © 2025, Isfahan University of Medical Sciences(IUMS). All rights reserved.