Ukrainian Journal of Perinatology and Pediatrics. 2025.4(104): 82-89. doi: 10.15574/PP.2025.4(104).8289
Kostenko O. Yu., Proshchenko O. M., Avramenko S. O.
Bogomolets National Medical University, Kyiv, Ukraine

For citation: Kostenko OYu, Proshchenko OM, Avramenko SO. (2025). Endometriosis: current perspectives on etiology, pathogenesis, and molecular mechanisms of disease development (literature review). Ukrainian Journal of Perinatology and Pediatrics. 4(104): 82-89. doi: 10.15574/PP.2025.4(104).8289.
Article received: Jul 04, 2025. Accepted for publication: Nov 27, 2025.

Endometriosis (EM) is a multifactorial, estrogen-dependent chronic inflammatory disease characterized by the growth of endometrium-like cells outside the uterine cavity.
Aim – to summarize the main hypotheses of EM development based on current literature.
A narrative review of PubMed, Scopus, Web of Science, and Google Scholar publications (2000-2025) was conducted. Included were original studies, systematic reviews, meta-analyses, and international guidelines on EM pathogenesis. Excluded were duplicates, low-evidence studies, and off-topic publications. Literature was categorized by theories: retrograde menstruation, metaplastic, immunological, genetic, hormonal, inflammatory, and epigenetic. Current concepts – the immunological, inflammatory, genetic, and epigenetic theories – explain mechanisms of EM survival, growth, angiogenesis, and progression. The hormonal theory emphasizes hyperestrogenism (elevated estrogen) and relative progesterone resistance. The genetic theory highlights hereditary predisposition and mutations in ESR1 and ESR2 (estrogen receptors), VEGF (vascular endothelial growth factor), KRAS and WNT4 (regulation of cell growth and invasion), and HLA-G (immune tolerance). Immunological dysfunction supports survival of ectopic lesions through impaired macrophage and regulatory T-cell activity. The most promising approach is an integrative model combining retrograde cell transport, immune dysfunction, hormonal imbalance, genetic susceptibility, and epigenetic modifications.
Conclusions. EM is a polyetiologic disease. An integrative approach provides a foundation for the implementation of individualized diagnosis and molecularly targeted therapy.
The authors declare that there is no conflict of interest.
Keywords: endometriosis, pathogenesis, retrograde menstruation, metaplastic, immunological, genetic, hormonal, inflammatory, epigenetic.

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