Endometriosis Patofizyolojisi
Özet
Endometriosis, endometrial gland ve stromanın uterin kavite dışında yerleşmesiyle karakterize, östrojen bağımlı kronik inflamatuar bir hastalıktır. Üreme çağındaki kadınların yaklaşık %10'unu etkileyen bu durum; pelvik ağrı, dismenore, disparonü ve infertiliteye yol açarak yaşam kalitesini, akademik ve ekonomik hayatı olumsuz etkiler. Hastalığın patogenezini açıklayan en önemli teorilerden biri retrograd menstrüasyon ve transplantasyondur; bu teori adet kanının geriye akarak batın içine yayılmasını esas alır. Bunun yanı sıra, periton yüzeyindeki hücrelerin dönüşümünü savunan çölemik metaplazi, embriyonik hücre kalıntılarına dayanan müllerian kalıntılar ile ekstrapelvik yayılımı açıklayan vasküler/lenfatik yayılım teorileri de mevcuttur. Endometriosis gelişiminde bağışıklık sistemindeki bozukluklar, makrofaj ve doğal öldürücü (DK) hücrelerin aktivitelerindeki değişimler ile kronik inflamasyon süreçleri kilit rol oynar. Ailevi kümelenmeler genetik bir arka planı işaret ederken; HOXA10, PR-B ve ER-ß genlerindeki DNA metilasyonları gibi epigenetik değişiklikler ve mikroRNA ekspresyonlarındaki bozulmalar progesteron direncine ve kontrolsüz hücre proliferasyonuna neden olur. Sonuç olarak endometriosis; genetik, epigenetik, immünolojik ve çevresel faktörlerin karmaşık etkileşimiyle gelişen multifaktöryel bir hastalıktır.
Endometriosis is an estrogen-dependent chronic inflammatory disease characterized by the presence of endometrial glands and stroma outside the uterine cavity. Affecting approximately 10% of reproductive-aged women, this condition causes pelvic pain, dysmenorrhea, dyspareunia, and infertility, thereby negatively impacting the quality of life, academic endeavors, and economic status. One of the most widely accepted theories explaining its pathogenesis is retrograde menstruation and transplantation, which is based on the reflux of menstrual blood spreading into the peritoneal cavity. In addition, there are theories of coelomic metaplasia advocating the transformation of peritoneal cells, müllerian remnants based on embryonic cell residues, and vascular/lymphatic dissemination explaining extrapelvic spread. Immune system dysfunctions, alterations in the activities of macrophages and natural killer (NK) cells, and chronic inflammatory processes play key roles in the development of endometriosis. While familial clustering points to a genetic background, epigenetic alterations such as DNA methylations in HOXA10, PR-B, and ER-ß genes, along with disruptions in microRNA expressions, lead to progesterone resistance and uncontrolled cell proliferation. Consequently, endometriosis is a multifactorial disease that develops through the complex interaction of genetic, epigenetic, immunological, and environmental factors.
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