The combination of letrozole and melatonin causes regression in size not histopathological scores on endometriosis in an experimental rat model

To determine the effects of the combination of letrozole and melatonin on surgically induced endometriosis.This prospective, randomized, controlled, experimental study was carried out at Yeditepe University Experimental Research Center (YUDETAM). Female non-pregnant, 17 nulligravid Wistar - Hannover albino rats with surgically induced endometriosis were used in this study. Endometriosis was induced by using homologous uterine horn transplantation in the rats. Four operations were performed on each rat. The induction of endometriosis was performed in the first operation. After two weeks of estradiol treatment the second operation was performed and endometriotic lesions were evaluated. Estrogen was then discontinued and in the study groups medications were started. During two weeks the rats were given medications and the third operation was performed for the assessment of the effects of the medications on the endometriotic foci. Then all the medications were stopped and estrogen was started again. Two weeks later all the rats were euthanized and recurrence of endometriosis was evaluated.The sum of the lesion volumes in the control group was 93.6±31.7 mm(3) at the end of the second week. After the cessation of estradiol it decreased to 85.0±23.8 mm(3) (P=0.31) and increased to 119.7±29.4 mm(3) at the sixth week (P=0.02). A significant reduction in histopathologic scores were seen after cessation of the estradiol (p=0.04). At the end of the sixth week, histopathological scores reached the pretreatment values. In the letrozole and melatonin group the sum of the lesion volumes decreased significantly after the treatment (82.8±21.0 mm(3) and 15.7±8.0 mm(3) respectively). At the end of the sixth week, the mean volume was calculated as 43.9±31.8 mm(3) (p=0.002). Histopathologic scores were 2.3±0.1, 2.0±0.2 and 2.2±0.3 at the end of the second, fourth and sixth weeks, respectively, in the letrozole and melatonin group.Letrozole and melatonin caused a significant regression in lesion volumes; however, histopathological scores of endometriotic lesions did not change significantly.Kombine letrozol ve melatonin tedavisinin cerrahi olarak indüklenmiş endometriosis üzerindeki etkisini belirlemek.Bu prospektif randomize kontrollü bir deneysel çalışma olarak dizayn edildi ve Yeditepe Üniversitesi Deneysel Hayvanlar Araştırma Merkezinde (YUDETAM) gerçekleştirildi. Cerrahi olarak endometriosis oluşturulmuş 17 tane nulligravida dişi Wistar – Hannover albino rat kullanıldı. Ratlara homolog uterin boynuz inokülasyonu yapılarak endometriosis oluşturuldu ve iki hafta aralar ile dört operasyon yapıldı. Endometriosis indüksiyonu ilk operasyonda yapıldı. İki haftalık östradiol tedavisini takiben ikinci operasyon yapıldı. Sonra östrojen kesildi ve çalışma grubuna ilaç başlandı. Takip eden iki haftanın sonunda üçüncü operasyon yapılarak endometriyal odaklar üzerinde ilaçların etkinliği araştırıldı. Üçüncü operasyondan sonra bütün ilaçlar kesildi ve östrojen tekrar başlandı. Iki haftalık östrojen tedavisinin ardından tüm ratlara ötanazi yapıldı ve rekürrens oranlarına bakıldı.Kontrol grubunda tedavinin başında lezyonların volüm ortalaması 93.6±31.7 mmÇalışmamızda Letrozol ve Melatonin endometriotik lezyonların boyutlarında gerileme oratya çıkarırken, histopatolojik skorlarda değişikliğe yol açmadı.