The effects of levonorgestrel implants on vascular endothelial growth factor expression in the endometrium

Vascular endothelial growth factor (VEGF) expression and the microvascular density of the endometrium were studied in Norplant users and normal contro ls, using immunohistochemistry on formalin-fixed paraffin-embedded endometr ial sections. The VEGF staining index was quantified using computerized ima ge analysis. The VEGF staining index between stages of the menstrual cycle and between normal and Norplant endometria were compared. Norplant VEGF sta ining index was analysed for correlation with microvascular density, durati on of Norplant use, the number of bleeding/spotting days in the reference p eriod up to 90 days prior to biopsy, and the length of time since the last bleeding/spotting episode. The results showed that immunoreactive VEGF was detected predominantly in endometrial glands but weakly expressed in the st roma throughout the menstrual cycle, and also in Norplant users. Large vari ation in the VEGF staining index between individuals was observed and no si gnificant difference in the VEGF staining index was detected between stages of the menstrual cycle for the glands and stroma. The glandular and stroma l VEGF staining indices were significantly higher in Norplant than in norma l endometrium (P <1x10(-4)). No correlation was found between the Norplant VEGF staining index and endometrial microvascular density, duration of Norp lant use, the number of bleeding/spotting days in the reference period, and the length of time since the last bleeding/spotting episode. The VEGF stai ning index was higher in glands than stroma for both normal and Norplant en dometrium. The results suggest a differential control of endometrial glandu lar Versus stromal VEGF expression, and possible positive effects of levono rgestrel on VEGF expression.