IMMUNOHISTOCHEMICAL STAINING OF VON-WILLEBRAND-FACTOR IN ENDOMETRIUM OF WOMEN DURING THE FIRST YEAR OF NORPLANT(R) IMPLANTS USE

The mechanisms responsible for Norplant implants-induced menstrual irr egularities remain poorly understood. It is unclear whether local chan ges in endometrial haemostasis are involved. The aim of the present st udy was to examine the immunohistochemical staining for von Willebrand factor (VWF) in endometrial biopsies taken from 37 women exposed to N orplant implants for 3-12 months and to compare it with 73 controls at various phases of the normal menstrual cycle. The vWF staining intens ity was quantified by subjective scoring and by objective computerised colour image analysis. Results from the Norplant implants group were additionally correlated with their bleeding patterns, endometrial hist ology, and plasma oestradiol (E(2)) and progesterone (P-4) levels. No differences were found between control and Norplant implants subjects in the localization of vWF staining, which was specifically confined t o the endothelium of endometrial blood vessels. vWF staining intensity in Norplant implants endometrium was significantly lower than in cont rols during mid cycle, and reached a mean(+/-SE) level (subjective sta ining score 2.05 +/- 0.13, n=37) in the range of the early proliferati ve and mid secretory phase normal endometrium; nevertheless, it remain ed significantly higher than that of menstrual and late secretory phas e normal endometrium. No significant variations in vWF staining could be related to either the histology of the endometrium or the bleeding pattern of the users. Correlation of vWF staining with either serum E( 2) or serum P-4 prior to biopsy, or to the number of days of Norplant implants exposure revealed no significant relationships. However, vWF staining was positively correlated (r=0.429, P<0.02) to the number of bleeding/spotting days within a 90-day reference period prior to biops ies being taken. These results demonstrate that there are major differ ences in the mechanism responsible for normal menstruation and Norplan t implants-induced intermenstrual bleeding and spotting, and show that menstrual disturbances associated with the use of Norplant implants a re unlikely to be due to changes in vWF levels in endometrial endothel ial cells.