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  • Title: Immunohistochemical staining of von Willebrand factor in endometrium of women during the first year of Norplant implants use.
    Author: Au CL, Affandi B, Rogers PA.
    Journal: Contraception; 1994 Nov; 50(5):477-89. PubMed ID: 7859456.
    Abstract:
    The mechanisms responsible for Norplant implants-induced menstrual irregularities remain poorly understood. It is unclear whether local changes in endometrial haemostasis are involved. The aim of the present study was to examine the immunohistochemical staining for von Willebrand factor (vWF) in endometrial biopsies taken from 37 women exposed to Norplant implants for 3-12 months and to compare it with 73 controls at various phases of the normal menstrual cycle. The vWF staining intensity 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 histology, and plasma oestradiol (E2) and progesterone (P4) levels. No differences were found between control and Norplant implants subjects in the localization of vWF staining, which was specifically confined to the endothelium of endometrial blood vessels. vWF staining intensity in Norplant implants endometrium was significantly lower than in controls during mid cycle, and reached a mean (+/- SE) level (subjective staining score 2.05 +/- 0.13, n = 37) in the range of the early proliferative and mid secretory phase normal endometrium; nevertheless, it remained significantly higher than that of menstrual and late secretory phase 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 E2 or serum P4 prior to biopsy, or to the number of days of Norplant implants exposure revealed no significant relationships. However, vWF staining was positively correlated (r = 0.419, P < 0.01) to the number of bleeding/spotting days within a 90-day reference period prior to biopsies being taken. These results demonstrate that there are major differences in the mechanism responsible for normal menstruation and Norplant implants-induced intermenstrual bleeding and spotting, and show that menstrual disturbances associated with the use of Norplant implants are unlikely to be due to changes in vWF levels in endometrial endothelial cells. Changes in the bleeding pattern during women's menstrual cycle have been associated with Norplant subdermal contraceptive implants, which release levonorgestrel (LNG). This article reports the findings of a study on possible effects of LNG on endometrial hemostasis and coagulation, with particular emphasis on the von Willebrand Factor (VWF). Endometrial VWF was examined by immunohistochemical staining. 37 Indonesian women who were exposed to Norplant implants for 3-12 months were studied. Endometrial biopsies were taken during the 3-12 month period following insertion of the implant. Biopsies were taken using a microhysteroscope or a Pipelle suction curette. 73 Australian women with normal menstrual cycles served as controls in this study. Blood analysis was used for establishing baseline and subsequent hormone measurements. Of the 37 exposed women, 9 were classified as histopathologically atrophic, 11 as iatrogenic progestogenic, 4 as proliferative, 4 as secretory, and 9 as shedding. No significant differences were observed in the localization of VWF staining between implant-exposed and control groups. VWF immunostaining, correlated against the number of implant days exposed, showed no significant relationship (r = 0.054, P 0.01). Levels of VWF staining in the endometrium of Norplant users were significantly higher than those in women whose menstrual and late secretory phase endometrium were normal. Levels of VWF were lower than normal mid-cycle bleeding patterns. VWF levels are unlikely to be associated with observed menstrual disturbances.
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