Immunohistochemical staining of von Willebrand factor in endometrium of women during the first year of Norplant®1 1 NORPLANT® is a trademark of the Population Council, Inc. implants use

Chak L. Au, Biran Affandi, Peter A.W. Rogers

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9 Citations (Scopus)


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 endome trium; 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.

Original languageEnglish
Pages (from-to)477-489
Number of pages13
Issue number5
Publication statusPublished - 1 Jan 1994


  • Endometrium
  • Norplant
  • immunohistochemistry
  • levonorgestrel
  • von Willebrand factor

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