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  • Title: Immunohistochemical study of endometrial microvascular basement membrane components in women using Norplant.
    Author: Palmer JA, Lau TM, Hickey M, Simbah M, Rogers PA.
    Journal: Hum Reprod; 1996 Oct; 11(10):2142-50. PubMed ID: 8943519.
    Abstract:
    The mechanisms responsible for progestogen-induced breakthrough bleeding remain unexplained. The aim of the present study was to examine the expression of three basement membrane components, collagen IV (CIV), laminin and heparan sulphate proteoglycan (HSPG), by immunohistochemistry in sections of endometrium from women receiving the subdermal levonorgestrel implant (Norplant) and normally cycling women. Control biopsies were obtained from 20 normal subjects from Melbourne, Australia, and pre- and post-Norplant-insertion biopsies were obtained from 11 women from Sydney, Australia, with between 3 and 6 months Norplant exposure. It was postulated that in Norplant users a decrease in the amount of basement membrane material present around endometrial vessels may be responsible for increased capillary fragility. The results, however, showed that for all three components, Norplant biopsies exhibited vascular basement membrane immunostaining at least as intense as that found in the mid-late secretory phase of the normal cycle. During the normal cycle, HSPG was only detected in approximately 40% of vessels with CIV and laminin immunoreactivity, and menstrual biopsies demonstrated reduced staining for all three components. Several biopsies exhibited a degree of regional variability in staining intensity, and Norplant biopsies exhibited areas of discrete, decidual-like stromal immunostaining for CIV and laminin. Although no differences were found in microvascular basement membranes in Norplant users that might explain capillary fragility, it is possible that other techniques could yield information on changes in the integrity of basement membrane components that might influence basement membrane strength. In Australia, endometrial biopsy data on 11 women 18-40 years old from Sydney, who had accepted the contraceptive implant Norplant, were compared with similar data on 20 controls from Melbourne who used no contraception, and endometrial biopsy data before Norplant insertion were compared with similar data 3-6 months after Norplant insertion. The aim was to examine the distribution and staining pattern of endometrial microvascular basement membranes (BMs) in biopsies of these women. The BM components considered were collagen IV (CIV), laminin, and heparan sulphate proteoglycan (HSPG). It was hypothesized that a reduction in the amount of BM material around endometrial vessels in Norplant users might effect increased capillary fragility. Vascular BM immunostaining in the Norplant biopsies was similar to that in the mid-late secretory phase of the normal cycle. HSPG was present in only about 40% of vessels with CIV and laminin immunoreactivity. Reduced staining of all BM components was the case in the menstrual biopsies. Regional variability in staining intensity was present in several biopsies. Endometrial biopsies of Norplant users had areas of distinct, decidual-like stromal immunostaining for CIV and laminin. These findings did not identify a mechanism for progestogen-induced breakthrough bleeding. Other techniques could provide information on changes in the integrity of FM components that might effect BM strength.
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