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Human Reproduction, Vol. 14, No. 3, 716-721, March 1999
© 1999 European Society of Human Reproduction and Embryology

Changes in vascular basement membrane in the endometrium of Norplant users

M. Hickey1,4, M. Simbar2, R. Markham2, L. Young2, F. Manconi2, P. Russell3 and I.S. Fraser2

1 Department of Obstetrics and Gynaecology, Imperial College School of Medicine at St. Mary's, Norfolk Place, London W2 1PG, 2 Department of Obstetrics and Gynaecology and 3 Department of Anatomical Pathology, University of Sydney, NSW 2006, Australia

Progestogen-only contraception is almost invariably associated with changes in menstrual bleeding patterns. Changes in the endometrial vasculature, and in particular an increase in vascular fragility, may contribute to this bleeding. In this study, endometrial vascular density and endothelial cell basement membrane components were examined using immunohistochemistry before and after insertion of Norplant®. Endometrial vascular density was increased from a mean (± SEM) of 189.6 ± 7.0 vessels/mm2 during the control cycle to 253.9 ± 80.7 vessels/mm2 at 2–13 weeks of Norplant exposure, and to 212.7 ± 12.9 vessels/mm2 at 14–42 weeks. During the control cycle, a mean of 161.4 ± 4.5 vessels/mm2 stained for collagen IV (85% of all vessels), while at 2–13 weeks, 144.5 ± 13.0 vessels/mm2 stained for collagen IV (57% of all vessels) (t ratio = 2.08, P = 0.0057). By 14–42 weeks, 71% of vessels (151.0 ± 9.8) vessels/mm2 were surrounded by collagen IV. This was not significantly different from control values (t ratio = 2.03). Endometrial vascular laminin was also reduced following Norplant insertion, from a mean of 176.0 ± 4.2 vessels/mm2 in the control cycle (93% of vessels), to 156.3 ± 6.7 vessels/mm2 at 2–13 weeks of exposure (57% of vessels) (t ratio = 2.08, P = 0.01). By 14–42 weeks of exposure to Norplant, 162.5 ± 9 vessels/mm2 (76%) stained for laminin. This was not significantly different from control values (t ratio = 2.04). Endometrial vascular heparan sulphate proteoglycan (HSPG) was reduced from 58.6 ± 3.0 vessels/mm2 during the control cycle (31% of vessels) to 43.6 ± 5.6 vessels/mm2 (only 17% of vessels) at 2–13 weeks (t ratio = 2.08, P = 0.025). At 14–42 weeks, only 19% of vessels stained for HSPG (41.3 ± 5.8 vessels/mm2; t ratio = 2.04, P = 0.009).

Key words: basement membrane/collagen IV/endometrium/endothelial/laminin/Norplant/proteoglycan

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