Changes in vascular basement membrane in the endometrium of Norplant users
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Norplant use increased endometrial vascular density while decreasing collagen IV, laminin, and heparan sulphate proteoglycan in the vascular basement membrane, suggesting increased vascular fragility.
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Abstract
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).
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Cited by (21)
- Is adenomyosis a problem in reproduction and fertility? 2014
- Long-term progestin contraceptives (LTPOC) induce aberrant angiogenesis, oxidative stress and apoptosis in the guinea pig uterus: A model for abnormal uterine bleeding in humans 2010
- Abnormal bleeding in postmenopausal hormone users—What do we know today? 2009
- Best Practice & Research Clinical Obstetrics and Gynaecology 2009
- Bleeding with menopausal hormone therapy 2008
- Human uterine vascular structures in normal and diseased states 2003
- Effects of levonorgestrel-releasing intra-uterine system on the expression of vascular endothelial growth factor and adrenomedullin in the endometrium in adenomyosis 2003
- Impact of different progestins on endometrial vascularisation of postmenopausal women. A retrospective image analysis—morphometric study 2003
- Pathophysiology of endometrial bleeding 2003
- Changes in endometrial blood vessels in the endometrium of women with hormone replacement therapy-related irregular bleeding 2003
- Surface vascularization and endometrial appearance in women with menorrhagia or using levonorgestrel contraceptive implants. Implications for the mechanisms of breakthrough bleeding 2002
- Decreased tissue inhibitor of metalloproteinase in the endometrium of women using depot medroxyprogesterone acetate: a role for altered endometrial matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in the pathogenesis of abnormal uterine bleeding? 2002
- Hormone replacement therapy and irregular bleeding 2001
- Hormone replacement therapy and irregular bleeding 2001
- The Clinical Relevance of Disturbances of Uterine Vascular Growth, Remodeling, and Repair 2001
- The structure of endometrial microvessels 2000
- A functional model for progestogen-induced breakthrough bleeding 2000
- Endometrial vascular changes and bleeding disturbances with long-acting progestins 2000
- Disturbances of endometrial bleeding with hormone replacement therapy 2000
- Superficial endometrial vascular fragility in Norplant users and in women with ovulatory dysfunctional uterine bleeding 2000
- The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium 1999
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