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Published on: May 23, 2014
Mifepristone-induced amenorrhoea is associated with an increase in microvessel density and glucocorticoid receptor
Nitish Narvekar1, Hilary O D Critchley, Linan Cheng
1Contraceptive Development Network, Centre for Reproductive Biology, Edinburgh, UK.
Human Reproduction (Oxford, England)
|June 30, 2006
Summary
Low-dose mifepristone, used as a contraceptive, causes amenorrhoea by altering endometrial vascular function. This study investigated changes in microvasculature, VEGF, and GR in women taking mifepristone.
Area of Science:
- Reproductive endocrinology
- Pharmacology
- Gynecology
Background:
- Progesterone antagonist mifepristone demonstrates contraceptive properties at low daily doses (2-5 mg).
- Mifepristone treatment leads to amenorrhoea, unlike other progestogen-only pills (POP).
- Investigated endometrial changes related to mifepristone's contraceptive effect, focusing on microvasculature, VEGF, and GR.
Purpose of the Study:
- To examine the impact of low-dose mifepristone on endometrial microvasculature.
- To assess changes in vascular endothelial growth factor (VEGF) and glucocorticoid receptor (GR) content within the endometrium.
- To correlate these endometrial changes with the observed amenorrhoea in women using mifepristone as a contraceptive.
Main Methods:
- Endometrial biopsies from 16 women before and after 120 days of daily mifepristone (2 or 5 mg).
- Histological analysis of endometrial lining and microvessel density.
- Immunocytochemistry to evaluate glucocorticoid receptor (GR) and vascular endothelial growth factor (VEGF) expression.
Main Results:
- Amenorrhoea occurred in 7/8 women on 2 mg and all 8 women on 5 mg mifepristone.
- Endometrial histology remained proliferative; however, stromal density and microvessel density significantly increased (P < 0.05 and P < 0.01).
- Glucocorticoid receptor (GR) nuclear expression upregulated in glands and epithelium (P < 0.05, P < 0.01), while stromal VEGF significantly decreased (P ≤ 0.01) by day 120.
Conclusions:
- Increased endometrial microvasculature and altered GR/VEGF expression correlate with mifepristone's contraceptive effect.
- The high incidence of amenorrhoea may stem from mifepristone-induced modifications in endometrial vascular regulation.
- Low-dose mifepristone shows potential as an estrogen-free contraceptive with a favorable bleeding profile.
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