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Abstract / Description of output
BACKGROUND: We have previously shown that the progesterone antagonist mifepristone is a contraceptive when given in a dose of 2 or 5 mg per day. The majority of women experience amenorrhoea rather than the irregular break through bleeding usually occurring with other estrogen-free contraceptive pills, such as progestogen-only pill (POP). We investigated the effects of low-dose mifepristone on endometrial parameters which may be associated with changes in endometrial function, such as microvasculature, vascular endothelial growth factor (VEGF) and glucocorticoid receptor (GR) content.
METHODS AND RESULTS: Endometrial biopsies were collected from 16 women before (late proliferative phase) and 60 and 120 days after taking 2 or 5 mg mifepristone daily for 120 days. Seven of the eight women who received 2 mg mifepristone and all eight women who received 5 mg were amenorrhoeic during the study. Mean estradiol (E(2)) concentrations remained in the mid-proliferative range, and the majority (9/16) of women showed proliferative endometrial histology at 60 and 120 days following treatment. There was a significant increase in the density of the endometrial stroma (P < 0.05) and microvessels (P < 0.01) following 120 days of treatment. Immunocytochemistry showed that GR, hitherto localized specifically in endometrial stroma, was up-regulated in the nuclei of glands (P < 0.05) and surface (luminal) epithelium (P < 0.01) by 60 days and maintained at 120 days. There was a significant reduction in stromal VEGF protein expression by day 120 of treatment (P < or = 0.01).
CONCLUSION: The high incidence of amenorrhoea in women taking mifepristone may be related to changes in the regulation of vascular function.
Keywords / Materials (for Non-textual outputs)
- Antigens, CD31
- Cell Proliferation
- Contraceptive Agents
- Contraceptives, Oral, Synthetic
- Receptors, Glucocorticoid
- Vascular Endothelial Growth Factor A
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- 1 Finished
1/08/00 → 31/07/05