Mifepristone-induced amenorrhoea is associated with an increase in microvessel density and glucocorticoid receptor and a decrease in stromal vascular endothelial growth factor

Nitish Narvekar, Hilary O D Critchley, Linan Cheng, David T Baird

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2312-8
Number of pages7
JournalHuman Reproduction
Volume21
Issue number9
DOIs
Publication statusPublished - Sep 2006

Keywords

  • Amenorrhea
  • Antigens, CD31
  • Cell Proliferation
  • Contraceptive Agents
  • Contraceptives, Oral, Synthetic
  • Endometrium
  • Female
  • Glucocorticoids
  • Humans
  • Immunohistochemistry
  • Microcirculation
  • Mifepristone
  • Receptors, Glucocorticoid
  • Vascular Endothelial Growth Factor A

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