Document Detail

Effects of daily low dose mifepristone on endometrial maturation and proliferation.
MedLine Citation:
PMID:  8981147     Owner:  NLM     Status:  MEDLINE    
Following an ovulatory control cycle, six women took 2 mg of mifepristone daily for 30 days. Endometrial biopsies were collected in the control cycle between 7 and 11 days after the plasma luteinizing hormone (LH) surge and on the corresponding day of the treatment cycle (days 19-28). In order to investigate the effects of unopposed oestrogen on the endometrium, persistent proliferative endometrium was obtained from six women with anovulatory infertility due to polycystic ovarian syndrome (PCOS) on a similar cycle day (days 21-23) following a progestogen-induced withdrawal bleed. Endometrium was evaluated for histology and immunolocalization of oestrogen receptors (ER), progesterone receptors (PR) and the cell proliferation markers [proliferating cell nuclear antigen (PCNA) and Ki67]. Treatment with mifepristone inhibited ovulation in four of the six subjects. In the two subjects in whom ovulation did occur, secretory transformation was delayed, suggesting that successful implantation of a blastocyst would be unlikely. In subjects who remained anovulatory during treatment, the histology and pattern of steroid receptor expression was similar to proliferative phase endometrium. In women with PCOS, mitoses and intense immunostaining for ER, PR and cell proliferation markers were observed in both glands and stroma. Although PCNA and Ki67 immunostaining were also present in mifepristone-treated endometrium from subjects who did not ovulate, there were no mitoses and significantly less ER immunostaining in spite of exposure to unopposed oestrogen for a similar duration. Since PCNA and Ki67 detect cells throughout all stages of the cell cycle this would suggest that mifepristone might affect the entry of cells into the mitotic phase of the cell cycle and, therefore, might prevent endometrial hyperplasia. These findings add further evidence to support the contraceptive potential and antiproliferative activity of daily low dose mifepristone.
S T Cameron; H O Critchley; K J Thong; C H Buckley; A R Williams; D T Baird
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human reproduction (Oxford, England)     Volume:  11     ISSN:  0268-1161     ISO Abbreviation:  Hum. Reprod.     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1997-03-20     Completed Date:  1997-03-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8701199     Medline TA:  Hum Reprod     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2518-26     Citation Subset:  IM    
Department of Obstetrics and Gynaecology, University of Edinburgh, UK.
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MeSH Terms
Cell Division / drug effects
Endometrium / chemistry,  cytology*,  drug effects*
Estradiol / blood
Hormone Antagonists / pharmacology*
Ki-67 Antigen / analysis
Mifepristone / administration & dosage*
Ovulation / drug effects
Polycystic Ovary Syndrome
Progesterone / antagonists & inhibitors
Proliferating Cell Nuclear Antigen / analysis
Receptors, Estrogen / analysis
Receptors, Progesterone / analysis
Reg. No./Substance:
0/Hormone Antagonists; 0/Ki-67 Antigen; 0/Proliferating Cell Nuclear Antigen; 0/Receptors, Estrogen; 0/Receptors, Progesterone; 50-28-2/Estradiol; 57-83-0/Progesterone; 84371-65-3/Mifepristone

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