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Stimulation of epithelial repair is a likely mechanism for the action of mifepristone in reducing duration of bleeding in users of progestogen-only contraceptives.

N Morison, Prince Henry's Institute, Melbourne, Australia
T Kaitu'u-Lino, Prince Henry's Institute, Melbourne, Australia
I Fraser, FPA Health, Sydney Centre for Reproductive Health Research, Sydney, Australia
L Salamonsen, Prince Henry's Institute, Melbourne, 3168, Australia

Correspondence: Lois Salamonsen, Email: lois.salamonsen{at}princehenrys.org

Abstract

Many women using progestagen (P)-only contraceptives experience uterine bleeding problems. In clinical trials, a single low dose of mifepristone, given to Implanon users at the beginning of a bleeding episode reduced the number of bleeding days by 50% compared to controls. In this study, a single dose of mifepristone was administered to etonogestrel-exposed, pseudopregnant mice, 5 days after artificial decidualization was induced when the endometrium showed signs of bleeding. Control mice received vehicle alone. Mice were culled 12, 18, 24 and 48 hours post-treatment. In the continued presence of etonogestrel, a single dose of mifepristone stimulated tissue breakdown followed by very rapid repair: most treated tissues were fully restored to the pre-decidualised state by 48h post-treatment. During repair, proliferating cells (Ki67 immunostained) were localized to a band of cells around the basal area in breaking-down tissues and to the repairing luminal epithelium and glands. Progesterone receptor positive cells were largely localized to the basal area of the breaking-down tissue in treated mice, compared to decidual cells in controls. Oestrogen receptor positive cells were observed in the repairing luminal epithelium and glands compared to the decidua and the basal region in control tissues. It is concluded that mifepristone treatment stimulates rapid restoration of luminal epithelial integrity: such action may be a key event in reducing the number of bleeding days observed in women using Implanon who were treated with a single dose of mifepristone.