Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel

Liu, Cheng; Zhu, Han; Wang, A.; Ren, Fangming; Chen, J.; Glasier, A

doi:10.1093/humrep/15.9.1969

Cited by 80 publications

(37 citation statements)

References 9 publications

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“…In women, chronic oral administration of mifepristone suppressed endometrial mitotic activity, induced amenorrhea, and was contraceptive [11]. Periodic treatment with mifepristone in women treated with Norplant reduced BTB [12].…”

Section: Introductionmentioning

confidence: 99%

Antiprogestin-releasing intrauterine devices: a novel approach to endometrial contraception

et al. 2007

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Intrauterine devices (IUDs) that release progestins are highly effective contraceptives, but they induce breakthrough bleeding that some women find unacceptable. Because progesterone (P) antagonists (AP) are known to suppress the endometrium, induce amenorrhea, and inhibit fertility, AP IUDs may provide an effective contraceptive that also controls endometrial bleeding. Here we assessed the effects of empty (blank) vs AP-releasing (ZK 230 211) IUDs on bleeding patterns and endometrial growth in ovariectomized, artificially cycled macaques. The AP IUDs (but not the blank controls) induced extended, frank menstruation when inserted during the late luteal phase, an indication of local AP action. Over time, endometrial glandular and arterial proliferation were inhibited, steroid receptors were elevated, spiral arteries showed degenerative changes, progesterone withdrawal bleeding was prevented and estradiol-dependent proliferation was suppressed by the AP IUDs. In sum, AP IUDs suppressed the effects of P on endometrial progestational development and blocked the effects of estradiol on endometrial proliferation as previously shown for systemic treatment with APs. Therefore, AP IUDs may provide novel contraceptive devices with minimal breakthrough bleeding.

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Section: Introductionmentioning

confidence: 99%

Antiprogestin-releasing intrauterine devices: a novel approach to endometrial contraception

et al. 2007

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“…A recent clinical trial in Australia has shown that a single Mifepristone restores endometrial epithelial integrity low dose of mifepristone reduces the number of days of a bleeding episode when administered to Implanon users early within this episode (Weisberg et al 2006), supporting earlier studies in Chinese women using Norplant and complaining of frequent and irregular bleeding. In these women, a single monthly dose of mifepristone reduced the length of bleeding episodes over a 90-d treatment period (Cheng et al 2000). Although the mechanisms by which anti-progestogens reduce bleeding episodes has not been understood, the functional experiments described in the present study suggest that mifepristone, by stimulating tissue breakdown, induces very rapid repair, particularly re-epithelialization of the endometrium, thus restoring epithelial integrity and stopping the bleeding.…”

Section: Discussionmentioning

confidence: 49%

“…Importantly, treatment with EE renders the idea of a progestogen only and therefore oestrogen-free contraceptive regime futile. By contrast, short-term administration of the anti-progestogen, mifepristone, has been successful in reducing bleeding days in women using P-only contraception in a number of independent studies (Cheng et al 2000, Glasier et al 2002, Jain et al 2003, Massai et al 2004, Weisberg et al 2006. A further reduction in the bleeding days was observed upon mifepristone treatment in conjunction with oestrogen (Weisberg et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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Many women using progestogen (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 w50% compared with controls. In this study, a single dose of mifepristone was administered to etonogestrel (ENG)-exposed pseudo-pregnant 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-h post-treatment. In the continued presence of ENG, a single dose of mifepristone stimulated tissue breakdown followed by very rapid repair: most treated tissues were fully restored to the pre-decidualized state by 48 h 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 with decidual cells in controls. Oestrogen receptor-positive cells were observed in the repairing luminal epithelium and glands compared with 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.

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“…1000 mg) durchgeführt. Die Ergebnisse waren sehr ermutigend und zeigten dem damals noch üblichen Yuzpe-Regime [5,20]. Ähn-lich günstige Ergebnisse konnten auch mit anderen neuren Antigestagenen, wie z.…”

Section: Mifepriston Zur Notfallkontrazeptionunclassified

Antigestagene

Schwenkhagen¹,

Schaudig²

2008

Gynäkologische Endokrinologie

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Antigestagene Neue Einsatzmöglichkeiten in der GynäkologieLeitthema Progesteron spielt für den Eintritt und den Erhalt einer Schwanger schaft eine wichtige Rolle. Da Anti gestagene die Effekte von Progeste ron antagonisieren können, stellen sie eine Gruppe hochinteressanter Substanzen dar, die nicht nur zum Schwangerschaftsabbruch bzw. zur Abortinduktion, sondern auch zur Fa milienplanung eingesetzt werden könnten.

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Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel

Cited by 80 publications

References 9 publications

Antiprogestin-releasing intrauterine devices: a novel approach to endometrial contraception

Antiprogestin-releasing intrauterine devices: a novel approach to endometrial contraception

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

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