Contraception
Volume 81, Issue 4 , Pages 336-342, April 2010

Intrauterine administration of CDB-2914 (Ulipristal) suppresses the endometrium of rhesus macaques

  • Robert M. Brenner

      Affiliations

    • Division of Reproductive Sciences, Oregon National Primate Research Center, OHSU, Beaverton, OR 97006, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 503 690 5331; fax: +1 503 690 5532.
    • ,
  • Ov D. Slayden

      Affiliations

    • Division of Reproductive Sciences, Oregon National Primate Research Center, OHSU, Beaverton, OR 97006, USA
    • ,
  • Anita Nath

      Affiliations

    • Center for Biomedical Research, Population Council, New York, NY 10065, USA
    • ,
  • Y.Y. Tsong

      Affiliations

    • Center for Biomedical Research, Population Council, New York, NY 10065, USA
    • ,
  • Regine Sitruk-Ware

      Affiliations

    • Research and Development, Center for Biomedical Research, Population Council and The Rockefeller University, New York, NY 10065, USA

Received 8 September 2009; received in revised form 6 November 2009; accepted 10 November 2009. published online 17 December 2009.

Abstract 

Background

Ulipristal (UPA; CDB-2914) is a progesterone receptor modulator with contraceptive potential. To test its effects when delivered by an intrauterine system (IUS), we prepared control and UPA-filled IUS and evaluated their effects in rhesus macaques.

Study Design

Short lengths of Silastic tubing either empty (n=3) or containing UPA (n=5) were inserted into the uteri of 8 ovariectomized macaques. Animals were cycled by sequential treatment with estradiol and progesterone. After 3.5 cycles, the uterus was removed.

Results

During treatment, animals with an empty IUS menstruated for a mean total of 11.66±0.88 days, while UPA-IUS treated animals bled for only 1±0.45 days. Indices of endometrial proliferation were significantly reduced by UPA-IUS treatment. The UPA exposed endometria were atrophied with some glandular cysts while the blank controls displayed a proliferative morphology without cysts. Androgen receptors were more intensely stained in the glands of the UPA-IUS treated endometria than in the blank-IUS treated controls.

Conclusions

In rhesus macaques, a UPA-IUS induced endometrial atrophy and amenorrhea. The work provides proof of principle that an IUS can deliver effective intrauterine concentrations of Ulipristal.

Keywords: CDB-2914, Ulipristal, Intrauterine, Rhesus macaque, Endometrium

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PII: S0010-7824(09)00488-0

doi:10.1016/j.contraception.2009.11.004

Contraception
Volume 81, Issue 4 , Pages 336-342, April 2010

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