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


METHODS
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.
Division of Reproductive Sciences, Oregon National Primate Research Center, OHSU, Beaverton, OR 97006, USA. brennerr@ohsu.edu
Robert M
RM
Brenner
Ov D
OD
Slayden
Anita
A
Nath
Y Y
YY
Tsong
Regine
R
Sitruk-Ware
D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D005260:Female; D007434:Intrauterine Devices; D008253:Macaca mulatta; D008598:Menstruation / Q000187:drug effects*; D009649:Norpregnadienes / Q000008:administration & dosage* / Q000009:adverse effects; D011944:Receptors, Androgen / Q000378:metabolism; D014599:Uterus
D003271:Contraceptive Agents, Female; D009649:Norpregnadienes; D011944:Receptors, Androgen; C094854:ulipristal