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.
Brenner
Robert M
RM
Division of Reproductive Sciences, Oregon National Primate Research Center, OHSU, Beaverton, OR 97006, USA. brennerr@ohsu.edu
Slayden
Ov D
OD
Nath
Anita
A
Tsong
Y Y
YY
Sitruk-Ware
Regine
R
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