Intrauterine administration of CDB-2914 (Ulipristal) suppresses the endometrium of rhesus macaques (HTML)
Brenner,Robert M.; Slayden,Ov D.; Nath,Anita; Tsong,Yun-yen; Sitruk-Ware,Regine
Contraception 81(4): 336-342
Publication date: 2010
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.
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.
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.
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.
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