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