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

Robert M. Brenner; Ov D. Slayden; Anita Nath; Y. Y. Tsong; Regine Sitruk-Ware

doi:10.1016/j.contraception.2009.11.004

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

Robert M. Brenner
, Ov D. Slayden
, Anita Nath
, Y. Y. Tsong
, Regine Sitruk-Ware

Oregon National Primate Research Center

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

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.

Original language	English (US)
Pages (from-to)	336-342
Number of pages	7
Journal	Contraception
Volume	81
Issue number	4
DOIs	https://doi.org/10.1016/j.contraception.2009.11.004
State	Published - Apr 2010

Funding

We thank Kunie Mah for her expert work in immunocytochemistry, Andrea Lawson for help with computerized morphometrics, and the morphology core of the Eunice Kennedy Shriver NICHD/NIH Cooperative Agreement U54 (HD 18185) for histology support. This work was further supported by NIH grants RR00163 and HD 43209 as well as the Population Council .

Funders	Funder number
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	HD 43209, RR00163
Population Council
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health	P30HD018185

Keywords

CDB-2914
Endometrium
Intrauterine
Rhesus macaque
Ulipristal

ASJC Scopus subject areas

Reproductive Medicine
Obstetrics and Gynecology

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10.1016/j.contraception.2009.11.004

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@article{328ed258f8ce4cfea896170dba26be67,

title = "Intrauterine administration of CDB-2914 (Ulipristal) suppresses the endometrium of rhesus macaques",

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, Endometrium, Intrauterine, Rhesus macaque, Ulipristal",

author = "Brenner, \{Robert M.\} and Slayden, \{Ov D.\} and Anita Nath and Tsong, \{Y. Y.\} and Regine Sitruk-Ware",

note = "Funding Information: We thank Kunie Mah for her expert work in immunocytochemistry, Andrea Lawson for help with computerized morphometrics, and the morphology core of the Eunice Kennedy Shriver NICHD/NIH Cooperative Agreement U54 (HD 18185) for histology support. This work was further supported by NIH grants RR00163 and HD 43209 as well as the Population Council .",

year = "2010",

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doi = "10.1016/j.contraception.2009.11.004",

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volume = "81",

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journal = "Contraception",

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T1 - Intrauterine administration of CDB-2914 (Ulipristal) suppresses the endometrium of rhesus macaques

AU - Brenner, Robert M.

AU - Slayden, Ov D.

AU - Nath, Anita

AU - Tsong, Y. Y.

AU - Sitruk-Ware, Regine

N1 - Funding Information: We thank Kunie Mah for her expert work in immunocytochemistry, Andrea Lawson for help with computerized morphometrics, and the morphology core of the Eunice Kennedy Shriver NICHD/NIH Cooperative Agreement U54 (HD 18185) for histology support. This work was further supported by NIH grants RR00163 and HD 43209 as well as the Population Council .

PY - 2010/4

Y1 - 2010/4

N2 - 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.

AB - 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.

KW - CDB-2914

KW - Endometrium

KW - Intrauterine

KW - Rhesus macaque

KW - Ulipristal

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SN - 0010-7824

VL - 81

SP - 336

EP - 342

JO - Contraception

JF - Contraception

IS - 4

ER -

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

Abstract

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Keywords

ASJC Scopus subject areas

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