Endometrial effects of a single early luteal dose of the selective progesterone receptor modulator CDB-2914.
OBJECTIVE
To test potential contraceptive mechanisms of the selective P receptor modulator CDB-2914 in the early luteal phase.


METHODS
Prospective randomized clinical trial.


METHODS
Clinical research center.


METHODS
Fifty-six women with regular cycles.


METHODS
Women received a single dose of CDB-2914 (10, 50, or 100 mg) or placebo given after ovulation and within 2 days of the LH surge. Four to 6 days later, a transvaginal ultrasound scan measured endometrial thickness, and an endometrial biopsy specimen was obtained.


METHODS
The endometrium was evaluated by thickness and by immunohistochemical analysis for P-dependent markers; safety laboratory tests were performed, and E(2) and P levels were obtained.


RESULTS
CDB-2914 caused a significant dose-dependent decrease in endometrial thickness, an increase in glandular P receptors, and a decrease in peripheral node addressins. Estradiol and P levels and menstrual cycle timing were not altered. No adverse effects were observed.


CONCLUSIONS
The alteration in endometrial thickness and P-dependent markers of implantation in the absence of changes in hormone levels and cycle length suggests that CDB-2914 may have contraceptive properties.
Stratton
Pamela
P
Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892-1109, USA.
Levens
Eric D
ED
Hartog
Beth
B
Piquion
Johann
J
Wei
Qingxiang
Q
Merino
Maria
M
Nieman
Lynnette K
LK
D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008183:Luteal Phase / Q000097:blood / Q000187:drug effects* / Q000502:physiology; D009649:Norpregnadienes / Q000008:administration & dosage* / Q000009:adverse effects; D009929:Organ Size / Q000187:drug effects; D010919:Placebos; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000009:adverse effects; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D014463:Ultrasonography; D055815:Young Adult
D012739:Gonadal Steroid Hormones; D006727:Hormone Antagonists; D009649:Norpregnadienes; D010919:Placebos; D045167:Progesterone Congeners; D011980:Receptors, Progesterone; C094854:ulipristal