Luteal phase dose-response relationships of the antiprogestin CDB-2914 in normally cycling women

Passaro, Maureen

doi:10.1093/humrep/deg342

Cited by 35 publications

(44 citation statements)

References 42 publications

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“…Although reports are conflicting, one study suggested that endometrial hyperplasia was more frequent in postmenopausal women treated for 6 weeks with oral estradiol at 1 mg/day plus 10 mg/day or 50 mg/day of ulipristal acetate, than in those treated with estradiol plus placebo or medroxyprogesterone. Based on this finding, it appears that PR antagonism by ulipristal acetate can increase the estradiol-induced effects of endometrial proliferation in postmenopausal women (Passaro et al, 2003;Levens et al, 2008;Spitz, 2009;Stratton et al, 2010;Nieman et al, 2011).…”

Section: Selective Progesterone Receptor Modulatorsmentioning

confidence: 84%

Nuclear Receptors and Their Selective Pharmacologic Modulators

et al. 2013

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Section: Selective Progesterone Receptor Modulatorsmentioning

confidence: 84%

Nuclear Receptors and Their Selective Pharmacologic Modulators

et al. 2013

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“…It binds the human progesterone but not the estrogen receptor. 7,8 Although structurally similar to mifepristone, CDB-2914 has less antiglucocorticoid activity, providing a potential advantage for long-term use. The goal of this study was to evaluate whether chronic daily administration of CDB-2914 at 10 mg or 20 mg is an effective treatment for women with uterine leiomyomata.…”

Section: Clinical Trial Registrationmentioning

confidence: 99%

CDB-2914 for Uterine Leiomyomata Treatment: A Randomized Controlled Trial

Levens

Nieman

2008

Obstetrics &Amp; Gynecology

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OBJECTIVE-To evaluate whether 3-month administration of CDB-2914, a selective progesterone receptor modulator, reduces leiomyoma size and symptoms.METHODS-Premenopausal women with symptomatic uterine leiomyomata were randomly assigned to CDB-2914 at 10 mg (T1) or 20 mg (T2) daily or to placebo (PLC) for 3 cycles or 90-102 days if no menses occurred. The primary outcome was leiomyoma volume change determined by magnetic resonance imaging at study entry and within 2 weeks of hysterectomy. Secondary outcomes included the proportion of amenorrhea, change in hemoglobin and hematocrit, ovulation inhibition, and quality-of-life assessment. RESULTS-Twenty-two patients were allocated, and 18 completed the trial. Age and body mass index were similar among groups. Leiomyoma volume was significantly reduced with CDB-2914 administration (PLC 6%; CDB-2914 −29%; P=.01), decreasing 36% and 21% in the T1 and T2 groups, respectively. During treatment, hemoglobin was unchanged, and the median estradiol was greater than 50 pg/mL in all groups. CDB-2914 eliminated menstrual bleeding and inhibited ovulation (% ovulatory cycles: CDB-2914, 20%; PLC, 83%; P=.001). CDB-2914 improved the concern scores of the uterine leiomyoma symptom quality-of-life subscale (P=.04). One CDB-2914 woman developed endometrial cystic hyperplasia without evidence of atypia. No serious adverse events were reported.CONCLUSION-Compared with PLC, CDB-2914 significantly reduced leiomyoma volume after three cycles, or 90-102 days. CDB-2914 treatment resulted in improvements in the concern subscale of the Uterine Fibroid Symptom Quality of Life assessment. In this small study, CDB-2914 was welltolerated without serious adverse events. Thus, there may be a role for CDB-2914 in the treatment of leiomyomata. Copyright © American College of Obstetricians and GynecologistsCorresponding author: Lynnette K. Nieman, MD, Reproductive Biology and Medicine Branch, NICHD, NIH, Building 10, CRC, Room E1-3140, 10 Center Drive, Bethesda, MD 20892; e-mail: niemanl@mail.nih.gov). Presented in part at the 54th Annual Meeting of the Society for Gynecologic Investigation, Reno, Nevada, March 14-17, 2007. Financial DisclosureThe authors have no potential conflicts of interest to disclose. Uterine leiomyomata are the most common benign soft tissue tumors in women and frequently cause excessive uterine bleeding, chronic pelvic pain/pressure, and dyspareunia. 1 Hysterectomy remains the major therapeutic option for leiomyomata, resulting in more than 200,000 cases per year. 2 Despite the increasing use of uterus-preserving procedures, 3 the overall invasive procedure rate for leiomyomata is unchanged, highlighting the paucity of effective, longterm medical therapies. CLINICAL TRIAL REGISTRATION:Because gonadal hormones induce or maintain leiomyoma growth, 4,5 selective progesterone receptor modulators have been evaluated as therapeutic agents. When given for 3-6 months, mifepristone reduced leiomyoma size and symptoms and induced amenorrhea in 63-100% of women. 6 However, there was...

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“…The first steroidal PR antagonist to be developed was mifepristone (RU486), which is marketed since 1988 in France and since 2000 in USA. Despite its high potency in antagonizing the action of P4 in subnanomolar concentration ranges, RU486 binds to and inactivates the glucocorticoid receptor (GR), to a lesser extent the androgen receptor (AR), and weakly the mineralocorticoid receptor (MR) [3][4][5][6][7][8]. Other steroidal compounds were then developed by pharmaceutical companies, which were intended to reduce their cross-reactivity with the other oxo-steroid receptors [9].…”

Section: Introductionmentioning

confidence: 99%