Progesterone receptor modulator eyed for EC
What if you could offer your patients emergency contraception (EC) in a single tablet with one-time dosing? Scientists are looking at CDB-2914, a new progesterone receptor modulator (PRM), that may provide EC in such a dosing regimen.1
Although other emergency contraceptive methods appear to be equally effective even with a single-dose treatment, recent research suggests that this new drug may have improved efficacy as compared to other products as the time from unprotected intercourse increases — specifically beyond 48 hours, says Mitchell Creinin, MD, professor of obstetrics, gynecology, and reproductive sciences and associate professor of epidemiology at the University of Pittsburgh.
"With currently available methods, efficacy decreases as time passes from the act of unprotected intercourse," says Creinin, who serves as lead author of the current paper. "Further studies will be needed that focus on women with longer intervals since unprotected intercourse to see if CDB-2914 truly has advantages."
Check the results
CDB-2914 [17-acetoxy-11-(4-N, N-dimethylaminophenyl)-19-norpregna-4, 9-diene-3,20 dione] is a second-generation progesterone receptor modulator that is akin to mifepristone, a first generation progesterone receptor modulator. To perform the current study, a randomized, double-blinded trial, scientists enrolled 1,672 women seeking emergency contraception within 72 hours of unprotected intercourse. Participants were randomly assigned to receive a single 50 mg dose of CDB-2914, plus a placebo 12 hours later, or two doses of 0.75 mg of levonorgestrel taken 12 hours apart. Follow-up was scheduled five to seven days after the expected onset of the next menstrual period.
Product efficacy data was evaluated in 775 CDB-2914 users and 774 levonorgestrel users. Pregnancies occurred in seven CDB-2914 users (0.9%, 95% confidence interval 0.2-1.6%) and 13 levonorgestrel users (1.7%, 95% confidence interval 0.8-2.6%).1 Based on the estimated cycle day of unprotected intercourse, 85% and 69% of anticipated pregnancies, respectively, were prevented.
When it came to side effects, nausea was reported by 29% of CDB-2914 users, compared to 24% of levonorgestrel users. Distribution of other adverse effects, such as headache, fatigue, and breast tenderness, was similar in both groups. Women in both groups experienced considerable variation in menstrual cycle length as compared with their reported individual normal cycle lengths, the researchers observed.1
CDB-2914 is at least as effective as levonorgestrel in preventing pregnancies after unprotected intercourse and has a similar side effect profile, the scientists concluded.1 Larger studies are necessary to determine whether either treatment will provide better protection from unwanted pregnancy.
Other uses in view
What are some other potential reproductive health uses for CDB-2914? Look to similar applications now studied in mifepristone, such as labor induction and fibroid treatment, says Creinin. More research will be needed to determine its effectiveness in such areas, he notes.
The New York City-based research group The Population Council is looking at the drug as a possible contraceptive, says Régine Sitruk-Ware, MD, the council's executive director of product research and development. Council scientists are testing the drug's effect as a regular contraceptive when delivered from a vaginal ring that would work over three consecutive months, says Sitruk-Ware. The goal is to develop an "estrogen-free, bleeding-free" contraceptive, she states.
"The compound acts in preventing ovulation but does not suppress the endogenous production of estrogen from the woman; therefore, there is no need to add an estrogen in a combination with this PRM," she explains. "In addition, it acts directly on the endometrium to make it atrophic, decrease its thickness, and hence prevents the withdrawal bleeding or 'menses.'"
Similar council research also is aimed at developing an intrauterine system that will ensure contraception via its mechanical properties while delivering a very small dose of CDB 2914 in the uterine cavity, reports Sitruk-Ware. Such drug delivery would avoid any action on ovulation and would serve only to decrease bleeding, she notes.
The council also is looking at use of the drug in vaginal ring or intrauterine system delivery as a potential treatment for fibroids. Researchers performed in vitro culture studies mixing CDB-2914 with cells from uterine fibroids and with cells from normal uterine smooth muscle. They looked at levels of various proteins and checked for growth/nongrowth in cultured cells from tissues taken from women with normal menstrual cycles who underwent fibroid removal or hysterectomy. Results suggest that CDB-2914 may inhibit the growth of uterine fibroids, while having no effect on surrounding healthy smooth muscle.2,3
References
- Creinin MD, Schlaff W, Archer DF, et al. Progesterone receptor modulator for emergency contraception: a randomized controlled trial. Obstet Gynecol 2006; 108:1,089-1,097.
- Xu Q, Ohara N, Chen W, et al. Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells. Hum Reprod 2006; 21:2,408-2,416.
- Xu Q, Takekida S, Ohara N, et al. Progesterone receptor modulator CDB-2914 down-regulates proliferative cell nuclear antigen and Bcl-2 protein expression and up-regulates caspase-3 and poly(adenosine 5'-diphosphate-ribose) polymerase expression in cultured human uterine leiomyoma cells. Clin Endocrinol Metab 2005; 90:953-961.
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