The recent trial by Zigler et al. showed that ulipristal acetate may reduce bleeding days in contraceptive implant users, but larger studies are needed, and concerns about logistics, dose, and toxicity must be addressed before clinical roll out, according to Eve Espey, MD.
In the study, women with bothersome bleeding received ulipristal 15 mg or placebo for 7 days. A 30-day follow-up period evaluated number of bleeding days and satisfaction with treatment. “Results indicated that women randomized to ulipristal acetate had fewer bleeding days and higher satisfaction than women in the placebo group,” Dr. Espey said. “The authors are to be applauded for conducting the first study to investigate use of ulipristal acetate to reduce bothersome bleeding with the contraceptive implant. Although the findings are promising, there are several reasons that ulipristal should not yet be used in clinical practice for this indication: The study is small and only followed participants for 30 days – larger confirmatory studies of longer duration and possibly with lower medication dose with the outcome measure of implant discontinuation would strengthen the results; because ulipristal is only Food and Drug Administration approved for emergency contraception, it is currently available only as a 30 mg pill, making it inconvenient to use the studied dosage, and as above, it’s possible that a lower dose of the medication could be effective. Finally, the study was halted because of concerns identified with ulipristal acetate used for another indication in a different dose; liver effects of ulipristal should undergo more study.”
The FDA halted the present trial after another ulipristal study overseas detected liver toxicity. The overseas study (for uterine leiomyoma) involved daily administration of ulipristal (5 mg) for 3 months, which is significantly longer than the present study for breakthrough bleeding. The European Medicines Agency has since determined that women with liver issues should not receive ulipristal and that others should have close liver monitoring before, during, and after ulipristal therapy.
Despite the above concerns, ulipristal still holds promise for a common clinical problem.
“This study contributes to the literature on management of bothersome bleeding with the contraceptive implant,” Dr. Espey said. “It is an important area because bothersome bleeding leads both to dissatisfaction and method discontinuation. As a recent Cochrane review pointed out, although several different medications have been used, studies are small and not yet conclusive. Despite these caveats, the findings were promising, similar to findings of prior work with a similar compound, mifepristone. Future directions would include clinical trials utilizing ulipristal acetate in a larger population powered for discontinuation.”
Dr. Espey is a professor in and chair of the department of obstetrics and gynecology and the family planning fellowship director at the University of New Mexico, Albuquerque. These comments are adapted from an interview. Dr. Espey said she had no relevant financial disclosures.
