From the Journals

Ulipristal reduces bleeding with contraceptive implant

 

Key clinical point: Ulipristal acetate reduced unscheduled bleeding days in women with etonogestrel implants.

Major finding: Treatment with ulipristal was associated with 5 fewer bleeding days per month, compared with placebo (P = .002).

Study details: The double-blind, placebo-controlled trial involved 65 women with etonogestrel implants who reported more than one bleeding episode in a 24-day time frame.

Disclosures: The study was funded by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences (NCATS). The authors reported financial disclosures related to Bayer and Merck.

Source: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.

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Ulipristal requires a closer look

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.

Dr. Eve Espey of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque

Dr. Eve Espey

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.


 

FROM OBSTETRICS & GYNECOLOGY

Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.

After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.

About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.

“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.

Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”

The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.

Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.

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