To evaluate whether ulipristal acetate reduces the number of bleeding days in etonogestrel implant users in a 30-day period as compared with placebo.
We performed a single-center, randomized, double-blind, placebo-controlled trial. Eligible participants were women aged 18–45 years with an etonogestrel implant in place for greater than 90 days and less than 3 years who reported greater than one bleeding episode in a 24-day period. Enrolled participants were randomized to receive 15 mg ulipristal acetate compared with an identical-appearing placebo daily for 7 days. Participants completed daily bleeding diaries using automated text messaging to evaluate whether ulipristal acetate reduces the number of bleeding days as compared with placebo. Secondary outcomes included participant satisfaction with bleeding and the effect of ulipristal acetate on ovulation status. A sample size of 52 per group (n=104) was planned, calculated with an effect size of a 30% reduction in bleeding days, SD of 10 days, and dropout of 15%. Our study was terminated early (N=65) as a result of a U.S. Food and Drug Administration hold, but power was sufficient for analysis. The effect of ulipristal acetate on ovulatory potential was evaluated in a subset with weekly serum progesterone.
From May 2017 to January 2018, 65 women were allocated to receive 15 mg ulipristal acetate (n=32) or placebo (n=33) daily for 7 days. Demographic characteristics were similar between groups. Women randomized to ulipristal acetate reported 5 fewer days of bleeding over a 30-day reference period after treatment (P=.002). At the conclusion of the 30-day follow-up period, women in the ulipristal acetate group were more satisfied with their bleeding profile than the placebo group (87.5% vs 60%, respectively; P<.001). Serum progesterone levels were nonovulatory in a subset of each group (placebo group range: less than 0.2–1.3 ng/mL; ulipristal acetate group range: less than 0.2–4.4 ng/mL).
Ulipristal acetate is well-tolerated and reduced the number of bleeding days in etonogestrel implant users in our study.
Ulipristal acetate decreases the amount of bleeding days in etonogestrel contraceptive implant users in a 30-day period compared with placebo.
Department of Obstetrics and Gynecology, Division of Clinical Research and Family Planning, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Corresponding author: Rachel E. Zigler, MD, MSCI, 4901 Forest Park Avenue, Mailstop 8064-37-1005, St. Louis, MO 63108; email: firstname.lastname@example.org.
Supported by the Society of Family Planning Research Fund grant SFPRF17-18. Research reported in this publication was also supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR000448 from the National Center for Advancing Translational Sciences (NCATS).
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The REDCap program was used, which is supported by Clinical and Translational Science Award (CTSA) Grant UL1TR000448 and Siteman Comprehensive Cancer Center and National Cancer Institute Cancer Center Support Grant P30 CA091842.
Financial Disclosure Dr. Madden serves on a scientific advisory board for Bayer Healthcare Pharmaceuticals and on a data safety monitoring board for phase 4 safety studies of Bayer contraceptive products. Dr. McNicholas receives research support from Merck and serves on the Merck Global Advisory Board for Contraception. The other authors did not report any potential conflicts of interest.
Presented at the Fellowship in Family Planning Annual Meeting, June 3, 2018, Salt Lake City, Utah.
Each author has indicated that he or she has met the journal's requirements for authorship.
Received May 03, 2018
Received in revised form June 13, 2018
Accepted June 21, 2018