Tamoxifen for the treatment of breakthrough bleeding with the etonogestrel implant: a randomized controlled trial

Abstract Objective The etonogestrel (ENG) subdermal implant can cause frequent breakthrough bleeding in some users. The objective of this study was to evaluate whether a short course of tamoxifen reduces bleeding/spotting days compared to placebo in ENG implant users. Study design In this double-blind trial, we randomized ENG implant users with frequent or prolonged bleeding or spotting to tamoxifen 10 mg or placebo twice daily for 7 days, to be started after 3 consecutive days of bleeding/spotting. Treatment was repeated as needed up to three times in 180 days. Subjects completed a daily text message bleeding diary. A sample size of 56 provided 80% power to detect a difference of 6 days of bleeding/spotting per 30 days by two-sample t test. Ovulation was monitored by urinary metabolites of progesterone. Results From March 2014 to February 2015, 56 women enrolled. Fifty-one completed at least 30 days of follow up, and 34 completed 180 days. Compared to women randomized to placebo, women randomized to tamoxifen reported 5 fewer days of bleeding/spotting over 30 days (95% confidence interval [CI] −9.9 to −0.05, p=.05), and 15.2 more continuous bleeding-free days (95% CI 2.8–27.5 days, p=.02) after first use of study drug. Conclusions could not be drawn after 30 days due to higher-than-expected dropout. No ovulation was detected. Conclusion First use of tamoxifen by ENG implant users reduces bleeding/spotting days and provides a longer cessation of bleeding/spotting than placebo, without compromising ovulation suppression. Further study is needed to determine whether this effect is maintained with repeat use. Implications Women with frequent ENG implant-related breakthrough bleeding may experience a reduction in bleeding/spotting days and an increase in continuous bleeding-free days in the month following first use of tamoxifen. This short course of tamoxifen was well tolerated with bleeding cessation noted within a median of 5 days.