Tamoxifen for the prevention of unscheduled bleeding in new users of the Levonorgestrel 52 mg intrauterine system: a randomized controlled trial

Abstract Objective To determine if a course of oral tamoxifen initiated following placement of a levonorgestrel 52 mg intrauterine system (IUS) reduces bleeding/spotting days over 30 days. Study design In this single-center, double-blind, placebo-controlled trial, we recruited women ages 15–45 years initiating the levonorgestrel 52 mg IUS. We randomized eligible women to tamoxifen 10 mg or placebo twice daily for 7 days starting 21 days after levonorgestrel 52 mg IUS insertion. Participants tracked bleeding/spotting days via daily electronic diaries for 30 days after starting drug treatment. We assessed participant satisfaction with their bleeding pattern and the IUS using a visual analog scale (0-100 mm). A sample size of 42 provided 80% power to detect a difference of 7 bleeding/spotting days in 30 days by two-sample t -test, accounting for an expected 20% dropout rate. Results From September 2016 to January 2018, 42 women enrolled. A total of 34 women provided complete bleeding/spotting data, and 30 women provided satisfaction data. Mean bleeding/spotting days over 30 days did not differ between tamoxifen (12.0±5.8 days) and placebo users (16.8±9.0 days), p=.08. We found no significant differences in mean satisfaction with bleeding profiles (51 mm tamoxifen vs. 59 mm placebo, p=.48) or with the IUS (83 mm vs. 75 mm, p=.36) between groups. Both groups reported similar rates of adverse events, with no serious adverse events reported. Conclusion A course of oral tamoxifen did not improve early breakthrough bleeding or satisfaction in new users of the levonorgestrel 52 mg IUS. Implications. Although tamoxifen treatment caused a trend toward modest bleeding/spotting day reduction in new levonorgestrel 52 mg IUS users, bleeding satisfaction did not improve. Future studies of tamoxifen treatment for IUS-related bleeding issues may be best targeted toward users with ongoing bleeding irregularities or lower-dose IUS products which cause more bleeding irregularities.