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.

Trial registration: ClinicalTrials.gov NCT02824224.

Keywords: Contraception; Levonorgestrel intrauterine system; Tamoxifen; Unscheduled bleeding.

Conflict of interest statement

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

Fig. 1.

CONSORT 2010 flow diagram for a randomized, placebo-controlled trial investigating a 7-day course of tamoxifen for prevention of unscheduled bleeding in new users of the levonorgestrel 52-mg IUS.

Fig. 2.

Box and whisker plot of number of bleeding/spotting days over 30 days after initiation of study drug by study group for 34 participants in a randomized, placebo-controlled trial investigating a 7-day course of tamoxifen for prevention of unscheduled bleeding in new users of the levonorgestrel 52-mg IUS.