Treatment of Unfavorable Bleeding Patterns in Contraceptive Implant Users: A Randomized Controlled Trial

Abstract

Objective: To evaluate whether a short course of tamoxifen decreases bothersome bleeding in etonogestrel contraceptive implant users.

Methods: In a 90-day, double-blind randomized control trial, we enrolled etonogestrel implant users with frequent or prolonged bleeding or spotting. A sample size of 40 per group (N=80) was planned to compare 10 mg tamoxifen or placebo twice daily for 7 days after 3 consecutive days of bleeding or spotting no more than once per 30 days (maximum three treatments). Participants then entered a 90-day open-label study where all received tamoxifen if needed every 30 days (maximum three treatments). Participants used text messages to record daily bleeding patterns. Our primary outcome was the total number of consecutive amenorrhea days after the first treatment. Secondary outcomes included time to bleeding or spotting cessation and restart after first treatment, overall bleeding patterns, and satisfaction.

Results: From January 2017 to November 2018, 112 women enrolled in the study; 88 (79%) completed 90 days, and 79 (71%) completed 180 days. Participant characteristics did not differ between groups; mean age 24, majority identified as white not Hispanic with at least some college education. After the first treatment, the tamoxifen group reported an average of 9.8 (95% CI 4.6-15.0) more consecutive days of amenorrhea and more total days of no bleeding (amenorrhea or spotting) in the first 90 days (median 73.5 [range 24-89] vs 68 [range 11-81], P=.001). The placebo group showed a similar treatment benefit after first active use of tamoxifen in the open-label phase. At the end of the randomized study (first 90 days), women who received tamoxifen reported higher satisfaction (median 62 mm [range 16-100]) than those treated with placebo (46 mm [range 0-100]; P=.023).

Conclusion: A short course of tamoxifen reduces problematic bleeding and improves satisfaction in users of etonogestrel implants.

Clinical trial registration: ClinicalTrials.gov, NCT02903121.

Figures

Figure 1.

Consort flow diagram. The timing of treatments was dictated by each participant’s individual bleeding patterns. Consequently, the number of participants completing each treatment does not match the numbers completing each 30- or 90-day period reported in the text.

Figure 2.

Kaplan-Meier curves for time to restart bleeding (in days) after cessation following the first study treatment in the randomized phase of the study (red and blue lines) and after the placebo group received their first active tamoxifen treatment (green line). The groups that received active tamoxifen treatment had a similar response with a prolonged period of amenorrhea as compared to placebo.

Figure 3.

Percentage of participants that took each treatment, with total number in each group at the beginning of each treatment (at top of bar). All participants had to experience 3 days of bleeding or spotting at the beginning of the study within 30 days of enrollment; otherwise, they were withdrawn. Study drug could be taken no sooner than every 30 days and up to a total of 3 times in each 90-day treatment period or a maximum of 6 total treatments over the entire study. All participants received tamoxifen treatment in the second 90-day period.