A randomized controlled trial of treatment options for troublesome uterine bleeding in Implanon users

Abstract

Background: Pilot data have indicated that both doxycycline alone and mifepristone combined with ethinyl estradiol (EE) are effective in stopping episodes of bleeding in Implanon users with troublesome bleeding. We compared four treatments against a placebo in Implanon users and tested whether repeated treatment improved subsequent bleeding patterns.

Method: Implanon users aged 18-45 years were randomized to treatment with (i) mifepristone 25 mg given twice on day 1 followed by 4 days of EE 20 microg; (ii) doxycycline 100 mg twice daily for 5 days; (iii) mifepristone 25 mg given twice on day 1 plus doxycycline 100 mg twice daily for 5 days; (iv) doxycycline 100 mg twice daily with EE 20 microg daily; and (v) placebo twice daily for 5 days. The primary end-point was the number of days of bleeding/spotting immediately following initiation of the first 5-day course of each therapy, compared with placebo.

Results: There were 204 women assigned to treatment. Mifepristone in combination with either EE or doxycycline was significantly more effective in stopping an episode of bleeding (mean 4.0 days (CI 3.5-4.6) and 4.4 days (CI 3.8-5.2), respectively) than doxycycline alone or in combination with EE, or placebo (6.4 days (CI 4.4-9.2), 6.4 days (CI 4.8-8.6) and 6.4 days (CL 5.1-8.0), respectively).

Conclusion: Mifepristone combined with either EE or doxycycline was significantly more effective than placebo in terminating an episode of bleeding in Implanon users. However there was no improvement in subsequent bleeding patterns.

Trial registration number: ACTR # 012605000206628.

Figures

Figure 1

Study design.

Figure 2

Consort participation table.

Figure 3

Total number of days to stop bleeding according to drug allocation from the day of starting the first treatment (median plus 25th and 75th percentiles).

Figure 4

This figure shows a comparison between the Pilot Study and the Main Study of the times taken to stop bleeding by individual women in the three treatment groups, which were the same in both studies. The pattern of responses was very similar in both studies for mifepristone plus EE, but there were apparently different response patterns between the two studies for the women in the placebo and the doxycycline alone groups.