Hum. Reprod. Advance Access published online on April 15, 2009
Human Reproduction, doi:10.1093/humrep/dep081
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A randomized controlled trial of treatment options for troublesome uterine bleeding in Implanon users
1 Sydney Centre for Reproductive Health Research, Research Division of Family Planning NSW, 328-336 Liverpool Road, Ashfield, Sydney, NSW 2131, Australia 2 Department of Obstetrics and Gynaecology, University of Sydney, Sydney, Australia 3 School of Women's and Infants' Health, University of Western Australia and King Edward Memorial Hospital, Perth, Australia 4 Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, Melbourne, Australia 5 Department of Medicine, Bond University, Gold Coast, QLD, Australia 6 Prince Henry's Institute of Medical Research, Melbourne, Australia
7 Correspondence address. E-mail: edithw{at}fpnsw.org.au
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 µg; (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 µg 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.
Key words: bleeding/ethinyl estradiol/doxycycline/Implanon/mifepristone
Submitted on January 5, 2009; resubmitted on February 22, 2009; accepted on March 13, 2009.