title: Tamoxifen for the treatment of breakthrough bleeding with the etonogestrel implant: a randomized controlled trial.
abstract: OBJECTIVE
  The etonogestrel (ENG) subdermal implant can cause frequent breakthrough bleeding in some users. The objective of this study was to evaluate whether a short course of tamoxifen reduces bleeding/spotting days compared to placebo in ENG implant users.
  
  
  METHODS
  In this double-blind trial, we randomized ENG implant users with frequent or prolonged bleeding or spotting to tamoxifen 10 mg or placebo twice daily for 7 days, to be started after 3 consecutive days of bleeding/spotting. Treatment was repeated as needed up to three times in 180 days. Subjects completed a daily text message bleeding diary. A sample size of 56 provided 80% power to detect a difference of 6 days of bleeding/spotting per 30 days by two-sample t test. Ovulation was monitored by urinary metabolites of progesterone.
  
  
  RESULTS
  From March 2014 to February 2015, 56 women enrolled. Fifty-one completed at least 30 days of follow up, and 34 completed 180 days. Compared to women randomized to placebo, women randomized to tamoxifen reported 5 fewer days of bleeding/spotting over 30 days (95% confidence interval [CI] -9.9 to -0.05, p=.05), and 15.2 more continuous bleeding-free days (95% CI 2.8-27.5 days, p=.02) after first use of study drug. Conclusions could not be drawn after 30 days due to higher-than-expected dropout. No ovulation was detected.
  
  
  CONCLUSIONS
  First use of tamoxifen by ENG implant users reduces bleeding/spotting days and provides a longer cessation of bleeding/spotting than placebo, without compromising ovulation suppression. Further study is needed to determine whether this effect is maintained with repeat use.
  
  
  CONCLUSIONS
  Women with frequent ENG implant-related breakthrough bleeding may experience a reduction in bleeding/spotting days and an increase in continuous bleeding-free days in the month following first use of tamoxifen. This short course of tamoxifen was well tolerated with bleeding cessation noted within a median of 5 days.
authors.affiliation: Oregon Health & Science University, Department of Obstetrics and Gynecology, 3181 SW Sam Jackson Park Road, UHN 50, Portland, OR 97239, USA. Electronic address: simmonka@ohsu.edu.
authors.forename: Katharine B
authors.initials: KB
authors.lastname: Simmons
authors.affiliation: Oregon Health & Science University, Department of Obstetrics and Gynecology, 3181 SW Sam Jackson Park Road, UHN 50, Portland, OR 97239, USA.
authors.forename: Alison B
authors.initials: AB
authors.lastname: Edelman
authors.affiliation: Oregon Health & Science University, School of Public Health, 3181 SW Sam Jackson Park Road, CB669, Portland, OR 97239, USA; Oregon Health & Science University, Department of Emergency Medicine, 3181 SW Sam Jackson Park Road, CDW-EM, Portland, OR 97239, USA.
authors.forename: Rongwei
authors.initials: R
authors.lastname: Fu
authors.affiliation: Oregon Health & Science University, Department of Obstetrics and Gynecology, 3181 SW Sam Jackson Park Road, UHN 50, Portland, OR 97239, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Jensen
mesh_terms: D000293:Adolescent; D000328:Adult; D003271:Contraceptive Agents, Female; D017135:Desogestrel / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D004343:Drug Implants; D005260:Female; D006801:Humans; D008796:Metrorrhagia / Q000139:chemically induced* / Q000188:drug therapy*; D008875:Middle Aged; D010060:Ovulation / Q000652:urine; D010919:Placebos; D011374:Progesterone / Q000652:urine; D013629:Tamoxifen / Q000627:therapeutic use*; D014592:Uterine Hemorrhage; D055815:Young Adult
chemical_list: D003271:Contraceptive Agents, Female; D004343:Drug Implants; D010919:Placebos; D013629:Tamoxifen; C044815:etonogestrel; D011374:Progesterone; D017135:Desogestrel
keywords: Breakthrough bleeding; Contraception; Etonogestrel implant; Tamoxifen