Tamoxifen for the Treatment of Unfavorable Bleeding in Contraceptive Implant Users

Tamoxifen for the Treatment of Unfavorable Bleeding Patterns in Etonogestrel Contraceptive Implant Users

The purpose of this study is to study whether a drug called tamoxifen can reduce vaginal bleeding in women who are using the Etonogestrel contraceptive implant.

Study Overview

• Status: Completed
• Conditions: Menstruation Disturbances
• Intervention / Treatment: Drug: Tamoxifen; Drug: Placebo

Detailed Description

Nearly all of the 3 million unintended pregnancies in the United States each year result from inconsistent or non-use of contraception. Increasing use of the most effective methods of contraception will reduce unintended pregnancies and their social, medical and economic consequences. The contraceptive etonogestrel implant (ENG implant) is 20 times more effective at pregnancy prevention than oral contraceptive pills, but it has bleeding side effects that make it unappealing for many women. Tamoxifen, a selective estrogen receptor modulator (SERM) used most commonly for adjuvant treatment of breast cancer, has previously been shown to dramatically reduce bleeding in users of an older levonorgestrel-based contraceptive implant (Norplant tm). It has not been studied in newer progestin-based methods such as the ENG implant. If tamoxifen could stop bleeding in users of the ENG implant, it would give patients and physicians a valuable option for management of progestin-induced irregular bleeding. This research project will test the effectiveness of tamoxifen taken on an as-needed basis to treat abnormal bleeding in ENG implant users. If tamoxifen can be established as an effective treatment for frequent or prolonged bleeding, it will increase the acceptability of the ENG implant, increase its use and reduce unintended pregnancies. This is the first project to evaluate tamoxifen for treatment of unfavorable bleeding in users of the ENG contraceptive implant.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University (OHSU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 43 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Current user of the etonogestrel implant (Nexplanon, Implanon) for at least one month
• Experiencing bleeding episodes more frequently than every 24 days, or a single episode of bleeding lasting longer than 14 days
• English or Spanish speaking
• Planning to continue implant use for six months
• Access to a cell phone that can accept and send text messages

Exclusion Criteria:

• Postpartum within six months
• Post-abortion within six weeks
• Pregnant
• Breast-feeding
• Undiagnosed abnormal uterine bleeding pre-dating placement of contraceptive implant
• Bleeding dyscrasia
• Anticoagulation use
• Active cervicitis
• Allergy to tamoxifen
• History of venous thromboembolism
• Current or past breast or uterine malignancy
• Use of medication contraindicated with tamoxifen (coumadin, letrozole, bromocriptine, rifampicin, aminoglutethimide, phenobarbital)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tamoxifen; Participants will be randomized to receive either tamoxifen 10mg twice daily for seven days, or placebo twice daily for seven days, to be started on the third day of an episode of bleeding.	Drug: Tamoxifen; 7 day course of tamoxifen during an episode of irregular vaginal bleeding; Other Names: Nolvadex
Placebo Comparator: Placebo; Placebo tablets twice daily for seven days, to be started on the third day of a bleeding episode.	Drug: Placebo; 7 day course of placebo during an episode of irregular vaginal bleeding

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding Days	The primary objective of this study is to determine whether tamoxifen taken by users of the ENG implant on an as-needed basis for frequent or prolonged bleeding can reduce the number of bleeding days by at least 40% over 180 days, when compared to placebo.	180 days
Bleeding/Spotting Days	Bleeding/spotting days	30 days
Consecutive Bleeding-free Days After Study Drug	Consecutive bleeding-free days after study drug	up to 180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Satisfaction (as Recorded on a 100mm Visual Analog Scale Where 0 is Not at All Satisfied and 100mm is Completely Satisfied)	Secondary objective is to determine whether tamoxifen can improve satisfaction with the implant and with bleeding patterns.	180 days
Number of Participants Experiencing Ovulation After First Use of Study Drug	A third secondary objective is to determine whether taking tamoxifen at this dose compromises ovulation suppression in ENG users. Tamoxifen is known to transiently raise serum estradiol levels, but does not affect gonadotropin release in premenopausal women. Therefore, it is unlikely to interact with the ovulation suppression provided by the implant. However, to further investigate any theoretical interaction between tamoxifen and etonogestrel, urine markers of ovulation will be collected to document ongoing ovulation suppression with intermittent tamoxifen use.	30 days

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: Society of Family Planning

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: February 21, 2014
• First Submitted That Met QC Criteria: February 21, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 13, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Contraceptive implant; Etonogestrel implant; Irregular vaginal bleeding
• Additional Relevant MeSH Terms: Pathologic Processes; Menstruation Disturbances; Hemorrhage; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: SFPRF14-1 (Other Grant/Funding Number: Society of Family Planning)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Study under review for publication