Tamoxifen for the Treatment of Unfavorable Bleeding in Contraceptive Implant Users

Phase 4

Completed

Conditions: Menstruation Disturbances

Interventions: Drug: Placebo
Drug: Tamoxifen

Registration Number: NCT02070692

Lead Sponsor: Oregon Health and Science University

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 56

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo tablets twice daily for seven days, to be started on the third day of a bleeding episode.
Tamoxifen	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.

Primary Outcome Measures

Name	Time	Method
Bleeding Days	180 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.
Bleeding/Spotting Days	30 days	Bleeding/spotting days
Consecutive Bleeding-free Days After Study Drug	up to 180 days	Consecutive bleeding-free days after study drug

Secondary Outcome Measures

Name	Time	Method
Satisfaction (as Recorded on a 100mm Visual Analog Scale Where 0 is Not at All Satisfied and 100mm is Completely Satisfied)	180 days	Secondary objective is to determine whether tamoxifen can improve satisfaction with the implant and with bleeding patterns.
Number of Participants Experiencing Ovulation After First Use of Study Drug	30 days	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.