Tamoxifen for the Treatment of Unfavorable Bleeding in Contraceptive Implant Users

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Menstruation Disturbances

Intervention / Treatment
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* Drug: Tamoxifen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tamoxifen<br>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<br>* 7 day course of tamoxifen during an episode of irregular vaginal bleeding<br>* Other names: Nolvadex;|
| Placebo Comparator: Placebo<br>Placebo tablets twice daily for seven days, to be started on the third day of a bleeding episode. | Drug: Placebo<br>* 7 day course of placebo during an episode of irregular vaginal bleeding<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Contraceptive implant, Irregular vaginal bleeding, Etonogestrel implant