Menstruation Disturbances
Conditions
Keywords
Contraceptive implant, Irregular vaginal bleeding, Etonogestrel implant
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.
Interventions
DRUGTamoxifen
7 day course of tamoxifen during an episode of irregular vaginal bleeding
DRUGPlacebo
7 day course of placebo during an episode of irregular vaginal bleeding
Sponsors
Society of Family Planning
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
15 Years to 45 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Tamoxifen: 7 day course of tamoxifen during an episode of irregular vaginal bleeding | 28 |
| Placebo Placebo tablets twice daily for seven days, to be started on the third day of a bleeding episode.
Placebo: 7 day course of placebo during an episode of irregular vaginal bleeding | 28 |
| Total | 56 |
Baseline characteristics
| Characteristic | Tamoxifen | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 25.4 years | 23.9 years | 24.6 years |
| Days of bleeding/spotting in 30 days prior to enrollment | 17.3 days STANDARD_DEVIATION 8.5 | 22.2 days STANDARD_DEVIATION 6.6 | 19.75 days STANDARD_DEVIATION 7.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 25 Participants | 20 Participants | 45 Participants |
| Sex: Female, Male Female | 28 Participants | 28 Participants | 56 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 28 | 0 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
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.
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen | Bleeding Days | 65.6 days | Standard Deviation 37.5 |
| Placebo | Bleeding Days | 46.9 days | Standard Deviation 28.1 |
Primary
Bleeding/Spotting Days
Bleeding/spotting days
Time frame: 30 days
Population: Number of patients analyzed is number of patients who completed 30 days of follow up. Two subjects in the tamoxifen arm and three in the placebo arm were lost to follow up prior to 30 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen | Bleeding/Spotting Days | 10.5 days | Standard Deviation 9 |
| Placebo | Bleeding/Spotting Days | 15.5 days | Standard Deviation 8.5 |
Primary
Consecutive Bleeding-free Days After Study Drug
Consecutive bleeding-free days after study drug
Time frame: up to 180 days
Population: Number of subjects analyzed is the number of subjects who started taking the study drug. One subject in the tamoxifen arm and there in the placebo arm did not initiate study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen | Consecutive Bleeding-free Days After Study Drug | 28.8 days | Standard Deviation 24.5 |
| Placebo | Consecutive Bleeding-free Days After Study Drug | 13.6 days | Standard Deviation 19.2 |
Secondary
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.
Time frame: 30 days
Population: Number of subjects analyzed are those that provided urine samples. No subject who provided urine samples was excluded from this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tamoxifen | Number of Participants Experiencing Ovulation After First Use of Study Drug | 0 Participants |
| Placebo | Number of Participants Experiencing Ovulation After First Use of Study Drug | 0 Participants |
Secondary
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.
Time frame: 180 days
Population: Number of subjects analyzed is the number of subjects who completed a final study visit (either completion of full study or early termination visit) to provide a final estimation of satisfaction.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen | Satisfaction (as Recorded on a 100mm Visual Analog Scale Where 0 is Not at All Satisfied and 100mm is Completely Satisfied) | 61.4 units on a scale | Standard Deviation 24.7 |
| Placebo | Satisfaction (as Recorded on a 100mm Visual Analog Scale Where 0 is Not at All Satisfied and 100mm is Completely Satisfied) | 53.6 units on a scale | Standard Deviation 33.3 |