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Pilot Study of Femring Estrogen Supplementation During Depo-Provera Initiation

Sponsor
Columbia University (Other)
Overall Status
Completed
CT.gov ID
NCT00563576
Collaborator
(none)
71
Enrollment
1
Location
2
Arms
17.1
Actual Duration (Months)
4.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Many women choose Depo-Provera for birth control because it is easy to use and very effective. However, a significant number of Depo-Provera users experience irregular bleeding during the first 90 days. Many users discontinue after their first injection due to irregular bleeding. This study will evaluate the effect of using an estrogen vaginal ring during the first 90 days of Depo-Provera use to see if it is acceptable to women and whether it decreases irregular bleeding during the first 90 days of use and increases continuation to a second injection.

Condition or Disease Intervention/Treatment Phase
N/A

Detailed Description

Many women choose depot medroxyprogesterone acetate (DMPA) for contraception because it is long-acting, highly effective, and requires minimal user involvement. One of the most common side effects of DMPA use during the first 90 day cycle is irregular bleeding. There are few studies that report mean number of bleeding days among DMPA users. A large World Health Organization (WHO) trial including ten international centers and menstrual data on 748 women using DMPA including 372 woman-years of follow-up reported 23.6 mean days of spotting and bleeding during the first cycle with a standard deviation of 18.9 days (WHO). Another study sponsored by WHO (n=575) reported that 25% of subjects had bleeding/spotting episodes during the first cycle of DMPA that exceeded 13 days. The number of bleeding/spotting days and number of bleeding/spotting episodes decreased over successive reference periods (Said 1987).

Discontinuation rates are high after the first injection and related to irregular bleeding. Rates of discontinuation after the first injection range from 15-60% but were around 30% in most studies (Harel, Paul, Polaneczy, Lim, Hubacher, Sangi, Rickert). Several studies noted that the largest percentage of discontinuation during the first year of DMPA use occurs after the first injection (Rickert, Hubacher, Lim). Irregular bleeding is uniformly cited as one of the most common reasons for discontinuation, accounting for 17-60% of all reasons given (Harel, Paul, Polaneczy, Lim, Sangi). An intervention to prevent or minimize irregular bleeding during the first 90 days of DMPA use could potentially minimize or prevent this bothersome side effect and thus improve continuation.

Few studies have examined the effect of prophylactic or therapeutic estrogen supplementation on irregular bleeding in DMPA users. A randomized trial (n=132) of cyclic transdermal estradiol 0.1 mg/day (Climara) for 3 months versus placebo in women initiating DMPA immediately post-abortion showed no difference in continuation rates at 12 months; however, the authors of this study reported a high rate of non-compliance with the study protocol and lacked an adequate sample size to detect a difference (Goldberg). This is the only study to report on prophylactic estrogen supplementation in DMPA users.

Two studies evaluated therapeutic estrogen supplementation in DMPA users. In 1996, WHO published results of a trial in which women using DMPA and experiencing a bleeding episode greater than 7 days during the first or second injection interval were offered treatment. Subjects (n=278) were randomized to a 14 day course of 50 mcg ethinyl estradiol, 2.5 mg oestrone sulphate, or placebo. The authors found that subjects treated with ethinyl estradiol had shorter median time to cessation of bleeding and fewer bleeding/spotting days (Said 1996). An observational study (n=131) of adolescents reporting vaginal bleeding on DMPA who were treated with monophasic oral contraceptive pills identified improvement of bleeding patterns and a high rate of continuation in those receiving treatment (Rager).

Estrogen supplementation appears to be more effective than placebo in stopping and decreasing bleeding in Norplant users. Women who presented with a spontaneous complaint of prolonged or irregular bleeding were randomly assigned to receive 20 days of treatment with a combined oral contraceptive, 50 mcg ethinyl estradiol, or placebo. Both combined oral contraceptive pills and estradiol were significantly more effective than placebo in stopping bleeding and decreasing the mean number of bleeding days during treatment (Alvarez).

To summarize, prior studies have not identified an acceptable or effective prophylactic intervention to prevent or minimize irregular bleeding or improve continuation rates in DMPA users. The first cycle of DMPA is a critical time for such an intervention. Our study will evaluate estrogen supplementation with an estrogen vaginal ring during the first 90 days of DMPA use versus no estrogen supplementation and report on acceptability, bleeding patterns, and continuation rates. Femring®, an estradiol vaginal ring currently used for treatment of postmenopausal symptoms, provides 100 mcg of estradiol per day with one ring designed for 90 days of consecutive use. This dose provides systemic levels sufficient to suppress vasomotor symptoms in postmenopausal women (Speroff). The vaginal ring would require minimal user involvement when placed at the time of DMPA initiation. If acceptable and effective, this intervention could prevent or minimize irregular bleeding and improve continuation rates of this highly effective contraceptive method.

Study Design

Study Type:
Interventional
Actual Enrollment :
71 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Pilot Study of Femring Estrogen Supplementation During Depo-Provera Initiation
Actual Study Start Date :
Sep 1, 2007
Actual Primary Completion Date :
Feb 1, 2009
Actual Study Completion Date :
Feb 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Depo-Provera/Femring

Subjects will receive an estrogen vaginal ring (100 mcg) during the first 90 days of Depo-Provera use.

Drug: Femring®
Estrogen vaginal ring (100 mcg) placed for the first 90 days of Depo-Provera use. Femring® (estradiol acetate vaginal ring) is a flexible off-white ring designed for vaginal insertion with measurements that include an outer diameter of 56 mm, cross-sectional diameter of 7.6 mm, and core diameter of 2 mm. Femring® 0.1 mg/day has a central core containing 24.8 mg of estradiol acetate which releases at a rate equivalent to 0.1 mg of estradiol per day for 3 months.
Other Names:
  • Estradiol Acetate Vaginal Ring

    • Drug: DepoProvera ®
    Medroxyprogesterone intramuscular injection comes as a suspension (liquid) to be injected into the buttocks or upper arm. It is usually given once every 3 months (13 weeks), and the recommended dose is 150 mg.
    Other Names:
  • Depot Medroxyprogesterone Acetate (DMPA)

    		•
    Other: Depo-Provera Injection Alone

    Subjects will receive Depo-Provera intramuscular injection.

    Drug: DepoProvera ®
    Medroxyprogesterone intramuscular injection comes as a suspension (liquid) to be injected into the buttocks or upper arm. It is usually given once every 3 months (13 weeks), and the recommended dose is 150 mg.
    Other Names:
  • Depot Medroxyprogesterone Acetate (DMPA)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Mean Number of Bleeding or Spotting Days [3 months]

      Bleeding and spotting were defined using World Health Organization criteria and measured through daily diaries given to participants and collected at the 3 and 6 month followup. In addition, a study staff member called participants weekly to collect the daily bleeding and spotting calendar for that week to optimize the accuracy of this information.

    Secondary Outcome Measures

    1. Percentage of Users Who Were Satisfied With Femring [3 months]

      Acceptability was measured using questionnaires that assessed satisfaction of Femring and usage of the ring. This outcome was only measured among the intervention group of women who actually were randomized to use of Femring. Acceptability of the vaginal ring was high among those in the intervention group.

    2. Number of Subjects Who Receive a 2nd Injection of Depo-Provera [3 months]

    3. Percentage of Subjects Who Receive a 3rd Injection [6 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Women age 18 or older who are initiating Depo-Provera for contraception

    • English or Spanish-speaking

    • Have a negative urine pregnancy test

    Exclusion Criteria:

    • Contraindications to either Depo-Provera or Femring (estrogen vaginal ring)

    • Have used Depo-Provera or Mirena in the prior 6 months

    • Have had an induced abortion, spontaneous abortion, or birth in prior 8 weeks

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Title X Family Planning Clinic New York New York United States 10032

    Sponsors and Collaborators

    • Columbia University

    Investigators

    • Principal Investigator: Angela R Dempsey, MD, MPH, Medical University of South Carolina
    • Principal Investigator: Carolyn Westhoff, MD, MSc, Columbia University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Carolyn Westhoff, Professor of Obstetrics and Gynecology, Population and Family Health and Epidemiology at the New York-Presbyterian Hospital at the Columbia University Medical Center, Columbia University
    ClinicalTrials.gov Identifier:
    NCT00563576
    Other Study ID Numbers:
    • AAAC6363
    First Posted:
    Nov 26, 2007
    Last Update Posted:
    Dec 15, 2021
    Last Verified:
    Dec 1, 2021
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Carolyn Westhoff, Professor of Obstetrics and Gynecology, Population and Family Health and Epidemiology at the New York-Presbyterian Hospital at the Columbia University Medical Center, Columbia University
    Depo-Provera
    Medroxyprogesterone Acetate
    Metrorrhagia
    Irregular Bleeding
    Additional relevant MeSH terms:
    Metrorrhagia
    Medroxyprogesterone Acetate
    Medroxyprogesterone
    Estradiol

    Study Results

    Participant Flow

    Recruitment Details Participants were recruited from a Title X Family Planning Clinic in New York City.
    Pre-assignment Detail Women seeking DMPA eligible to participate it 18 years old, English or Spanish speaking, had not used DMPA or Levonorgestrel intrauterine system in the preceeding 120 days. Women reporting oligomenorrheas (defined as fewer that 4 periods in the last 6 months), amenorrhea, or contraindications to either DMPA or estrogen were excluded.
    Arm/Group Title Femring Depot Medroxyprogesterone Acetate (DMPA) Alone
    Arm/Group Description Subjects will receive an estrogen vaginal ring (100mcg) during the first 90 days of Depo-Provera use. Subjects will receive Depo-Provera intramuscular injection.
    Period Title: Overall Study
    STARTED 35 36
    COMPLETED 21 22
    NOT COMPLETED 14 14

    Baseline Characteristics

    Arm/Group Title Femring Depot Medroxyprogesterone Acetate (DMPA) Alone Total
    Arm/Group Description Subjects will receive an estrogen vaginal ring (100mcg) during the first 90 days of Depo-Provera use. Subjects will receive Depo-Provera intramuscular injection. Total of all reporting groups
    Overall Participants 35 36 71
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    35
    100%
    36
    100%
    71
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    35
    100%
    36
    100%
    71
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    35
    100%
    36
    100%
    71
    100%

    Outcome Measures

    1. Primary Outcome
    Title Mean Number of Bleeding or Spotting Days
    Description Bleeding and spotting were defined using World Health Organization criteria and measured through daily diaries given to participants and collected at the 3 and 6 month followup. In addition, a study staff member called participants weekly to collect the daily bleeding and spotting calendar for that week to optimize the accuracy of this information.
    Time Frame 3 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Femring Depot Medroxyprogesterone Acetate (DMPA) Alone
    Arm/Group Description Subjects will receive an estrogen vaginal ring (100mcg) during the first 90 days of Depo-Provera use. Subjects will receive Depo-Provera intramuscular injection.
    Measure Participants 35 36
    Mean (Standard Deviation) [days]
    16
    (0.19)
    28
    (0.19)
    2. Secondary Outcome
    Title Percentage of Users Who Were Satisfied With Femring
    Description Acceptability was measured using questionnaires that assessed satisfaction of Femring and usage of the ring. This outcome was only measured among the intervention group of women who actually were randomized to use of Femring. Acceptability of the vaginal ring was high among those in the intervention group.
    Time Frame 3 months

    Outcome Measure Data

    Analysis Population Description
    Acceptability was reported among the 26 participants in the Femring group who were available for followup, i.e., per protocol.
    Arm/Group Title Femring Depot Medroxyprogesterone Acetate (DMPA) Alone
    Arm/Group Description Subjects will receive an estrogen vaginal ring (100mcg) during the first 90 days of Depo-Provera use. Subjects will receive Depo-Provera intramuscular injection.
    Measure Participants 26 0
    Number [participants]
    84
    240%
    3. Secondary Outcome
    Title Number of Subjects Who Receive a 2nd Injection of Depo-Provera
    Description
    Time Frame 3 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Femring Depot Medroxyprogesterone Acetate (DMPA) Alone
    Arm/Group Description Subjects will receive an estrogen vaginal ring (100mcg) during the first 90 days of Depo-Provera use. Subjects will receive Depo-Provera intramuscular injection.
    Measure Participants 35 36
    Number [participants]
    20
    57.1%
    16
    44.4%
    4. Secondary Outcome
    Title Percentage of Subjects Who Receive a 3rd Injection
    Description
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    Only the women who completed the study up to the secondary endpoint were included in this analysis.
    Arm/Group Title Femring Depot Medroxyprogesterone Acetate (DMPA) Alone
    Arm/Group Description Subjects will receive an estrogen vaginal ring (100mcg) during the first 90 days of Depo-Provera use. Subjects will receive Depo-Provera intramuscular injection.
    Measure Participants 17 16
    Count of Participants [Participants]
    13
    37.1%
    10
    27.8%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Femring Depot Medroxyprogesterone Acetate (DMPA) Alone
    Arm/Group Description Subjects will receive an estrogen vaginal ring (100mcg) during the first 90 days of Depo-Provera use. Subjects will receive Depo-Provera intramuscular injection.
    All Cause Mortality
    Femring Depot Medroxyprogesterone Acetate (DMPA) Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Femring Depot Medroxyprogesterone Acetate (DMPA) Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/35 (0%) 0/36 (0%)
    Other (Not Including Serious) Adverse Events
    Femring Depot Medroxyprogesterone Acetate (DMPA) Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/35 (0%) 0/36 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Carolyn Westhoff
    Organization Columiba University
    Phone 212-305-4805
    Email clw3@columbia.edu
    Responsible Party:
    Carolyn Westhoff, Professor of Obstetrics and Gynecology, Population and Family Health and Epidemiology at the New York-Presbyterian Hospital at the Columbia University Medical Center, Columbia University
    ClinicalTrials.gov Identifier:
    NCT00563576
    Other Study ID Numbers:
    • AAAC6363
    First Posted:
    Nov 26, 2007
    Last Update Posted:
    Dec 15, 2021
    Last Verified:
    Dec 1, 2021