Breakthrough Bleeding
Conditions
Keywords
continuous oral contraceptives, Matrix Metalloproteinase expression
Brief summary
The purpose of this study is to compare the effects (good and bad) of subantimicrobial dose doxycycline on the irregular bleeding women experience when taking continuous oral contraceptive pills. This research is being done because currently, there is no effective treatment for this condition. Findings from this study could help to decrease the side effects of birth control pills and decrease unplanned pregnancies.
Detailed description
Continuous oral contraceptive administration entails women taking hormonally active pills for 28 days without a seven day placebo week to avoid hormonal withdrawal bleeding. Unfortunately, with continuous administration, timed, regular bleeding can be replace by irregular, unscheduled bleeding, which often leads to dissatisfaction, discontinuation and the possibility of unplanned pregnancy. Matrix Metalloproteinases, a group of zinc-dependant proteases, are hypothesized to play a role in endometrial degradation. The purpose of this study is to describe the expression of Matrix Metalloproteinases in endometrial biopsy specimens collected 1) prior to initiating oral contraceptives 2) while taking cyclic oral contraceptive 3) while taking continuous oral contraceptives and 4) while taking continuous oral contraceptives along with sub-antimicrobial doxycycline.
Interventions
DRUGDoxycycline
40 mg orally at the start of cycle 3 (study day 57) for 28 days.
Sponsors
Charles Drew University of Medicine and Science
Meharry Medical College
University of Hawaii
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Women between the ages 18 and 45 who are ovulatory as demonstrated by a pre-treatment Progesterone (P) greater than or equal to 3.0 ng/mL prior to oral contraceptive use
Exclusion criteria
* Women with any absolute contraindications to ethinyl estradiol and levonorgestrel; * Women who are pregnant or breastfeeding * Use of oral contraceptives, patch, ring, intrauterine or implantable hormonal contraception within 4-weeks; * Medroxyprogesterone acetate use within six months; * Current use of drugs that interfere with sex steroid metabolism.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endometrial Matrix Metalloproteinase Expression by Gel Densitometry | 49 days | Baseline Matrix Metalloproteinase expression (activity level) will be determined on day 19-21 of cycle 1. During cycle 2, when women are taking the cyclic oral contraceptive, the endometrial biopsy will be performed between cycle day 19-21 (study day 47-49), prior to endometrial degradation and activity level will be noted. Of note, the outcome is MMP activity level, not a change in level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Matrix Metalloproteinase Expression and Activity by Gel Densitometry | 84 days | Based on doxycycline's action as an Matrix Metalloproteinase inhibitor, it is hypothesized that Matrix Metalloproteinase expression and activity level will be decreased in women taking sub-antimicrobial doxycycline compared to women on continuous oral contraceptives only. The outcome is activity level (not a change in activity level) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Comparator: Subantimicrobial Doxycycline Active comparator: Subantimicrobial doxycycline | 11 |
| No Intervention: Continuous Oral Contraceptive Pill No intervention: Continuous oral contraceptive pill | 9 |
| Total | 20 |
Baseline characteristics
| Characteristic | Active Comparator: Subantimicrobial Doxycycline | No Intervention: Continuous Oral Contraceptive Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 9 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 9 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 2 Participants | 7 Participants |
| Region of Enrollment United States | 11 Participants | 9 Participants | 20 Participants |
| Sex: Female, Male Female | 11 Participants | 9 Participants | 20 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 / 11 | 0 / 9 |
| serious Total, serious adverse events | 0 / 11 | 0 / 9 |
Outcome results
Primary
Endometrial Matrix Metalloproteinase Expression by Gel Densitometry
Baseline Matrix Metalloproteinase expression (activity level) will be determined on day 19-21 of cycle 1. During cycle 2, when women are taking the cyclic oral contraceptive, the endometrial biopsy will be performed between cycle day 19-21 (study day 47-49), prior to endometrial degradation and activity level will be noted. Of note, the outcome is MMP activity level, not a change in level.
Time frame: 49 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sub-antimicrobial Doxycycline Group | Endometrial Matrix Metalloproteinase Expression by Gel Densitometry | 1.33 relative expression | Standard Deviation 0.41 |
| Control | Endometrial Matrix Metalloproteinase Expression by Gel Densitometry | 2.49 relative expression | Standard Deviation 0.72 |
Secondary
Matrix Metalloproteinase Expression and Activity by Gel Densitometry
Based on doxycycline's action as an Matrix Metalloproteinase inhibitor, it is hypothesized that Matrix Metalloproteinase expression and activity level will be decreased in women taking sub-antimicrobial doxycycline compared to women on continuous oral contraceptives only. The outcome is activity level (not a change in activity level)
Time frame: 84 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sub-antimicrobial Doxycycline Group | Matrix Metalloproteinase Expression and Activity by Gel Densitometry | 1.52 relative expression | Standard Deviation 0.63 |
| Control | Matrix Metalloproteinase Expression and Activity by Gel Densitometry | 1.98 relative expression | Standard Deviation 0.87 |