Oral Contraceptives and Subantimicrobial Doxycycline: Effect on Endometrial Matrix Metalloproteinases

Study Overview
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Brief Summary
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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
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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.

Official Title
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Oral Contraceptives and Subantimicrobial Doxycycline: Effect on Endometrial Matrix Metalloproteinases

Conditions
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Breakthrough Bleeding

Intervention / Treatment
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* Drug: Doxycycline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sub-antimicrobial doxycycline<br>Women will take sub-antimicrobial doxycyline in addition to the continuous oral contraceptive pill. | Drug: Doxycycline<br>* 40 mg orally at the start of cycle 3 (study day 57) for 28 days.<br>* Other names: Oracea;|
| No Intervention: Continuous Oral Contraceptive Pill<br>Women will take only the continuous oral contraceptive. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 49 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 84 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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continuous oral contraceptives, Matrix Metalloproteinase expression