Oral Contraceptives and Subantimicrobial Doxycycline: Effect on Endometrial Matrix Metalloproteinases

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.

Study Overview

• Status: Completed
• Conditions: Breakthrough Bleeding
• Intervention / Treatment: Drug: Doxycycline

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Sub-antimicrobial doxycycline; Women will take sub-antimicrobial doxycyline in addition to the continuous oral contraceptive pill.	Drug: Doxycycline; 40 mg orally at the start of cycle 3 (study day 57) for 28 days.; Other Names: Oracea
NO_INTERVENTION: Continuous Oral Contraceptive Pill; Women will take only the continuous oral contraceptive.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Hawaii
• Collaborators: Meharry Medical College; Charles Drew University of Medicine and Science
• Investigators: Principal Investigator: Bliss Kaneshiro, MD, MPH, University of Hawaii John A. Burns School of Medicine Department of Obstetrics and Gynecology

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): May 1, 2012
• Study Completion (ACTUAL): May 1, 2012

Study Registration Dates

• First Submitted: November 8, 2011
• First Submitted That Met QC Criteria: November 8, 2011
• First Posted (ESTIMATE): November 10, 2011

Study Record Updates

• Last Update Posted (ACTUAL): December 17, 2020
• Last Update Submitted That Met QC Criteria: November 23, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: continuous oral contraceptives; Matrix Metalloproteinase expression
• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Hemorrhage; Uterine Hemorrhage; Metrorrhagia; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: UH DOXY RTRN