Clinically, a high percentage of women using progestin-only contraception experience breakthrough bleeding spotting that causes impaired lifestyle and results in decreased compliance with this contraceptive method. There is a need for an effective, low-cost, easily adapted treatment to reduce the bleeding and spotting in progestin only contraceptives. The molecular environment of the endometrium of women with breakthrough bleeding [BTB] and spotting, like many other inflammatory disorders, contains abnormally high levels of pro-inflammatory cytokines (TNF-alpha and IL-1beta)and abnormally high levels of proteases (matrix metalloproteinases [MMPs] and neutrophil elastase), which prevent normal tissue repair. Doxycycline [DOX] is an inexpensive, FDA approved antibiotic that inhibits MMPs, TACE activity, and reduces NO synthesis. The therapeutic benefit of DOX in animal models and clinical studies of periodontal and ulcerative diseases is due to its inhibition of MMPs, not to its antibiotic effect. We do not anticipate any reduction in contraceptive efficacy with the use of DOX. We propose to clinically evaluate DOX treatment of progestin-only contraceptive induced BTB and spotting, and to biochemically characterize the endometrial molecular biologic changes that occur in DOX treated patients. If successful, DOX treatment could become an important adjuvant for treatment of this and possibly other inflammatory disorders effecting reproductive tract tissues.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD043175-05
Application #
7086287
Study Section
Special Emphasis Panel (ZHD1-DRG-D (16))
Program Officer
Mackay, H Trent
Project Start
2002-09-27
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2008-06-30
Support Year
5
Fiscal Year
2006
Total Cost
$310,776
Indirect Cost
Name
Eastern Virginia Medical School
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
058625146
City
Norfolk
State
VA
Country
United States
Zip Code
23501
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