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.
