Trial Information

A Prospective Randomized Clinical Trial of Doxycycline 20mg Twice a Day Versus Placebo on the Bleeding and Spotting in Women After Insertion of a Levonorgestrel Implant (Norplant) Protocol #2002-1

A high percentage of women using progestin-only contraception experience breakthrough
bleeding (BTB) and 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 BTB and spotting
contains abnormally high levels of pro-inflammatory cytokines (TNF-alpha and IL-1 beta) 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 and reduces nitric oxide synthesis. This study will
evaluate DOX treatment of progestin-only contraceptive induced BTB and spotting,
characterize the endometrial molecular biologic changes that occur in DOX treated patients,
and determine the effect of Norplant on sexual functioning and testosterone levels.

All participants in this study will receive Norplant. Participants will then be randomized
to receive either DOX (20 mg twice a day) or placebo for 6 months. Participants will have 9
study visits during the 24 weeks of the study. Study visits will include a medical history,
physical exam, and blood and urine tests. Participants will also have three periodontal
evaluations and three endometrial biopsies. At the end of the study, participants may
choose to have the Norplant implant removed if they wish to discontinue Norplant use;
otherwise the implant may remain in for up to 5 years.