Norplant and Irregular Bleeding/Spotting
Norplant and Irregular Bleeding/Spotting
Irregular or prolonged menstrual bleeding and/or spotting are common side effects in patients
 using progestin-only hormonal contraception such as levonorgestrel implants (Norplant).
 Doxycycline, a drug approved by the Food and Drug Administration (FDA) to treat gum disease,
 may reduce the occurrence of uterine bleeding and spotting in women who use Norplant. This
 study will evaluate the effects of doxycycline on uterine bleeding/spotting in women using
 Norplant.
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.
Inclusion Criteria

 -  Regular menstrual periods for the last 2 cycles

 -  Currently not using hormonal contraceptives, including oral contraceptives, patch,
 ring, or Norplant in 2 months prior to study entry, or Depo-Provera in 12 months prior
 to study entry

 -  Currently not using tetracycline-class antibiotics

 -  Normal Pap smear

 Exclusion criteria

 -  Pregnancy or breastfeeding within 2 months of study entry

 -  Chronic migraine headaches

 -  Uncontrolled high blood pressure

 -  Untreated sexually transmitted diseases

 -  Alcoholism or drug abuse within 12 months of study entry

 -  Insulin dependent diabetes

 -  Liver, kidney, or gallbladder disease

 -  Participation in another clinical trial within 30 days of study entry

 -  History of cancer

 -  History of blood clots, strokes, or heart disease