title: A randomized controlled trial of subantimicrobial-dose doxycycline to prevent unscheduled bleeding with continuous oral contraceptive pill use.
abstract: BACKGROUND
  Unscheduled bleeding is the main side effect of continuous oral contraceptive pills (OCPs) and has been correlated with the up-regulation of matrix metalloprotineases (MMPs). The study objective was to determine if prophylactic administration of doxycycline (an MMP inhibitor at low subantimicrobial doses) would prevent unscheduled bleeding during the initiation of a continuous OCP.
  
  
  METHODS
  Subjects using cyclic hormonal contraceptives (combined OCPs, patch or ring) without unscheduled bleeding were switched to continuous OCPs (20 mcg ethinyl estradiol/100 mcg levonorgestrel). They were randomized to receive daily doxycycline [sustained-release subantimicrobial dose (40 mg daily)] or placebo for the first 84 days and then observed for an additional 28 days on the continuous OCP alone. The number of bleeding/spotting days and the time in days it took to achieve amenorrhea were compared using a t test.
  
  
  RESULTS
  Sixty-five subjects were randomized. Although the use of doxycycline did not significantly decrease the number of mean bleeding/spotting days in the first 84 days of the study [doxycycline 14.75 (SE 2.30), placebo 17.78 (2.31), p=.36], women who received doxycycline had a significantly earlier onset of amenorrhea [mean last day of bleeding/spotting doxycycline 61.7 (7.7), placebo 85.2 (6.7), p=.03].
  
  
  CONCLUSIONS
  The coadministration of subantimicrobial-dose doxycycline during initiation of continuous OCPs results in a significant reduction in the length of time needed to achieve amenorrhea.
authors: Department of Obstetrics & Gynecology, University of Hawaii, Honolulu, HI 96826, USA. bkaneshiro@ucera.org
authors: Bliss
authors: B
authors: Kaneshiro
authors: Alison
authors: A
authors: Edelman
authors: Nichole E
authors: NE
authors: Carlson
authors: Mark
authors: M
authors: Nichols
authors: Marci Messerle
authors: MM
authors: Forbes
authors: Jeffrey
authors: J
authors: Jensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use*; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000009:adverse effects / Q000627:therapeutic use*; D008796:Metrorrhagia / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D004318:Doxycycline