title: Effect of oral contraceptives and doxycycline on endometrial MMP-2 and MMP-9 activity.
abstract: OBJECTIVE
  To describe the effect of combined oral contraceptives (COCs) on matrix metalloproteinases MMP-2 and MMP-9 activity and compare MMP activity in women taking a COC with or without doxycycline.
  
  
  METHODS
  Subjects (n=20) underwent endometrial biopsies (1) in the late luteal phase of a baseline cycle prior to initiating COCs, (2) on days 19-21 while taking COCs in a standard 28-day cycle (7-day hormone-free interval) and (3) on days 26-28 while taking active COCs continuously for a 28-day cycle. During the continuous COC cycle, they were randomized to receive daily subantimicrobial dose doxycycline 40mg or placebo.
  
  
  RESULTS
  Compared to baseline, COC treatment increased MMP-2 (p<.001) and MMP-9 (p<.001). MMP activity was lower in subjects taking a COC with doxycycline compared to those receiving placebo although only significantly lower for MMP-2 latent form (p=.002).
  
  
  CONCLUSIONS
  Unscheduled bleeding with COCs may be the result of increased endometrial MMPs. Sample size limitations prevent us from determining how doxycycline affects MMP activity in COC users.
authors.affiliation: John A. Burns School of Medicine, University of Hawaii at Manoa, 1319 Punahou Street, Suite 824, Honolulu, HI 96826, USA. Electronic address: blissk@hawaii.edu.
authors.forename: Bliss
authors.initials: B
authors.lastname: Kaneshiro
authors.affiliation: Oregon Health & Science University, 3181 SW Sam Jackson Park Road, UHN 50, Portland, OR 97239, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Edelman
authors.affiliation: Meharry Medical College, 1005 Dr. D. B. Todd Jr. Boulevard, Suite 5131, Nashville, TN 37208, USA.
authors.forename: Chandravanu
authors.initials: C
authors.lastname: Dash
authors.affiliation: Meharry Medical College, 1005 Dr. D. B. Todd Jr. Boulevard, Suite 5131, Nashville, TN 37208, USA.
authors.forename: Jui
authors.initials: J
authors.lastname: Pandhare
authors.affiliation: RMATRIX, John A. Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo Street, Medical Education Building, Office of the Dean, 2nd Floor, Honolulu, HI 96813, USA.
authors.forename: Faapisa M
authors.initials: FM
authors.lastname: Soli
authors.affiliation: Oregon Health & Science University, 3181 SW Sam Jackson Park Road, UHN 50, Portland, OR 97239, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Jensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects / Q000494:pharmacology*; D004318:Doxycycline / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000378:metabolism; D008796:Metrorrhagia / Q000139:chemically induced; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D003277:Contraceptives, Oral, Combined; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline
keywords: Combined oral contraceptives; Doxycycline; Endometrial biopsy; Matrix metalloproteinase-2 (MMP-2); Matrix metalloproteinase-9 (MMP-9)