Contraception
Volume 79, Issue 6 , Pages 469-478 , June 2009

Effects of doxycycline on serum and endometrial levels of MMP-2, MMP-9 and TIMP-1 in women using a levonorgestrel-releasing subcutaneous implant

  • Shumei Zhao

      Affiliations

    • Department of Obstetrics and Gynecology, CONRAD Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 757 446 7056; fax: +1 757 446 8998.
    • ,
  • Chainarong Choksuchat

      Affiliations

    • Department of Obstetrics and Gynecology, Prince of Songkla University, Songkla, Thailand 90110
    • ,
  • Yueqin Zhao

      Affiliations

    • Epidemiology and Biostatistics Core, Graduate Program of Public Health, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • Susan A. Ballagh

      Affiliations

    • Department of Obstetrics and Gynecology, CONRAD Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • George A. Kovalevsky

      Affiliations

    • Department of Obstetrics and Gynecology, CONRAD Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • David F. Archer

      Affiliations

    • Department of Obstetrics and Gynecology, CONRAD Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA

Received 5 November 2008 ,Revised 22 December 2008 ,Accepted 23 December 2008.

References 

  1. Abdel-Aleem H, d'Arcangues C, Vogelsong K, Gulmezoglu AM. Treatment of vaginal bleeding irregularities induced by progestin only contraceptives.. Cochrane Database Syst Rev. 2007;CD003449
  2. Livingstone M, Fraser IS. Mechanisms of abnormal uterine bleeding. Hum Reprod Update. 2002;8:60–67
  3. Weisberg E, Hickey M, Palmer D, et al. A pilot study to assess the effect of three short-term treatments on frequent and/or prolonged bleeding compared to placebo in women using Implanon. Hum Reprod. 2006;21:295–302
  4. Brache V, Faundes A, Alvarez F. Risk–benefit effects of implantable contraceptives in women. Expert Opin Drug Saf. 2003;2:321–332
  5. Colli E, Tong D, Penhallegon R, Parazzini F. Reasons for contraceptive discontinuation in women 20–39 years old in New Zealand. Contraception. 1999;59:227–231
  6. Vekemans M, Delvigne A, Paesmans M. Continuation rates with a levonorgestrel-releasing contraceptive implant (Norplant). A prospective study in Belgium. Contraception. 1997;56:291–299
  7. Diaz J, Faundes A, Olmos P, Diaz M. Bleeding complaints during the first year of norplant implants use and their impact on removal rate. Contraception. 1996;53:91–95
  8. Guillebaud J. The levonorgestrel intrauterine system: a clinical perspective from the UK. Ann N Y Acad Sci. 2003;997:185–193
  9. del Carmen Cravioto M, Alvarado G, Canto-de-Cetina T, et al. A multicenter comparative study on the efficacy, safety, and acceptability of the contraceptive subdermal implants Norplant and Norplant-II. Contraception. 1997;55:359–367
  10. Riphagen FE. Intrauterine application of progestins in hormone replacement therapy: a review. Climacteric. 2000;3:199–211
  11. Shoupe D, Mishell DR, Bopp BL, Fielding M. The significance of bleeding patterns in Norplant implant users. Obstet Gynecol. 1991;77:256–260
  12. Fraser IS, Hickey M. Endometrial vascular changes and bleeding disturbances with long-acting progestins. Steroids. 2000;65:665–670
  13. Hickey M, d'Arcangues C. Mechanisms underlying menstrual bleeding disturbances with progestogens. Ernst Schering Res Found Workshop. 2005;52:191–217
  14. Marsh MM, Butt AR, Riley SC, et al. Immunolocalization of endothelin and neutral endopeptidase in the endometrium of users of subdermally implanted levonorgestrel (Norplant). Hum Reprod. 1995;10:2584–2589
  15. Goodger AM, Rogers PA, Affandi B. Endometrial endothelial cell proliferation in long-term users of subdermal levonorgestrel. Hum Reprod. 1994;9:1647–1651
  16. Hickey M, Fraser I, Dwarte D, Graham S. Endometrial vasculature in Norplant users: preliminary results from a hysteroscopic study. Hum Reprod. 1996;11(Suppl 2):35–44
  17. Hickey M, Dwarte D, Fraser IS. Superficial endometrial vascular fragility in Norplant users and in women with ovulatory dysfunctional uterine bleeding. Hum Reprod. 2000;15:1509–1514
  18. Vincent AJ, Zhang J, Ostor A, et al. Matrix metalloproteinase-1 and -3 and mast cells are present in the endometrium of women using progestin-only contraceptives. Hum Reprod. 2000;15:123–130
  19. Vincent AJ, Malakooti N, Zhang J, Rogers PA, Affandi B, Salamonsen LA. Endometrial breakdown in women using Norplant is associated with migratory cells expressing matrix metalloproteinase-9 (gelatinase B). Hum Reprod. 1999;14:807–815
  20. Hampton AL, Nie G, Salamonsen LA. Progesterone analogues similarly modulate endometrial matrix metalloproteinase-1 and matrix metalloproteinase-3 and their inhibitor in a model for long-term contraceptive effects. Mol Hum Reprod. 1999;5:365–371
  21. Birkedal-Hansen H, Moore WG, Bodden MK, et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med. 1993;4:197–250
  22. Salamonsen LA, Woolley DE. Matrix metalloproteinases in normal menstruation. Hum Reprod. 1996;11(Suppl 2):124–133
  23. Salamonsen LA, Woolley DE. Menstruation: induction by matrix metalloproteinases and inflammatory cells. J Reprod Immunol. 1999;44:1–27
  24. Singer CF, Marbaix E, Lemoine P, Courtoy PJ, Eeckhout Y. Local cytokines induce differential expression of matrix metalloproteinases but not their tissue inhibitors in human endometrial fibroblasts. Eur J Biochem. 1999;259:40–45
  25. Chegini N, Rhoton-Vlasak A, Williams RS. Expression of matrix metalloproteinase-26 and tissue inhibitor of matrix metalloproteinase-3 and -4 in endometrium throughout the normal menstrual cycle and alteration in users of levonorgestrel implants who experience irregular uterine bleeding. Fertil Steril. 2003;80:564–570
  26. Di Nezza LA, Jobling T, Salamonsen LA. Progestin suppresses matrix metalloproteinase production in endometrial cancer. Gynecol Oncol. 2003;89:325–333
  27. Kaitu'u TJ, Shen J, Zhang J, Morison NB, Salamonsen LA. Matrix metalloproteinases in endometrial breakdown and repair: functional significance in a mouse model. Biol Reprod. 2005;73:672–680
  28. Li R, Luo X, Archer DF, Chegini N. Doxycycline alters the expression of matrix metalloproteases in the endometrial cells exposed to ovarian steroids and pro-inflammatory cytokine. J Reprod Immunol. 2007;73:118–129
  29. Borkakoti N. Matrix metalloproteases: variations on a theme. Prog Biophys Mol Biol. 1998;70:73–94
  30. Rogers PA, Au CL, Affandi B. Endometrial microvascular density during the normal menstrual cycle and following exposure to long-term levonorgestrel. Hum Reprod. 1993;8:1396–1404
  31. Hiscock N, Chan MH, Bisucci T, Darby IA, Febbraio MA. Skeletal myocytes are a source of interleukin-6 mRNA expression and protein release during contraction: evidence of fiber type specificity. FASEB J. 2004;18:992–994
  32. Maximova OA, Taffs RE, Pomeroy KL, Piccardo P, Asher DM. Computerized morphometric analysis of pathological prion protein deposition in scrapie-infected hamster brain. J Histochem Cytochem. 2006;54:97–107
  33. Brey EM, Lalani Z, Johnston C, et al. Automated selection of DAB-labeled tissue for immunohistochemical quantification. J Histochem Cytochem. 2003;51:575–584
  34. Aasmundstad TA, Haugen OA, Johannesen E, Hoe AL, Kvinnsland S. Oestrogen receptor analysis: correlation between enzyme immunoassay and immunohistochemical methods. J Clin Pathol. 1992;45:125–129
  35. Lehr HA, Mankoff DA, Corwin D, Santeusanio G, Gown AM. Application of Photoshop-based image analysis to quantification of hormone receptor expression in breast cancer. J Histochem Cytochem. 1997;45:1559–1565
  36. Lehr HA, Jacobs TW, Yaziji H, Schnitt SJ, Gown AM. Quantitative evaluation of HER-2/neu status in breast cancer by fluorescence in situ hybridization and by immunohistochemistry with image analysis. Am J Clin Pathol. 2001;115:814–822
  37. Meckstroth KR, Darney PD. Implantable contraception. Obstet Gynecol Clin North Am. 2000;27:781–815
  38. Kovalevsky G, Barnhart K. Norplant and other implantable contraceptives. Clin Obstet Gynecol. 2001;44:92–100
  39. Galant C, Vekemans M, Lemoine P, et al. Temporal and spatial association of matrix metalloproteinases with focal endometrial breakdown and bleeding upon progestin-only contraception. J Clin Endocrinol Metab. 2000;85:4827–4834
  40. Bischof P, Meisser A, Campana A, Tseng L. Effects of decidua-conditioned medium and insulin-like growth factor binding protein-1 on trophoblastic matrix metalloproteinases and their inhibitors. Placenta. 1998;19:457–464
  41. Labied S, Galant C, Nisolle M, et al. Differential elevation of matrix metalloproteinase expression in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time. Hum Reprod. 2009;24:113–121
  42. Malik S, Day K, Perrault I, Charnock-Jones DS, Smith SK. Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-alpha in menstrual endometrium and effluent in women with menorrhagia. Hum Reprod. 2006;21:2158–2166
  43. Marbaix E, Kokorine I, Henriet P, Donnez J, Courtoy PJ, Eeckhout Y. The expression of interstitial collagenase in human endometrium is controlled by progesterone and by oestradiol and is related to menstruation. Biochem J. 1995;305(Pt 3):1027–1030
  44. Skinner JL, Riley SC, Gebbie AE, Glasier AF, Critchley HO. Regulation of matrix metalloproteinase-9 in endometrium during the menstrual cycle and following administration of intrauterine levonorgestrel. Hum Reprod. 1999;14:793–799
  45. Vincent AJ, Zhang J, Ostor A, et al. Decreased tissue inhibitor of metalloproteinase in the endometrium of women using depot medroxyprogesterone acetate: a role for altered endometrial matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in the pathogenesis of abnormal uterine bleeding?. Hum Reprod. 2002;17:1189–1198
  46. Golub LM, Sorsa T, Lee HM, et al. Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva. J Clin Periodontol. 1995;22:100–109
  47. Greenwald RA. Treatment of destructive arthritic disorders with MMP inhibitors. Potential role of tetracyclines. Ann N Y Acad Sci. 1994;732:181–198
  48. Murphy G, Stanton H, Cowell S, et al. Mechanisms for pro matrix metalloproteinase activation. Apmis. 1999;107:38–44
  49. Jiang Y, Goldberg ID, Shi YE. Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene. 2002;21:2245–2252
  50. Galant C, Berliere M, Dubois D, et al. Focal expression and final activity of matrix metalloproteinases may explain irregular dysfunctional endometrial bleeding. Am J Pathol. 2004;165:83–94
  51. Corcoran ML, Hewitt RE, Kleiner DE, Stetler-Stevenson WG. MMP-2: expression, activation and inhibition. Enzyme Protein. 1996;49:7–19
  52. Hu J, Zhang X, Nothnick WB, Spencer TE. Matrix metalloproteinases and their tissue inhibitors in the developing neonatal mouse uterus. Biol Reprod. 2004;71:1598–1604
  53. Petrinec D, Liao S, Holmes DR, Reilly JM, Parks WC, Thompson RW. Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: preservation of aortic elastin associated with suppressed production of 92 kD gelatinase. J Vasc Surg. 1996;23:336–346
  54. Vincent AJ, Salamonsen LA. The role of matrix metalloproteinases and leukocytes in abnormal uterine bleeding associated with progestin-only contraceptives. Hum Reprod. 2000;15(Suppl 3):135–143

☆ The research was supported by NIH Grant R01 HD43175-01.

☆☆ Dr. Shumei Zhao, Dr. Chainarong Choksuchat, Ms. Yueqin Zhao and Dr. George Kovalevsky have no conflicts of interest. Dr. David Archer is a paid consultant for Abbott Laboratories, Agile Therapeutics, Bayer Healthcare, Berlex, ConCert Pharmaceutical, Novo Nordisk, Radius, Schering Plough, Warner Chilcott and Wyeth Laboratories; he has Industry-Supported Research from Bayer Healthcare, Duramed, Organon-Schering Plough, Solvay, Warner Chilcott and Wyeth Laboratories; he receives Direct Industry Lecture Fees from Novo Nordisk, Organon, Schering Plough, Solvay, Upsher-Smith Laboratories and Wyeth Laboratories. Dr. Susan Ballagh is a paid consultant for Contraception Online, Gerson-Lehrman Group, Organon and Wyeth Laboratories; she has Industry-Support Research from Duramed Research, Bayer Healthcare, Conceptus, Pfizer, Organon, Warner-Chilcott and Wyeth Laboratories; she receives Direct Industry Lecture Fees from ARHP, Cardinal Health, Organon and Wyeth Laboratories.

PII: S0010-7824(08)00579-9

doi: 10.1016/j.contraception.2008.12.010

Contraception
Volume 79, Issue 6 , Pages 469-478 , June 2009

Article Tools

* Image Usage & Resolution