Fertility and Sterility
Volume 75, Issue 2 , Pages 288-296, February 2001

Endometrial bleeding in hormone replacement therapy users: preliminary findings regarding the role of matrix metalloproteinase 9 (MMP-9) and tissue inhibitors of MMPs

  • Martha Hickey, M.D. (abc)

      Affiliations

    • Department of Obstetrics and Gynecology at St. Mary’s, Imperial College School of Medicine, London, England, United Kingdom
    • Department of Maternal and Fetal Medicine, Queen Charlotte’s and Chelsea Hospital, Imperial College School of Medicine, London, England, United Kingdom
    • Sydney Centre for Reproductive Health Research, Department of Obstetrics and Gynaecology, University of Sydney, NSW 2006, Sydney, Australia
    • Corresponding Author InformationReprint requests: Martha Hickey, M.D., Clinical Lecturer/Senior Registrar in Obstetrics and Gynaecology, ICSM at St. Mary’s Hospital, Norfolk Place, London W2 1PG (FAX: +44 0207 886 6054 )
  • ,
  • Jenny Higham, M.D. (ab)

      Affiliations

    • Department of Obstetrics and Gynecology at St. Mary’s, Imperial College School of Medicine, London, England, United Kingdom
    • Department of Maternal and Fetal Medicine, Queen Charlotte’s and Chelsea Hospital, Imperial College School of Medicine, London, England, United Kingdom
    • Sydney Centre for Reproductive Health Research, Department of Obstetrics and Gynaecology, University of Sydney, NSW 2006, Sydney, Australia
  • ,
  • Mark Sullivan, Ph.D. (ab)

      Affiliations

    • Department of Obstetrics and Gynecology at St. Mary’s, Imperial College School of Medicine, London, England, United Kingdom
    • Department of Maternal and Fetal Medicine, Queen Charlotte’s and Chelsea Hospital, Imperial College School of Medicine, London, England, United Kingdom
    • Sydney Centre for Reproductive Health Research, Department of Obstetrics and Gynaecology, University of Sydney, NSW 2006, Sydney, Australia
  • ,
  • Lyn Miles (B.Sc.a,b)

      Affiliations

    • Department of Obstetrics and Gynecology at St. Mary’s, Imperial College School of Medicine, London, England, United Kingdom
    • Department of Maternal and Fetal Medicine, Queen Charlotte’s and Chelsea Hospital, Imperial College School of Medicine, London, England, United Kingdom
    • Sydney Centre for Reproductive Health Research, Department of Obstetrics and Gynaecology, University of Sydney, NSW 2006, Sydney, Australia
  • ,
  • Ian S Fraser (M.D.abc)

      Affiliations

    • Department of Obstetrics and Gynecology at St. Mary’s, Imperial College School of Medicine, London, England, United Kingdom
    • Department of Maternal and Fetal Medicine, Queen Charlotte’s and Chelsea Hospital, Imperial College School of Medicine, London, England, United Kingdom
    • Sydney Centre for Reproductive Health Research, Department of Obstetrics and Gynaecology, University of Sydney, NSW 2006, Sydney, Australia

Received 12 October 1999; received in revised form 9 August 2000; accepted 9 August 2000.

Abstract 

Objective: To establish the effect of hormone replacement therapy (HRT) on the expression of matrix metalloproteinase 9 (MMP-9) and the tissue inhibitor of MMPs, TIMP-1, in the endometrium of postmenopausal and perimenopausal women.

Design: Prospective observational study.

Setting: United Kingdom teaching hospital.

Patient(s): Thirty-one perimenopausal and postmenopausal HRT recipients, with a control group of eight postmenopausal women not undergoing HRT.

Intervention(s): Prospective record of bleeding patterns and endometrial biopsy.

Main Outcome Measure(s): Endometrial histology, bleeding patterns, MMP-9, and TIMP-1 expression.

Result(s): MMP-9 and TIMP-1 are expressed in benign postmenopausal endometrium. Expression of both molecules is reduced in HRT recipients compared with non–HRT recipients.

Conclusion(s): Exposure to HRT appears to alter endometrial expression of MMP-9 and TIMP-1 and also the local balance between these molecules. This alteration may promote breakdown of the endometrial extracellular matrix and blood vessels and hence bleeding.

Keywords:  MMP-9, TIMP-1, endometrium, menopause, bleeding

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PII: S0015-0282(00)01690-3

Fertility and Sterility
Volume 75, Issue 2 , Pages 288-296, February 2001