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

Fertil Steril. 2001 Feb;75(2):288-96. doi: 10.1016/s0015-0282(00)01690-3.

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.

MeSH terms

  • Base Sequence
  • Biopsy
  • Endometrium / pathology
  • Estradiol / administration & dosage
  • Estrogen Replacement Therapy*
  • Female
  • Gene Expression
  • Humans
  • In Situ Hybridization
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / physiology*
  • Menopause
  • Molecular Sequence Data
  • Postmenopause
  • Progestins / administration & dosage
  • Prospective Studies
  • RNA, Messenger / analysis
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / physiology*
  • Uterine Hemorrhage / enzymology*
  • Uterine Hemorrhage / pathology

Substances

  • Progestins
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Estradiol
  • Matrix Metalloproteinase 9