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


METHODS
Prospective observational study.


METHODS
United Kingdom teaching hospital.


METHODS
Thirty-one perimenopausal and postmenopausal HRT recipients, with a control group of eight postmenopausal women not undergoing HRT.


METHODS
Prospective record of bleeding patterns and endometrial biopsy.


METHODS
Endometrial histology, bleeding patterns, MMP-9, and TIMP-1 expression.


RESULTS
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.


CONCLUSIONS
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.
Hickey
M
M
Department of Obstetrics and Gynecology at St. Mary's, Imperial College School of Medicine, London, England, UK. m.hickey@ic.ac.uk
Higham
J
J
Sullivan
M
M
Miles
L
L
Fraser
I S
IS
D001483:Base Sequence; D001706:Biopsy; D004717:Endometrium / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage; D015914:Estrogen Replacement Therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000502:physiology*; D008593:Menopause; D008969:Molecular Sequence Data; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000502:physiology*; D014592:Uterine Hemorrhage / Q000201:enzymology* / Q000473:pathology
D011372:Progestins; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D004958:Estradiol; D020780:Matrix Metalloproteinase 9