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Human Reproduction, Vol. 15, No. 1, 123-130, January 2000
© 2000 European Society of Human Reproduction and Embryology

Matrix metalloproteinase-1 and -3 and mast cells are present in the endometrium of women using progestin-only contraceptives

A.J. Vincent1, J. Zhang1, A. Ostor2, P.A.W. Rogers3, B. Affandi4, G. Kovacs5 and L.A. Salamonsen1,6

1 Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia, 2 Royal Women's Hospital, Carlton, Victoria, 3 Monash University Dept of Obstetrics and Gynaecology, Clayton, Victoria, 4 Human Reproduction Study Group, Department of Obstetrics and Gynaecology, University of Indonesia, Jakarta, Indonesia and 5 Monash University Dept of Obstetrics and Gynaecology, Box Hill Hospital, Box Hill, Victoria, Australia

Progestin-only contraceptives are associated with menstrual bleeding disturbances; a major reason why these agents are discontinued. The pathogenesis of such abnormal uterine bleeding associated with progestin-only contraceptives remains ill-defined. Matrix metalloproteinases (MMP)s and mast cells (MC)s are postulated to be involved in endometrial breakdown observed in normal menstruation. In this study comparisons were made of the immunolocalization of MMP-1 and -3 and MC in endometrium from women using Norplant or depot medroxyprogesterone acetate (DMPA) with normal controls. Positive MMP immunostaining was observed focally in stromal cells and adjacent extracellular matrix. Quantitative assessment revealed significantly higher MMP-1 immunostaining associated with the use of Norplant compared with DMPA or menstrual phase controls. Endometrial MMP-1 immunostaining in DMPA users was similar to that in menstrual controls. Positive MMP-3 immunolocalization was observed in a minority of endometrial samples. Activated MC, shown by the presence of extracellular MC tryptase, predominated in the endometrium of Norplant and DMPA users as also observed in menstrual phase controls. There was no correlation between MMP immunostaining, number of MC and number of bleeding days reported. These results indicate that in women using progestin-only contraceptives, endometrial MMP-1, -3 and MC demonstrate similarities to menstrual phase controls but also variation with different progestins.

Key words: abnormal uterine bleeding/depot medroxyprogesterone acetate/leukocytes/levonorgestrel/matrix metalloproteinases

6 To whom correspondence should be addressed


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