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Human Reproduction, Vol. 15, No. suppl_3, pp. 135-143, 2000
© 2000 European Society of Human Reproduction and Embryology

The role of matrix metalloproteinases and leukocytes in abnormal uterine bleeding associated with progestinonly contraceptives

A.J. Vincent and L.A. Salamonsen1

Prince Henry's Institute of Medical Research Clayton, Victoria, 3168, Australia

Correspondence: 1To whom correspondence should be addressed at: Prince Henry's Institute of Medical Research, P.O.Box 5152, Clayton, Victoria, 3168, Australia. E-mail: lois.salamonsen{at}med.monash.edu.au

Progestin-only contraceptives are associated with menstrual bleeding disturbances; a major reason why these agents are discontinued. The pathogenesis of abnormal uterine bleeding associated with progestin-only contraceptives remains ill-defined. Matrix metalloproteinases (MMPs) and leukocytes are postulated to be involved in the process of normal menstruation. Immunolocalization of MMPs and leukocytes in endometrium from women using the progestinonly contraceptives, Norplant® or depot medroxyprogesterone acetate (DMPA) compared with normal controls, revealed foci of positive MMP-1 and -3 immunostaining in stromal cells and adjacent extracellular matrix, the presence of MMP-9 in various subtypes of leukocytes and alterations in mast cell phenotype. In women using progestin-only contraceptives, the extent of endometrial MMP, neutrophil and eosinophil immunolocalization and the mast cell activation state was similar to or greater than that observed in perimenstrual control women. However, differences in MMP immunostaining were observed in endometrial samples from women using different progestin-only contraceptive agents; in particular, significantly higher MMP-1 immunostaining was observed associated with the use of Norplant compared with DMPA. No correlation was observed with the number of bleeding days recorded. These results suggest that MMP and leukocytes may be involved in endometrial breakdown in women using progestin-only contraceptives.

Key words: contraceptive/leukocytes/matrix metalloproteinases/Norplant/progestin


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