title: Matrix metalloproteinase-1 and -3 and mast cells are present in the endometrium of women using progestin-only contraceptives.
abstract: 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.
authors.affiliation: Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Vincent
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Ostor
authors.forename: P A
authors.initials: PA
authors.lastname: Rogers
authors.forename: B
authors.initials: B
authors.lastname: Affandi
authors.forename: G
authors.initials: G
authors.lastname: Kovacs
authors.forename: L A
authors.initials: LA
authors.lastname: Salamonsen
mesh_terms: D000328:Adult; D001706:Biopsy; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects*; D003692:Delayed-Action Preparations; D004717:Endometrium / Q000166:cytology* / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects; D008407:Mast Cells; D020781:Matrix Metalloproteinase 1 / Q000032:analysis*; D019278:Matrix Metalloproteinase 3 / Q000032:analysis*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000009:adverse effects*; D014592:Uterine Hemorrhage / Q000139:chemically induced
chemical_list: D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D045167:Progesterone Congeners; D016912:Levonorgestrel; D017258:Medroxyprogesterone Acetate; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1