title: Oral contraceptive containing chlormadinone acetate and ethinylestradiol reduces plasma concentrations of matrix metalloproteinase-2 in women with polycystic ovary syndrome.
abstract: Biochemical markers of cardiovascular disease, including matrix metalloproteinases (MMPs), are altered in women with polycystic ovary syndrome (PCOS), with many of these alterations thought to be due to excess androgen concentrations. Despite oral contraceptives (OCs) being the first-line pharmacological treatment in women with PCOS and the importance of MMPs in many physiological conditions and pathological states, including cardiovascular diseases, no study has yet evaluated whether OCs alter plasma concentrations of MMPs. We therefore assessed whether treatment with an OC containing the anti-androgenic progestogen alters MMP profiles in women with PCOS. We analysed 20 women with PCOS who wanted hormonal contraception (OC-PCOS group), 20 ovulatory women who required hormonal contraception (OC-control group) and 20 ovulatory women who wanted non-hormonal contraception (non-OC-control group). OC consisted of cyclic use of 2 mg chlormadinone acetate/30 μg ethinylestradiol for 6 months. Plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by gelatin zymography or enzyme-linked immunoassays. OC treatment for 6 months significantly reduced plasma MMP-2 concentrations in the OC-control and OC-PCOS groups and TIMP-2 and TIMP-1 concentrations levels in the OC-control group (all p < 0.05), but had no effects on MMP-9 concentrations or on MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in any group (all p > 0.05). These findings indicated that long-term treatment with an OC containing chlormadinone acetate plus ethinylestradiol reduced plasma MMP-2 concentrations in both healthy and PCOS women. As the latter have imbalances in circulating matrix MMPs, treatment of these women with an OC may be beneficial.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Valéria A
authors.initials: VA
authors.lastname: Gomes
authors.forename: Carolina S
authors.initials: CS
authors.lastname: Vieira
authors.forename: Anna L
authors.initials: AL
authors.lastname: Jacob-Ferreira
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Belo
authors.forename: Gustavo M
authors.initials: GM
authors.lastname: Soares
authors.forename: Janaína B
authors.initials: JB
authors.lastname: França
authors.forename: Rui A
authors.initials: RA
authors.lastname: Ferriani
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D000726:Androgen Antagonists / Q000627:therapeutic use; D000886:Anthropometry; D001938:Brazil; D002715:Chlormadinone Acetate / Q000627:therapeutic use*; D003276:Contraceptives, Oral / Q000627:therapeutic use*; D004997:Ethinyl Estradiol / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D055815:Young Adult
chemical_list: D000726:Androgen Antagonists; D003276:Contraceptives, Oral; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D002715:Chlormadinone Acetate; D019716:Tissue Inhibitor of Metalloproteinase-2; D004997:Ethinyl Estradiol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9