title: The effect of 17 beta-oestradiol on variables of coagulation and fibrinolysis in postmenopausal women with type 2 diabetes mellitus.
abstract: Type 2 diabetes mellitus is frequently accompanied by hypercoagulability and hypofibrinolysis. Both are related to increased cardiovascular risk, but possibly with endothelial injury as well. Studies with nondiabetic persons indicate that unopposed oestrogen replacement therapy (oERT) decreases cardiovascular risk, possibly mediated in part by effects on coagulation and fibrinolysis. In a double-blind, randomised placebo-controlled trial, we assessed the effect of oral 17 beta-oestradiol daily during 6 weeks on indicators of coagulation and of fibrinolysis in postmenopausal women with type 2 diabetes mellitus. We observed significant increases of Factor VII (FVII) and von Willebrand factor (vWF) after oERT and no change in the already high fibrinogen. Prothrombin fragment 1 + 2 (F1 + 2) increased after oERT, whereas thrombin-antithrombin (TAT) complexes was unchanged, but increments of F1 + 2 and TAT correlated. Soluble fibrin (SF) levels remained stable. In fibrinolysis, a clear reduction in plasminogen activator inhibitor 1 (PAI-1) was observed, but no significant change in tissue-type plasminogen activator antigen (t-PA-Ag) or activity was found, although fibrinolytic activity assessed as t-PA activity (t-PA-Act) tended to increase after oERT. Indicators of fibrinolytic activity (plasmin-antiplasmin complexes and fibrin degradation products) however did not change. oERT increased C-reactive protein (CRP) but none of the coagulation or fibrinolysis changes significantly associated with the CRP changes. It is concluded that oERT increases the coagulation potency as well as the fibrinolytic potency raising the question of the net effect in their balance. Increase in F1 + 2 suggests that in diabetic women oERT effectively increases the chronic, continuous activation of coagulation, which appears to be compensated for or not effective in the blood compartment as judged from the unchanged levels of SF. Suspected increased fibrin formation in the vascular wall is at least not followed by increases in fibrinogen degradation products (TDP), which suggests the possibility of accumulation and increased cardiovascular risk. The results indicate that specific attention should be paid to fibrin turnover in studying other categories of women and the effects of the addition of progesterone.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, University Hospital, Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands.
authors.forename: Hanny E
authors.initials: HE
authors.lastname: Brussaard
authors.forename: Jan A Gevers
authors.initials: JA
authors.lastname: Leuven
authors.forename: H Michiel J
authors.initials: HM
authors.lastname: Krans
authors.forename: Cornelis
authors.initials: C
authors.lastname: Kluft
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D018709:Statistics, Nonparametric
chemical_list: D004958:Estradiol