title: Increased thrombin generation in women with polycystic ovary syndrome: A pilot study on the effect of metformin and oral contraceptives.
abstract: OBJECTIVE
  Polycystic ovary syndrome (PCOS) is associated with risk factors for cardiovascular disease (CVD) which may be modified by the use of metformin and oral contraceptives (OC). Thrombin generation (TG) measures are risk markers of CVD and address the composite of multiple factors that influence blood coagulation. This prospective, randomized, intervention study evaluated the potential influence of PCOS on TG measures and the effect of OC and/or metformin on TG measures in women with PCOS.
  
  
  METHODS
  Ninety patients with PCOS and 35 controls were included. Patients were randomized to 12 months of treatment with metformin, metformin+OC or OC alone. C-reactive protein (CRP), fibrinogen, total cholesterol, trunk fat mass, body mass index, estradiol, testosterone, sex hormone binding globulin (SHBG) as well as TG measures, i.e. the lag time for formation of thrombin, the endogenous thrombin potential (ETP), peak thrombin concentration (peak) and time to peak were determined at baseline and after 12 months of treatment.
  
  
  RESULTS
  CRP and total testosterone were significantly higher and SHBG significantly lower in PCOS women than in controls (P=0.012, P<0.001 and P=0.008, respectively). The TG measures ETP, peak and lag time were increased in women with PCOS compared to controls (P<0.01). Significant correlations were observed between TG measures and fibrinogen, CRP, SHBG and fat trunk mass (P>0.01). ETP (P=0.006), peak (P=0.003) and lag time (P=0.023) remained increased after adjustment for these potential confounders. Treatment with OC and metformin+OC further increased ETP (P<0.001) and peak (P<0.005) and reduced time to peak (P<0.04). The increase in ETP was significantly lower in the metformin+OC group than in the OC group (P<0.05). Metformin alone did not affect TG significantly.
  
  
  CONCLUSIONS
  PCOS is associated with increase in TG measures independent of other risk factors of CVD. OC increase TG measures further and may thus add to the increased risk of CVD already present in women with PCOS.
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, 5000 Odense C, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Glintborg
authors.affiliation: Unit for Thrombosis Research, Department of Public Health, University of Southern Denmark, Niels Bohrs Vej 9, 6700 Esbjerg, Denmark. Electronic address: jjsidelmann@health.sdu.dk.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Sidelmann
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, 5000 Odense C, Denmark.
authors.forename: Magda Lambaa
authors.initials: ML
authors.lastname: Altinok
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, 5000 Odense C, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Mumm
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, 5000 Odense C, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Andersen
mesh_terms: D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D003276:Contraceptives, Oral / Q000627:therapeutic use*; D017135:Desogestrel / Q000008:administration & dosage; D004997:Ethinyl Estradiol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008687:Metformin / Q000627:therapeutic use*; D010865:Pilot Projects; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000188:drug therapy*; D013917:Thrombin / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: D003276:Contraceptives, Oral; D004997:Ethinyl Estradiol; D017135:Desogestrel; D002097:C-Reactive Protein; D008687:Metformin; D013917:Thrombin
keywords: Blood coagulation; Metformin; Oral contraceptives; Polycystic ovary syndrome; Thrombin generation