title: Raised plasminogen activator inhibitor-1 (PAI-1) is not an independent risk factor in the polycystic ovary syndrome (PCOS).
abstract: BACKGROUND
  It has been postulated that an insulin-driven increase in plasminogen activator inhibitor-1 (PAI-1) levels may link insulin resistance to anovulatory infertility in women with PCOS and that it may place them at increased risk of thromboembolic disease. However, previous studies have been conflicting because many have failed to control for body mass index (BMI) which may affect PAI-1. The aim of this study was to investigate PAI-1 activity in women with PCOS and to compare it with unaffected controls of a similar BMI.
  
  
  METHODS
  41 women with PCOS and 25 weight-matched controls participated in this cross-sectional study. Patients were evaluated clinically and by pelvic ultrasound and fasting blood samples were taken for haematological and biochemical tests.
  
  
  METHODS
  PAI-1 activity, insulin, glucose, triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, FSH, LH, PRL, testosterone, SHBG, 17-hydroxyprogesterone, plasminogen, fibrinogen (alpha2 antiplasmin, blood pressure and insulin sensitivity with a homeostasis model assessment (HOMA) computer programme.
  
  
  RESULTS
  There was no significant difference in BMI or in (log) PAI-1 activity in women with PCOS compared with controls (BMI 29.5 +/- 5.6 vs. 28.4 +/- 6.3 kg/m2, P = 0.25 and PAI-1 2.56 (SD 0.85) vs. 2.14 (SD 0.98) au/ml, P = 0.07). The median fasting insulin level was significantly higher (17 (4.6-134.5) vs. 9.6 (3.7-41.5) mU/l, P < 0.01), and insulin sensitivity significantly lower in the PCOS group, ( 43.17% (5. 48-160) vs. 82.8% (21.8-193), P < 0.01). Women with PCOS also had a significantly higher free androgen index, LH/FSH ratio and a lower HDL/total cholesterol ratio. However blood pressure and all other lipid and haematological measurements were not significantly different between both groups. There were significant positive correlations between (log) PAI-1 activity and BMI (rho = 0.61), triglycerides (rho = 0.49) and fasting insulin (rho = 0.60) and a negative correlation with HDL cholesterol (rho = - 0.46). Triglyceride concentrations showed the most significant relationship with (log) PAI-1 activity on multiple regression. 29% of PCO women (12/41) gave a positive family history of thrombosis compared to 8% (2/25) in the control group.
  
  
  CONCLUSIONS
  Plasminogen activator inhibitor-1 activity is not raised in women with PCOS independent of obesity and these results do not support the hypothesis that it may contribute to their anovulatory infertility, or increase their risk of thrombosis. The only significant metabolic features of the PCOS independent of obesity are insulin resistance, hyperinsulinaemia and lower HDL/total cholesterol ratio. The higher frequency of a positive family history of thrombosis in these women nevertheless requires further explanation.
authors.affiliation: Departments of Gynaecology, Haematology and Endocrinology, Derriford Hospital, Plymouth, UK. watiomo@hotmail.com
authors.forename: W U
authors.initials: WU
authors.lastname: Atiomo
authors.forename: R
authors.initials: R
authors.lastname: Fox
authors.forename: J E
authors.initials: JE
authors.lastname: Condon
authors.forename: S
authors.initials: S
authors.lastname: Shaw
authors.forename: J
authors.initials: J
authors.lastname: Friend
authors.forename: A G
authors.initials: AG
authors.lastname: Prentice
authors.forename: T J
authors.initials: TJ
authors.lastname: Wilkin
mesh_terms: D000328:Adult; D000728:Androgens / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007986:Luteinizing Hormone / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D012044:Regression Analysis; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D000728:Androgens; D008076:Cholesterol, HDL; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002784:Cholesterol