title: The effect of levonorgestrel-releasing intrauterine system use on menstrual blood loss and the hemostatic, fibrinolytic/inhibitor systems in women with menorrhagia.
abstract: BACKGROUND
  Menorrhagia is known to be associated with uterine fibroids, adenomyosis, pelvic infections, endometrial polyps and clotting defects. A viable alternative therapy to hysterectomy should alleviate heavy menstrual blood flow and consequently improve the quality-of-life measures in women presenting with menorrhagia. The levonorgestrel-releasing intrauterine system (LNG-IUS) ranks higher than medical treatments in terms of efficacy, comparable improvements in quality of life and psychological well-being.
  
  
  OBJECTIVE
  The purpose of the study was to determine the effects of 6 months of LNG-IUS use on menstrual blood loss and the hemostatic, fibrinolytic/inhibitor systems in blood and the endometrium in women with menorrhagia with known pathologic causes.
  
  
  METHODS
  Samples from 41 women were analyzed. Hemoglobin, hematocrit, thrombelastography, tissue-type plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), u-PA receptor (u-PAR), plasminogen activator inhibitor-1/2 (PAI-1/2), D-dimer and von Willebrand factor (VWF) were determined, and t-PA, u-PA and PAI-1/2 were also determined in endometrial tissue extracts.
  
  
  RESULTS
  Menorrhagia was reduced in 89% of women by 3 months; by 6 months all women had no menorrhagia, and 39% of women had become amenorrhoeic. Hemoglobin and hematocrit levels showed improvement, and reached normal reference levels by 6 months. There were no systemic changes in the fibrinolytic/inhibitor systems and VWF, except for a decreased u-PAR level. However, in the endometrium, significant elevations in PAI-1/2 together with u-PAR levels were seen at 6 months.
  
  
  CONCLUSIONS
  The slow levonorgestrel-release intrauterine device use results in high expression of fibrinolytic inhibitors (PAI-1/2) and upregulated u-PAR expression in the endometrium. Systemic hemostasis was not significantly altered. The study demonstrated that LNG-IUS is highly effective in the treatment of menorrhagia with known pathologic causes.
authors.affiliation: Department of Obstetrics and Gynaecology, National University of Singapore, Yong Loo Lin School of Medicine, National University Hospital, Singapore, Singapore. obgkohcl@nus.edu.sg
authors.forename: S C L
authors.initials: SC
authors.lastname: Koh
authors.forename: K
authors.initials: K
authors.lastname: Singh
mesh_terms: D000328:Adult; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D004909:Erythrocyte Indices; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D005500:Follow-Up Studies; D006400:Hematocrit; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007436:Intrauterine Devices, Medicated; D016912:Levonorgestrel / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008137:Longitudinal Studies; D008595:Menorrhagia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008598:Menstruation / Q000187:drug effects*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000097:blood / Q000378:metabolism; D010960:Plasminogen Activators / Q000097:blood / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D013916:Thrombelastography; D013997:Time Factors; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D003280:Contraceptives, Oral, Synthetic; D005338:Fibrin Fibrinogen Degradation Products; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C036309:fibrin fragment D; D014841:von Willebrand Factor; D016912:Levonorgestrel; D010960:Plasminogen Activators