title: Multinational, multicentre, randomised, open-label study evaluating the impact of a 91-day extended regimen combined oral contraceptive, compared with two 28-day traditional combined oral contraceptives, on haemostatic parameters in healthy women.
abstract: OBJECTIVE
  To evaluate the impact of a 91-day extended regimen combined oral contraceptive (150 μg levonorgestrel [LNG]/30 μg ethinylestradiol [EE] for 84 days, followed by 10 μg EE for seven days [Treatment 1]) compared with two traditional 21/7 regimens (21 days 150 μg LNG/30 μg EE [Treatment 2] or 150 μg desogestrel [DSG]/30 μg EE [Treatment 3], both with seven days' hormone free), on several coagulation factors and thrombin formation markers.
  
  
  METHODS
  Randomised, open-label, parallel-group comparative study involving healthy women (18-40 years). The primary endpoint was change from baseline in prothrombin fragment 1 + 2 (F1 + 2) levels over six months.
  
  
  RESULTS
  A total of 187 subjects were included in the primary analysis. In all groups, mean F1 + 2 values were elevated after six months of treatment. Changes were comparable between Treatments 1 and 2 (least squares mean change: 170 pmol/L and 158 pmol/L, respectively) but noticeably larger after Treatment 3 (least squares mean change: 592 pmol/L). The haemostatic effects of Treatment 1 were comparable to those of Treatment 2 and noninferior to those of Treatment 3 (lower limit of 95% confidence interval [- 18.3 pmol/L] > - 130 pmol/L).
  
  
  CONCLUSIONS
  The LNG/EE regimens had similar effects on F1 + 2. Noninferiority was demonstrated between extended regimen LNG/EE and DSG/EE.
authors.affiliation: * Research Center for Reproductive Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia , Pavia , Italy.
authors.forename: Rossella E
authors.initials: RE
authors.lastname: Nappi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Paoletti
authors.forename: Annibale
authors.initials: A
authors.lastname: Volpe
authors.forename: Luca
authors.initials: L
authors.lastname: Chiovato
authors.forename: Brandon
authors.initials: B
authors.lastname: Howard
authors.forename: Herman
authors.initials: H
authors.lastname: Weiss
authors.forename: Nancy
authors.initials: N
authors.lastname: Ricciotti
mesh_terms: D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000627:therapeutic use; D017135:Desogestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D005167:Factor VII / Q000032:analysis; D005169:Factor VIII / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000032:analysis; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D003692:Delayed-Action Preparations; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D017135:Desogestrel; D005167:Factor VII; D011516:Prothrombin; D005169:Factor VIII
keywords: Coagulation; Combined oral contraceptives; Desogestrel; Haemostatic; Levonorgestrel