title: The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study.
abstract: OBJECTIVE
  To assess the thrombotic risk associated with oral contraceptive use with a focus on dose of oestrogen and type of progestogen of oral contraceptives available in the Netherlands.
  
  
  METHODS
  Population based case-control study.
  
  
  METHODS
  Six participating anticoagulation clinics in the Netherlands (Amersfoort, Amsterdam, The Hague, Leiden, Rotterdam, and Utrecht).
  
  
  METHODS
  Premenopausal women <50 years old who were not pregnant, not within four weeks postpartum, and not using a hormone excreting intrauterine device or depot contraceptive. Analysis included 1524 patients and 1760 controls.
  
  
  METHODS
  First objectively diagnosed episodes of deep venous thrombosis of the leg or pulmonary embolism. Odds ratios calculated by cross-tabulation with a 95% confidence interval according to Woolf's method; adjusted odds ratios estimated by unconditional logistic regression, standard errors derived from the model.
  
  
  RESULTS
  Currently available oral contraceptives increased the risk of venous thrombosis fivefold compared with non-use (odds ratio 5.0, 95% CI 4.2 to 5.8). The risk clearly differed by type of progestogen and dose of oestrogen. The use of oral contraceptives containing levonorgestrel was associated with an almost fourfold increased risk of venous thrombosis (odds ratio 3.6, 2.9 to 4.6) relative to non-users, whereas the risk of venous thrombosis compared with non-use was increased 5.6-fold for gestodene (5.6, 3.7 to 8.4), 7.3-fold for desogestrel (7.3, 5.3 to 10.0), 6.8-fold for cyproterone acetate (6.8, 4.7 to 10.0), and 6.3-fold for drospirenone (6.3, 2.9 to 13.7). The risk of venous thrombosis was positively associated with oestrogen dose. We confirmed a high risk of venous thrombosis during the first months of oral contraceptive use irrespective of the type of oral contraceptives.
  
  
  CONCLUSIONS
  Currently available oral contraceptives still have a major impact on thrombosis occurrence and many women do not use the safest brands with regard to risk of venous thrombosis.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, C7-P, PO Box 9600, NL-2300 RC Leiden, Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: van Hylckama Vlieg
authors.forename: F M
authors.initials: FM
authors.lastname: Helmerhorst
authors.forename: J P
authors.initials: JP
authors.lastname: Vandenbroucke
authors.forename: C J M
authors.initials: CJ
authors.lastname: Doggen
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects*; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects*; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011372:Progestins / Q000008:administration & dosage / Q000009:adverse effects*; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000453:epidemiology; D012307:Risk Factors; D020246:Venous Thrombosis / Q000139:chemically induced* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D003278:Contraceptives, Oral, Hormonal; D003280:Contraceptives, Oral, Synthetic; D004967:Estrogens; D011372:Progestins
references.citation: World Health Organ Tech Rep Ser. 1998;877:i-vii, 1-89
references.pmid: 9615606
references.citation: Arch Intern Med. 1999 Jan 11;159(1):65-70
references.pmid: 9892332
references.citation: Cutis. 2002 Apr;69(4 Suppl):2-15
references.pmid: 12096825
references.citation: Acta Obstet Gynecol Scand Suppl. 1979;88:33-42
references.pmid: 160741
references.citation: Ann N Y Acad Sci. 1995 Jun 12;761:311-35
references.pmid: 7625729
references.citation: Lancet. 1995 Dec 16;346(8990):1575-82
references.pmid: 7500748
references.citation: Lancet. 2000 Jun 17;355(9221):2133-4
references.pmid: 10902629
references.citation: Contraception. 1998 May;57(5):291-301
references.pmid: 9673836
references.citation: J Thromb Haemost. 2005 Nov;3(11):2471-8
references.pmid: 16241945
references.citation: Thromb Haemost. 2000 Jul;84(1):15-21
references.pmid: 10928463
references.citation: Lancet. 1995 Dec 16;346(8990):1593-6
references.pmid: 7500751
references.citation: Hum Reprod Update. 1999 Nov-Dec;5(6):721-35
references.pmid: 10652981
references.citation: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD006586
references.pmid: 18254106
references.citation: Pharmacoepidemiol Drug Saf. 2004 Jul;13(7):427-36
references.pmid: 15269926
references.citation: BMJ. 2001 Jul 21;323(7305):131-4
references.pmid: 11463678
references.citation: Lancet. 1995 Dec 16;346(8990):1589-93
references.pmid: 7500750
references.citation: Am J Epidemiol. 1991 Jan;133(1):32-7
references.pmid: 1983896
references.citation: J Thromb Haemost. 2007 Apr;5(4):692-9
references.pmid: 17367492
references.citation: BMJ. 2002 Apr 13;324(7342):869
references.pmid: 11950727
references.citation: BMJ. 2003 Feb 1;326(7383):257
references.pmid: 12560278
references.citation: Lancet. 1997 Jan 11;349(9045):83-8
references.pmid: 8996419
references.citation: Contraception. 1998 Mar;57(3):169-81
references.pmid: 9617533
references.citation: Contraception. 2007 May;75(5):344-54
references.pmid: 17434015
references.citation: Contraception. 1993 Dec;48(6):557-75
references.pmid: 8131397
references.citation: Contraception. 2002 Mar;65(3):187-96
references.pmid: 11929640
references.citation: Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004425
references.pmid: 17253506
references.citation: Int J Epidemiol. 1992 Feb;21(1):48-52
references.pmid: 1544757
references.citation: J Clin Endocrinol Metab. 1995 Jun;80(6):1816-21
references.pmid: 7775629
references.citation: Hum Reprod. 2005 Feb;20(2):563-8
references.pmid: 15539435
references.citation: Lancet. 1994 Nov 26;344(8935):1453-7
references.pmid: 7968118
references.citation: Obstet Gynecol. 2007 Sep;110(3):587-93
references.pmid: 17766604
references.citation: Thromb Haemost. 2002 Feb;87(2):199-205
references.pmid: 11859850
references.citation: Lancet. 2001 Oct 27;358(9291):1427-9
references.pmid: 11705493
references.citation: Br Med J (Clin Res Ed). 1986 Feb 22;292(6519):526
references.pmid: 3081157
references.citation: Lancet. 1995 Dec 16;346(8990):1582-8
references.pmid: 7500749
references.citation: Br J Haematol. 2003 Aug;122(3):465-70
references.pmid: 12877675
references.citation: J Thromb Haemost. 2004 Nov;2(11):2060-2
references.pmid: 15550051
references.citation: Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003987
references.pmid: 16437470
references.citation: Thromb Haemost. 2000 Jul;84(1):4-8
references.pmid: 10928461
references.citation: Am J Obstet Gynecol. 1997 Oct;177(4):887-91
references.pmid: 9369840